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1.  Publication trends in newspapers and scientific journals for SSRIs and suicidality: a systematic longitudinal study 
BMJ Open  2011;1(2):e000290.
Background
In the period 2003–2008, the regulatory authorities issued several warnings restricting the use of selective serotonin re-uptake inhibitors (SSRIs) in paediatrics, in reaction to safety concerns regarding the risk of suicidality. In this study, the SSRIs and suicidality controversy serves as a template to analyse the long-term publication trends regarding the benefit/risk profile of medications. The aim is to ascertain differences (in terms of numbers, categories and timing) between negative and positive newspaper and journal articles on SSRIs and suicidality and to ascertain correlations between changes in the reports and regulatory warnings.
Methods
A systematic review of scientific articles (Embase) and the Netherlands (NL) and the UK newspapers (LexisNexis) was performed between 2000 and 2010. Categorisation was done by ‘effect’ (related treatment effect), ‘type of article’ and ‘age group’. The articles' positive-to-negative effect ratio was determined. Differences in distribution of effect categories were analysed across sources, type of article and age group using the Mann–Whitney (two subgroups) or Kruskal–Wallis test (three or more).
Findings
In total, 1141 articles were categorised: 352 scientific, 224 Dutch and 565 British newspaper articles. Scientific articles were predominantly on research and were positive, whereas newspaper articles were negative (ratios=3.50—scientific, 0.69—NL and 0.94—UK; p<0.001). Articles on paediatrics were less positive in scientific journals and more negative in newspapers (ratios=2.29—scientific, 0.26—NL and 0.20—UK; p<0.001), while articles on adults were positive overall (ratios=10.0—scientific, 1.06—NL and 1.70—UK; p<0.001). In addition, negative-effect reporting trends were exacerbated following regulatory warnings and were generally opinion articles, both in scientific journals and in newspapers (2003/2004 and after 2007).
Interpretation
The authors found a positive publication tendency inherent in journal research articles. This apparent positive publication bias present in scientific journals, however, does not seem to prevent the dissemination of ‘bad’ news about medications. The negative tendency present in Dutch and British newspapers was perceivable in the paediatrics group and during the warnings, indicating that national news media have informed the public about this international drug safety controversy on time.
Article summary
Article focus
Publication trends of the benefit/risk profile of medications might differ in time and during a drug safety case.
We analysed the long-term dynamics of publication trends in the context of the SSRIs and suicidality controversy.
The number of articles (in terms of positive, negative and neutral, as well as the type of article and age groups) were analysed in scientific journals and the Netherlands and the UK dailies from January 2000 to December 2009.
Key messages
We found a positive publication tendency in scientific journals that did not influence the dissemination of negative news in newspapers in the Netherlands and the UK.
The negative tendency in newspapers was predominant in paediatrics and during the warnings.
The public was informed on time about this drug safety controversy, although the information conveyed was not uniform (from scientific journals to newspapers).
Strengths and limitations of this study
Definition of the categories is limited by the researchers' criteria.
Two independent scorers reviewed the articles to avoid subjectivity during scoring.
More than 95% agreements between both research scorers were documented.
doi:10.1136/bmjopen-2011-000290
PMCID: PMC3236820  PMID: 22146889
2.  Early dental journalism: a mirror of the development of dentistry as a profession. 
The rise of dentistry from a mechanical trade to a profession has often been attributed to the so-called "triumvirate" of organization, education, and journal literature. This essay focuses on one part of the triumvirate, examining the role of journals in the growth of dentistry as a profession, from the appearance of the first journal in 1839 to the publication of the Index to Dental Literature in 1921. Rather than discussing the history of individual titles, it identifies some of the broader issues and problems that confronted early dental journalism. The evolution of dental journals from trade house publications to independent scientific literature mirrored the movement toward professional status in dentistry during the late 19th and early 20th centuries.
PMCID: PMC227717  PMID: 3902129
3.  Relationship between Funding Source and Conclusion among Nutrition-Related Scientific Articles 
PLoS Medicine  2007;4(1):e5.
Background
Industrial support of biomedical research may bias scientific conclusions, as demonstrated by recent analyses of pharmaceutical studies. However, this issue has not been systematically examined in the area of nutrition research. The purpose of this study is to characterize financial sponsorship of scientific articles addressing the health effects of three commonly consumed beverages, and to determine how sponsorship affects published conclusions.
Methods and Findings
Medline searches of worldwide literature were used to identify three article types (interventional studies, observational studies, and scientific reviews) about soft drinks, juice, and milk published between 1 January, 1999 and 31 December, 2003. Financial sponsorship and article conclusions were classified by independent groups of coinvestigators. The relationship between sponsorship and conclusions was explored by exact tests and regression analyses, controlling for covariates. 206 articles were included in the study, of which 111 declared financial sponsorship. Of these, 22% had all industry funding, 47% had no industry funding, and 32% had mixed funding. Funding source was significantly related to conclusions when considering all article types (p = 0.037). For interventional studies, the proportion with unfavorable conclusions was 0% for all industry funding versus 37% for no industry funding (p = 0.009). The odds ratio of a favorable versus unfavorable conclusion was 7.61 (95% confidence interval 1.27 to 45.73), comparing articles with all industry funding to no industry funding.
Conclusions
Industry funding of nutrition-related scientific articles may bias conclusions in favor of sponsors' products, with potentially significant implications for public health.
In 111 scientific articles on nonalcoholic beverages, articles with all industry funding were more than 7 times more likely to have favorable conclusions compared with articles with no industry funding.
Editors' Summary
Background.
Much of the money available for doing medical research comes from companies, as opposed to government agencies or charities. There is some evidence that when a research study is sponsored by an organization that has a financial interest in the outcome, the study is more likely to produce results that favor the funder (this is called “sponsorship bias”). This phenomenon is worrying, because if our knowledge about effectiveness and safety of medicines is based on biased findings, patients could suffer. However, it is not clear whether sponsorship bias extends beyond research into drugs, but also affects other types of research that is in the public interest. For example, research into the health benefits, or otherwise, of different types of food and drink may affect government guidelines, regulations, and the behavior patterns of members of the public. Were sponsorship bias also to exist in this area of research, the health of the wider public could be affected.
Why Was This Study Done?
There is not a great deal of evidence about whether sponsorship bias affects nutritional research (scientific studies that look at the relationship between food and/or drink, and health or disease states). Therefore, the group of researchers here set out to collect information from published nutritional research papers, to see if the type of sponsorship for the research studies was in any way linked with whether the main conclusions were favorable or unfavorable to the sponsor.
What Did the Researchers Do and Find?
The research study reported here used the scientific literature as a source of data. The researchers chose to examine one particular area of nutrition (nonalcoholic drinks including soft drinks, juices, and milk), so that their investigation would not be affected too much by variability between the different types of nutritional research. Using literature searches, the researchers identified all original research and scientific review articles published between January 1999 and December 2003 that examined soft drinks, juices, and milk; described research carried out in humans; and at the same time drew conclusions relevant to health or disease. Then, information from each published article was categorized: the conclusions were coded as either favorable, unfavorable, or neutral in relation to the health effects of the products being studied, and the article's funding was coded as either all industry (ie, food/drinks companies), no industry, or mixed. 206 published articles were analyzed and only 54% declared funding. The researchers found that, overall, there was a strong association between the type of funding available for these articles and the conclusions that were drawn. Articles sponsored exclusively by food/drinks companies were four to eight times more likely to have conclusions favorable to the financial interests of the sponsoring company than articles which were not sponsored by food or drinks companies.
What Do These Findings Mean?
These findings suggest that a high potential for bias exists in research into the health benefits or harms of nonalcoholic drinks. It is not clear from this research study why or how this bias comes about, but there are many different mechanisms that might cause it. The researchers suggest that certain initiatives might help to reduce bias, for example, increasing independent funding of nutrition research.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/doi:10.1371/journal.pmed.0040005.
