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1.  Heart Failure Care in Low- and Middle-Income Countries: A Systematic Review and Meta-Analysis 
PLoS Medicine  2014;11(8):e1001699.
In a systematic review and meta-analysis, Kazem Rahimi and colleagues examine the burden of heart failure in low- and middle-income countries.
Please see later in the article for the Editors' Summary
Background
Heart failure places a significant burden on patients and health systems in high-income countries. However, information about its burden in low- and middle-income countries (LMICs) is scant. We thus set out to review both published and unpublished information on the presentation, causes, management, and outcomes of heart failure in LMICs.
Methods and Findings
Medline, Embase, Global Health Database, and World Health Organization regional databases were searched for studies from LMICs published between 1 January 1995 and 30 March 2014. Additional unpublished data were requested from investigators and international heart failure experts. We identified 42 studies that provided relevant information on acute hospital care (25 LMICs; 232,550 patients) and 11 studies on the management of chronic heart failure in primary care or outpatient settings (14 LMICs; 5,358 patients). The mean age of patients studied ranged from 42 y in Cameroon and Ghana to 75 y in Argentina, and mean age in studies largely correlated with the human development index of the country in which they were conducted (r = 0.71, p<0.001). Overall, ischaemic heart disease was the main reported cause of heart failure in all regions except Africa and the Americas, where hypertension was predominant. Taking both those managed acutely in hospital and those in non-acute outpatient or community settings together, 57% (95% confidence interval [CI]: 49%–64%) of patients were treated with angiotensin-converting enzyme inhibitors, 34% (95% CI: 28%–41%) with beta-blockers, and 32% (95% CI: 25%–39%) with mineralocorticoid receptor antagonists. Mean inpatient stay was 10 d, ranging from 3 d in India to 23 d in China. Acute heart failure accounted for 2.2% (range: 0.3%–7.7%) of total hospital admissions, and mean in-hospital mortality was 8% (95% CI: 6%–10%). There was substantial variation between studies (p<0.001 across all variables), and most data were from urban tertiary referral centres. Only one population-based study assessing incidence and/or prevalence of heart failure was identified.
Conclusions
The presentation, underlying causes, management, and outcomes of heart failure vary substantially across LMICs. On average, the use of evidence-based medications tends to be suboptimal. Better strategies for heart failure surveillance and management in LMICs are needed.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
A healthy heart pumps about 23,000 liters of blood around the body every day. This blood delivers oxygen and nutrients to the rest of the body and carries carbon dioxide and waste products away from the tissues and organs. A healthy heart is therefore essential for life. Unfortunately, many people (particularly elderly people) develop heart failure, a life-threatening condition in which the heart no longer pumps enough blood to meet all the body's needs because it has become too weak or too stiff to work properly. Heart failure can affect the left, right, or both sides of the heart, and it can develop slowly (chronic heart failure) or quickly (acute heart failure). Its symptoms include swelling (edema) of the feet, ankles, and legs, tiredness, and shortness of breath. Heart failure, which is most commonly caused by coronary heart disease (blockage with fatty deposits of the blood vessels that supply the heart) or high blood pressure (hypertension), cannot be cured. However, lifestyle changes (for example, losing weight and avoiding salty food) and various medications can control heart failure and improve the quality of life of patients.
Why Was This Study Done?
In high-income countries (HICs), heart failure is a common condition that typically consumes 1%–2% of healthcare resources. Experts believe that heart failure may soon become a major public health issue in low- and middle-income countries (LMICs) because fewer people are dying of infectious diseases in these countries than in the past. LMICs need to plan for this eventuality, but little is known about the current burden of heart failure in LMICs. Here, the researchers undertake a systematic review and meta-analysis of published and unpublished information on the presentation, causes, management, and outcomes of heart failure in LMICs. A systematic review uses predefined criteria to identify all the research on a given topic; a meta-analysis uses statistical approaches to combine the results of several studies.
What Did the Researchers Do and Find?
The researchers identified 49 published studies and four unpublished databases that provided information on nearly 240,000 hospitalizations for acute and chronic heart failure in 31 LMICs. Across these LMICs, the average age of patients admitted to hospital for heart failure was 63 years, more than ten years younger than the average admission age in HICs. Differences in mean age at presentation, which ranged from 42 years in Cameroon and Ghana to 75 years in Argentina, largely correlated with the human development index (a measure of national well-being) of individual LMICs. Notably, acute heart failure accounted for 2.2% of all hospital admissions in the LMICs for which data were available. Hypertension was the main cause of heart failure in Africa and the Americas, whereas ischemic heart disease was the main cause in all other regions. More than two-thirds of patients were prescribed diuretics for heart failure, whereas only 57% of patients were treated with angiotensin-converting enzyme inhibitors, only 34% were treated with beta-blockers, and only 32% were treated with mineralocorticoid receptor antagonists, the three treatments currently recommended in guidelines for managing heart failure. Finally, on average, patients admitted to hospital for heart failure in LMICs spent ten days in hospital, and 8.3% of them died in hospital (compared to 6.7% and 4% of similar patients across Europe and the US, respectively).
What Do These Findings Mean?
These findings show that the presentation, causes, management, and outcomes of heart failure vary substantially across LMICs. Importantly, however, these findings reveal that heart failure is already a major burden in LMICs and that the use of recommended medications for heart failure is currently suboptimal in these countries. Because the studies included in this systematic review and meta-analysis set out to answer different research questions and used different methods to diagnose heart failure, the estimates of the burden of heart failure in LMICs provided here may not be completely accurate. Moreover, because the data were derived mainly from urban tertiary referral hospitals, these findings may not reflect the broader picture of heart failure in the community in LMICs. However, although additional studies are needed to completely assess the burden of heart failure in LMICs, the present findings nevertheless highlight the need to implement better strategies for the management of heart failure in LMICs.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001699.
This study is further discussed in a PLOS Medicine Perspective by Druin Burch
The US National Heart, Lung, and Blood Institute provides information for patients about heart failure
The UK National Health Service Choices website provides information about all aspects of heart failure
The American Heart Association, a not-for-profit organization, also provides detailed information about heart failure for patients and their carers
The British Heart Foundation, a not-for-profit organization, provides additional information about heart failure, including a personal story about heart failure; further personal stories about heart failure are provided by the not-for-profit organization Healthtalkonline
Heart Failure Matters provides practical information about heart failure for patients, families, and caregivers in several languages; its website includes an animated journey through heart failure and several personal stories about the condition
MedlinePlus provides links to further resources about heart failure (in English and Spanish)
doi:10.1371/journal.pmed.1001699
PMCID: PMC4130667  PMID: 25117081
2.  Patient-Safety-Related Hospital Deaths in England: Thematic Analysis of Incidents Reported to a National Database, 2010–2012 
PLoS Medicine  2014;11(6):e1001667.
Sukhmeet Panesar and colleagues classified reports of patient-safety-related hospital deaths in England to identify patterns of cases where improvements might be possible.
Please see later in the article for the Editors' Summary
Background
Hospital mortality is increasingly being regarded as a key indicator of patient safety, yet methodologies for assessing mortality are frequently contested and seldom point directly to areas of risk and solutions. The aim of our study was to classify reports of deaths due to unsafe care into broad areas of systemic failure capable of being addressed by stronger policies, procedures, and practices. The deaths were reported to a patient safety incident reporting system after mandatory reporting of such incidents was introduced.
Methods and Findings
The UK National Health Service database was searched for incidents resulting in a reported death of an adult over the period of the study. The study population comprised 2,010 incidents involving patients aged 16 y and over in acute hospital settings. Each incident report was reviewed by two of the authors, and, by scrutinising the structured information together with the free text, a main reason for the harm was identified and recorded as one of 18 incident types. These incident types were then aggregated into six areas of apparent systemic failure: mismanagement of deterioration (35%), failure of prevention (26%), deficient checking and oversight (11%), dysfunctional patient flow (10%), equipment-related errors (6%), and other (12%). The most common incident types were failure to act on or recognise deterioration (23%), inpatient falls (10%), healthcare-associated infections (10%), unexpected per-operative death (6%), and poor or inadequate handover (5%). Analysis of these 2,010 fatal incidents reveals patterns of issues that point to actionable areas for improvement.
Conclusions
Our approach demonstrates the potential utility of patient safety incident reports in identifying areas of service failure and highlights opportunities for corrective action to save lives.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Being admitted to the hospital is worrying for patients and for their relatives. Will the patient recover or die in the hospital? Some seriously ill patients will inevitably die, but in an ideal world, no one should die in the hospital because of inadequate or unsafe care (an avoidable death). No one should die, for example, because healthcare professionals fail to act on signs that indicate a decline in a patient's clinical condition. Hospital mortality (death) is often regarded as a key indicator of patient safety in hospitals, and death rate indicators such as the “hospital standardized mortality ratio” (the ratio of the actual number of acute in-hospital deaths to the expected number of in-hospital deaths) are widely used to monitor and improve hospital safety standards. In England, for example, a 2012 report that included this measure as an indicator of hospital performance led to headlines of “worryingly high” hospital death rates and to a review of the quality of care in the hospitals with the highest death rates.
Why Was This Study Done?
Hospital standardized mortality ratios and other measures of in-patient mortality can be misleading because they can, for example, reflect the burden of disease near the hospital rather than the hospital's quality of care or safety levels. Moreover, comparative data on hospital mortality rates are of limited value in identifying areas of risk to patients or solutions to the problem of avoidable deaths. In this study, to identify areas of service failure amenable to improvement through strengthened clinical policies, procedures, and practices, the researchers undertake a thematic analysis of deaths in hospitals in England that were reported by healthcare staff to a mandatory patient-safety-related incident reporting system. Since 2004, staff in the UK National Health Service (the NHS comprises the publicly funded healthcare systems in England, Scotland, Wales, and Northern Ireland) have been encouraged to report any unintended or unexpected incident in which they believe a patient's safety was compromised. Since June 2010, it has been mandatory for staff in England and Wales to report deaths due to patient-safety-related incidents. A thematic analysis examines patterns (“themes”) within nonnumerical (qualitative) data.
What Did the Researchers Do and Find?
By searching the NHS database of patient-safety-related incidents, the researchers identified 2010 incidents that occurred between 1 June 2010 and 31 October 2012 that resulted in the death of adult patients in acute hospital settings. By scrutinizing the structured information in each incident report and the associated free text in which the reporter described what happened and why they think it happened, the researchers classified the reports into 18 incident categories. These categories fell into six broad areas of systemic failure—mismanagement of deterioration (35% of incidents), failure of prevention (26%), deficient checking and oversight (11%), dysfunctional patient flow (10%), equipment-related errors (6%), and other (12%, incidents where the problem underlying death was unclear). Management of deterioration, for example, included the incident categories “failure to act on or recognize deterioration” (23% of reported incidents), “failure to give ordered treatment/support in a timely manner,” and “failure to observe.” Failure of prevention included the incident categories “falls” (10% of reported incidents), “healthcare-associated infections” (also 10% of reported incidents), “pressure sores,” “suicides,” and “deep vein thrombosis/pulmonary embolism.”
What Do These Findings Mean?
Although the accuracy of these findings may be limited by data quality and by other aspects of the study design, they reveal patterns of patient-safety-related deaths in hospitals in England and highlight areas of healthcare that can be targeted for improvement. The finding that the mismanagement of deterioration of acutely ill patients is involved in a third of patient-safety-related deaths identifies an area of particular concern in the NHS and, potentially, in other healthcare systems. One way to reduce deaths associated with the mismanagement of deterioration, suggest the researchers, might be to introduce a standardized early warning score to ensure uniform identification of this population of patients. The researchers also suggest that more effort should be put into designing programs to prevent falls and other incidents and into ensuring that these programs are effectively implemented. More generally, the classification system developed here has the potential to help hospital boards and clinicians identify areas of patient care that require greater scrutiny and intervention and thereby save the lives of many hospital patients.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001667.
The NHS provides information about patient safety, including a definition of a patient safety incident and information on reporting patient safety incidents
The NHS Choices website includes several “Behind the Headlines” articles that discuss patient safety in hospitals, including an article that discusses the 2012 report of high hospital death rates in England, “Fit for the Future?” and another that discusses the Keogh review of the quality of care in the hospitals with highest death rates
The US Agency for Healthcare Research and Quality provides information on patient safety in the US
Wikipedia has pages on thematic analysis and on patient safety (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
doi:10.1371/journal.pmed.1001667
PMCID: PMC4068985  PMID: 24959751
3.  Advice from a Medical Expert through the Internet on Queries about AIDS and Hepatitis: Analysis of a Pilot Experiment 
PLoS Medicine  2006;3(7):e256.
Background
Advice from a medical expert on concerns and queries expressed anonymously through the Internet by patients and later posted on the Web, offers a new type of patient–doctor relationship. The aim of the current study was to perform a descriptive analysis of questions about AIDS and hepatitis made to an infectious disease expert and sent through the Internet to a consumer-oriented Web site in the Spanish language.
Methods and Findings
Questions were e-mailed and the questions and answers were posted anonymously in the “expert-advice” section of a Web site focused on AIDS and hepatitis. We performed a descriptive study and a temporal analysis of the questions received in the first 12 months after the launch of the site. A total of 899 questions were received from December 2003 to November 2004, with a marked linear growth pattern. Questions originated in Spain in 68% of cases and 32% came from Latin America (the Caribbean, Central America, and South America). Eighty percent of the senders were male. Most of the questions concerned HIV infection (79%) with many fewer on hepatitis (17%) . The highest numbers of questions were submitted just after the weekend (37% of questions were made on Mondays and Tuesdays). Risk factors for contracting HIV infection were the most frequent concern (69%), followed by the window period for detection (12.6%), laboratory results (5.9%), symptoms (4.7%), diagnosis (2.7%), and treatment (2.2%).
Conclusions
Our results confirm a great demand for this type of “ask-the-expert” Internet service, at least for AIDS and hepatitis. Factors such as anonymity, free access, and immediate answers have been key factors in its success.
Editors' Summary
Background.
Although substantial progress has been made in the fight against HIV/AIDS, in terms of developing new treatments and understanding factors that cause the disease to worsen, putting this knowledge into practice can be difficult. Two main barriers exist that can prevent individuals seeking information or treatment. The first is the considerable social stigma still associated with HIV; the second is the poverty of the developing countries—such as those in Latin America—where the disease has reached pandemic proportions. In addition, the disease, which used to be spread mainly through the sharing of injecting drug needles or through sex between men, has now entered the general population. When healthcare services are limited, people are often unable to seek information about HIV, and even when services do exist, the cost of accessing them can be too high. The same is true for other diseases such as hepatitis infection, which often co-exists with HIV. The Internet has the potential to go some way to filling this health information gap. And, many patients seek information on the Internet before consulting their doctor.
Why Was This Study Done?
In 2003, the Madrid-based newspaper El Mundo launched an HIV and hepatitis information resource situated in the health section of its existing Web site. One aspect of this resource was an “ask-the-expert” section, in which readers could anonymously e-mail questions about HIV and hepatitis that would be answered by an infectious disease expert. These ranged from how the diseases can be transmitted and who is most at risk, to what to do if an individual thinks they might have the disease. There seems to be a clear need for this Spanish-language service; in Latin America, 2.1 million people are infected with HIV, with 230,000 new cases in 2005. In the Caribbean, AIDS is the leading cause of death in people aged 15–44 years. In Spain, 71,000 people were infected with HIV in 2005. Although the Internet contains a vast store of health information, and many aspects of patient–doctor interactions have been made electronic, little is known about what format is ideal. The researchers, who included employees of the newspaper, decided to investigate the effectiveness of the question–answer format used by El Mundo.
What Did the Researchers Do and Find?
In the first 12 months after the service was launched, the researchers recorded several details: what day of the week questions were sent, what the questions were about, and whether they were sent by the person needing the information or by a family member or friend. They also noted demographic information, such as the age, sex, and country of origin of the person e-mailing the question.
Of 899 questions sent to the Web site between December 2003 and November 2004, most (80%) were sent by males. Most questions came from Spain, followed by Latin America, and most questions were sent on Mondays and Tuesdays. Some e-mails were from people who felt they had been waiting too long for an answer to their first e-mail—despite the mean time for answering a question being fewer than seven days. Messages of support for the Web site rose during the year from 2% to 22%.
What Do These Findings Mean?
The messages of support and encouragement sent in by users indicated that the service was well-received and useful. Most of the questions were about HIV rather than about hepatitis, which the researchers say could represent the more prominent media coverage of HIV. However, despite the disease's high profile, the questions about HIV were very basic. It could also mean that people hold a false impression that hepatitis is a less serious illness or that they have more information about it than about HIV.
Since most questions were sent in at the start of the week, the researchers believe that many individuals wrote in after engaging in potentially risky sexual behaviour over the weekend.
The researchers also found that existing information on the Web site already answered many of the new questions, indicating that people prefer a question-and-answer model over ready-prepared information. The anonymity, free access, and immediacy of the Internet-based service suggest this could be a model for providing other types of health information.
The findings also suggest that such a service can highlight the needs and concerns of specific populations and can help health planners and policymakers respond to those needs in their countries.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030256.