Conflict of Interest definition from Wikipedia (Wikipedia is an internet encyclopedia that anyone can edit)
The International Committee of Medical Journal Editors provides standard guidelines for practices at medical journals, including a section on sponsorship, authorship, and accountability
The Committee on Publication Ethics is a forum for journal editors to discuss issues related to the integrity of the scientific record, and it provides guidelines for editors and case studies for reference
The Good Publication Practice guidelines outline standards for responsible publication of research sponsored by pharmaceutical companies
doi:10.1371/journal.pmed.0040005
PMCID: PMC1764435  PMID: 17214504
4.  Reporting Characteristics of Cancer Pain: A Systematic Review and Quantitative Analysis of Research Publications in Palliative Care Journals 
Objective:
A common disorder requiring symptom palliation in palliative and end-of-life care is cancer. Cancer pain is recognized as a global health burden. This paper sought to systematically examine the extent to which there is an adequate scientific research base on cancer pain and its reporting characteristics in the palliative care journal literature.
Materials and Methods:
Search conducted in MEDLINE and CINAHL sought to locate all studies published in 19 palliative/ hospice/ supportive/ end-of-life care journals from 2009 to 2010. The journals included were: American Journal of Hospice and Palliative Care, BMC Palliative Care, Current Opinion in Supportive and Palliative Care, End of Life Care Journal, European Journal of Palliative Care, Hospice Management Advisor, Indian Journal of Palliative Care, International Journal of Palliative Nursing, Internet Journal of Pain Symptom Control and Palliative Care, Journal of Pain and Palliative Care Pharmacotherapy, Journal of Palliative Care, Journal of Palliative Medicine, Journal of Social Work in End-of-life and Palliative Care, Journal of Supportive Oncology, Palliative Medicine, Palliative and Supportive Care, and Supportive Care in Cancer. Journal contents were searched to identify studies that included cancer pain in abstract.
Results:
During the years 2009 and 2010, of the selected 1,569 articles published in the journals reviewed, only 5.86% (92 articles) were on cancer pain.
Conclusion:
While researchers in the field of palliative care have studied cancer pain, the total percentage for studies is still a low 5.86%. To move the field of palliative care forward so that appropriate guidelines for cancer pain management can be developed, it is critical that more research be reported upon which to base cancer pain therapy in an evidence-based palliative care model.
doi:10.4103/0973-1075.78451
PMCID: PMC3098545  PMID: 21633623
Cancer pain; Palliative care research; Reporting characteristics
5.  Study designs and statistical methods in the Journal of Family and Community Medicine: 1994-2010 
Introduction:
The Journal of Family and Community Medicine (JFCM) is the official peer reviewed scientific publication of the Saudi Society of Family and Community Medicine. Unlike many peer medical journals, the contents of JFCM, have never been analyzed. The objective of this study was to perform an analysis of the contents of the JFCM over a 16-year period to discern the study designs and statistical methods used with a view to improving future contents of the journal.
Materials and Methods:
All volumes of the JFCM, from 1 January 1994 to 31 December 2010 were hand searched for research articles. All papers identified as original articles were selected. For every article, the study designs and the statistical methods used were recorded. Articles were then classified according to their statistical methods and study designs. The frequency of study designs was calculated as a simple percentage of the total number of articles, while the frequency of statistical methods was calculated as a percentage of articles that used those statistical methods.
Results:
A total of 229 articles were analyzed. Of these, 66 (28.8%) either reported no statistics or reported simple summaries. The cross-sectional design was used in 175 (76.4%) of all analyzed articles. Statistical methods were used in 163 (71.2%) articles. Chi-squared test was used in 111 (68.1%) articles, and t-test used in 48 (29.4%) articles. Other common statistical tests were: Regression, which was used in 35 (21.5%) articles, ANOVA used in 23 (14.1%) articles, and odds ratio and relative risk tests which were used in 22 (13.5%) articles.
Conclusions:
The JFCM has a wide range of study designs and statistical methods. However, no article on experimental studies has been published in the JFCM since its inception.
doi:10.4103/2230-8229.108175
PMCID: PMC3663167  PMID: 23723725
Community medicine; family medicine; research methodology; Saudi Arabia
6.  Randomized Trials in Emergency Medicine Journals, 2008-2011 
Study Objective
Knowledge of current areas of activity in emergency medicine research may improve collaboration among investigators and may help inform decisions about future research priorities. Randomized controlled trials are a key component of research activity and an essential tool for improving care. We investigated the characteristics of randomized trials recently published in emergency medicine journals.
Methods
This was a retrospective analysis of randomized trials published in the five highest-impact emergency medicine journals. Pubmed was searched for reports of randomized trials involving human subjects indexed to MEDLINE between January 1, 2008 and December 31, 2011. Included trials were classified with respect to study topic, funding source, presence of age-related inclusion criteria, and country of origin.
Results
163 published studies were included for analysis. Pain management was the most commonly studied topic (N=28, 17%) followed by orthopedics (N = 24, 15%), cardiovascular disease (N=13, 8%), and pre-hospital medicine (N=13, 8%). Less than half of studies received extramural funding support. Children were specifically examined in 22 (13%) of trials; only 5 trials (3%) specifically examined patients age 60 or older.
Conclusions
Emergency medicine journals publish randomized trials addressing a wide range of clinical topics. Randomized trials focusing on geriatric patients are not commonly published in these journals.
doi:10.1016/j.ajem.2012.06.003
PMCID: PMC3494801  PMID: 22867836
Emergency medicine; randomized controlled trials; geriatrics
7.  Risk of bias of randomized controlled trials published in orthopaedic journals 
Background
The purpose of this study was to assess the quality of methodology in orthopaedics-related randomized controlled trials (RCTs) published from January 2006 to December 2010 in the top orthopaedic journals based on impact scores from the Thompson ISI citation reports (2010).
Methods
Journals included American Journal of Sports Medicine; Journal of Orthopaedic Research; Journal of Bone and Joint Surgery, American; Spine Journal; and Osteoarthritis and Cartilage. Each RCT was assessed on ten criteria (randomization method, allocation sequence concealment, participant blinding, outcome assessor blinding, outcome measurement, interventionist training, withdrawals, intent to treat analyses, clustering, and baseline characteristics) as having empirical evidence for biasing treatment effect estimates when not performed properly.
Results
A total of 232 RCTs met our inclusion criteria. The proportion of RCTs in published journals fell from 6% in 2006 to 4% in 2010. Forty-nine percent of the criteria were fulfilled across these journals, with 42% of the criteria not being amendable to assessment due to inadequate reporting. The results of our regression revealed that a more recent publication year was significantly associated with more fulfilled criteria (β = 0.171; CI = −0.00 to 0.342; p = 0.051).
Conclusion
In summary, very few studies met all ten criteria. Thus, many of these studies likely have biased estimates of treatment effects. In addition, these journals had poor reporting of important methodological aspects.
doi:10.1186/1471-2288-13-76
PMCID: PMC3724580  PMID: 23758875
8.  Neuroimaging for the Evaluation of Chronic Headaches 
Executive Summary
Objective
The objectives of this evidence based review are:
i) To determine the effectiveness of computed tomography (CT) and magnetic resonance imaging (MRI) scans in the evaluation of persons with a chronic headache and a normal neurological examination.
ii) To determine the comparative effectiveness of CT and MRI scans for detecting significant intracranial abnormalities in persons with chronic headache and a normal neurological exam.
iii) To determine the budget impact of CT and MRI scans for persons with a chronic headache and a normal neurological exam.
Clinical Need: Condition and Target Population
Headaches disorders are generally classified as either primary or secondary with further sub-classifications into specific headache types. Primary headaches are those not caused by a disease or medical condition and include i) tension-type headache, ii) migraine, iii) cluster headache and, iv) other primary headaches, such as hemicrania continua and new daily persistent headache. Secondary headaches include those headaches caused by an underlying medical condition. While primary headaches disorders are far more frequent than secondary headache disorders, there is an urge to carry out neuroimaging studies (CT and/or MRI scans) out of fear of missing uncommon secondary causes and often to relieve patient anxiety.
Tension type headaches are the most common primary headache disorder and migraines are the most common severe primary headache disorder. Cluster headaches are a type of trigeminal autonomic cephalalgia and are less common than migraines and tension type headaches. Chronic headaches are defined as headaches present for at least 3 months and lasting greater than or equal to 15 days per month. The International Classification of Headache Disorders states that for most secondary headaches the characteristics of the headache are poorly described in the literature and for those headache disorders where it is well described there are few diagnostically important features.