• The AIDSinfo Web site from the US Department of Health and Human Services provides information on all aspects of HIV/AIDS treatment and prevention and has sections specially written for patients and the general public
• AVERT, an international AIDS charity, has a section on HIV in Latin America that includes details of transmission, infection rates, and treatment
Marco and colleagues analyzed questions sent by the public to a Spanish language "ask-the-expert" Internet site, and found that 70% of queries were about risk factors for acquiring HIV.
doi:10.1371/journal.pmed.0030256
PMCID: PMC1483911  PMID: 16796404
4.  Inclusion of Ethical Issues in Dementia Guidelines: A Thematic Text Analysis 
PLoS Medicine  2013;10(8):e1001498.
Background
Clinical practice guidelines (CPGs) aim to improve professionalism in health care. However, current CPG development manuals fail to address how to include ethical issues in a systematic and transparent manner. The objective of this study was to assess the representation of ethical issues in general CPGs on dementia care.
Methods and Findings
To identify national CPGs on dementia care, five databases of guidelines were searched and national psychiatric associations were contacted in August 2011 and in June 2013. A framework for the assessment of the identified CPGs' ethical content was developed on the basis of a prior systematic review of ethical issues in dementia care. Thematic text analysis and a 4-point rating score were employed to assess how ethical issues were addressed in the identified CPGs. Twelve national CPGs were included. Thirty-one ethical issues in dementia care were identified by the prior systematic review. The proportion of these 31 ethical issues that were explicitly addressed by each CPG ranged from 22% to 77%, with a median of 49.5%. National guidelines differed substantially with respect to (a) which ethical issues were represented, (b) whether ethical recommendations were included, (c) whether justifications or citations were provided to support recommendations, and (d) to what extent the ethical issues were explained.
Conclusions
Ethical issues were inconsistently addressed in national dementia guidelines, with some guidelines including most and some including few ethical issues. Guidelines should address ethical issues and how to deal with them to help the medical profession understand how to approach care of patients with dementia, and for patients, their relatives, and the general public, all of whom might seek information and advice in national guidelines. There is a need for further research to specify how detailed ethical issues and their respective recommendations can and should be addressed in dementia guidelines.
Please see later in the article for the Editors' Summary
Editors’ Summary
Background
In the past, doctors tended to rely on their own experience to choose the best treatment for their patients. Faced with a patient with dementia (a brain disorder that affects short-term memory and the ability tocarry out normal daily activities), for example, a doctor would use his/her own experience to help decide whether the patient should remain at home or would be better cared for in a nursing home. Similarly, the doctor might have to decide whether antipsychotic drugs might be necessary to reduce behavioral or psychological symptoms such as restlessness or shouting. However, over the past two decades, numerous evidence-based clinical practice guidelines (CPGs) have been produced by governmental bodies and medical associations that aim to improve standards of clinical competence and professionalism in health care. During the development of each guideline, experts search the medical literature for the current evidence about the diagnosis and treatment of a disease, evaluate the quality of that evidence, and then make recommendations based on the best evidence available.
Why Was This Study Done?
Currently, CPG development manuals do not address how to include ethical issues in CPGs. A health-care professional is ethical if he/she behaves in accordance with the accepted principles of right and wrong that govern the medical profession. More specifically, medical professionalism is based on a set of binding ethical principles—respect for patient autonomy, beneficence, non-malfeasance (the “do no harm” principle), and justice. In particular, CPG development manuals do not address disease-specific ethical issues (DSEIs), clinical ethical situations that are relevant to the management of a specific disease. So, for example, a DSEI that arises in dementia care is the conflict between the ethical principles of non-malfeasance and patient autonomy (freedom-to-move-at-will). Thus, healthcare professionals may have to decide to physically restrain a patient with dementia to prevent the patient doing harm to him- or herself or to someone else. Given the lack of guidance on how to address ethical issues in CPG development manuals, in this thematic text analysis, the researchers assess the representation of ethical issues in CPGs on general dementia care. Thematic text analysis uses a framework for the assessment of qualitative data (information that is word-based rather than number-based) that involves pinpointing, examining, and recording patterns (themes) among the available data.
What Did the Researchers Do and Find?
The researchers identified 12 national CPGs on dementia care by searching guideline databases and by contacting national psychiatric associations. They developed a framework for the assessment of the ethical content in these CPGs based on a previous systematic review of ethical issues in dementia care. Of the 31 DSEIs included by the researchers in their analysis, the proportion that were explicitly addressed by each CPG ranged from 22% (Switzerland) to 77% (USA); on average the CPGs explicitly addressed half of the DSEIs. Four DSEIs—adequate consideration of advanced directives in decision making, usage of GPS and other monitoring techniques, covert medication, and dealing with suicidal thinking—were not addressed in at least 11 of the CPGs. The inclusion of recommendations on how to deal with DSEIs ranged from 10% of DSEIs covered in the Swiss CPG to 71% covered in the US CPG. Overall, national guidelines differed substantially with respect to which ethical issues were included, whether ethical recommendations were included, whether justifications or citations were provided to support recommendations, and to what extent the ethical issues were clearly explained.
What Do These Findings Mean?
These findings show that national CPGs on dementia care already address clinical ethical issues but that the extent to which the spectrum of DSEIs is considered varies widely within and between CPGs. They also indicate that recommendations on how to deal with DSEIs often lack the evidence that health-care professionals use to justify their clinical decisions. The researchers suggest that this situation can and should be improved, although more research is needed to determine how ethical issues and recommendations should be addressed in dementia guidelines. A more systematic and transparent inclusion of DSEIs in CPGs for dementia (and for other conditions) would further support the concept of medical professionalism as a core element of CPGs, note the researchers, but is also important for patients and their relatives who might turn to national CPGs for information and guidance at a stressful time of life.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001498.
Wikipedia contains a page on clinical practice guidelines (note: Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
The US National Guideline Clearinghouse provides information on national guidelines, including CPGs for dementia
The Guidelines International Network promotes the systematic development and application of clinical practice guidelines
The American Medical Association provides information about medical ethics; the British Medical Association provides information on all aspects of ethics and includes an essential tool kit that introduces common ethical problems and practical ways to deal with them
The UK National Health Service Choices website provides information about dementia, including a personal story about dealing with dementia
MedlinePlus provides links to additional resources about dementia and about Alzheimers disease, a specific type of dementia (in English and Spanish)
The UK Nuffield Council on Bioethics provides the report Dementia: ethical issues and additional information on the public consultation on ethical issues in dementia care
doi:10.1371/journal.pmed.1001498
PMCID: PMC3742442  PMID: 23966839
5.  Threats to Validity in the Design and Conduct of Preclinical Efficacy Studies: A Systematic Review of Guidelines for In Vivo Animal Experiments 
PLoS Medicine  2013;10(7):e1001489.
Background
The vast majority of medical interventions introduced into clinical development prove unsafe or ineffective. One prominent explanation for the dismal success rate is flawed preclinical research. We conducted a systematic review of preclinical research guidelines and organized recommendations according to the type of validity threat (internal, construct, or external) or programmatic research activity they primarily address.
Methods and Findings
We searched MEDLINE, Google Scholar, Google, and the EQUATOR Network website for all preclinical guideline documents published up to April 9, 2013 that addressed the design and conduct of in vivo animal experiments aimed at supporting clinical translation. To be eligible, documents had to provide guidance on the design or execution of preclinical animal experiments and represent the aggregated consensus of four or more investigators. Data from included guidelines were independently extracted by two individuals for discrete recommendations on the design and implementation of preclinical efficacy studies. These recommendations were then organized according to the type of validity threat they addressed. A total of 2,029 citations were identified through our search strategy. From these, we identified 26 guidelines that met our eligibility criteria—most of which were directed at neurological or cerebrovascular drug development. Together, these guidelines offered 55 different recommendations. Some of the most common recommendations included performance of a power calculation to determine sample size, randomized treatment allocation, and characterization of disease phenotype in the animal model prior to experimentation.
Conclusions
By identifying the most recurrent recommendations among preclinical guidelines, we provide a starting point for developing preclinical guidelines in other disease domains. We also provide a basis for the study and evaluation of preclinical research practice.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The development process for new drugs is lengthy and complex. It begins in the laboratory, where scientists investigate the causes of diseases and identify potential new treatments. Next, promising interventions undergo preclinical research in cells and in animals (in vivo animal experiments) to test whether the intervention has the expected effect and to support the generalization (extension) of this treatment–effect relationship to patients. Drugs that pass these tests then enter clinical trials, where their safety and efficacy is tested in selected groups of patients under strictly controlled conditions. Finally, the government bodies responsible for drug approval review the results of the clinical trials, and successful drugs receive a marketing license, usually a decade or more after the initial laboratory work. Notably, only 11% of agents that enter clinical testing (investigational drugs) are ultimately licensed.
Why Was This Study Done?
The frequent failure of investigational drugs during clinical translation is potentially harmful to trial participants. Moreover, the costs of these failures are passed onto healthcare systems in the form of higher drug prices. It would be good, therefore, to reduce the attrition rate of investigational drugs. One possible explanation for the dismal success rate of clinical translation is that preclinical research, the key resource for justifying clinical development, is flawed. To address this possibility, several groups of preclinical researchers have issued guidelines intended to improve the design and execution of in vivo animal studies. In this systematic review (a study that uses predefined criteria to identify all the research on a given topic), the authors identify the experimental practices that are commonly recommended in these guidelines and organize these recommendations according to the type of threat to validity (internal, construct, or external) that they address. Internal threats to validity are factors that confound reliable inferences about treatment–effect relationships in preclinical research. For example, experimenter expectation may bias outcome assessment. Construct threats to validity arise when researchers mischaracterize the relationship between an experimental system and the clinical disease it is intended to represent. For example, researchers may use an animal model for a complex multifaceted clinical disease that only includes one characteristic of the disease. External threats to validity are unseen factors that frustrate the transfer of treatment–effect relationships from animal models to patients.
What Did the Researchers Do and Find?
The researchers identified 26 preclinical guidelines that met their predefined eligibility criteria. Twelve guidelines addressed preclinical research for neurological and cerebrovascular drug development; other disorders covered by guidelines included cardiac and circulatory disorders, sepsis, pain, and arthritis. Together, the guidelines offered 55 different recommendations for the design and execution of preclinical in vivo animal studies. Nineteen recommendations addressed threats to internal validity. The most commonly included recommendations of this type called for the use of power calculations to ensure that sample sizes are large enough to yield statistically meaningful results, random allocation of animals to treatment groups, and “blinding” of researchers who assess outcomes to treatment allocation. Among the 25 recommendations that addressed threats to construct validity, the most commonly included recommendations called for characterization of the properties of the animal model before experimentation and matching of the animal model to the human manifestation of the disease. Finally, six recommendations addressed threats to external validity. The most commonly included of these recommendations suggested that preclinical research should be replicated in different models of the same disease and in different species, and should also be replicated independently.
What Do These Findings Mean?
This systematic review identifies a range of investigational recommendations that preclinical researchers believe address threats to the validity of preclinical efficacy studies. Many of these recommendations are not widely implemented in preclinical research at present. Whether the failure to implement them explains the frequent discordance between the results on drug safety and efficacy obtained in preclinical research and in clinical trials is currently unclear. These findings provide a starting point, however, for the improvement of existing preclinical research guidelines for specific diseases, and for the development of similar guidelines for other diseases. They also provide an evidence-based platform for the analysis of preclinical evidence and for the study and evaluation of preclinical research practice. These findings should, therefore, be considered by investigators, institutional review bodies, journals, and funding agents when designing, evaluating, and sponsoring translational research.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001489.
The US Food and Drug Administration provides information about drug approval in the US for consumers and for health professionals; its Patient Network provides a step-by-step description of the drug development process that includes information on preclinical research
The UK Medicines and Healthcare Products Regulatory Agency (MHRA) provides information about all aspects of the scientific evaluation and approval of new medicines in the UK; its My Medicine: From Laboratory to Pharmacy Shelf web pages describe the drug development process from scientific discovery, through preclinical and clinical research, to licensing and ongoing monitoring
The STREAM website provides ongoing information about policy, ethics, and practices used in clinical translation of new drugs
The CAMARADES collaboration offers a “supporting framework for groups involved in the systematic review of animal studies” in stroke and other neurological diseases
doi:10.1371/journal.pmed.1001489
PMCID: PMC3720257  PMID: 23935460
6.  Content and Functionality of Alcohol and Other Drug Websites: Results of an Online Survey 
Background
There is a growing trend for individuals to seek health information from online sources. Alcohol and other drug (AOD) use is a significant health problem worldwide, but access and use of AOD websites is poorly understood.
Objective
To investigate content and functionality preferences for AOD and other health websites.
Methods
An anonymous online survey examined general Internet and AOD-specific usage and search behaviors, valued features of AOD and health-related websites (general and interactive website features), indicators of website trustworthiness, valued AOD website tools or functions, and treatment modality preferences.
Results
Surveys were obtained from 1214 drug (n = 766) and alcohol website users (n = 448) (mean age 26.2 years, range 16-70). There were no significant differences between alcohol and drug groups on demographic variables, Internet usage, indicators of website trustworthiness, or on preferences for AOD website functionality. A robust website design/navigation, open access, and validated content provision were highly valued by both groups. While attractiveness and pictures or graphics were also valued, high-cost features (videos, animations, games) were minority preferences. Almost half of respondents in both groups were unable to readily access the information they sought. Alcohol website users placed greater importance on several AOD website tools and functions than did those accessing other drug websites: online screening tools (χ²2 = 15.8, P < .001, n = 985); prevention programs (χ²2 = 27.5, P < .001, n = 981); tracking functions (χ²2 = 11.5, P = .003, n = 983); self help treatment programs (χ²2 = 8.3, P = .02, n = 984); downloadable fact sheets for friends (χ²2 = 11.6, P = .003, n = 981); or family (χ²2 = 12.7, P = .002, n = 983). The most preferred online treatment option for both the user groups was an Internet site with email therapist support. Explorations of demographic differences were also performed. While gender did not affect survey responses, younger respondents were more likely to value interactive and social networking features, whereas downloading of credible information was most highly valued by older respondents.
Conclusions
Significant deficiencies in the provision of accessible information on AOD websites were identified, an important problem since information seeking was the most common reason for accessing these websites, and, therefore, may be a key avenue for engaging website users in behaviour change. The few differences between AOD website users suggested that both types of websites may have similar features, although alcohol website users may more readily be engaged in screening, prevention and self-help programs, tracking change, and may value fact sheets more highly. While the sociodemographic differences require replication and clarification, these differences support the notion that the design and features of AOD websites should target specific audiences to have maximal impact.
doi:10.2196/jmir.1449
PMCID: PMC3057306  PMID: 21169168
Alcohol; drugs; Internet; online survey; stress; health; website interactivity; website trustworthiness; Web-based interventions
7.  Patented Drug Extension Strategies on Healthcare Spending: A Cost-Evaluation Analysis 
PLoS Medicine  2013;10(6):e1001460.
In a cost-evaluation analysis of pharmacy invoice data in one Canton in Switzerland, Nathalie Vernaz and colleagues find that “evergreening” strategies pursued by drug manufacturers have been successful in maintaining market share and contribute to increased overall healthcare costs.
Please see later in the article for the Editors' Summary
Background
Drug manufacturers have developed “evergreening” strategies to compete with generic medication after patent termination. These include marketing of slightly modified follow-on drugs. We aimed to estimate the financial impact of these drugs on overall healthcare costs and also to examine the impact of listing these drugs in hospital restrictive drug formularies (RDFs) on the healthcare system as a whole (“spillover effect”).
Methods and Findings
We used hospital and community pharmacy invoice office data in the Swiss canton of Geneva to calculate utilisation of eight follow-on drugs in defined daily doses between 2000 and 2008. “Extra costs” were calculated for three different scenarios assuming replacement with the corresponding generic equivalent for prescriptions of (1) all brand (i.e., initially patented) drugs, (2) all follow-on drugs, or (3) brand and follow-on drugs. To examine the financial spillover effect we calculated a monthly follow-on drug market share in defined daily doses for medications prescribed by hospital physicians but dispensed in community pharmacies, in comparison to drugs prescribed by non-hospital physicians in the community.
Estimated “extra costs” over the study period were €15.9 (95% CI 15.5; 16.2) million for scenario 1, €14.4 (95% CI 14.1; 14.7) million for scenario 2, and €30.3 (95% CI 29.8; 30.8) million for scenario 3. The impact of strictly switching all patients using proton-pump inhibitors to esomeprazole at admission resulted in a spillover “extra cost” of €330,300 (95% CI 276,100; 383,800), whereas strictly switching to generic cetirizine resulted in savings of €7,700 (95% CI 4,100; 11,100). Overall we estimated that the RDF resulted in “extra costs” of €503,600 (95% CI 444,500; 563,100).