The global prevalence of headache in general in the adult population is estimated at 46%, for tension-type headache it is 42% and 11% for migraine headache. The estimated prevalence of cluster headaches is 0.1% or 1 in 1000 persons. The prevalence of chronic daily headache is estimated at 3%.
Neuroimaging
Computed Tomography
Computed tomography (CT) is a medical imaging technique used to aid diagnosis and to guide interventional and therapeutic procedures. It allows rapid acquisition of high-resolution three-dimensional images, providing radiologists and other physicians with cross-sectional views of a person’s anatomy. CT scanning poses risk of radiation exposure. The radiation exposure from a conventional CT scanner may emit effective doses of 2-4mSv for a typical head CT.
Magnetic Resonance Imaging
Magnetic resonance imaging (MRI) is a medical imaging technique used to aid diagnosis but unlike CT it does not use ionizing radiation. Instead, it uses a strong magnetic field to image a person’s anatomy. Compared to CT, MRI can provide increased contrast between the soft tissues of the body. Because of the persistent magnetic field, extra care is required in the magnetic resonance environment to ensure that injury or harm does not come to any personnel while in the environment.
Research Questions
What is the effectiveness of CT and MRI scanning in the evaluation of persons with a chronic headache and a normal neurological examination?
What is the comparative effectiveness of CT and MRI scanning for detecting significant intracranial abnormality in persons with chronic headache and a normal neurological exam?
What is the budget impact of CT and MRI scans for persons with a chronic headache and a normal neurological exam.
Research Methods
Literature Search
Search Strategy
A literature search was performed on February 18, 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, 2005 to February, 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 an unknown eligibility were reviewed with a second clinical epidemiologist and then a group of epidemiologists until consensus was established.
Inclusion Criteria
Systematic reviews, randomized controlled trials, observational studies
Outpatient adult population with chronic headache and normal neurological exam
Studies reporting likelihood ratio of clinical variables for a significant intracranial abnormality
English language studies
2005-present
Exclusion Criteria
Studies which report outcomes for persons with seizures, focal symptoms, recent/new onset headache, change in presentation, thunderclap headache, and headache due to trauma
Persons with abnormal neurological examination
Case reports
Outcomes of Interest
Primary Outcome
Probability for intracranial abnormality
Secondary Outcome
Patient relief from anxiety
System service use
System costs
Detection rates for significant abnormalities in MRI and CT scans
Summary of Findings
Effectiveness
One systematic review, 1 small RCT, and 1 observational study met the inclusion and exclusion criteria. The systematic review completed by Detsky, et al. reported the likelihood ratios of specific clinical variables to predict significant intracranial abnormalities. The RCT completed by Howard et al., evaluated whether neuroimaging persons with chronic headache increased or reduced patient anxiety. The prospective observational study by Sempere et al., provided evidence for the pre-test probability of intracranial abnormalities in persons with chronic headache as well as minimal data on the comparative effectiveness of CT and MRI to detect intracranial abnormalities.
Outcome 1: Pre-test Probability.
The pre-test probability is usually related to the prevalence of the disease and can be adjusted depending on the characteristics of the population. The study by Sempere et al. determined the pre-test probability (prevalence) of significant intracranial abnormalities in persons with chronic headaches defined as headache experienced for at least a 4 week duration with a normal neurological exam. There is a pre-test probability of 0.9% (95% CI 0.5, 1.4) in persons with chronic headache and normal neurological exam. The highest pre-test probability of 5 found in persons with cluster headaches. The second highest, that of 3.7, was reported in persons with indeterminate type headache. There was a 0.75% rate of incidental findings.
Likelihood ratios for detecting a significant abnormality
Clinical findings from the history and physical may be used as screening test to predict abnormalities on neuroimaging. The extent to which the clinical variable may be a good predictive variable can be captured by reporting its likelihood ratio. The likelihood ratio provides an estimate of how much a test result will change the odds of having a disease or condition. The positive likelihood ratio (LR+) tells you how much the odds of having the disease increases when a test is positive. The negative likelihood ratio (LR-) tells you how much the odds of having the disease decreases when the test is negative.
Detsky et al., determined the likelihood ratio for specific clinical variable from 11 studies. There were 4 clinical variables with both statistically significant positive and negative likelihood ratios. These included: abnormal neurological exam (LR+ 5.3, LR- 0.72), undefined headache (LR+ 3.8, LR- 0.66), headache aggravated by exertion or valsalva (LR+ 2.3, LR- 0.70), and headache with vomiting (LR+ 1.8, and LR- 0.47). There were two clinical variables with a statistically significant positive likelihood ratio and non significant negative likelihood ratio. These included: cluster-type headache (LR+ 11, LR- 0.95), and headache with aura (LR+ 12.9, LR- 0.52). Finally, there were 8 clinical variables with both statistically non significant positive and negative likelihood ratios. These included: headache with focal symptoms, new onset headache, quick onset headache, worsening headache, male gender, headache with nausea, increased headache severity, and migraine type headache.
Outcome 2: Relief from Anxiety
Howard et al. completed an RCT of 150 persons to determine if neuroimaging for headaches was anxiolytic or anxiogenic. Persons were randomized to receiving either an MRI scan or no scan for investigation of their headache. The study population was stratified into those persons with a Hospital Anxiety and Depression scale (HADS) > 11 (the high anxiety and depression group) and those < 11 (the low anxiety and depression) so that there were 4 groups:
Group 1: High anxiety and depression, no scan group
Group 2: High anxiety and depression, scan group
Group 3: Low anxiety and depression, no scan group
Group 4: Low anxiety and depression, scan group
Anxiety
There was no evidence for any overall reduction in anxiety at 1 year as measured by a visual analogue scale of ‘level of worry’ when analysed by whether the person received a scan or not. Similarly, there was no interaction between anxiety and depression status and whether a scan was offered or not on patient anxiety. Anxiety did not decrease at 1 year to any statistically significant degree in the high anxiety and depression group (HADS positive) compared with the low anxiety and depression group (HADS negative).
There are serious methodological limitations in this study design which may have contributed to these negative results. First, when considering the comparison of ‘scan’ vs. ‘no scan’ groups, 12 people (16%) in the ‘no scan group’ actually received a scan within the follow up year. If indeed scanning does reduce anxiety then this contamination of the ‘no scan’ group may have reduced the effect between the groups results resulting in a non significant difference in anxiety scores between the ‘scanned’ and the ‘no scan’ group. Second, there was an inadequate sample size at 1 year follow up in each of the 4 groups which may have contributed to a Type II statistical error (missing a difference when one may exist) when comparing scan vs. no scan by anxiety and depression status. Therefore, based on the results and study limitations it is inconclusive as to whether scanning reduces anxiety.
Outcome 3: System Services
Howard et al., considered services used and system costs a secondary outcome. These were determined by examining primary care case notes at 1 year for consultation rates, symptoms, further investigations, and contact with secondary and tertiary care.
System Services
The authors report that the use of neurologist and psychiatrist services was significantly higher for those persons not offered as scan, regardless of their anxiety and depression status (P<0.001 for neurologist, and P=0.033 for psychiatrist)
Outcome 4: System Costs
System Costs
There was evidence of statistically significantly lower system costs if persons with high levels of anxiety and depression (Hospital Anxiety and Depression Scale score >11) were provided with a scan (P=0.03 including inpatient costs, and 0.047 excluding inpatient costs).
Comparative Effectiveness of CT and MRI Scans
One study reported the detection rate for significant intracranial abnormalities using CT and MRI. In a cohort of 1876 persons with a non acute headache defined as any type of headache that had begun at least 4 weeks before enrolment Sempere et al. reported that the detection rate was 19/1432 (1.3%) using CT and 4/444 (0.9%) using MRI. Of 119 normal CT scans 2 (1.7%) had significant intracranial abnormality on MRI. The 2 cases were a small meningioma, and an acoustic neurinoma.
Summary
The evidence presented can be summarized as follows:
Pre-test Probability
Based on the results by Sempere et al., there is a low pre-test probability for intracranial abnormalities in persons with chronic headaches and a normal neurological exam (defined as headaches experiences for a minimum of 4 weeks). The Grade quality of evidence supporting this outcome is very low.