Conclusions
Evergreening strategies have been successful in maintaining market share in Geneva, offsetting competition by generics and cost containment policies. Hospitals may be contributing to increased overall healthcare costs by listing follow-on drugs in their RDF. Therefore, healthcare providers and policy makers should be aware of the impact of evergreening strategies.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
The development of a new medical drug—from discovery of a new compound to regulatory approval for its use—can take many years and cost millions of dollars. In 1995 the World Trade Organization adopted an international law (Trade-Related Aspects of Intellectual Property Rights—TRIPS) by which pharmaceutical companies can protect their intellectual property through patents. Under TRIPS, pharmaceutical companies are granted exclusive manufacturing rights for up to 20 years for each new drug, generating large revenues that often exceed initial investments costs, thus providing an incentive for pharmaceutical companies to continue to invest in the research and development of new drugs. However, recent stricter regulatory procedures for drug approval, national price control policies, and increased competition from generic manufacturers (that produce drugs similar to the brand drug once the patent has expired) have meant that pharmaceutical company profits have increasingly come under pressure.
Why Was This Study Done?
One of the tactics that pharmaceutical companies currently use in response to this situation is to extend their market monopoly. This practice is known as “evergreening” and refers to the situation in which pharmaceutical companies slightly change the formulation of their brand drug into “follow on” drugs, for example, by combining formulations or producing slow-release forms, so that they can extend the patent. The impact of such follow-on drugs on overall healthcare costs in high-resource settings is unclear and has received little attention. In this study, the researchers assessed the overall costs associated with the prescribing of follow-on drugs in the Swiss canton of Geneva.
What Did the Researchers Do and Find?
The researchers identified prescriptions of eight follow-on drugs issued by hospital and community pharmacists in Geneva between 2000 and 2008. To analyze the impact of evergreening strategies on healthcare spending, they calculated the market share score (an indicator of market competitiveness) for all prescriptions of the originally patented (brand) drug, the follow-on drug, and generic versions of the drug. The researchers then used hospital and community databases to analyze the costs of replacing brand and/or follow-on drugs with a corresponding generic drug (when available) under three scenarios (1) replacing all brand drug prescriptions, (2) replacing all follow-on drug prescriptions, and (3) replacing both follow-on and brand prescriptions.
Using these methods, the researchers found that over the study period, the number of patients receiving either a brand or follow-on drug increased from 56,686 patients in 2001 to 131,193 patients in 2008. The total cost for all studied drugs was €171.5 million, of which €103.2 million was for brand drugs, €41.1 million was for follow-on drugs, and €27.2 million was for generic drugs. Based on scenario 1 (all brand drugs being replaced by generics) and scenario 2 (all follow-on drugs being replaced by generics), over the study period, the healthcare system could have saved €15.9 million and €14.4 million in extra costs, respectively. The researchers also found some evidence that hospital prescribing patterns (through a restrictive drug formulary) influenced prescribing in the community: over the study period, the influence of hospital prescription patterns on the community resulted in an extra cost of €503,600 (mainly attributable to two drugs, esomeprazole and escitalopram). However, this influence also resulted in some savings because of a generic drug listed in the hospital formulary: use of the generic version of the drug cetirizine resulted in savings of €7,700.
What Do These Findings Mean?
These findings show that in a high-income setting, evergreening strategies developed by pharmaceutical companies for follow-on drugs substantially contributed to an increase in overall healthcare costs. These findings also provide further evidence that policies encouraging prescribing of generic medicines could have substantial savings on healthcare expenditure and, if implemented in hospital formularies, could also influence prescribing outside of the hospital setting, resulting in further savings. However, in their analysis, the researchers assumed that the health outcomes of patients would be the same whatever type of drug they used (brand, generic, or follow-on), as they had no information on health outcomes. Nevertheless, this study provides useful information for healthcare providers and policy makers about the cost implications of the evergreening strategies used by the pharmaceutical industry, particularly for follow-on drugs.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001460.
This study is further discussed in a PLOS Medicine Perspective by Aaron Kesselheim
Wikipedia provides an explanation of evergreening (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
The World Trade Organization has detailed information on TRIPS
doi:10.1371/journal.pmed.1001460
PMCID: PMC3672218  PMID: 23750120
8.  An evaluation of the content and quality of tinnitus information on websites preferred by General Practitioners 
Background
Tinnitus is a prevalent and complex medical complaint often co-morbid with stress, anxiety, insomnia, depression, and cognitive or communication difficulties. Its chronicity places a major burden on primary and secondary healthcare services. In our recent national survey of General Practitioners (GPs) from across England, many reported that their awareness of tinnitus was limited and as a result were dissatisfied with the service they currently provide. GPs identified 10 online sources of information they currently use in clinical practice, but welcomed further concise and accurate information on tinnitus assessment and management. The purpose of this study was to assess the content, reliability, and quality of the information related to primary care tinnitus assessment and management on these 10 websites.
Methods
Tinnitus related content on each website was assessed using a summative content analysis approach. Reliability and quality of the information was assessed using the DISCERN questionnaire.
Results
Quality of information was rated using the validated DISCERN questionnaire. Significant inter-rater reliability was confirmed by Kendall’s coefficient of concordance (Wt) which ranged from 0.48 to 0.92 across websites. The website Map of Medicine achieved the highest overall DISCERN score. However, for information on treatment choice, the British Tinnitus Association was rated best. Content analysis revealed that all websites lacked a number of details relating to either tinnitus assessment or management options.
Conclusions
No single website provides comprehensive information for GPs on tinnitus assessment and management and so GPs may need to refer to more than one if they want to maximise their coverage of the topic. From those preferred by GPs we recommend several specific websites as the current ‘best’ sources. Our findings should guide healthcare website providers to improve the quality and inclusiveness of the information they publish on tinnitus. In the case of one website, our preliminary findings are already doing so. Such developments will in turn help facilitate best practice in primary care.
doi:10.1186/1472-6947-12-70
PMCID: PMC3439701  PMID: 22788751
World wide web; Education; Good practice guidelines; Tinnitus management
9.  Yellow Fever in Africa: Estimating the Burden of Disease and Impact of Mass Vaccination from Outbreak and Serological Data 
PLoS Medicine  2014;11(5):e1001638.
Neil Ferguson and colleagues estimate the disease burden of yellow fever in Africa, as well as the impact of mass vaccination campaigns.
Please see later in the article for the Editors' Summary
Background
Yellow fever is a vector-borne disease affecting humans and non-human primates in tropical areas of Africa and South America. While eradication is not feasible due to the wildlife reservoir, large scale vaccination activities in Africa during the 1940s to 1960s reduced yellow fever incidence for several decades. However, after a period of low vaccination coverage, yellow fever has resurged in the continent. Since 2006 there has been substantial funding for large preventive mass vaccination campaigns in the most affected countries in Africa to curb the rising burden of disease and control future outbreaks. Contemporary estimates of the yellow fever disease burden are lacking, and the present study aimed to update the previous estimates on the basis of more recent yellow fever occurrence data and improved estimation methods.
Methods and Findings
Generalised linear regression models were fitted to a dataset of the locations of yellow fever outbreaks within the last 25 years to estimate the probability of outbreak reports across the endemic zone. Environmental variables and indicators for the surveillance quality in the affected countries were used as covariates. By comparing probabilities of outbreak reports estimated in the regression with the force of infection estimated for a limited set of locations for which serological surveys were available, the detection probability per case and the force of infection were estimated across the endemic zone.
The yellow fever burden in Africa was estimated for the year 2013 as 130,000 (95% CI 51,000–380,000) cases with fever and jaundice or haemorrhage including 78,000 (95% CI 19,000–180,000) deaths, taking into account the current level of vaccination coverage. The impact of the recent mass vaccination campaigns was assessed by evaluating the difference between the estimates obtained for the current vaccination coverage and for a hypothetical scenario excluding these vaccination campaigns. Vaccination campaigns were estimated to have reduced the number of cases and deaths by 27% (95% CI 22%–31%) across the region, achieving up to an 82% reduction in countries targeted by these campaigns. A limitation of our study is the high level of uncertainty in our estimates arising from the sparseness of data available from both surveillance and serological surveys.
Conclusions
With the estimation method presented here, spatial estimates of transmission intensity can be combined with vaccination coverage levels to evaluate the impact of past or proposed vaccination campaigns, thereby helping to allocate resources efficiently for yellow fever control. This method has been used by the Global Alliance for Vaccines and Immunization (GAVI Alliance) to estimate the potential impact of future vaccination campaigns.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Yellow fever is a flavivirus infection that is transmitted to people and to non-human primates through the bites of infected mosquitoes. This serious viral disease affects people living in and visiting tropical regions of Africa and Central and South America. In rural areas next to forests, the virus typically causes sporadic cases or even small-scale epidemics (outbreaks) but, if it is introduced into urban areas, it can cause large explosive epidemics that are hard to control. Although many people who contract yellow fever do not develop any symptoms, some have mild flu-like symptoms, and others develop a high fever with jaundice (yellowing of the skin and eyes) or hemorrhaging (bleeding) from the mouth, nose, eyes, or stomach. Half of patients who develop these severe symptoms die. Because of this wide spectrum of symptoms, which overlap with those of other tropical diseases, it is hard to diagnose yellow fever from symptoms alone. However, serological tests that detect antibodies to the virus in the blood can help in diagnosis. There is no specific antiviral treatment for yellow fever but its symptoms can be treated.
Why Was This Study Done?
Eradication of yellow fever is not feasible because of the wildlife reservoir for the virus but there is a safe, affordable, and highly effective vaccine against the disease. Large-scale vaccination efforts during the 1940s, 1950s, and 1960s reduced the yellow fever burden for several decades but, after a period of low vaccination coverage, the number of cases rebounded. In 2005, the Yellow Fever Initiative—a collaboration between the World Health Organization (WHO) and the United Nations Children Fund supported by the Global Alliance for Vaccines and Immunization (GAVI Alliance)—was launched to create a vaccine stockpile for use in epidemics and to implement preventive mass vaccination campaigns in the 12 most affected countries in West Africa. Campaigns have now been implemented in all these countries except Nigeria. However, without an estimate of the current yellow fever burden, it is hard to determine the impact of these campaigns. Here, the researchers use recent yellow fever occurrence data, serological survey data, and improved estimation methods to update estimates of the yellow fever burden and to determine the impact of mass vaccination on this burden.
What Did the Researchers Do and Find?
The researchers developed a generalized linear statistical model and used data on the locations where yellow fever was reported between 1987 and 2011 in Africa, force of infection estimates for a limited set of locations where serological surveys were available (the force of infection is the rate at which susceptible individuals acquire a disease), data on vaccination coverage, and demographic and environmental data for their calculations. They estimate that about 130,000 yellow fever cases with fever and jaundice or hemorrhage occurred in Africa in 2013 and that about 78,000 people died from the disease. By evaluating the difference between this estimate, which takes into account the current vaccination coverage, and a hypothetical scenario that excluded the mass vaccination campaigns, the researchers estimate that these campaigns have reduced the burden of disease by 27% across Africa and by up to 82% in the countries targeted by the campaigns (an overall reduction of 57% in the 12 targeted countries).
What Do These Findings Mean?
These findings provide a contemporary estimate of the burden of yellow fever in Africa. This estimate is broadly similar to the historic estimate of 200,000 cases and 30,000 deaths annually, which was based on serological survey data obtained from children in Nigeria between 1945 and 1971. Notably, both disease burden estimates are several hundred-fold higher than the average number of yellow fever cases reported annually to WHO, which reflects the difficulties associated with the diagnosis of yellow fever. Importantly, these findings also provide an estimate of the impact of recent mass vaccination campaigns. All these findings have a high level of uncertainty, however, because of the lack of data from both surveillance and serological surveys. Other assumptions incorporated in the researchers' model may also affect the accuracy of these findings. Nevertheless, the framework for burden estimation developed here provides essential new information about the yellow fever burden and the impact of vaccination campaigns and should help the partners of the Yellow Fever Initiative estimate the potential impact of future vaccination campaigns and ensure the efficient allocation of resources for yellow fever control.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001638.
The World Health Organization provides detailed information about yellow fever (in several languages), including photo stories about vaccination campaigns in the Sudan and Mali; it also provides information about the Yellow Fever Initiative (in English and French)
The GAVI Alliance website includes detailed of its support for yellow fever vaccination
The US Centers for Disease Control and Prevention provides information about yellow fever for the public, travelers, and health care providers
The UK National Health Service Choices website also has information about yellow fever
Wikipedia has a page on yellow fever that includes information about the history of the disease (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
doi:10.1371/journal.pmed.1001638
PMCID: PMC4011853  PMID: 24800812
10.  Content and Quality of Information Websites About Congenital Heart Defects Following a Prenatal Diagnosis 
Background
Pregnant women and their partners use the Internet to search for information following a prenatal diagnosis of congenital heart defect.
Objective
Our aim was to explore central subjects of content and to assess the accessibility, reliability, usability, and quality of written information on publicly available information websites about congenital heart defects following a prenatal diagnosis.
Methods
Following searches on Bing and Google, we included websites containing patient information in English. Hits ranged from 340,000-67,500,000 and the first 50 hits from each search were screened for inclusion (N=600). Of these hits, 39.3% (236/600) were irrelevant. A total of 67 websites were included, of which 37% (25/67) were affiliated with independent information websites, 25% (17/67) with charity/private organizations, 25% (17/67) with hospitals/clinics, and 13% (8/67) had other affiliations. The majority of the websites (76%, 51/67) could not be attributed to an author. A manifest content analysis was performed to explore central subjects of content. The DISCERN instrument was used to assess the quality of information, and the LIDA tool was used to assess accessibility, usability, and reliability of the included websites.
Results
The content on the majority of the websites included care and treatment of children with congenital heart defects (88%, 59/67), causes of congenital heart defects (88%, 59/67), symptoms of congenital heart defects (85%, 57/67), prevalence of congenital heart defects (81%, 54/67), potential complications of congenital heart defects (75%, 50/67), prenatal diagnostics/screening methods (72%, 48/67), and specific congenital heart defects (72%, 48/67), whereas less than 10% included information about termination of pregnancy (6%, 4/67), care during pregnancy (5%, 3/67), and information specifically directed to partners (1%, 1/67). The mean of the total DISCERN score was 27.9 (SD 9.7, range 16-53). According to the instrument, a majority of the websites were categorized as very poor regarding information about effects of no treatment (88%, 59/67), support for shared decision making (85%, 57/67), achievement of its aims (84%, 56/67), explicit aims (82%, 55/67), risks of each treatment (82%, 55/67), how treatment choices affect overall quality of life (76%, 51/67), and areas of uncertainty (76%, 51/67). The mean of the total LIDA score was 92.3 (SD 13.1, range 61-127). According to the tool, a majority of the websites were categorized as good with regard to registration (97%, 65/67) and browser test (75%, 50/67), whereas a majority were categorized as poor with regard to currency (87%, 58/67), content production (84%, 56/67), and engagability (75%, 50/67).
Conclusions
Difficulties in finding relevant information sources using Web search engines and quality deficits on websites are an incentive for health professionals to take an active part in providing adequate and reliable information online about congenital heart defects.
doi:10.2196/ijmr.3819
PMCID: PMC4319076  PMID: 25608457
consumer health information; heart defects, congenital; Internet; prenatal diagnosis
11.  Experiences of Living and Dying With COPD 
Executive Summary
In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions.
After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses.
The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at: http://www.hqontario.ca/en/mas/mas_ohtas_mn.html.
Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework
Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Pulmonary Rehabilitation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Long-Term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Chronic Respiratory Failure Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Hospital-at-Home Programs for Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Home Telehealth for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease Using an Ontario Policy Model
Experiences of Living and Dying With COPD: A Systematic Review and Synthesis of the Qualitative Empirical Literature
For more information on the qualitative review, please contact Mita Giacomini at: http://fhs.mcmaster.ca/ceb/faculty_member_giacomini.htm.
For more information on the economic analysis, please visit the PATH website: http://www.path-hta.ca/About-Us/Contact-Us.aspx.
The Toronto Health Economics and Technology Assessment (THETA) collaborative has produced an associated report on patient preference for mechanical ventilation. For more information, please visit the THETA website: http://theta.utoronto.ca/static/contact.
Objective of Analysis
The objective of this analysis was to review empirical qualitative research on the experiences of patients with chronic obstructive pulmonary disease (COPD), informal caregivers (“carers”), and health care providers—from the point of diagnosis, through daily living and exacerbation episodes, to the end of life.
Clinical Need and Target Population
Qualitative empirical studies (from social sciences, clinical, and related fields) can offer important information about how patients experience their condition. This exploration of the qualitative literature offers insights into patients’ perspectives on COPD, their needs, and how interventions might affect their experiences. The experiences of caregivers are also explored.
Research Question
What do patients with COPD, their informal caregivers (“carers”), and health care providers experience over the course of COPD?
Research Methods
Literature Search
Search Strategy
Literature searches for studies published from January 1, 2000, to November 2010 were performed on November 29, 2010, using OVID MEDLINE; on November 26, 2010, using ISI Web of Science; and on November 28, 2010, using EBSCO Cumulative Index to Nursing and Allied Health Literature (CINAHL). Titles and abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. One additional report, highly relevant to the synthesis, appeared in early 2011 during the drafting of this analysis and was included post hoc.