Likelihood Ratios
Based on the systematic review by Detsky et al., there is a statistically significant positive and negative likelihood ratio for the following clinical variables: abnormal neurological exam, undefined headache, headache aggravated by exertion or valsalva, headache with vomiting. Grade quality of evidence supporting this outcome is very low.
Based on the systematic review by Detsky et al. there is a statistically significant positive likelihood ratio but non statistically significant negative likelihood ratio for the following clinical variables: cluster headache and headache with aura. The Grade quality of evidence supporting this outcome is very low.
Based on the systematic review by Detsky et al., there is a non significant positive and negative likelihood ratio for the following clinical variables: headache with focal symptoms, new onset headache, quick onset headache, worsening headache, male gender, headache with nausea, increased headache severity, migraine type headache. The Grade quality of evidence supporting this outcome is very low.
Relief from Anxiety
Based on the RCT by Howard et al., it is inconclusive whether neuroimaging scans in persons with a chronic headache are anxiolytic. The Grade quality of evidence supporting this outcome is low.
System Services
Based on the RCT by Howard et al. scanning persons with chronic headache regardless of their anxiety and/or depression level reduces service use. The Grade quality of evidence is low.
System Costs
Based on the RCT by Howard et al., scanning persons with a score greater than 11 on the High Anxiety and Depression Scale reduces system costs. The Grade quality of evidence is moderate.
Comparative Effectiveness of CT and MRI Scans
There is sparse evidence to determine the relative effectiveness of CT compared with MRI scanning for the detection of intracranial abnormalities. The Grade quality of evidence supporting this is very low.
Economic Analysis
Ontario Perspective
Volumes for neuroimaging of the head i.e. CT and MRI scans, from the Ontario Health Insurance Plan (OHIP) data set were used to investigate trends in the province for Fiscal Years (FY) 2004-2009.
Assumptions were made in order to investigate neuroimaging of the head for the indication of headache. From the literature, 27% of all CT and 13% of all MRI scans for the head were assumed to include an indication of headache. From that same retrospective chart review and personal communication with the author 16% of CT scans and 4% of MRI scans for the head were for the sole indication of headache. From the Ministry of Health and Long-Term Care (MOHLTC) wait times data, 73% of all CT and 93% of all MRI scans in the province, irrespective of indication were outpatient procedures.
The expenditure for each FY reflects the volume for that year and since volumes have increased in the past 6 FYs, the expenditure has also increased with a pay-out reaching 3.0M and 2.8M for CT and MRI services of the head respectively for the indication of headache and a pay-out reaching 1.8M and 0.9M for CT and MRI services of the head respectively for the indication of headache only in FY 08/09.
Cost per Abnormal Finding
The yield of abnormal finding for a CT and MRI scan of the head for the indication of headache only is 2% and 5% respectively. Based on these yield a high-level estimate of the cost per abnormal finding with neuroimaging of the head for headache only can be calculated for each FY. In FY 08/09 there were 37,434 CT and 16,197 MRI scans of the head for headache only. These volumes would generate a yield of abnormal finding of 749 and 910 with a CT scan and MRI scan respectively. The expenditure for FY 08/09 was 1.8M and 0.9M for CT and MRI services respectively. Therefore the cost per abnormal finding would be $2,409 for CT and $957 for MRI. These cost per abnormal finding estimates were limited because they did not factor in comparators or the consequences associated with an abnormal reading or FNs. The estimates only consider the cost of the neuroimaging procedure and the yield of abnormal finding with the respective procedure.
PMCID: PMC3377587  PMID: 23074404
9.  Bracing and Taping Techniques and Patellofemoral Pain Syndrome 
Journal of Athletic Training  2012;47(3):358-359.
Reference/Citation:
D'hondt NE, Struijs PA, Kerkhoffs GM, et al. Orthotic devices for treating patellofemoral pain syndrome. Cochrane Database Syst Rev. 2002;(2):CD002267.
Clinical Question:
Is there an effective bracing or taping technique for treating patellofemoral pain?
Data Sources:
The authors searched the Cochrane Musculoskeletal Injuries Group specialized register (December 2001), the Cochrane Controlled Trials Register (2000, issue 2), MEDLINE (January 1966 to March 2000), EMBASE (January 1988 to March 2000), CINAHL (January 1982 to March 2000), and PEDro (up to March 2000) without language limitations. They also contacted relevant orthotic companies and searched the included reference lists of the retrieved articles. The search terms for MEDLINE were anterior knee pain, arthralgia, knee joint, patella, and patellofemoral pain. The search terms for EMBASE were brace, chondropathy, dynamic splint, knee, orthosis, orthotics, patella, patella chondromalacia, patellofemoral joint, randomized control trial, and strap. The search terms for CINAHL were anterior knee pain, brace, orthot, orthos, randomi, strap, tape, patell, and patellofemoral. In PEDro, the subsequent composite of search terms was therapy: manipulation, massage, mobilization, orthoses, splinting, stretching, strength training, taping; subdiscipline: musculoskeletal, orthopaedics, sports; method: clinical trial; problem: muscle weakness, pain, reduced joint compliance; body part: foot or ankle, lower leg or knee.
Study Selection:
All randomized and quasi-randomized trials comparing the effectiveness of knee or foot orthotics for treatment of patellofemoral pain syndrome were included. Any trials that described the use of orthotic devices in conjunction with operative treatment were excluded from this review. Using these inclusion criteria, 2 reviewers independently assessed the potentially eligible studies and resolved any disagreements through conversation and negotiation by a third reviewer. Although the authors mentioned that the review's purpose was to assess knee and foot orthoses, none of the included studies assessed foot orthoses. Therefore, all trials that examined foot orthotics were excluded.
Data Extraction:
Using a preset extraction form, 2 reviewers independently entered data into a review manager software program (RevMan 2000; The Cochrane Collaboration, Oxford, United Kingdom). This program was produced by the Cochrane Collaboration to support systematic reviews. Any further information needed regarding methods and data was requested from the authors. Because of heterogeneity of the study population, interventions, and follow-up periods, statistical pooling was not conducted. In place of statistical pooling, the strength of scientific evidence was graded based on a scale of A through D, with A being the strongest evidence-based research and D being the weakest evidence-based research.
Main Results:
The search strategy identified 15 trials, of which only 5 trials met all the inclusion criteria and had enough data to be considered for pooling. The 5 trials involved 362 participants who were assessed for pain, functional improvement, isokinetic muscular strength, motivation, subjective success, worst pain, usual pain, subjective clinical pain, and patellofemoral congruence angle. Of the 5 studies included in the review, only the following statistically significant differences were found. The Protonics orthosis significantly decreased pain and improved function based on the Kujala score versus no treatment. A home exercise program with McConnell taping and biofeedback decreased pain and improved function based on the Functional Index Questionnaire versus home exercise and monitored therapy. In addition, the Protonics orthosis versus no treatment resulted in a patellofemoral congruence angle change; McConnell taping versus Couman bandage improved satisfaction with applied therapy and isokinetic muscle strength at 300°/s of knee flexion. No other findings included in the review studies were statistically significant. The included studies were inadequate in their methodologic quality and incomplete in their research-based evidence, which was obtained by their investigators.
Conclusions:
According to the systematic review by D'hondt et al, the strength of retrieved research-based evidence of effectiveness of orthotic devices in the treatment of patellofemoral pain syndrome was graded C. This grade was appropriate because all trials had low-quality methodologic evidence to support or reject the effectiveness of orthotics and taping techniques in reducing pain. Although very little scientific evidence is available regarding the use of orthotics and taping techniques, D'hondt et al identified trends in orthotics and taping techniques that should be considered in clinical practice. A comprehensive exercise and stretching program with tape application was more effective in decreasing worst pain and usual pain and increasing functional improvement. This finding indicates that patellofemoral pain syndrome is best treated by using more than 1 intervention. In addition, no difference was apparent in pain outcomes between McConnell taping technique and Couman bandage: neither technique resolved pain. The Protonics orthosis actively affected patellar tracking by reducing internal rotation of the femur and compression on the lateral aspect of the patella. As a result, the Protonics orthosis reduced pain compared with no treatment. In contrast, the Couman bandage is used only to guide the patellar tracking pattern and massage the structures around the patella during motion. Yet a home exercise program with the addition of a stretching program and McConnell taping decreased pain and increased function, which may suggest that a combination of treatment approaches is needed to effectively treat the condition, as found in previous studies.
PMCID: PMC3392166  PMID: 22892417
knee orthotics; knee pain; rehabilitation
10.  A Systematic Review of Studies That Aim to Determine Which Outcomes to Measure in Clinical Trials in Children  
PLoS Medicine  2008;5(4):e96.
Background
In clinical trials the selection of appropriate outcomes is crucial to the assessment of whether one intervention is better than another. Selection of inappropriate outcomes can compromise the utility of a trial. However, the process of selecting the most suitable outcomes to include can be complex. Our aim was to systematically review studies that address the process of selecting outcomes or outcome domains to measure in clinical trials in children.
Methods and Findings
We searched Cochrane databases (no date restrictions) in December 2006; and MEDLINE (1950 to 2006), CINAHL (1982 to 2006), and SCOPUS (1966 to 2006) in January 2007 for studies of the selection of outcomes for use in clinical trials in children. We also asked a group of experts in paediatric clinical research to refer us to any other relevant studies. From these articles we extracted data on the clinical condition of interest, description of the method used to select outcomes, the people involved in the selection process, the outcomes selected, and limitations of the method as defined by the authors. The literature search identified 8,889 potentially relevant abstracts. Of these, 70 were retrieved, and 25 were included in the review. These studies described the work of 13 collaborations representing various paediatric specialties including critical care, gastroenterology, haematology, psychiatry, neurology, respiratory paediatrics, rheumatology, neonatal medicine, and dentistry. Two groups utilised the Delphi technique, one used the nominal group technique, and one used both methods to reach a consensus about which outcomes should be measured in clinical trials. Other groups used semistructured discussion, and one group used a questionnaire-based survey. The collaborations involved clinical experts, research experts, and industry representatives. Three groups involved parents of children affected by the particular condition.
Conclusions
Very few studies address the appropriate choice of outcomes for clinical research with children, and in most paediatric specialties no research has been undertaken. Among the studies we did assess, very few involved parents or children in selecting outcomes that should be measured, and none directly involved children. Research should be undertaken to identify the best way to involve parents and children in assessing which outcomes should be measured in clinical trials.
Ian Sinha and colleagues show, in a systematic review of published studies, that there are very few studies that address the appropriate choice of outcomes for clinical research with children.
Editors' Summary
Background.
When adult patients are given a drug for a disease by their doctors, they can be sure that its benefits and harms will have been carefully studied in clinical trials. Clinical researchers will have asked how well the drug does when compared to other drugs by giving groups of patients the various treatments and determining several “outcomes.” These are measurements carefully chosen in advance by clinical experts that ensure that trials provide as much information as possible about how effectively a drug deals with a specific disease and whether it has any other effects on patients' health and daily life. The situation is very different, however, for pediatric (child) patients. About three-quarters of the drugs given to children are “off-label”—they have not been specifically tested in children. The assumption used to be that children are just small people who can safely take drugs tested in adults provided the dose is scaled down. However, it is now known that children's bodies handle many drugs differently from adult bodies and that a safe dose for an adult can sometimes kill a child even after scaling down for body size. Consequently, regulatory bodies in the US, Europe, and elsewhere now require clinical trials to be done in children and drugs for pediatric use to be specifically licensed.
Why Was This Study Done?
Because children are not small adults, the methodology used to design trials involving children needs to be adapted from that used to design trials in adult patients. In particular, the process of selecting the outcomes to include in pediatric trials needs to take into account the differences between adults and children. For example, because children's brains are still developing, it may be important to include outcome measures that will detect any effect that drugs have on intellectual development. In this study, therefore, the researchers undertook a systematic review of the medical literature to discover how much is known about the best way to select outcomes in clinical trials in children.
What Did the Researchers Do and Find?
The researchers used a predefined search strategy to identify all the studies published since 1950 that examined the selection of outcomes in clinical trials in children. They also asked experts in pediatric clinical research for details of relevant studies. Only 25 studies, which covered several pediatric specialties and were published by 13 collaborative groups, met the strict eligibility criteria laid down by the researchers for their systematic review. Several approaches previously used to choose outcomes in clinical trials in adults were used in these studies to select outcomes. Two groups used the “Delphi” technique, in which opinions are sought from individuals, collated, and fed back to the individuals to generate discussion and a final, consensus agreement. One group used the “nominal group technique,” which involves the use of structured face-to-face discussions to develop a solution to a problem followed by a vote. Another group used both methods. The remaining groups (except one that used a questionnaire) used semistructured discussion meetings or workshops to decide on outcomes. Although most of the groups included clinical experts, people doing research on the specific clinical condition under investigation, and industry representatives, only three groups asked parents about which outcomes should be included in the trials, and none asked children directly.
What Do These Findings Mean?
These findings indicate that very few studies have addressed the selection of appropriate outcomes for clinical research in children. Indeed, in many pediatric specialties no research has been done on this important topic. Importantly, some of the studies included in this systematic review clearly show that it is inappropriate to use the outcomes used in adult clinical trials in pediatric populations. Overall, although the studies identified in this review provide some useful information on the selection of outcomes in clinical trials in children, further research is urgently needed to ensure that this process is made easier and more uniform. In particular, much more research must be done to determine the best way to involve children and their parents in the selection of outcomes.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050096.
A related PLoSMedicine Perspective article is available
The European Medicines Agency provides information about the regulation of medicines for children in Europe
The US Food and Drug Administration Office of Pediatric Therapeutics provides similar information for the US
The UK Medicines and Healthcare products Regulatory Agency also provides information on why medicines need to be tested in children
The UK Medicines for Children Research Network aims to facilitate the conduct of clinical trials of medicines for children
The James Lind Alliance has been established in the UK to increase patient involvement in medical research issues such as outcome selection in clinical trials
doi:10.1371/journal.pmed.0050096
PMCID: PMC2346505  PMID: 18447577
11.  Noninvasive Positive Pressure Ventilation for Chronic Respiratory Failure Patients With Stable 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 health technology assessment was to determine the effectiveness and cost-effectiveness of noninvasive ventilation for stable chronic obstructive pulmonary disease (COPD).
Clinical Need: Condition and Target Population
Noninvasive ventilation is used for COPD patients with chronic respiratory failure. Chronic respiratory failure in COPD patients may be due to the inability of the pulmonary system to coordinate ventilation, leading to adverse arterial levels of oxygen and carbon dioxide. Noninvasive ventilation in stable COPD patients has the potential to improve quality of life, prolong survival, and improve gas exchange and sleep quality in patients who are symptomatic after optimal therapy, have hypercapnia or nocturnal hypoventilation and mild hypercapnia, and are frequently hospitalized.
Technology
Noninvasive positive pressure ventilation (NPPV) is any form of positive ventilatory support without the use of an endotracheal tube. For stable COPD, the standard of care when using noninvasive ventilation is bilevel positive airway pressure (BiPAP). Bilevel positive airway pressure involves both inspiratory and expiratory pressure, high during inspiration and lower during expiration. It acts as a pressure support to accentuate a patient’s inspiratory efforts. The gradient between pressures maintains alveolar ventilation and helps to reduce carbon dioxide levels. Outpatients typically use BiPAP at night. Additional advantages of using BiPAP include resting of respiratory muscles, decreased work of breathing, and control of obstructive hypopnea.
Research Question
What is the effectiveness and cost-effectiveness of noninvasive ventilation, compared with no ventilation while receiving usual care, for stable COPD patients?
Research Methods
Literature Search
Search Strategy
A literature search was performed on December 3, 2010, using OVID MEDLINE, OVID MEDLINE In-Process and Other Non-Indexed Citations, OVID EMBASE, EBSCO Cumulative Index to Nursing & Allied Health Literature (CINAHL), the Wiley Cochrane Library, and the Centre for Reviews and Dissemination database for studies published from January 1, 2004 to December 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. When the reviewer was unsure of the eligibility of articles, a second clinical epidemiologist and then a group of epidemiologists reviewed these until consensus was reached.
Inclusion Criteria
full-text English language articles,
studies published between January 1, 2004 and December 3, 2010,
journal articles that report on the effectiveness or cost-effectiveness of noninvasive ventilation,
clearly described study design and methods, and
health technology assessments, systematic reviews, meta-analyses, randomized controlled trials (RCTs).