Inclusion Criteria
English-language full reports
studies published between January 1, 2000, and November 2010
primary qualitative empirical research (using any descriptive or interpretive qualitative methodology, including the qualitative component of mixed-methods studies) and secondary syntheses of primary qualitative empirical research
studies addressing any aspect of the experiences of living or dying with COPD from the perspective of persons at risk, patients, health care providers, or informal carers; studies addressing multiple conditions were included if COPD was addressed explicitly
Exclusion Criteria
studies addressing topics other than the experiences of living or dying with COPD from the perspective of persons at risk, patients, health care providers, or informal carers
studies labelled “qualitative” but not using a qualitative descriptive or interpretive methodology (e.g., case studies, experiments, or observational analysis using qualitative categorical variables)
quantitative research (i.e., using statistical hypothesis testing, using primarily quantitative data or analyses, or expressing results in quantitative or statistical terms)
studies that did not pose an empirical research objective or question, or involve the primary or secondary analysis of empirical data
Outcomes of Interest
qualitative descriptions and interpretations (narrative or theoretical) of personal and social experiences of COPD
Summary of Findings
Experiences at Diagnosis
Patients typically seek initial treatment for an acute episode rather than for chronic early symptoms of COPD.
Many patients initially misunderstand terms such as COPD, chronic obstructive pulmonary disease, or exacerbation.
Patients may not realize that COPD is incurable and fatal; some physicians themselves do not consider early COPD to be a fatal disease.
Smokers may not readily understand or agree with the idea that smoking caused or worsens their COPD. Those who believe there is a causal link may feel regret or shame.
Experiences of Living Day to Day
COPD patients experience alternating good days and bad days. A roller-coaster pattern of ups and downs becomes apparent, and COPD becomes a way of life.
Patients use many means (social, psychological, medical, organizational) to control what they can, and to cope with what they cannot. Economic hardship, comorbidities, language barriers, and low health literacy can make coping more difficult.
Increasing vulnerability and unpredictable setbacks make patients dependent on others for practical assistance, but functional limitations, institutional living or self-consciousness can isolate patients from the people they need.
For smokers, medical advice to quit can conflict with increased desire to smoke as a coping strategy.
Many of the factors that isolate COPD patients from social contact also isolate them from health care.
Experiences of Exacerbations
Patients may not always attribute repeated exacerbations to advancing disease, instead seeing them as temporary setbacks caused by activities, environmental factors, faltering self-management, or infection.
Lack of confidence in community-based services leads some patients to seek hospital admission, but patients also feel vulnerable when hospitalized. They may feel dependent on others for care or traumatized by hospital care routines.
Upon hospital discharge following an exacerbation, patients may face new levels of uncertainty about their illness, prognosis, care providers, and supports.
Experiences of the End of Life
Patients tend to be poorly informed about the long-term prognosis of COPD and what to expect toward the end of life; this lack of understanding impairs quality of life as the disease progresses.
As the end of life approaches, COPD patients face the usual challenges of daily living, but in a context of increasing exacerbations and deepening dependency. Activities and mobility decrease, and life may become confined.
Some clinicians have difficulty identifying the beginning of “the end of life,” given the unpredictable course of COPD. Long-term physician-patient relationships, familiarity and understanding, trust, good communication skills, sensitivity, and secure discussion settings can help facilitate end-of-life discussions.
Divergent meanings and goals of palliative care in COPD lead to confusion about whether such services are the responsibility of home care, primary care, specialty care, or even critical care. Palliative end-of-life care may not be anticipated prior to referral for such care. A palliative care referral can convey the demoralizing message that providers have “given up.”
Experiences of Carers
Carers’ challenges often echo patients’ challenges, and include anxiety, uncertainty about the future, helplessness, powerlessness, depression, difficulties maintaining employment, loss of mobility and freedoms, strained relationships, and growing social isolation.
Carers feel pressured by their many roles, struggling to maintain patience when they feel overwhelmed, and often feeling guilty about not doing enough.
Carers often face their own health problems and may have difficulty sustaining employment.
Synthesis: A Disease Trajectory Reflecting Patient Experiences
The flux of needs in COPD calls for service continuity and flexibility to allow both health care providers and patients to respond to the unpredictable yet increasing demands of the disease over time.
PMCID: PMC3384365  PMID: 23074423
12.  Canadian medical tourism companies that have exited the marketplace: Content analysis of websites used to market transnational medical travel 
Background
Medical tourism companies play an important role in promoting transnational medical travel for elective, out-of-pocket medical procedures. Though researchers are paying increasing attention to the global phenomenon of medical tourism, to date websites of medical tourism companies have received limited scrutiny. This article analyzes websites of Canadian medical tourism companies that advertised international healthcare but ultimately exited the marketplace. Using content analysis of company websites as an investigative tool, the article provides a detailed account of medical tourism companies that were based in Canada but no longer send clients to international health care facilities.
Methods
Internet searches, Google Alerts, searches on Google News Canada and ProQuest Newsstand, and searches of an Industry Canada database were used to locate medical tourism companies located in Canada. Once medical tourism companies were identified, the social science research method of content analysis was used to extract relevant information from company websites. Company websites were analyzed to determine: 1) where these businesses were based; 2) the destination countries and medical facilities that they promoted; 3) the health services they advertised; 4) core marketing messages; and 5) whether businesses marketed air travel, hotel accommodations, and holiday excursions in addition to medical procedures.
Results
In total, 25 medical tourism companies that were based in Canada are now defunct. Given that an estimated 18 medical tourism companies and 7 regional, cross-border medical travel facilitators now operate in Canada, it appears that approximately half of all identifiable medical tourism companies in Canada are no longer in business. 13 of the previously operational companies were based in Ontario, 7 were located in British Columbia, 4 were situated in Quebec, and 1 was based in Alberta. 14 companies marketed medical procedures within a single country, 9 businesses marketed health care at 2 or more destination nations, and 2 companies did not specify particular health care destinations. 22 companies operated as "generalist" businesses marketing many different types of medical procedures. 3 medical tourism companies marketed "specialist" services restricted to dental procedures or organ transplants. In general, medical tourism companies marketed health services on the basis of access to affordable, timely, and high-quality care. 16 businesses offered to make travel arrangements, 20 companies offered to book hotel reservations, and 17 medical tourism companies advertised holiday excursions.
Conclusions
This article provides a detailed empirical analysis of websites of medical tourism companies that were based in Canada but exited the marketplace and are now inoperative. The article identifies where these companies were located in Canada, what countries and health care facilities they selected as destination sites, the health services they advertised, how they marketed themselves in a competitive environment, and what travel-related services they promoted in addition to marketing health care. The paper reveals a fluid marketplace, with many medical tourism companies exiting this industry. In addition, by disclosing identities of companies, providing their websites, archiving these websites or print copies of websites for future studies, and analyzing content of medical tourism company websites, the article can serve as a useful resource for future studies. Citizens, health policy-makers, clinicians, and researchers can all benefit from increased insight into Canada's medical tourism industry.
doi:10.1186/1744-8603-7-40
PMCID: PMC3223128  PMID: 21995598
medical tourism; Canada; cross-border healthcare; globalization; websites
13.  Readmissions after Hospitalization for Heart Failure, Acute Myocardial Infarction, or Pneumonia among Young and Middle-Aged Adults: A Retrospective Observational Cohort Study 
PLoS Medicine  2014;11(9):e1001737.
Isuru Ranasinghe and colleagues compare readmissions after hospitalization for heart failure, acute myocardial infarction, or pneumonia in adults aged 18 to 64 years with readmissions in those aged 65 and older.
Please see later in the article for the Editors' Summary
Background
Patients aged ≥65 years are vulnerable to readmissions due to a transient period of generalized risk after hospitalization. However, whether young and middle-aged adults share a similar risk pattern is uncertain. We compared the rate, timing, and readmission diagnoses following hospitalization for heart failure (HF), acute myocardial infarction (AMI), and pneumonia among patients aged 18–64 years with patients aged ≥65 years.
Methods and Findings
We used an all-payer administrative dataset from California consisting of all hospitalizations for HF (n = 206,141), AMI (n = 107,256), and pneumonia (n = 199,620) from 2007–2009. The primary outcomes were unplanned 30-day readmission rate, timing of readmission, and readmission diagnoses. Our findings show that the readmission rate among patients aged 18–64 years exceeded the readmission rate in patients aged ≥65 years in the HF cohort (23.4% vs. 22.0%, p<0.001), but was lower in the AMI (11.2% vs. 17.5%, p<0.001) and pneumonia (14.4% vs. 17.3%, p<0.001) cohorts. When adjusted for sex, race, comorbidities, and payer status, the 30-day readmission risk in patients aged 18–64 years was similar to patients ≥65 years in the HF (HR 0.99; 95%CI 0.97–1.02) and pneumonia (HR 0.97; 95%CI 0.94–1.01) cohorts and was marginally lower in the AMI cohort (HR 0.92; 95%CI 0.87–0.96). For all cohorts, the timing of readmission was similar; readmission risks were highest between days 2 and 5 and declined thereafter across all age groups. Diagnoses other than the index admission diagnosis accounted for a substantial proportion of readmissions among age groups <65 years; a non-cardiac diagnosis represented 39–44% of readmissions in the HF cohort and 37–45% of readmissions in the AMI cohort, while a non-pulmonary diagnosis represented 61–64% of patients in the pneumonia cohort.
Conclusion
When adjusted for differences in patient characteristics, young and middle-aged adults have 30-day readmission rates that are similar to elderly patients for HF, AMI, and pneumonia. A generalized risk after hospitalization is present regardless of age.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Many elderly people who are admitted to hospital, successfully treated, and discharged are readmitted soon after, often for an unrelated illness. In the US, for example, nearly a fifth of Medicare beneficiaries are readmitted to hospital within 30 days of discharge (Medicare is a national insurance program that primarily pays for health care services for Americans aged 65 and older). Experts have recently coined the term “post-hospital syndrome” for the transient period of increased susceptibility to a range of adverse health events that elderly patients seem to experience and have suggested that exposure to stress during hospital stays may underlie the syndrome. For example, hospital patients frequently have their sleep disrupted because of hospital routines, they are often in pain, they may have insufficient food intake (sometimes because they are waiting for an operation), and they may lose physical conditioning because they are confined to bed. These and other stressors can reduce individuals' natural reserves and increase their vulnerability to a range of illnesses and conditions.
Why Was This Study Done?
Although stress is one possible determinant of the post-hospital syndrome, the underlying causes and patterns of hospital readmission are generally poorly understood. In particular, it is not known whether the post-hospital syndrome affects young and middle-aged patients as well as elderly patients. Importantly, a better understanding of the post-hospital syndrome is needed before effective strategies to reduce hospital readmissions can be developed. In this retrospective observational cohort study, the researchers compare readmission rates, timing, and diagnoses after hospitalization for heart failure (HF), acute myocardial infarction (AMI; heart attack), and pneumonia among patients aged 18–64 years living in California with readmission rates, timing, and diagnoses among patients aged 65 years or older hospitalized for the same conditions. A retrospective observational cohort study analyzes data that has been already been collected for a group (cohort) of people. Readmission is common among people of all ages who are admitted to hospital for HF, AMI, and pneumonia, and readmissions after hospitalization for these conditions among elderly Medicare patients are used in the US as a measure of hospital quality; hospitals with high readmission rates are subject to a Medicare reimbursement penalty.
What Did the Researchers Do and Find?
The researchers used the Healthcare Cost and Utilization Project inpatient dataset for California to identify all the hospitalizations for HF, AMI, and pneumonia in California in 2007–2009 and to obtain data on the 30-day unplanned rehospitalization rate, timing of readmission, and readmission diagnoses for the identified patients (more than half a million patients). Nearly 30% of all hospital readmissions after hospitalization for HF, AMI, and pneumonia in California occurred among patients aged 18–64. After hospitalization for AMI, pneumonia, and HF, 11.2%, 14.4%, and 23.4%, respectively, of young and middle-aged patients were readmitted. Notably, the 30-day readmission rate among patients aged 18–64 admitted for HF exceeded the readmission rate among elderly patients admitted for the same condition. After allowing for other factors likely to affect the risk of readmission such as other illnesses, the 30-day readmission risk in patients aged 18–64 was similar to that in patients aged 65 years or older admitted for HF and pneumonia and only marginally lower among patients admitted for AMI. Finally, the timing of readmission was similar in both age groups and diagnoses other than the index admission diagnosis accounted for a substantial proportion of readmissions in both age groups.
What Do These Findings Mean?
This study shows that after adjusting for differences in patient characteristics, the 30-day hospital readmission rates among young and middle-aged patients after hospitalization for HF, AMI, and pneumonia were similar to those among elderly patients. Moreover, the timing of readmission and the reasons for readmission among young and middle-aged patients were similar to those among elderly patients. These findings may not apply to other US states or to other countries and may not reflect the pattern of hospital readmissions following conditions other than HF, AMI, and pneumonia. Nevertheless, these findings suggest that the post-hospital syndrome affects young and middle-aged as well as elderly patients. Hospital readmission should therefore be considered as a potential problem for people of all ages and broad-based, multidisciplinary strategies that target patients of all ages should be developed to mitigate the risk of hospital readmissions.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001737.
The Institute for Healthcare Improvement provides information about reducing avoidable hospital readmissions
Information about the US Centers for Medicare & Medicaid Services readmissions reduction program is available
An article written by one of the study authors about the post-hospital syndrome is available
doi:10.1371/journal.pmed.1001737
PMCID: PMC4181962  PMID: 25268126
14.  Dissecting Inflammatory Complications in Critically Injured Patients by Within-Patient Gene Expression Changes: A Longitudinal Clinical Genomics Study 
PLoS Medicine  2011;8(9):e1001093.
By studying gene expression changes over time in a cohort of trauma patients, Keyur Desai and colleagues identify genes and pathways strongly associated with longer-term complications, which could lead to improved outcome prediction in the first 80 hours after injury.
Background
Trauma is the number one killer of individuals 1–44 y of age in the United States. The prognosis and treatment of inflammatory complications in critically injured patients continue to be challenging, with a history of failed clinical trials and poorly understood biology. New approaches are therefore needed to improve our ability to diagnose and treat this clinical condition.
Methods and Findings
We conducted a large-scale study on 168 blunt-force trauma patients over 28 d, measuring ∼400 clinical variables and longitudinally profiling leukocyte gene expression with ∼800 microarrays. Marshall MOF (multiple organ failure) clinical score trajectories were first utilized to organize the patients into five categories of increasingly poor outcomes. We then developed an analysis framework modeling early within-patient expression changes to produce a robust characterization of the genomic response to trauma. A quarter of the genome shows early expression changes associated with longer-term post-injury complications, captured by at least five dynamic co-expression modules of functionally related genes. In particular, early down-regulation of MHC-class II genes and up-regulation of p38 MAPK signaling pathway were found to strongly associate with longer-term post-injury complications, providing discrimination among patient outcomes from expression changes during the 40–80 h window post-injury.
Conclusions
The genomic characterization provided here substantially expands the scope by which the molecular response to trauma may be characterized and understood. These results may be instrumental in furthering our understanding of the disease process and identifying potential targets for therapeutic intervention. Additionally, the quantitative approach we have introduced is potentially applicable to future genomics studies of rapidly progressing clinical conditions.
Trial Registration
ClinicalTrials.gov NCT00257231
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Trauma—a serious injury to the body caused by violence or by an accident—is a major global health problem. Every year, events that include traffic collisions, falls, blows, and fires cause injuries that kill more than 5 million people (9% of annual global deaths). Road traffic accidents alone are responsible for 1.3 million deaths a year and, if current trends continue, will be the fifth leading cause of death worldwide by 2030. Moreover, in many countries, including the US, trauma is the number one killer of individuals aged 1–44 y. Trauma can kill people rapidly through loss of blood or serious physical damage to internal organs, but it can also lead to localized infections and to sepsis, an infection of the bloodstream that is characterized by an amplified, body-wide (systemic) inflammatory response. Inflammation—redness, pain, and swelling—is an immune system response that normally provides protection against infections, but systemic inflammation can result in multiple organ failure (MOF) and death.
Why Was This Study Done?
Inflammatory complications of trauma are responsible for more than half of late trauma deaths, but at present it is impossible to predict which patients with major injuries will recover and which will spiral down into MOF and death, because the biological processes that underlie post-injury inflammatory complications are poorly understood. If the changes in gene expression (the process that converts the information encoded in genes into functional proteins) that accompany systemic inflammation could be elucidated, it might be possible to improve the diagnosis of MOF and to develop better treatments for post-trauma inflammatory complications. In this prospective, longitudinal clinical genomics study (part of the Inflammation and Host Response to Injury multi-disciplinary research program [IHRI]), the researchers developed an approach to associate early within-patient gene expression changes with later clinical outcomes. A prospective study is one in which patients with a specific condition are enrolled and then followed to see how various factors affect their outcomes; a longitudinal study analyzes multiple samples taken at different times from individual patients; a clinical genomics study investigates how genes and gene expression affect clinical outcomes.
What Did the Researchers Do and Find?