Exclusion Criteria
non-English papers
animal or in vitro studies
case reports, case series, or case-case studies
cross-over RCTs
studies on noninvasive negative pressure ventilation (e.g., iron lung)
studies that combine ventilation therapy with other regimens (e.g., daytime NPPV plus exercise or pulmonary rehabilitation)
studies on heliox with NPPV
studies on pulmonary rehabilitation with NPPV
Outcomes of Interest
mortality/survival
hospitalizations/readmissions
length of stay in hospital
forced expiratory volume
arterial partial pressure of oxygen
arterial partial pressure of carbon dioxide
dyspnea
exercise tolerance
health-related quality of life
Note: arterial pressure of oxygen and carbon dioxide are surrogate outcomes.
Statistical Methods
A meta-analysis and an analysis of individual studies were performed using Review Manager Version 5. For continuous data, a mean difference was calculated, and for dichotomous data, a relative risk ratio was calculated for RCTs. For continuous variables with mean baseline and mean follow-up data, a change value was calculated as the difference between the 2 mean values.
Quality of Evidence
The quality of each included study was assessed taking into consideration allocation concealment, randomization, blinding, power/sample size, withdrawals/dropouts, and intention-to-treat analyses.
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
Conclusions
The following conclusions refer to stable, severe COPD patients receiving usual care.
Short-Term Studies
Based on low quality of evidence, there is a beneficial effect of NPPV compared with no ventilation on oxygen gas exchange, carbon dioxide gas exchange, and exercise tolerance measured using the 6 Minute Walking Test.
Based on very low quality of evidence, there is no effect of NPPV therapy on lung function measured as forced expiratory volume in 1 second (Type II error not excluded).
Long-Term Studies
Based on moderate quality of evidence, there is no effect of NPPV therapy for the outcomes of mortality, lung function measured as forced expiratory volume in 1 second, and exercise tolerance measured using the 6 Minute Walking Test.
Based on low quality of evidence, there is no effect of NPPV therapy for the outcomes of oxygen gas exchange and carbon dioxide gas exchange (Type II error not excluded).
Qualitative Assessment
Based on low quality of evidence, there is a beneficial effect of NPPV compared with no ventilation for dyspnea based on reduced Borg score or Medical Research Council dyspnea score.
Based on moderate quality of evidence, there is no effect of NPPV therapy for hospitalizations.
Health-related quality of life could not be evaluated.
PMCID: PMC3384378  PMID: 23074437
12.  Creutzfeldt-Jakob disease in Sweden 
OBJECTIVES—To find and investigate, retrospectively, as many cases as possible of Creutzfeldt-Jakob disease (CJD) in Sweden dying during the period 1 January 1985 to 31 December 1996 and to detect any possible case(s) of new variant CJD.
METHODS—The patients were found through computer search of all death certificates in Sweden on which CJD was mentioned, through information from the Swedish neuropathologists, and spontaneous reports from Swedish doctors and hospitals. Data concerning the patients were then collected from patients' case records and from brain histopathology reports.
RESULTS—In total 72 cases of spongiform encephalopathy were confirmed as definite by neuropathology, one of them with Gerstmann-Stäussler-Scheinker disease. In 51 further cases there were no brain pathology data but the diagnosis "probable" (37 patients) or "possible" (14 patients) CJD according to WHO criteria could be made on clinical grounds. There was a variation in number of deaths/year, from a minimum of five (1985) to a maximum of 16 (1990). Sixty patients died during the period 1985-90 and 62 during 1991-6. The sex ratio was nearly 1:1. Calculated for a population of 8.6 million (mean of 12 years) in Sweden this gives 1.18/million/year. Age at the time of the presenting symptoms ranged from 34 to 84 years. Only one patient was under 40 at the onset of symptoms. He had a spongiform encephalopathy but prion protein staining was negative. The duration of symptoms that could be attributed to CJD was 6 months or less in 75 cases, 7-12 months in 16 cases, 1 to 2 years in 15 cases, and more than 2 years in 16 patients. By definition all patients were demented. Other more common symptoms and signs were aphasia, dysphasia, dysathria, ataxia, myoclonus, pareses of the extremities, rigidity or spasticity, different types of hyperkinesias, and other psychiatric symptoms (depression, anxiety, and aggressiveness). Less common symptoms were hallucinations (mainly visual), visual defects, sensory symptoms (paraesthesias, itching, or pain), apraxia of swallowing, and disorders of eye movements.
CONCLUSIONS—The incidence, the symptomatology, the age distribution (age in years at onset and at death), and the duration of illness were similar to those of other countries except for the cases of new variant CJD in the United Kingdom. There is so far no indication of any cases of new variant CJD in Sweden.


PMCID: PMC2170389  PMID: 9854958
13.  Task-specific journal extracts for using the medical literature. 
Clinicians and researchers use the medical literature in a variety of ways. The overwhelming volume of clinical journals necessitates tools to help healthcare professionals identify and employ relevant information. The structured abstract can facilitate browsing articles, but may not contain appropriate types of information or sufficient detail for all uses of the medical literature. We have created customized views of journal articles that provide information for specific research or clinical tasks, such as evaluating the scientific validity of a clinical trial. These summaries are called extracts because we literally extract information of a particular type from the full text of an article. We employ a context-based indexing scheme, previously designed for improving precision in literature searches, to automatically generate extracts from clinical research articles. In this paper, we present an evaluation of the content and utility of these task-specific extracts. Our results provide preliminary evidence that such extracts contain information that is relevant to clinical and research tasks and may facilitate understanding and use of the medical literature.
PMCID: PMC2232547  PMID: 10566512
14.  Contributions of Indian conservative dentists and endodontists to the Medline database during 1996–2009: A bibliometric analysis 
Background:
Analysis of publication trends will guide the policy framers, administrators, and dentists to frame future policies and design programs for the development of scientific and technological policies in the field of dentistry.
Aims and Objectives:
This study was undertaken to assess the trends in Indian Conservative dentists and endodontists’ Publication in PubMed-Medline database during 1996–2009.
Materials and Methods:
Using the time limitation of publication date limit of 1st January 1996 to 31st December 2009, all articles where authors’ affiliation had the words Dental AND India were selected. From this collection of articles, the following were noted down: year of publication, number of authors, name of the journal, reach of the journal, status of the journal, specialty of the first, state of origin, and type of research. From this database, the performance of department of conservative dentistry and endodontics was analyzed.
Results:
The number of articles published by conservative dentists and endodontists was 124. Among them, 63 got published in international journals and 61 in Indian journals. A majority of 33 journals were published in Indian Journal of Dental Research followed by 25 in the Journal of Conservative Dentistry. Out of these articles, 66 were on the basis of original research done by the authors. Nearly 45.2% of the published articles were from the institutes in Tamil Nadu, followed by Karnataka (30.6%), and Maharashtra (8.1%). Although the overall distribution of the publication trends seems to be constant from 1996 to 2006, there seems to be boom in the publication trend since 2007.
doi:10.4103/0972-0707.73374
PMCID: PMC3010020  PMID: 21217943
Conservative dentists and endodontists in India; conservative dentists and endodontists’ publications; publication trends
15.  Hidden Empirical Research Ethics: A Review of Three Health Journals from 2005 through 2006 
We hypothesized that a significant amount of empirical data pertinent to research ethics is currently inaccessible to research ethics committee or Institutuional Review Board (IRB) members for at least three reasons: it is published in non-ethics journals; articles are not adequately indexed using ethics-related keywords; and articles do not discuss the ethical significance of their data. We reviewed all articles from three health journals from January 2005 to December 2006, and identified 26 articles that contained data pertinent to research ethics. Only 7 articles contained keywords clearly related to research ethics; 15 of the articles contained no discussion of the ethical significance of their findings. Overall the articles we found constituted 2.2% of the research articles published in the three journals during the two-year period. If the same average number of articles were extrapolated to the top 100 of the approximately 5,000 journals indexed in MEDLINE, then at least 433 hidden ethics articles would be published each year. We conclude that better indexing of articles is needed, that IRB members and researchers need training to identify relevant data in the literature, and that IRB composition should include members from diverse disciplines familiar with ethics-relevant empirical data in their respective disciplines.
doi:10.1525/jer.2008.3.3.7
PMCID: PMC2679173  PMID: 19385766
research ethics; review article; institutional review boards; human experimentation; vulnerable populations
16.  Accuracy of References in Indian Journal of Otolaryngology and Head & Neck Surgery 
This study was done to observe the accuracy of references in articles published in Indian Journal of Otolaryngology and Head & Neck Surgery. There were 63 references randomly selected from different issues of Indian Journal of Otolaryngology and Head & Neck Surgery (IJOHNS). It includes: Volume 61, Number 4, December 2009 and Volume 62, Number 1, January 2010. References were examined in details by dividing them into six elements and they were compared with the original for accuracy. References not cited from indexed journals were excluded. Statistical analysis was done by using frequency and percentage. Results show that 30.1% references in Indian Journal of Otolaryngology and Head & Neck Surgery were incorrect. Most common errors were author’s name and journal name. Author’s names were found to be incorrect in 11.1% references while journal name were found to be incorrect in 6.3%. Errors in citing the references are also found in the Indian Journal of Otolaryngology and Head & Neck Surgery. The quoted error in this study is comparable to other international literatures. The majority of errors are avoidable. So, the authors, editors and the reviewers have to check for any errors seriously before publication in the journal.
doi:10.1007/s12070-010-0048-y
PMCID: PMC3266089  PMID: 22319688
References; Accuracy; Indian Journal of Otolaryngology and Head & Neck Surgery (IJOHNS)
17.  The developing world in The New England Journal of Medicine 
Background
Rampant disease in poor countries impedes development and contributes to growing North-South disparities; however, leading international medical journals underreport on health research priorities for developing countries.
Methods
We examined 416 weekly issues of the New England Journal of Medicine (NEJM) over an eight-year period, January 1997 to December 2004. A total of 8857 articles were reviewed by both authors. The content of each issue was evaluated in six categories: research, review articles, editorial, correspondence, book reviews and miscellaneous. If the title or abstract concerned a topic pertinent to any health issue in the developing world, the article was reviewed.
Results
Over the eight years covered in this study, 1997–2004, in the three essential categories of original research articles, review articles and editorials, less than 3.0 percent of these addressed health issues in the developing world. Publications relevant to DC were largely concerned with HIV and communicable diseases and constituted 135 of the 202 articles of which 63 were devoted to HIV. Only 23 articles addressed non-communicable disease in the DC and only a single article – a book review – discussed heart disease.
Conclusion
The medical information gap between rich and poor countries as judged by publications in the NEJM appears to be larger than the gap in the funding for research. Under-representation of developing world health issues in the medical literature is a global phenomenon. International medical journals cannot rectify global inequities, but they have an important role in educating their constituencies about the global divide.
doi:10.1186/1744-8603-2-3
PMCID: PMC1459140  PMID: 16542448
18.  Summary of the Scientific Literature for Pain and Anxiety Control in Dentistry: Journal Literature, January 1986-December 1987 
Anesthesia Progress  1988;35(6):247-265.
This bibliography contains both foreign (in brackets) and English language citations obtained from Index to Dental Literature, Index Medicus, and Psychological Abstracts for the period January 1986 to December 1987. Although a careful search of these indexes was performed, every relevant citation may not be included. Comments or suggestions regarding this bibliography are welcomed by the author.
PMCID: PMC2167771  PMID: 12487126
19.  A Hierarchy of Patient-Reported Outcomes for Meta-Analysis of Knee Osteoarthritis Trials: Empirical Evidence from a Survey of High Impact Journals 
Arthritis  2012;2012:136245.
Objectives. To develop a prioritised list based on responsiveness for extracting patient-reported outcomes (PROs) measuring pain and disability for performing meta-analyses in knee osteoarthritis (OA). Methods. A systematic search was conducted in 20 highest impact factor general and rheumatology journals chosen a priori. Eligible studies were randomised controlled trials, using two or more PROs measuring pain and/or disability. Results. A literature search identified 402 publications and 38 trials were included, resulting in 54 randomised comparisons. Thirty-five trials had sufficient data on pain and 15 trials on disability. The WOMAC “pain” and “function” subscales were the most responsive composite scores. The following list was developed. Pain: (1) WOMAC “pain” subscale, (2) pain during activity (VAS), (3) pain during walking (VAS), (4) general knee pain (VAS), (5) pain at rest (VAS), (6) other composite pain scales, and (7) other single item measures. Disability: (1) WOMAC “function” subscale, (2) SF-36 “physical function” subscale, (3) SF-36 (Physical composite score), and (4) Other composite disability scores. Conclusions. As choosing the PRO most favourable for the intervention from individual trials can lead to biased estimates, using a prioritised list as developed in this study is recommended to reduce risk of biased selection of PROs in meta-analyses.
doi:10.1155/2012/136245
PMCID: PMC3389647  PMID: 22792458
20.  Spinal Cord Stimulation for Neuropathic Pain 
Executive Summary
Objective
The objective of this health technology policy assessment was to determine the effectiveness of spinal cord stimulation (SCS) to manage chronic intractable neuropathic pain and to evaluate the adverse events and Ontario-specific economic profile of this technology.
Clinical Need
SCS is a reversible pain therapy that uses low-voltage electrical pulses to manage chronic, intractable neuropathic pain of the trunk or limbs. Neuropathic pain begins or is caused by damage or dysfunction to the nervous system and can be difficult to manage.
The prevalence of neuropathic pain has been estimated at about 1.5% of the population in the United States and 1% of the population in the United Kingdom. These prevalence rates are generalizable to Canada.
Neuropathic pain is extremely difficult to manage. People with symptoms that persist for at least 6 months or who have symptoms that last longer than expected for tissue healing or resolution of an underlying disease are considered to have chronic pain. Chronic pain is an emotional, social, and economic burden for those living with it. Depression, reduced quality of life (QOL), absenteeism from work, and a lower household income are positively correlated with chronic pain.
Although the actual number is unknown, a proportion of people with chronic neuropathic pain fail to obtain pain relief from pharmacological therapies despite adequate and reasonable efforts to use them. These people are said to have intractable neuropathic pain, and they are the target population for SCS.
The most common indication for SCS in North America is chronic intractable neuropathic pain due to failed back surgery syndrome (FBSS), a term that describes persistent leg or back and leg pain in patients who have had back or spine surgery. Neuropathic pain due to complex regional pain syndrome (CRPS), which can develop in the distal aspect of a limb a minor injury, is another common indication. To a lesser extent, chronic intractable pain of postherpetic neuralgia, which is a persistent burning pain and hyperesthesia along the distribution of a cutaneous nerve after an attack of herpes zoster, is also managed with SCS.
For each condition, SCS is considered as a pain management therapy only after conventional pain therapies, including pharmacological, nonpharmacological, and surgical treatments, if applicable, have been attempted and have failed.
The Technology
The SCS technology consists of 3 implantable components: a pulse generator, an extension cable, and a lead (a small wire). The pulse generator is the power source for the spinal cord stimulator. It generates low-voltage electrical pulses. The extension cable connects the pulse generator to the lead. The lead is a small, insulated wire that has a set of electrodes at one end. The lead is placed into the epidural space on the posterior aspect of the spinal cord, and the electrodes are positioned at the level of the nerve roots innervating the painful area. An electrical current from the electrodes induces a paresthesia, or a tingling sensation that masks the pain.
Before SCS is initiated, candidates must have psychological testing to rule out major psychological illness, drug habituation, and issues of secondary gain that can negatively influence the success of the therapy. Successful candidates will have a SCS test stimulation period (trial period) to assess their responsiveness to SCS. The test stimulation takes about 1 week to complete, and candidates who obtain at least 50% pain relief during this period are deemed suitable to receive a permanent implantation of a spinal cord stimulator
Review Strategy
The Medical Advisory Secretariat (MAS) reviewed all published health technology assessments of spinal cord stimulation. Following this, a literature search was conducted from 2000 to January, 2005 and a systematic review of the literature was completed. The primary outcome for the systematic review was pain relief. Secondary outcomes included functional status and quality of life. After applying the predetermined inclusion and exclusion criteria, 2 randomized controlled trials (MAS level 2 evidence), and 2 prospective non-randomized controlled trials with a before-and-after-treatment study design (MAS level 3a evidence) were retrieved and reviewed.