The researchers followed 168 patients for up to 28 d after they experienced blunt-force trauma (injuries caused when the human body hits or is hit by a large object such as a car). Using a molecular biology tool called a DNA microarray, they determined gene expression patterns in leukocytes (a type of immune system cell) isolated from multiple blood samples collected from each patient during the first few days after injury. Using clinical information collected by trained nurses, they organized the patients into five outcome categories based on a measure of MOF known as the Marshall score. Finally, they developed a statistical method (an analysis framework) to associate the early changes in gene expression with clinical outcomes.
A quarter of the patients' genes showed early expression changes that were associated with longer-term post-injury inflammatory complications. Among the associations revealed by this analysis, down-regulation (reduced expression) of MHC-class II genes (which encode proteins involved in antigen presentation, the process by which molecules from foreign invaders are presented to immune cells to initiate an immune response) and up-regulation of genes encoding components of the p38 MAPK signaling pathway (which helps to drive inflammatory responses) between 40 and 80 h post-injury were particularly strongly associated with longer-term post-injury complications and provided the strongest discrimination between patient outcomes.
What Do These Findings Mean?
The statistical approach used in this study to link the early changes in gene expression that occur after trauma to clinical outcomes provides a detailed picture of genome-wide gene expression responses to trauma. These findings could help scientists understand why some patients develop inflammatory complications of trauma while others do not, and they could help to identify those patients most at risk of developing complications. They could also help to identify targets for therapy, although further studies are needed to confirm and extend these findings. Importantly, the quantitative approach developed by the researchers for analyzing associations between within-patient gene changes over time and clinical outcomes should provide more robust predictions of outcomes than single measurements of gene expression and could be applicable to genomic studies of other rapidly progressing clinical conditions.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001093.
More details about the Inflammation and Host Response to Injury research program are available; the program's website includes a link to an article that explains how genomics can be used to understand the inflammatory complications of trauma
The World Health Organization provides information on injuries and on violence and injury prevention (in several languages)
The US National Institutes of Health has a factsheet on burns and traumatic injury in the USA
The US Centers for Disease Control and Prevention has information on injury and violence prevention and control
MedlinePlus provides links to further resources on injuries
doi:10.1371/journal.pmed.1001093
PMCID: PMC3172280  PMID: 21931541
15.  Comparative Performance of Private and Public Healthcare Systems in Low- and Middle-Income Countries: A Systematic Review 
PLoS Medicine  2012;9(6):e1001244.
A systematic review conducted by Sanjay Basu and colleagues reevaluates the evidence relating to comparative performance of public versus private sector healthcare delivery in low- and middle-income countries.
Introduction
Private sector healthcare delivery in low- and middle-income countries is sometimes argued to be more efficient, accountable, and sustainable than public sector delivery. Conversely, the public sector is often regarded as providing more equitable and evidence-based care. We performed a systematic review of research studies investigating the performance of private and public sector delivery in low- and middle-income countries.
Methods and Findings
Peer-reviewed studies including case studies, meta-analyses, reviews, and case-control analyses, as well as reports published by non-governmental organizations and international agencies, were systematically collected through large database searches, filtered through methodological inclusion criteria, and organized into six World Health Organization health system themes: accessibility and responsiveness; quality; outcomes; accountability, transparency, and regulation; fairness and equity; and efficiency. Of 1,178 potentially relevant unique citations, data were obtained from 102 articles describing studies conducted in low- and middle-income countries. Comparative cohort and cross-sectional studies suggested that providers in the private sector more frequently violated medical standards of practice and had poorer patient outcomes, but had greater reported timeliness and hospitality to patients. Reported efficiency tended to be lower in the private than in the public sector, resulting in part from perverse incentives for unnecessary testing and treatment. Public sector services experienced more limited availability of equipment, medications, and trained healthcare workers. When the definition of “private sector” included unlicensed and uncertified providers such as drug shop owners, most patients appeared to access care in the private sector; however, when unlicensed healthcare providers were excluded from the analysis, the majority of people accessed public sector care. “Competitive dynamics” for funding appeared between the two sectors, such that public funds and personnel were redirected to private sector development, followed by reductions in public sector service budgets and staff.
Conclusions
Studies evaluated in this systematic review do not support the claim that the private sector is usually more efficient, accountable, or medically effective than the public sector; however, the public sector appears frequently to lack timeliness and hospitality towards patients.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Health care can be provided through public and private providers. Public health care is usually provided by the government through national healthcare systems. Private health care can be provided through “for profit” hospitals and self-employed practitioners, and “not for profit” non-government providers, including faith-based organizations.
There is considerable ideological debate around whether low- and middle-income countries should strengthen public versus private healthcare services, but in reality, most low- and middle-income countries use both types of healthcare provision. Recently, as the global economic recession has put major constraints on government budgets—the major funding source for healthcare expenditures in most countries—disputes between the proponents of private and public systems have escalated, further fuelled by the recommendation of International Monetary Fund (an international finance institution) that countries increase the scope of private sector provision in health care as part of loan conditions to reduce government debt. However, critics of the private health sector believe that public healthcare provision is of most benefit to poor people and is the only way to achieve universal and equitable access to health care.
Why Was This Study Done?
Both sides of the public versus private healthcare debate draw on selected case reports to defend their viewpoints, but there is a widely held view that the private health system is more efficient than the public health system. Therefore, in order to inform policy, there is an urgent need for robust evidence to evaluate the quality and effectiveness of the health care provided through both systems. In this study, the authors reviewed all of the evidence in a systematic way to evaluate available data on public and private sector performance.
What Did the Researchers Do and Find?
The researchers used eight databases and a comprehensive key word search to identify and review appropriate published data and studies of private and public sector performance in low- and middle-income countries. They assessed selected studies against the World Health Organization's six essential themes of health systems—accessibility and responsiveness; quality; outcomes; accountability, transparency, and regulation; fairness and equity; and efficiency—and conducted a narrative review of each theme.
Out of the 102 relevant studies included in their comparative analysis, 59 studies were research studies and 13 involved meta-analysis, with the rest involving case reports or reviews. The researchers found that study findings varied considerably across countries studied (one-third of studies were conducted in Africa and a third in Southeast Asia) and by the methods used.
Financial barriers to care (such as user fees) were reported for both public and private systems. Although studies report that patients in the private sector experience better timeliness and hospitality, studies suggest that providers in the private sector more frequently violate accepted medical standards and have lower reported efficiency.
What Do These Findings Mean?
This systematic review did not support previous views that private sector delivery of health care in low- and middle-income settings is more efficient, accountable, or effective than public sector delivery. Each system has its strengths and weaknesses, but importantly, in both sectors, there were financial barriers to care, and each had poor accountability and transparency. This systematic review highlights a limited and poor-quality evidence base regarding the comparative performance of the two systems.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001244.
A previous PLoS Medicine study examined the outpatient care provided by the public and private sector in low-income countries
The WHO website provides more information on healthcare systems
The World Bank website provides information on health system financing
Oxfam provides an argument against increased private health care in poor countries
doi:10.1371/journal.pmed.1001244
PMCID: PMC3378609  PMID: 22723748
16.  Characterization of Regional Influenza Seasonality Patterns in China and Implications for Vaccination Strategies: Spatio-Temporal Modeling of Surveillance Data 
PLoS Medicine  2013;10(11):e1001552.
Cécile Viboud and colleagues describe epidemiological patterns of influenza incidence across China to support the design of a national vaccination program.
Please see later in the article for the Editors' Summary
Background
The complexity of influenza seasonal patterns in the inter-tropical zone impedes the establishment of effective routine immunization programs. China is a climatologically and economically diverse country, which has yet to establish a national influenza vaccination program. Here we characterize the diversity of influenza seasonality in China and make recommendations to guide future vaccination programs.
Methods and Findings
We compiled weekly reports of laboratory-confirmed influenza A and B infections from sentinel hospitals in cities representing 30 Chinese provinces, 2005–2011, and data on population demographics, mobility patterns, socio-economic, and climate factors. We applied linear regression models with harmonic terms to estimate influenza seasonal characteristics, including the amplitude of annual and semi-annual periodicities, their ratio, and peak timing. Hierarchical Bayesian modeling and hierarchical clustering were used to identify predictors of influenza seasonal characteristics and define epidemiologically-relevant regions. The annual periodicity of influenza A epidemics increased with latitude (mean amplitude of annual cycle standardized by mean incidence, 140% [95% CI 128%–151%] in the north versus 37% [95% CI 27%–47%] in the south, p<0.0001). Epidemics peaked in January–February in Northern China (latitude ≥33°N) and April–June in southernmost regions (latitude <27°N). Provinces at intermediate latitudes experienced dominant semi-annual influenza A periodicity with peaks in January–February and June–August (periodicity ratio >0.6 in provinces located within 27.4°N–31.3°N, slope of latitudinal gradient with latitude −0.016 [95% CI −0.025 to −0.008], p<0.001). In contrast, influenza B activity predominated in colder months throughout most of China. Climate factors were the strongest predictors of influenza seasonality, including minimum temperature, hours of sunshine, and maximum rainfall. Our main study limitations include a short surveillance period and sparse influenza sampling in some of the southern provinces.
Conclusions
Regional-specific influenza vaccination strategies would be optimal in China; in particular, annual campaigns should be initiated 4–6 months apart in Northern and Southern China. Influenza surveillance should be strengthened in mid-latitude provinces, given the complexity of seasonal patterns in this region. More broadly, our findings are consistent with the role of climatic factors on influenza transmission dynamics.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, millions of people worldwide catch influenza, a viral disease of the airways. Most infected individuals recover quickly but seasonal influenza outbreaks (epidemics) kill about half a million people annually. These epidemics occur because antigenic drift—frequent small changes in the viral proteins to which the immune system responds—means that an immune response produced one year provides only partial protection against influenza the next year. Annual vaccination with a mixture of killed influenza viruses of the major circulating strains boosts this natural immunity and greatly reduces the risk of catching influenza. Consequently, many countries run seasonal influenza vaccination programs. Because the immune response induced by vaccination decays within 4–8 months of vaccination and because of antigenic drift, it is important that these programs are initiated only a few weeks before the onset of local influenza activity. Thus, vaccination starts in early autumn in temperate zones (regions of the world that have a mild climate, part way between a tropical and a polar climate), because seasonal influenza outbreaks occur in the winter months when low humidity and low temperatures favor the transmission of the influenza virus.
Why Was This Study Done?
Unlike temperate regions, seasonal influenza patterns are very diverse in tropical countries, which lie between latitudes 23.5°N and 23.5°S, and in the subtropical countries slightly north and south of these latitudes. In some of these countries, there is year-round influenza activity, in others influenza epidemics occur annually or semi-annually (twice yearly). This complexity, which is perhaps driven by rainfall fluctuations, complicates the establishment of effective routine immunization programs in tropical and subtropical countries. Take China as an example. Before a national influenza vaccination program can be established in this large, climatologically diverse country, public-health experts need a clear picture of influenza seasonality across the country. Here, the researchers use spatio-temporal modeling of influenza surveillance data to characterize the seasonality of influenza A and B (the two types of influenza that usually cause epidemics) in China, to assess the role of putative drivers of seasonality, and to identify broad epidemiological regions (areas with specific patterns of disease) that could be used as a basis to optimize the timing of future Chinese vaccination programs.
What Did the Researchers Do and Find?
The researchers collected together the weekly reports of laboratory-confirmed influenza prepared by the Chinese national sentinel hospital-based surveillance network between 2005 and 2011, data on population size and density, mobility patterns, and socio-economic factors, and daily meteorological data for the cities participating in the surveillance network. They then used various statistical modeling approaches to estimate influenza seasonal characteristics, to assess predictors of influenza seasonal characteristics, and to identify epidemiologically relevant regions. These analyses indicate that, over the study period, northern provinces (latitudes greater than 33°N) experienced winter epidemics of influenza A in January–February, southern provinces (latitudes less than 27°N) experienced peak viral activity in the spring (April–June), and provinces at intermediate latitudes experienced semi-annual epidemic cycles with infection peaks in January–February and June–August. By contrast, influenza B activity predominated in the colder months throughout China. The researchers also report that minimum temperatures, hours of sunshine, and maximum rainfall were the strongest predictors of influenza seasonality.
What Do These Findings Mean?
These findings show that influenza seasonality in China varies between regions and between influenza virus types and suggest that, as in other settings, some of these variations might be associated with specific climatic factors. The accuracy of these findings is limited by the short surveillance period, by sparse surveillance data from some southern and mid-latitude provinces, and by some aspects of the modeling approach used in the study. Further surveillance studies need to be undertaken to confirm influenza seasonality patterns in China. Overall, these findings suggest that, to optimize routine influenza vaccination in China, it will be necessary to stagger the timing of vaccination over three broad geographical regions. More generally, given that there is growing interest in rolling out national influenza immunization programs in low- and middle-income countries, these findings highlight the importance of ensuring that vaccination strategies are optimized by taking into account local disease patterns.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/ 10.1371/journal.pmed.1001552.
This study is further discussed in a PLOS Medicine Perspective by Steven Riley
The UK National Health Service Choices website provides information for patients about seasonal influenza and about influenza vaccination
The World Health Organization provides information on seasonal influenza (in several languages) and on influenza surveillance and monitoring
The US Centers for Disease Control and Prevention also provides information for patients and health professionals on all aspects of seasonal influenza, including information about vaccination; its website contains a short video about personal experiences of influenza.
Flu.gov, a US government website, provides access to information on seasonal influenza and vaccination
Information about the Chinese National Influenza Center, which is part of the Chinese Center for Disease Control and Prevention: and which runs influenza surveillance in China, is available (in English and Chinese)
MedlinePlus has links to further information about influenza and about vaccination (in English and Spanish)
A recent PLOS Pathogens Research Article by James D. Tamerius et al. investigates environmental predictors of seasonal influenza epidemics across temperate and tropical climates
A study published in PLOS ONE by Wyller Alencar de Mello et al. indicates that Brazil, like China, requires staggered timing of vaccination from Northern to Southern states to account for different timings of influenza activity.
doi:10.1371/journal.pmed.1001552
PMCID: PMC3864611  PMID: 24348203
17.  Evaluating Clinical Trial Designs for Investigational Treatments of Ebola Virus Disease 
PLoS Medicine  2015;12(4):e1001815.
Background
Experimental treatments for Ebola virus disease (EVD) might reduce EVD mortality. There is uncertainty about the ability of different clinical trial designs to identify effective treatments, and about the feasibility of implementing individually randomised controlled trials during an Ebola epidemic.
Methods and Findings
A treatment evaluation programme for use in EVD was devised using a multi-stage approach (MSA) with two or three stages, including both non-randomised and randomised elements. The probabilities of rightly or wrongly recommending the experimental treatment, the required sample size, and the consequences for epidemic outcomes over 100 d under two epidemic scenarios were compared for the MSA, a sequential randomised controlled trial (SRCT) with up to 20 interim analyses, and, as a reference case, a conventional randomised controlled trial (RCT) without interim analyses.
Assuming 50% 14-d survival in the population treated with the current standard of supportive care, all designs had similar probabilities of identifying effective treatments correctly, while the MSA was less likely to recommend treatments that were ineffective. The MSA led to a smaller number of cases receiving ineffective treatments and faster roll-out of highly effective treatments. For less effective treatments, the MSA had a high probability of including an RCT component, leading to a somewhat longer time to roll-out or rejection. Assuming 100 new EVD cases per day, the MSA led to between 6% and 15% greater reductions in epidemic mortality over the first 100 d for highly effective treatments compared to the SRCT. Both the MSA and SRCT led to substantially fewer deaths than a conventional RCT if the tested interventions were either highly effective or harmful. In the proposed MSA, the major threat to the validity of the results of the non-randomised components is that referral patterns, standard of care, or the virus itself may change during the study period in ways that affect mortality. Adverse events are also harder to quantify without a concurrent control group.
Conclusions
The MSA discards ineffective treatments quickly, while reliably providing evidence concerning effective treatments. The MSA is appropriate for the clinical evaluation of EVD treatments.
Ben Cooper and colleagues model different trial designs, including a multi-stage approach that contains non-randomized and randomized elements.
Editors' Summary
Background
The current outbreak of Ebola virus disease (EVD)—a frequently fatal disease that first appeared in human populations in 1976 in remote villages in central Africa—has infected more than 24,000 people and killed more than 10,000 people in Guinea, Sierra Leone, and Liberia since early 2014. Ebola virus is transmitted to people from wild animals and spreads in human populations through direct contact with the bodily fluids (including blood, saliva, and urine) or with the organs of infected people or through contact with bedding and other materials contaminated with bodily fluids. The symptoms of EVD which start 2–21 days after infection, include fever, headache, vomiting, diarrhea, and internal and external bleeding. Infected individuals are not infectious until they develop symptoms but remain infectious as long as their bodily fluids contain virus. There is no proven treatment or vaccine for EVD, but supportive care—given under strict isolation conditions to prevent the spread of the disease to other patients or to healthcare workers—improves survival.
Why Was This Study Done?
Potential treatments for EVD include several antiviral drugs and injections of antibodies against Ebola virus from patients who have survived EVD. Before such therapies can be used clinically, their safety and effectiveness need to be evaluated, but experts disagree about how to undertake this evaluation. Drugs for clinical use are usually evaluated by undertaking a series of clinical trials. A phase I trial establishes the safety of the treatment and how the human body copes with it by giving several healthy volunteers the drug. Next, a phase II trial provides early indications of the drug’s efficacy by giving a few patients the drug. Finally, a large-scale multi-arm phase III randomized controlled trial (RCT) confirms the drug’s efficacy by comparing outcomes in patients randomly chosen to receive the investigational drug or standard care. This evaluation process is very lengthy. Moreover, it is hard to ethically justify undertaking an RCT in which only some patients receive a potentially life-saving drug during an Ebola epidemic. Here, the researchers evaluate a multi-stage approach (MSA) to EVD drug evaluation that comprises a single-arm phase II study followed by one or two phase III trials, one of which may be a sequential RCT (SRCT), a type of RCT that allows for multiple interim analyses, each of which may lead to study termination.
What Did the Researchers Do and Find?
The researchers used analytic methods and computer simulations to compare EVD drug evaluation using the MSA, an SRCT, and a conventional RCT without interim analyses. Specifically, they estimated the probabilities of rightly or wrongly recommending the experimental treatment and the consequences for epidemic outcomes over 100 days for the three approaches. Assuming 50% survival at 14 days after symptom development in patients treated with supportive care only, all three trial designs were equally likely to identify effective treatments, but the MSA was less likely than the other designs to incorrectly recommend an ineffective treatment. Notably, the MSA led to fewer patients receiving ineffective treatments and faster roll-out of highly effective treatments. In an epidemic where 100 new cases occurred per day, for highly effective treatments, the MSA led to between 6% and 15% larger reductions in epidemic mortality over the first 100 days of the epidemic than the SRCT did. Finally, both the MSA and the SRCT led to fewer deaths than the conventional RCT if the tested interventions were either highly effective or harmful.
What Do These Findings Mean?
These findings suggest that for experimental treatments that offer either no clinically significant benefit or large reductions in mortality the MSA can provide useful information about drug effectiveness faster than the other approaches tested. Thus, the MSA has the potential to reduce patient harm and the time to roll-out of an effective treatment for EVD. Although alternative evaluation designs are possible, the researchers suggest that including a non-randomized design in phase II is the quickest way to triage potential treatments and to decide how to test them further. For treatments that show strong evidence of benefit, it might even be possible to recommend the treatment without undertaking an RCT, they suggest. Moreover, for treatments that show only modest benefit in phase II, it should be easier (and more ethical) to set up RCTs to test the treatment further.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001815.
The World Health Organization (WHO) provides information about EVD, information about potential EVD therapies, and regular updates on the current EVD epidemic; a summary of the discussion of a WHO Ethics Working Group Meeting on the ethical issues related to study design for EVD drug trials is available; the WHO website also provides information about efforts to control Ebola in the field and personal stories from people who have survived EVD
The UK National Health Service Choices website provides detailed information on EVD
The US Centers for Disease Control and Prevention also provides information about EVD
Wikipedia provides information about adaptive clinical trial design; a Lancet Global Health blog argues why adaptive trial designs should be used to evaluate drugs for the treatment of EVD
doi:10.1371/journal.pmed.1001815
PMCID: PMC4397078  PMID: 25874579
18.  Age-Sensitive Design of Online Health Information: Comparative Usability Study 
Background
Older adults’ health maintenance may be enhanced by having access to online health information. However, usability issues may prevent older adults from easily accessing such information. Prior research has shown that aging is associated with a unique pattern of cognitive changes, and knowledge of these changes may be used in the design of health websites for older adults.
Objective
The goal of the current study was to examine whether older adults use of a health information website was affected by an alternative information architecture and access interface (hierarchical versus tag-based).
Methods
Fifty younger adults (aged 18-23) and 50 older adults (aged 60-80) navigated a health information website, which was organized hierarchically or used tags/keywords, to find answers to health-related questions while their performance was tracked. We hypothesized that older adults would perform better in the tag-based health information website because it placed greater demands on abilities that remain intact with aging (verbal ability and vocabulary).
Results
The pattern of age-related differences in computer use was consistent with prior research with older adults. We found that older adults had been using computers for less time (F 1,98= 10.6, P= .002) and used them less often (F 1,98= 11.3, P= .001) than younger adults. Also consistent with the cognitive aging literature, younger adults had greater spatial visualization and orientation abilities (F 1,98= 34.6, P< .001 and F 1,98= 6.8, P= .01) and a larger memory span (F 1,98= 5.7, P= .02) than older adults, but older adults had greater vocabulary (F 1,98= 11.4, P= .001). Older adults also took significantly more medications than younger adults (F 1,98= 57.7, P< .001). In the information search task, older adults performed worse than younger adults (F 1,96= 18.0, P< .001). However, there was a significant age × condition interaction indicating that while younger adults outperformed older adults in the hierarchical condition (F 1,96= 25.2, P< .001), there were no significant age-related differences in the tag-based condition, indicating that older adults performed as well as younger adults in this condition.
Conclusions
Access to online health information is increasing in popularity and can lead to a more informed health consumer. However, usability barriers may differentially affect older adults. The results of the current study suggest that the design of health information websites that take into account age-related changes in cognition can enhance older adults’ access to such information.
doi:10.2196/jmir.1220
PMCID: PMC2802567  PMID: 19917549
Internet; information organization; aging; health-related websites
19.  Associations between Intimate Partner Violence and Health among Men Who Have Sex with Men: A Systematic Review and Meta-Analysis 
PLoS Medicine  2014;11(3):e1001609.
Ana Maria Buller and colleagues review 19 studies and estimate the associations between the experience and perpetration of intimate partner violence and various health conditions and sexual risk behaviors among men who have sex with men.
Please see later in the article for the Editors' Summary
Background
Intimate partner violence (IPV) among men who have sex with men (MSM) is a significant problem. Little is known about the association between IPV and health for MSM. We aimed to estimate the association between experience and perpetration of IPV, and various health conditions and sexual risk behaviours among MSM.
Methods and Findings
We searched 13 electronic databases up to 23 October 2013 to identify research studies reporting the odds of health conditions or sexual risk behaviours for MSM experiencing or perpetrating IPV. Nineteen studies with 13,797 participants were included in the review. Random effects meta-analyses were performed to estimate pooled odds ratios (ORs). Exposure to IPV as a victim was associated with increased odds of substance use (OR = 1.88, 95% CIOR 1.59–2.22, I2 = 46.9%, 95% CII2 0%–78%), being HIV positive (OR = 1.46, 95% CIOR 1.26–1.69, I2 = 0.0%, 95% CII2 0%–62%), reporting depressive symptoms (OR = 1.52, 95% CIOR 1.24–1.86, I2 = 9.9%, 95% CII2 0%–91%), and engagement in unprotected anal sex (OR = 1.72, 95% CIOR 1.44–2.05, I2 = 0.0%, 95% CII2 0%–68%). Perpetration of IPV was associated with increased odds of substance use (OR = 1.99, 95% CIOR 1.33–2.99, I2 = 73.1%). These results should be interpreted with caution because of methodological weaknesses such as the lack of validated tools to measure IPV in this population and the diversity of recall periods and key outcomes in the identified studies.
Conclusions
MSM who are victims of IPV are more likely to engage in substance use, suffer from depressive symptoms, be HIV positive, and engage in unprotected anal sex. MSM who perpetrate IPV are more likely to engage in substance use. Our results highlight the need for research into effective interventions to prevent IPV in MSM, as well as the importance of providing health care professionals with training in how to address issues of IPV among MSM and the need to raise awareness of local and national support services.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Intimate partner violence (IPV, also called domestic violence) is a common and widespread problem. Globally, nearly a third of women are affected by IPV at some time in their life, but the prevalence of IPV (the proportion of the population affected by IPV) varies widely between countries. In central sub-Saharan Africa, for example, nearly two-thirds of women experience IPV during their lifetime, whereas in East Asia only one-sixth of women are affected. IPV is defined as physical, sexual, or emotional harm that is perpetrated on an individual by a current or former partner or spouse. Physical violence includes hitting, kicking, and other types of physical force; sexual violence means forcing a partner to take part in a sex act when the partner does not consent; and emotional abuse includes threatening a partner by, for example, stalking them or preventing them from seeing their family. The adverse effects of IPV for women include physical injury, depression and suicidal behaviour, and sexual and reproductive health problems such as HIV infection and unwanted pregnancies.
Why Was This Study Done?
IPV affects men as well as women. Men can be subjected to IPV either by a female partner or by a male partner in the case of men who have sex with men (MSM, a term that encompasses homosexual, bisexual, and transgender men, and heterosexual men who sometimes have sex with men). Recent reviews suggest that the prevalence of IPV in same-sex couples is as high as the prevalence of IPV for women in opposite-sex relationships: reported lifetime prevalences of IPV in homosexual male relationships range between 15.4% and 51%. Little is known, however, about the adverse health effects of IPV on MSM. It is important to understand how IPV affects the health of MSM so that appropriate services and interventions can be provided to support MSM who experience IPV. In this systematic review (a study that identifies all the research on a given topic using predefined criteria) and meta-analysis (a study that combines the results of several studies using statistical methods), the researchers investigate the associations between the experience and perpetration of IPV and various health conditions and sexual risk behaviours among MSM.
What Did the Researchers Do and Find?
The researchers identified 19 studies that investigated associations between IPV and various health conditions or sexual risk behaviours (for example, unprotected anal sex, a risk factor for HIV infection) among MSM. The associations were expressed as odds ratios (ORs); an OR represents the odds (chances) that an outcome will occur given a particular exposure, compared to the odds of the outcome occurring in the absence of that exposure. The researchers estimated pooled ORs from the data in the individual studies using meta-analysis. The pooled lifetime prevalence of experiencing any IPV (which was measured in six studies) was 48%. Exposure to IPV as a victim was associated with an increased risk of substance (alcohol or drug) use (OR = 1.88, data from nine studies), reporting depressive symptoms (OR = 1.52, data from three studies), being HIV positive (OR = 1.46, data from ten studies), and engagement in unprotected sex (OR = 1.72, data from eight studies). Perpetration of IPV was associated with an increased risk of substance abuse (OR = 1.99, data from six studies).
What Do These Findings Mean?
These findings suggest that MSM frequently experience IPV and that exposure to IPV is associated with several adverse health conditions and sexual risk behaviours. There were insufficient data to estimate the lifetime prevalence of IPV perpetration among MSM, but these findings also reveal an association between IPV perpetration and substance use. The accuracy of these findings is limited by heterogeneity (variability) between the studies included in the meta-analyses, by the design of these studies, and by the small number of studies. Despite these and other limitations, these findings highlight the need to undertake research to identify interventions to prevent IPV among MSM and to learn more about the health effects of IPV among MSM. They highlight the importance of health care professionals being aware that IPV is a problem for MSM and of training these professionals to assess MSM for IPV. Finally, these results highlight the need to improve the availability and effectiveness of support services to which health care professionals can refer MSM experiencing or perpetrating IPV.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001609.
The World Health Organization provides detailed information on intimate partner violence
The US Centers for Disease Control and Prevention provides information about IPV and a fact sheet on understanding IPV that includes links to further resources
The UK National Health Service Choices website has a webpage about domestic violence, which includes descriptions of personal experiences
The US National Domestic Violence Hotline provides confidential help and support to people experiencing IPV, including MSM; its website includes personal stories of IPV
The US Gay Men's Domestic Violence Project/GLBTQ Domestic Violence Project provides support and services to MSM experiencing IPV; its website includes some personal stories
The UK not-for-profit organization Respect runs two advice lines: the Men's Advice Line provides advice and support for men experiencing domestic violence and abuse and the Respect Phoneline provides advice for domestic violence perpetrators and for professionals who would like further information about services for those using violence/abuse in their intimate partner relationships
The UK not-for-profit organization ManKind Initiative also provides support for male victims of IPV
The UK not-for-profit organization Broken Rainbow UK provides help and support for lesbians and MSM experiencing IPV
MedlinePlus provides links to other resources about domestic violence (in English and Spanish)
The UK charity Galop gives advice and support to people who have experienced biphobia, homophobia, transphobia, sexual violence, or domestic abuse
doi:10.1371/journal.pmed.1001609
PMCID: PMC3942318  PMID: 24594975
20.  Factors Affecting the Delivery, Access, and Use of Interventions to Prevent Malaria in Pregnancy in Sub-Saharan Africa: A Systematic Review and Meta-Analysis 
PLoS Medicine  2013;10(7):e1001488.
Jenny Hill and colleagues conduct a systematic review and meta-analysis of qualitative, quantitative, and mixed methods studies to explore the factors that affect the delivery, access, and use of interventions to prevent malaria in pregnant women in sub-Saharan Africa.
Please see later in the article for the Editors' Summary
Background
Malaria in pregnancy has important consequences for mother and baby. Coverage with the World Health Organization–recommended prevention strategy for pregnant women in sub-Saharan Africa of intermittent preventive treatment in pregnancy (IPTp) and insecticide-treated nets (ITNs) is low. We conducted a systematic review to explore factors affecting delivery, access, and use of IPTp and ITNs among healthcare providers and women.
Methods and Results
We searched the Malaria in Pregnancy Library and Global Health Database from 1 January 1990 to 23 April 2013, without language restriction. Data extraction was performed by two investigators independently, and data was appraised for quality and content. Data on barriers and facilitators, and the effect of interventions, were explored using content analysis and narrative synthesis. We conducted a meta-analysis of determinants of IPTp and ITN uptake using random effects models, and performed subgroup analysis to evaluate consistency across interventions and study populations, countries, and enrolment sites. We did not perform a meta-ethnography of qualitative data.
Ninety-eight articles were included, of which 20 were intervention studies. Key barriers to the provision of IPTp and ITNs were unclear policy and guidance on IPTp; general healthcare system issues, such as stockouts and user fees; health facility issues stemming from poor organisation, leading to poor quality of care; poor healthcare provider performance, including confusion over the timing of each IPTp dose; and women's poor antenatal attendance, affecting IPTp uptake. Key determinants of IPTp coverage were education, knowledge about malaria/IPTp, socio-economic status, parity, and number and timing of antenatal clinic visits. Key determinants of ITN coverage were employment status, education, knowledge about malaria/ITNs, age, and marital status. Predictors showed regional variations.
Conclusions
Delivery of ITNs through antenatal clinics presents fewer problems than delivery of IPTp. Many obstacles to IPTp delivery are relatively simple barriers that could be resolved in the short term. Other barriers are more entrenched within the overall healthcare system or socio-economic/cultural contexts, and will require medium- to long-term strategies.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Half the world's population is at risk of malaria, a mosquito-borne parasite that kills a million people every year. Most of these deaths occur among young children in sub-Saharan Africa, but pregnant women and their unborn babies are also vulnerable to malaria. Infection with malaria during pregnancy can cause maternal death, severe maternal anemia, miscarriages, and pre-term and low-birth-weight babies. Malaria in pregnancy is responsible for about 100,000 babies and 10,000 women dying every year but is preventable by simple, inexpensive interventions that have been available for many years. The World Health Organization recommends a three-pronged approach to the prevention of malaria in pregnancy in areas with stable malaria transmission in Africa—delivery of the antimalarial drug sulfadoxine-pyrimethamine to pregnant women during antenatal clinic visits (intermittent preventative treatment in pregnancy; IPTp), the use of insecticide-treated bed nets (ITNs) to protect pregnant women from the bites of infected mosquitoes, and effective diagnosis and case management of pregnant women with malarial illness.
Why Was This Study Done?
Coverage with this prevention strategy is currently very low. Recent survey data from sub-Saharan African countries suggest that only about a quarter of pregnant women receive two doses of IPTp and only about a third use ITNs. To improve coverage, public health experts need to understand why coverage is so low, and they need to know the factors (determinants) that are associated with the uptake of IPTp and ITNs. In this systematic review and meta-analysis of qualitative, quantitative, and mixed methods studies, the researchers explore the factors that affect delivery, access, and use of IPTp and ITNs among pregnant women in sub-Saharan Africa. A systematic review uses predefined criteria to identify all the research on a given topic. Meta-analysis is a statistical method for combining the results of several studies. Qualitative studies collect non-quantitative data such as reasons for not accepting an intervention, whereas quantitative studies collect numerical data such as the proportion of a population accepting an intervention.
What Did the Researchers Do and Find?
The researchers' search of the Malaria in Pregnancy Library (a resource maintained by the Malaria in Pregnancy Consortium) and the Global Health Database identified 98 studies that provided data on barriers to and determinants of IPTp and ITN uptake and/or data on interventions designed to increase IPTp and ITN uptake. The researchers explored these data using content analysis (a research methodology that examines words and phrases within texts) and narrative synthesis (a method for summarizing results drawn from several qualitative studies). Key barriers to the provision and uptake of IPTp and ITNs included unclear policy and guidance on IPTp, general healthcare system issues such as drug shortages, healthcare facility issues such as unavailability of water for the provision of IPTp by directly observed therapy, poor healthcare provider performance such as confusion about the timing of IPTp doses, and the delayed antenatal care-seeking practices of pregnant women. The researchers' meta-analysis identified education, knowledge about malaria, socio-economic status, number and timing of antenatal clinic visits, and number of pregnancies as key determinants of IPTp uptake, and employment status, education, knowledge, age, and marital status as key determinants of coverage of ITN use. So, for example, highly educated women were more likely to receive IPTp or ITNs than poorly educated women.
What Do These Findings Mean?
These findings identify key interacting barriers to access, delivery, and use of IPTp and ITNs in sub-Saharan Africa and show that these barriers are relatively consistent across countries. Moreover, they suggest that there are fewer barriers to the delivery of ITNs through antenatal clinics than to the delivery of IPTp. Importantly, some of the barriers to IPTp uptake can be resolved in the short term (for example, simplification of country policies and guidance on IPTp might increase its uptake), but barriers to uptake that are entrenched within the overall healthcare system will only be resolved with medium- to long-term strategies that aim to improve the quality of antenatal services and to encourage antenatal clinic use among women. Overall, this analysis provides a checklist of factors that policy-makers involved in national malaria programs may be able to use to help them decide which interventions to prioritize. However, the researchers warn, multi-country studies are nevertheless urgently needed to evaluate targeted or multifaceted interventions designed to increase delivery and uptake of IPTp and ITNs, to reduce the adverse consequences of malaria in pregnancy.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001488.
Information is available from the World Health Organization on malaria (in several languages) and on IPTp; the World Malaria Report 2012 provides details of the current global malaria situation
The US Centers for Disease Control and Prevention also provides information on malaria and on IPTp; a personal story about malaria in pregnancy is available
Information is available from the Roll Back Malaria Partnership on all aspects of global malaria control, including information on malaria in pregnancy
The Malaria in Pregnancy Consortium is undertaking research into the prevention and treatment of malaria in pregnancy
MedlinePlus provides links to additional information on malaria (in English and Spanish)
doi:10.1371/journal.pmed.1001488
PMCID: PMC3720261  PMID: 23935459
21.  The Project Data Sphere Initiative: Accelerating Cancer Research by Sharing Data 
The Oncologist  2015;20(5):464-e20.
By providing access to large, late-phase, cancer-trial data sets, the Project Data Sphere initiative has the potential to transform cancer research by optimizing research efficiency and accelerating progress toward meaningful improvements in cancer care. This type of platform provides opportunities for unique research projects that can examine relatively neglected areas and that can construct models necessitating large amounts of detailed data.
Background.
In this paper, we provide background and context regarding the potential for a new data-sharing platform, the Project Data Sphere (PDS) initiative, funded by financial and in-kind contributions from the CEO Roundtable on Cancer, to transform cancer research and improve patient outcomes. Given the relatively modest decline in cancer death rates over the past several years, a new research paradigm is needed to accelerate therapeutic approaches for oncologic diseases. Phase III clinical trials generate large volumes of potentially usable information, often on hundreds of patients, including patients treated with standard of care therapies (i.e., controls). Both nationally and internationally, a variety of stakeholders have pursued data-sharing efforts to make individual patient-level clinical trial data available to the scientific research community.
Potential Benefits and Risks of Data Sharing.
For researchers, shared data have the potential to foster a more collaborative environment, to answer research questions in a shorter time frame than traditional randomized control trials, to reduce duplication of effort, and to improve efficiency. For industry participants, use of trial data to answer additional clinical questions could increase research and development efficiency and guide future projects through validation of surrogate end points, development of prognostic or predictive models, selection of patients for phase II trials, stratification in phase III studies, and identification of patient subgroups for development of novel therapies. Data transparency also helps promote a public image of collaboration and altruism among industry participants. For patient participants, data sharing maximizes their contribution to public health and increases access to information that may be used to develop better treatments. Concerns about data-sharing efforts include protection of patient privacy and confidentiality. To alleviate these concerns, data sets are deidentified to maintain anonymity. To address industry concerns about protection of intellectual property and competitiveness, we illustrate several models for data sharing with varying levels of access to the data and varying relationships between trial sponsors and data access sponsors.
The Project Data Sphere Initiative.
PDS is an independent initiative of the CEO Roundtable on Cancer Life Sciences Consortium, built to voluntarily share, integrate, and analyze comparator arms of historical cancer clinical trial data sets to advance future cancer research. The aim is to provide a neutral, broad-access platform for industry and academia to share raw, deidentified data from late-phase oncology clinical trials using comparator-arm data sets. These data are likely to be hypothesis generating or hypothesis confirming but, notably, do not take the place of performing a well-designed trial to address a specific hypothesis. Prospective providers of data to PDS complete and sign a data sharing agreement that includes a description of the data they propose to upload, and then they follow easy instructions on the website for uploading their deidentified data. The SAS Institute has also collaborated with the initiative to provide intrinsic analytic tools accessible within the website itself.
As of October 2014, the PDS website has available data from 14 cancer clinical trials covering 9,000 subjects, with hopes to further expand the database to include more than 25,000 subject accruals within the next year. PDS differentiates itself from other data-sharing initiatives by its degree of openness, requiring submission of only a brief application with background information of the individual requesting access and agreement to terms of use. Data from several different sponsors may be pooled to develop a comprehensive cohort for analysis. In order to protect patient privacy, data providers in the U.S. are responsible for deidentifying data according to standards set forth by the Privacy Rule of the U.S. Health Insurance Portability and Accountability Act of 1996.
Using Data Sharing to Improve Outcomes in Cancer: The “Prostate Cancer Challenge.”
Control-arm data of several studies among patients with metastatic castration-resistant prostate cancer (mCRPC) are currently available through PDS. These data sets have multiple potential uses. The “Prostate Cancer Challenge” will ask the cancer research community to use clinical trial data deposited in the PDS website to address key research questions regarding mCRPC.
General themes that could be explored by the cancer community are described in this article: prognostic models evaluating the influence of pretreatment factors on survival and patient-reported outcomes; comparative effectiveness research evaluating the efficacy of standard of care therapies, as illustrated in our companion article comparing mitoxantrone plus prednisone with prednisone alone; effects of practice variation in dose, frequency, and duration of therapy; level of patient adherence to elements of trial protocols to inform the design of future clinical trials; and age of subjects, regional differences in health care, and other confounding factors that might affect outcomes.
Potential Limitations and Methodological Challenges.
The number of data sets available and the lack of experimental-arm data limit the potential scope of research using the current PDS. The number of trials is expected to grow exponentially over the next year and may include multiple cancer settings, such as breast, colorectal, lung, hematologic malignancy, and bone marrow transplantation. Other potential limitations include the retrospective nature of the data analyses performed using PDS and its generalizability, given that clinical trials are often conducted among younger, healthier, and less racially diverse patient populations. Methodological challenges exist when combining individual patient data from multiple clinical trials; however, advancements in statistical methods for secondary database analysis offer many tools for reanalyzing data arising from disparate trials, such as propensity score matching. Despite these concerns, few if any comparable data sets include this level of detail across multiple clinical trials and populations.
Conclusion.
Access to large, late-phase, cancer-trial data sets has the potential to transform cancer research by optimizing research efficiency and accelerating progress toward meaningful improvements in cancer care. This type of platform provides opportunities for unique research projects that can examine relatively neglected areas and that can construct models necessitating large amounts of detailed data. The full potential of PDS will be realized only when multiple tumor types and larger numbers of data sets are available through the website.
doi:10.1634/theoncologist.2014-0431
PMCID: PMC4425388  PMID: 25876994
Project Data Sphere; Data sharing; Prostate cancer; Comparative effectiveness research
22.  Vaccination Persuasion Online: A Qualitative Study of Two Provaccine and Two Vaccine-Skeptical Websites 
Background
Current concerns about vaccination resistance often cite the Internet as a source of vaccine controversy. Most academic studies of vaccine resistance online use quantitative methods to describe misinformation on vaccine-skeptical websites. Findings from these studies are useful for categorizing the generic features of these websites, but they do not provide insights into why these websites successfully persuade their viewers. To date, there have been few attempts to understand, qualitatively, the persuasive features of provaccine or vaccine-skeptical websites.
Objective
The purpose of this research was to examine the persuasive features of provaccine and vaccine-skeptical websites. The qualitative analysis was conducted to generate hypotheses concerning what features of these websites are persuasive to people seeking information about vaccination and vaccine-related practices.
Methods
This study employed a fully qualitative case study methodology that used the anthropological method of thick description to detail and carefully review the rhetorical features of 1 provaccine government website, 1 provaccine hospital website, 1 vaccine-skeptical information website focused on general vaccine safety, and 1 vaccine-skeptical website focused on a specific vaccine. The data gathered were organized into 5 domains: website ownership, visual and textual content, user experience, hyperlinking, and social interactivity.
Results
The study found that the 2 provaccine websites analyzed functioned as encyclopedias of vaccine information. Both of the websites had relatively small digital ecologies because they only linked to government websites or websites that endorsed vaccination and evidence-based medicine. Neither of these websites offered visitors interactive features or made extensive use of the affordances of Web 2.0. The study also found that the 2 vaccine-skeptical websites had larger digital ecologies because they linked to a variety of vaccine-related websites, including government websites. They leveraged the affordances of Web 2.0 with their interactive features and digital media.
Conclusions
By employing a rhetorical framework, this study found that the provaccine websites analyzed concentrate on the accurate transmission of evidence-based scientific research about vaccines and government-endorsed vaccination-related practices, whereas the vaccine-skeptical websites focus on creating communities of people affected by vaccines and vaccine-related practices. From this personal framework, these websites then challenge the information presented in scientific literature and government documents. At the same time, the vaccine-skeptical websites in this study are repositories of vaccine information and vaccination-related resources. Future studies on vaccination and the Internet should take into consideration the rhetorical features of provaccine and vaccine-skeptical websites and further investigate the influence of Web 2.0 community-building features on people seeking information about vaccine-related practices.
doi:10.2196/jmir.4153
PMCID: PMC4468570  PMID: 26024907
vaccination; communication; Internet; social networking; Web 2.0; qualitative research
23.  Averting Obesity and Type 2 Diabetes in India through Sugar-Sweetened Beverage Taxation: An Economic-Epidemiologic Modeling Study 
PLoS Medicine  2014;11(1):e1001582.
In this modeling study, Sanjay Basu and colleagues estimate the potential health effects of a sugar-sweetened beverage taxation among various sub-populations in India over the period 2014 to 2023.
Please see later in the article for the Editors' Summary
Background
Taxing sugar-sweetened beverages (SSBs) has been proposed in high-income countries to reduce obesity and type 2 diabetes. We sought to estimate the potential health effects of such a fiscal strategy in the middle-income country of India, where there is heterogeneity in SSB consumption, patterns of substitution between SSBs and other beverages after tax increases, and vast differences in chronic disease risk within the population.
Methods and Findings
Using consumption and price variations data from a nationally representative survey of 100,855 Indian households, we first calculated how changes in SSB price alter per capita consumption of SSBs and substitution with other beverages. We then incorporated SSB sales trends, body mass index (BMI), and diabetes incidence data stratified by age, sex, income, and urban/rural residence into a validated microsimulation of caloric consumption, glycemic load, overweight/obesity prevalence, and type 2 diabetes incidence among Indian subpopulations facing a 20% SSB excise tax. The 20% SSB tax was anticipated to reduce overweight and obesity prevalence by 3.0% (95% CI 1.6%–5.9%) and type 2 diabetes incidence by 1.6% (95% CI 1.2%–1.9%) among various Indian subpopulations over the period 2014–2023, if SSB consumption continued to increase linearly in accordance with secular trends. However, acceleration in SSB consumption trends consistent with industry marketing models would be expected to increase the impact efficacy of taxation, averting 4.2% of prevalent overweight/obesity (95% CI 2.5–10.0%) and 2.5% (95% CI 1.0–2.8%) of incident type 2 diabetes from 2014–2023. Given current consumption and BMI distributions, our results suggest the largest relative effect would be expected among young rural men, refuting our a priori hypothesis that urban populations would be isolated beneficiaries of SSB taxation. Key limitations of this estimation approach include the assumption that consumer expenditure behavior from prior years, captured in price elasticities, will reflect future behavior among consumers, and potential underreporting of consumption in dietary recall data used to inform our calculations.
Conclusion
Sustained SSB taxation at a high tax rate could mitigate rising obesity and type 2 diabetes in India among both urban and rural subpopulations.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Non-communicable diseases (NCDs) and obesity (excessive body mass) are major threats to global health. Each year NCDs kill 36 million people (including 29 million people in low- and middle-income countries), thereby accounting for nearly two-thirds of the world's annual deaths. Cardiovascular diseases, cancers, respiratory diseases, and diabetes (a condition characterized by raised blood sugar levels) are responsible for most NCD-related deaths. Worldwide, diabetes alone affects about 360 million people and causes nearly 5 million deaths annually. And the number of people affected by NCDs is likely to rise over the next few decades. It is estimated, for example, that 101.2 million people in India will have diabetes by 2030, nearly double the current number. In Asia and other low- and middle-income countries overweight as well as obesity represent a risk factor for NCDs and the global prevalence of obesity (the proportion of the world's population that is obese) has nearly doubled since 1980. Worldwide, around 0.5 billion people are now classified as obese and about 1.5 billion more overweight. That is, they have a body mass index (BMI) of 30 kg/m2 or more (25–30 for overweight); BMI is calculated by dividing a person's weight in kilograms by the square of their height in meters. In India individuals with a BMI of 25 or more (overweight/obese) are at very high risk of diabetes.
Why Was This Study Done?
The consumption of sugar-sweetened beverages (SSBs, soft drinks sweetened with cane sugar or other caloric sweeteners) is a major risk factor for overweight/obesity and, independent of total energy consumption and BMI, for type 2 diabetes (the commonest form of diabetes). In high-income countries, SSB taxation has been proposed as a way to lower the risk of obesity and type 2 diabetes, however it is unknown if this approach will work in low- and middle-income countries. Here, in an economic-epidemiologic modeling study, researchers estimate the potential health effects of SSB taxation in India, a middle-income country in which total SSB consumption is rapidly increasing, but where SSB consumption and chronic disease risk vary greatly within the population and where people are likely to turn to other sugar-rich beverages (for example, fresh fruit juices) if SSBs are taxed.
What Did the Researchers Do and Find?
The researchers used survey data relating SSB consumption to price variations to calculate how changes in the price of SSBs affect the demand for SSBs (own-price elasticity) and for other beverages (cross-price elasticity) in India. They combined these elasticities and data on SSB sales trends, BMIs, and diabetes incidence (the frequency of new diabetes cases) into a mathematical microsimulation model to estimate the effect of a 20% tax on SSBs on caloric (energy) consumption, glycemic load (an estimate of how much a food or drink raises blood sugar levels after consumption; low glycemic load diets lower diabetes risk), the prevalence of overweight/obesity, and the incidence of diabetes among Indian subpopulations. According to the model, if SSB sales continue to increase at the current rate, compared to no tax, a 20% SSB tax would reduce overweight/obesity across India by 3.0% and the incidence of type 2 diabetes by 1.6% over the period 2014–2023. In absolute figures, a 20% SSB tax would avert 11.2 million cases of overweight/obesity and 400,000 cases of type 2 diabetes between 2014 and 2023. Notably, if SSB sales increase more steeply as predicted by drinks industry marketing models, the tax would avert 15.8 million cases of overweight/obesity and 600,000 cases of diabetes. Finally, the model predicted that the largest relative effect of an SSB tax would be among young men in rural areas.
What Do These Findings Mean?
The accuracy of these findings is likely to be affected by the assumptions incorporated in the model and by the data fed into it. In particular, the accuracy of the estimates of the health effects of a 20% tax on SSBs is limited by the assumption that future consumer behavior will reflect historic behavior and by potential underreporting of SSB consumption in surveys. Nevertheless, these findings suggest that a sustained high rate of tax on SSBs could mitigate the rising prevalence of obesity and the rising incidence of diabetes in India in both urban and rural populations by affecting both caloric intake and glycemic load. Thus, SSB taxation might be a way to control obesity and diabetes in India and other low- and middle-income countries where, to date, large-scale interventions designed to address these threats to global health have had no sustained effects.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001582.
The World Health Organization provides information about non-communicable diseases, obesity, and diabetes around the world (in several languages)
The US Centers for Disease Control and Prevention provides information on non-communicable diseases around the world and on overweight and obesity and diabetes (including some information in Spanish)
The US National Diabetes Information Clearinghouse provides information about diabetes for patients, health-care professionals, and the general public, including detailed information on weight control (in English and Spanish)
The UK National Health Service Choices website provides information for patients and carers about type 2 diabetes and about obesity; it includes personal stories about diabetes and about obesity
MedlinePlus provides links to further resources and advice about diabetes and diabetes prevention and about obesity (in English and Spanish)
A 2012 Policy brief from the Yale Rudd Center for food policy and obesity provides information about SSB taxes
doi:10.1371/journal.pmed.1001582
PMCID: PMC3883641  PMID: 24409102
24.  Urbanicity and Lifestyle Risk Factors for Cardiometabolic Diseases in Rural Uganda: A Cross-Sectional Study 
PLoS Medicine  2014;11(7):e1001683.
Johanna Riha and colleagues evaluate the association of lifestyle risk factors with elements of urbanicity, such as having a public telephone, a primary school, or a hospital, among individuals living in rural settings in Uganda.
Please see later in the article for the Editors' Summary
Background
Urban living is associated with unhealthy lifestyles that can increase the risk of cardiometabolic diseases. In sub-Saharan Africa (SSA), where the majority of people live in rural areas, it is still unclear if there is a corresponding increase in unhealthy lifestyles as rural areas adopt urban characteristics. This study examines the distribution of urban characteristics across rural communities in Uganda and their associations with lifestyle risk factors for chronic diseases.
Methods and Findings
Using data collected in 2011, we examined cross-sectional associations between urbanicity and lifestyle risk factors in rural communities in Uganda, with 7,340 participants aged 13 y and above across 25 villages. Urbanicity was defined according to a multi-component scale, and Poisson regression models were used to examine associations between urbanicity and lifestyle risk factors by quartile of urbanicity. Despite all of the villages not having paved roads and running water, there was marked variation in levels of urbanicity across the villages, largely attributable to differences in economic activity, civil infrastructure, and availability of educational and healthcare services. In regression models, after adjustment for clustering and potential confounders including socioeconomic status, increasing urbanicity was associated with an increase in lifestyle risk factors such as physical inactivity (risk ratio [RR]: 1.19; 95% CI: 1.14, 1.24), low fruit and vegetable consumption (RR: 1.17; 95% CI: 1.10, 1.23), and high body mass index (RR: 1.48; 95% CI: 1.24, 1.77).
Conclusions
This study indicates that even across rural communities in SSA, increasing urbanicity is associated with a higher prevalence of lifestyle risk factors for cardiometabolic diseases. This finding highlights the need to consider the health impact of urbanization in rural areas across SSA.
Please see later in the article for the Editors' Summary
Editors’ Summary
Background
Cardiometabolic diseases—cardiovascular diseases that affect the heart and/or the blood vessels and metabolic diseases that affect the cellular chemical reactions needed to sustain life—are a growing global health concern. In sub-Saharan Africa, for example, the prevalence (the proportion of a population that has a given disease) of adults with diabetes (a life-shortening metabolic disease that affects how the body handles sugars) is currently 3.8%. By 2030, it is estimated that the prevalence of diabetes among adults in this region will have risen to 4.6%. Similarly, in 2004, around 1.2 million deaths in sub-Saharan Africa were attributed to coronary heart disease, heart failure, stroke, and other cardiovascular diseases. By 2030, the number of deaths in this region attributable to cardiovascular disease is expected to double. Globally, cardiovascular disease and diabetes are now responsible for around 17.3 million and 1.3 million annual deaths, respectively, together accounting for about one-third of all deaths.
Why Was This Study Done?
Experts believe that increased consumption of saturated fats, sugar, and salt and reduced physical activity are partly responsible for the increasing global prevalence of cardiometabolic diseases. These lifestyle changes, they suggest, are related to urbanization—urban expansion into the countryside and migration from rural to urban areas. If this is true, the prevalence of unhealthy lifestyles should increase as rural areas adopt urban characteristics. Sub-Saharan Africa is the least urbanized region in the world, with about 60% of the population living in rural areas. However, rural settlements across the subcontinent are increasingly adopting urban characteristics. It is important to know whether urbanization is affecting the health of rural residents in sub-Saharan Africa to improve estimates of the future burden of cardiometabolic diseases in the region and to provide insights into ways to limit this burden. In this cross-sectional study (an investigation that studies participants at a single time point), the researchers examine the distribution of urban characteristics across rural communities in Uganda and the association of these characteristics with lifestyle risk factors for cardiometabolic diseases.
What Did the Researchers Do and Find?
For their study, the researchers used data collected in 2011 by the General Population Cohort study, a study initiated in 1989 to describe HIV infection trends among people living in 25 villages in rural southwestern Uganda that collects health-related and other information annually from its participants. The researchers quantified the “urbanicity” of the 25 villages using a multi-component scale that included information such as village size and economic activity. They then used statistical models to examine associations between urbanicity and lifestyle risk factors such as body mass index (BMI, a measure of obesity) and self-reported fruit and vegetable consumption for more than 7,000 study participants living in those villages. None of the villages had paved roads or running water. However, urbanicity varied markedly across the villages, largely because of differences in economic activity, civil infrastructure, and the availability of educational and healthcare services. Notably, increasing urbanicity was associated with an increase in lifestyle risk factors for cardiovascular diseases. So, for example, people living in villages with the highest urbanicity scores were nearly 20% more likely to be physically inactive and to eat less fruits and vegetables and nearly 50% more likely to have a high BMI than people living in villages with the lowest urbanicity scores.
What Do These Findings Mean?
These findings indicate that, across rural communities in Uganda, even a small increase in urbanicity is associated with a higher prevalence of potentially modifiable lifestyle risk factors for cardiometabolic diseases. These findings suggest, therefore, that simply classifying settlements as either rural or urban may not be adequate to capture the information needed to target strategies for cardiometabolic disease management and control in rural areas as they become more urbanized. Because this study was cross-sectional, it is not possible to say how long a rural population needs to experience a more urban environment before its risk of cardiometabolic diseases increases. Longitudinal studies are needed to obtain this information. Moreover, studies of other countries in sub-Saharan Africa are needed to show that these findings are generalizable across the region. However, based on these findings, and given that more than 553 million people live in rural areas across sub-Saharan Africa, it seems likely that increasing urbanization will have a substantial impact on the future health of populations throughout sub-Saharan Africa.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001683.
This study is further discussed in a PLOS Medicine Perspective by Fahad Razak and Lisa Berkman
The American Heart Association provides information on all aspects of cardiovascular disease and diabetes; its website includes personal stories about heart attacks, stroke, and diabetes
The US Centers for Disease Control and Prevention has information on heart disease, stroke, and diabetes (in English and Spanish)
The UK National Health Service Choices website provides information about cardiovascular disease and diabetes (including some personal stories)
The World Health Organization’s Global Noncommunicable Disease Network (NCDnet) aims to help low- and middle-income countries reduce illness and death caused by cardiometabolic and other non-communicable diseases
The World Heart Federation has recently produced a report entitled “Urbanization and Cardiovascular Disease”
Wikipedia has a page on urbanization (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
doi:10.1371/journal.pmed.1001683
PMCID: PMC4114555  PMID: 25072243
25.  Home Telehealth for Patients With Chronic Obstructive Pulmonary Disease (COPD) 
Executive Summary
In July 2010, the Medical Advisory Secretariat (MAS) began work on a Chronic Obstructive Pulmonary Disease (COPD) evidentiary framework, an evidence-based review of the literature surrounding treatment strategies for patients with COPD. This project emerged from a request by the Health System Strategy Division of the Ministry of Health and Long-Term Care that MAS provide them with an evidentiary platform on the effectiveness and cost-effectiveness of COPD interventions.
After an initial review of health technology assessments and systematic reviews of COPD literature, and consultation with experts, MAS identified the following topics for analysis: vaccinations (influenza and pneumococcal), smoking cessation, multidisciplinary care, pulmonary rehabilitation, long-term oxygen therapy, noninvasive positive pressure ventilation for acute and chronic respiratory failure, hospital-at-home for acute exacerbations of COPD, and telehealth (including telemonitoring and telephone support). Evidence-based analyses were prepared for each of these topics. For each technology, an economic analysis was also completed where appropriate. In addition, a review of the qualitative literature on patient, caregiver, and provider perspectives on living and dying with COPD was conducted, as were reviews of the qualitative literature on each of the technologies included in these analyses.
The Chronic Obstructive Pulmonary Disease Mega-Analysis series is made up of the following reports, which can be publicly accessed at the MAS website at: http://www.hqontario.ca/en/mas/mas_ohtas_mn.html.
Chronic Obstructive Pulmonary Disease (COPD) Evidentiary Framework
Influenza and Pneumococcal Vaccinations for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Smoking Cessation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Community-Based Multidisciplinary Care for Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Pulmonary Rehabilitation for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Long-term Oxygen Therapy for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Noninvasive Positive Pressure Ventilation for Chronic Respiratory Failure Patients With Stable Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Hospital-at-Home Programs for Patients With Acute Exacerbations of Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Home Telehealth for Patients With Chronic Obstructive Pulmonary Disease (COPD): An Evidence-Based Analysis
Cost-Effectiveness of Interventions for Chronic Obstructive Pulmonary Disease Using an Ontario Policy Model
Experiences of Living and Dying With COPD: A Systematic Review and Synthesis of the Qualitative Empirical Literature
For more information on the qualitative review, please contact Mita Giacomini at: http://fhs.mcmaster.ca/ceb/faculty_member_giacomini.htm.
For more information on the economic analysis, please visit the PATH website: http://www.path-hta.ca/About-Us/Contact-Us.aspx.
The Toronto Health Economics and Technology Assessment (THETA) collaborative has produced an associated report on patient preference for mechanical ventilation. For more information, please visit the THETA website: http://theta.utoronto.ca/static/contact.
Objective
The objective of this analysis was to conduct an evidence-based assessment of home telehealth technologies for patients with chronic obstructive pulmonary disease (COPD) in order to inform recommendations regarding the access and provision of these services in Ontario. This analysis was one of several analyses undertaken to evaluate interventions for COPD. The perspective of this assessment was that of the Ontario Ministry of Health and Long-Term Care, a provincial payer of medically necessary health care services.
Clinical Need: Condition and Target Population
Canada is facing an increase in chronic respiratory diseases due in part to its aging demographic. The projected increase in COPD will put a strain on health care payers and providers. There is therefore an increasing demand for telehealth services that improve access to health care services while maintaining or improving quality and equality of care. Many telehealth technologies however are in the early stages of development or diffusion and thus require study to define their application and potential harms or benefits. The Medical Advisory Secretariat (MAS) therefore sought to evaluate telehealth technologies for COPD.
Technology
Telemedicine (or telehealth) refers to using advanced information and communication technologies and electronic medical devices to support the delivery of clinical care, professional education, and health-related administrative services.
Generally there are 4 broad functions of home telehealth interventions for COPD:
to monitor vital signs or biological health data (e.g., oxygen saturation),
to monitor symptoms, medication, or other non-biologic endpoints (e.g., exercise adherence),
to provide information (education) and/or other support services (such as reminders to exercise or positive reinforcement), and
to establish a communication link between patient and provider.
These functions often require distinct technologies, although some devices can perform a number of these diverse functions. For the purposes of this review, MAS focused on home telemonitoring and telephone only support technologies.
Telemonitoring (or remote monitoring) refers to the use of medical devices to remotely collect a patient’s vital signs and/or other biologic health data and the transmission of those data to a monitoring station for interpretation by a health care provider.
Telephone only support refers to disease/disorder management support provided by a health care provider to a patient who is at home via telephone or videoconferencing technology in the absence of transmission of patient biologic data.
Research Questions
What is the effectiveness, cost-effectiveness, and safety of home telemonitoring compared with usual care for patients with COPD?
What is the effectiveness, cost-effectiveness, and safety of telephone only support programs compared with usual care for patients with COPD?
Research Methods
Literature Search
Search Strategy
A literature search was performed on November 3, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Cochrane Library, and the International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 2000 until November 3, 2010. Abstracts were reviewed by a single reviewer and, for those studies meeting the eligibility criteria, full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. Articles with unknown eligibility were reviewed with a second clinical epidemiologist, and then a group of epidemiologists until consensus was established. The quality of evidence was assessed as high, moderate, low, or very low according to GRADE methodology.
Inclusion Criteria – Question #1
frequent transmission of a patient’s physiological data collected at home and without a health care professional physically present to health care professionals for routine monitoring through the use of a communication technology;
monitoring combined with a coordinated management and feedback system based on transmitted data;
telemonitoring as a key component of the intervention (subjective determination);
usual care as provided by the usual care provider for the control group;
randomized controlled trials (RCTs), controlled clinical trials (CCTs), systematic reviews, and/or meta-analyses;
published between January 1, 2000 and November 3, 2010.
Inclusion Criteria – Question #2
scheduled or frequent contact between patient and a health care professional via telephone or videoconferencing technology in the absence of transmission of patient physiological data;
monitoring combined with a coordinated management and feedback system based on transmitted data;
telephone support as a key component of the intervention (subjective determination);
usual care as provided by the usual care provider for the control group;
RCTs, CCTs, systematic reviews, and/or meta-analyses;
published between January 1, 2000 and November 3, 2010.
Exclusion Criteria
published in a language other than English;
intervention group (and not control) receiving some form of home visits by a medical professional, typically a nurse (i.e., telenursing) beyond initial technology set-up and education, to collect physiological data, or to somehow manage or treat the patient;
not recording patient or health system outcomes (e.g., technical reports testing accuracy, reliability or other development-related outcomes of a device, acceptability/feasibility studies, etc.);
not using an independent control group that received usual care (e.g., studies employing historical or periodic controls).
Outcomes of Interest
hospitalizations (primary outcome)
mortality
emergency department visits
length of stay
quality of life
other […]
Subgroup Analyses (a priori)
length of intervention (primary)
severity of COPD (primary)
Quality of Evidence
The quality of evidence assigned to individual studies was determined using a modified CONSORT Statement Checklist for Randomized Controlled Trials. (1) The CONSORT Statement was adapted to include 3 additional quality measures: the adequacy of control group description, significant differential loss to follow-up between groups, and greater than or equal to 30% study attrition. Individual study quality was defined based on total scores according to the CONSORT Statement checklist: very low (0 to < 40%), low (≥ 40 to < 60%), moderate (≥ 60 to < 80%), and high (≥ 80 to 100%).
The quality of the body of evidence was assessed as high, moderate, low, or very low according to the GRADE Working Group criteria. The following definitions of quality were used in grading the quality of the evidence:
Summary of Findings
Six publications, representing 5 independent trials, met the eligibility criteria for Research Question #1. Three trials were RCTs reported across 4 publications, whereby patients were randomized to home telemonitoring or usual care, and 2 trials were CCTs, whereby patients or health care centers were nonrandomly assigned to intervention or usual care.
A total of 310 participants were studied across the 5 included trials. The mean age of study participants in the included trials ranged from 61.2 to 74.5 years for the intervention group and 61.1 to 74.5 years for the usual care group. The percentage of men ranged from 40% to 64% in the intervention group and 46% to 72% in the control group.
All 5 trials were performed in a moderate to severe COPD patient population. Three trials initiated the intervention following discharge from hospital. One trial initiated the intervention following a pulmonary rehabilitation program. The final trial initiated the intervention during management of patients at an outpatient clinic.
Four of the 5 trials included oxygen saturation (i.e., pulse oximetry) as one of the biological patient parameters being monitored. Additional parameters monitored included forced expiratory volume in one second, peak expiratory flow, and temperature.
There was considerable clinical heterogeneity between trials in study design, methods, and intervention/control. In relation to the telemonitoring intervention, 3 of the 5 included studies used an electronic health hub that performed multiple functions beyond the monitoring of biological parameters. One study used only a pulse oximeter device alone with modem capabilities. Finally, in 1 study, patients measured and then forwarded biological data to a nurse during a televideo consultation. Usual care varied considerably between studies.
Only one trial met the eligibility criteria for Research Question #2. The included trial was an RCT that randomized 60 patients to nurse telephone follow-up or usual care (no telephone follow-up). Participants were recruited from the medical department of an acute-care hospital in Hong Kong and began receiving follow-up after discharge from the hospital with a diagnosis of COPD (no severity restriction). The intervention itself consisted of only two 10-to 20-minute telephone calls, once between days 3 to 7 and once between days 14 to 20, involving a structured, individualized educational and supportive programme led by a nurse that focused on 3 components: assessment, management options, and evaluation.
Regarding Research Question #1:
Low to very low quality evidence (according to GRADE) finds non-significant effects or conflicting effects (of significant or non-significant benefit) for all outcomes examined when comparing home telemonitoring to usual care.
There is a trend towards significant increase in time free of hospitalization and use of other health care services with home telemonitoring, but these findings need to be confirmed further in randomized trials of high quality.
There is severe clinical heterogeneity between studies that limits summary conclusions.
The economic impact of home telemonitoring is uncertain and requires further study.
Home telemonitoring is largely dependent on local information technologies, infrastructure, and personnel, and thus the generalizability of external findings may be low. Jurisdictions wishing to replicate home telemonitoring interventions should likely test those interventions within their jurisdictional framework before adoption, or should focus on home-grown interventions that are subjected to appropriate evaluation and proven effective.
Regarding Research Question #2:
Low quality evidence finds significant benefit in favour of telephone-only support for self-efficacy and emergency department visits when compared to usual care, but non-significant results for hospitalizations and hospital length of stay.
There are very serious issues with the generalizability of the evidence and thus additional research is required.
PMCID: PMC3384362  PMID: 23074421

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