Summary of Findings
The authors of 6 health technology assessments concluded that evidence exists to support the effectiveness of SCS to decrease pain in various neuropathic pain syndromes. However, the quality of this evidence varied among reports from weak to moderate.
The systematic review completed by MAS found high quality level 2 evidence that SCS decreases pain and level 3a evidence that it improves functional status and quality of life in some people with neuropathic pain conditions. The rate of technical failures was approximately 11%, which included electrode lead migration and/or malposition. Procedural complications included infection and dural puncture; each occurred at a rate of 1.2%.
Conclusions
SCS may be considered for patients with chronic, neuropathic pain for whom standard pain treatments have failed and when there is no indication for surgical intervention to treat the underlying condition.
PMCID: PMC3382299  PMID: 23074473
21.  Public accessibility of biomedical articles from PubMed Central reduces journal readership—retrospective cohort analysis 
The FASEB Journal  2013;27(7):2536-2541.
Does PubMed Central—a government-run digital archive of biomedical articles—compete with scientific society journals? A longitudinal, retrospective cohort analysis of 13,223 articles (5999 treatment, 7224 control) published in 14 society-run biomedical research journals in nutrition, experimental biology, physiology, and radiology between February 2008 and January 2011 reveals a 21.4% reduction in full-text hypertext markup language (HTML) article downloads and a 13.8% reduction in portable document format (PDF) article downloads from the journals' websites when U.S. National Institutes of Health-sponsored articles (treatment) become freely available from the PubMed Central repository. In addition, the effect of PubMed Central on reducing PDF article downloads is increasing over time, growing at a rate of 1.6% per year. There was no longitudinal effect for full-text HTML downloads. While PubMed Central may be providing complementary access to readers traditionally underserved by scientific journals, the loss of article readership from the journal website may weaken the ability of the journal to build communities of interest around research papers, impede the communication of news and events to scientific society members and journal readers, and reduce the perceived value of the journal to institutional subscribers.—Davis, P. M. Public accessibility of biomedical articles from PubMed Central reduces journal readership—retrospective cohort analysis.
doi:10.1096/fj.13-229922
PMCID: PMC3688741  PMID: 23554455
digital repositories; downloads; open access; scientific publishing
22.  Noninvasive Positive Pressure Ventilation for Acute Respiratory Failure 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 evidence-based analysis was to examine the effectiveness, safety, and cost-effectiveness of noninvasive positive pressure ventilation (NPPV) in the following patient populations: patients with acute respiratory failure (ARF) due to acute exacerbations of chronic obstructive pulmonary disease (COPD); weaning of COPD patients from invasive mechanical ventilation (IMV); and prevention of or treatment of recurrent respiratory failure in COPD patients after extubation from IMV.
Clinical Need and Target Population
Acute Hypercapnic Respiratory Failure
Respiratory failure occurs when the respiratory system cannot oxygenate the blood and/or remove carbon dioxide from the blood. It can be either acute or chronic and is classified as either hypoxemic (type I) or hypercapnic (type II) respiratory failure. Acute hypercapnic respiratory failure frequently occurs in COPD patients experiencing acute exacerbations of COPD, so this is the focus of this evidence-based analysis. Hypercapnic respiratory failure occurs due to a decrease in the drive to breathe, typically due to increased work to breathe in COPD patients.
Technology
There are several treatment options for ARF. Usual medical care (UMC) attempts to facilitate adequate oxygenation and treat the cause of the exacerbation, and typically consists of supplemental oxygen, and a variety of medications such as bronchodilators, corticosteroids, and antibiotics. The failure rate of UMC is high and has been estimated to occur in 10% to 50% of cases.
The alternative is mechanical ventilation, either invasive or noninvasive. Invasive mechanical ventilation involves sedating the patient, creating an artificial airway through endotracheal intubation, and attaching the patient to a ventilator. While this provides airway protection and direct access to drain sputum, it can lead to substantial morbidity, including tracheal injuries and ventilator-associated pneumonia (VAP).
While both positive and negative pressure noninvasive ventilation exists, noninvasive negative pressure ventilation such as the iron lung is no longer in use in Ontario. Noninvasive positive pressure ventilation provides ventilatory support through a facial or nasal mask and reduces inspiratory work. Noninvasive positive pressure ventilation can often be used intermittently for short periods of time to treat respiratory failure, which allows patients to continue to eat, drink, talk, and participate in their own treatment decisions. In addition, patients do not require sedation, airway defence mechanisms and swallowing functions are maintained, trauma to the trachea and larynx are avoided, and the risk for VAP is reduced. Common complications are damage to facial and nasal skin, higher incidence of gastric distension with aspiration risk, sleeping disorders, and conjunctivitis. In addition, NPPV does not allow direct access to the airway to drain secretions and requires patients to cooperate, and due to potential discomfort, compliance and tolerance may be low.
In addition to treating ARF, NPPV can be used to wean patients from IMV through the gradual removal of ventilation support until the patient can breathe spontaneously. Five to 30% of patients have difficultly weaning. Tapering levels of ventilatory support to wean patients from IMV can be achieved using IMV or NPPV. The use of NPPV helps to reduce the risk of VAP by shortening the time the patient is intubated.
Following extubation from IMV, ARF may recur, leading to extubation failure and the need for reintubation, which has been associated with increased risk of nosocomial pneumonia and mortality. To avoid these complications, NPPV has been proposed to help prevent ARF recurrence and/or to treat respiratory failure when it recurs, thereby preventing the need for reintubation.
Research Questions
What is the effectiveness, cost-effectiveness, and safety of NPPV for the treatment of acute hypercapnic respiratory failure due to acute exacerbations of COPD compared with
usual medical care, and
invasive mechanical ventilation?
What is the effectiveness, cost-effectiveness, and safety of NPPV compared with IMV in COPD patients after IMV for the following purposes:
weaning COPD patients from IMV,
preventing ARF in COPD patients after extubation from IMV, and
treating ARF in COPD patients after extubation from IMV?
Research Methods
Literature Search
A literature search was performed on December 3, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, OVID EMBASE, the Cumulative Index to Nursing & Allied Health Literature (CINAHL), Wiley Cochrane, and the Centre for Reviews and Dissemination/International Agency for Health Technology Assessment (INAHTA) for studies published from January 1, 2004 until December 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.
Since there were numerous studies that examined the effectiveness of NPPV for the treatment of ARF due to exacerbations of COPD published before 2004, pre-2004 trials which met the inclusion/exclusion criteria for this evidence-based review were identified by hand-searching reference lists of included studies and systematic reviews.
Inclusion Criteria
English language full-reports;
health technology assessments, systematic reviews, meta-analyses, and randomized controlled trials (RCTs);
studies performed exclusively in patients with a diagnosis of COPD or studies performed with patients with a mix of conditions if results are reported for COPD patients separately;
patient population: (Question 1) patients with acute hypercapnic respiratory failure due to an exacerbation of COPD; (Question 2a) COPD patients being weaned from IMV; (Questions 2b and 2c) COPD patients who have been extubated from IMV.
Exclusion Criteria
< 18 years of age
animal studies
duplicate publications
grey literature
studies examining noninvasive negative pressure ventilation
studies comparing modes of ventilation
studies comparing patient-ventilation interfaces
studies examining outcomes not listed below, such as physiologic effects including heart rate, arterial blood gases, and blood pressure
Outcomes of Interest
mortality
intubation rates
length of stay (intensive care unit [ICU] and hospital)
health-related quality of life
breathlessness
duration of mechanical ventilation
weaning failure
complications
NPPV tolerance and compliance
Statistical Methods
When possible, results were pooled using Review Manager 5 Version 5.1, otherwise, the results were summarized descriptively. Dichotomous data were pooled into relative risks using random effects models and continuous data were pooled using weighted mean differences with a random effects model. Analyses using data from RCTs were done using intention-to-treat protocols; P values < 0.05 were considered significant. A priori subgroup analyses were planned for severity of respiratory failure, location of treatment (ICU or hospital ward), and mode of ventilation with additional subgroups as needed based on the literature. Post hoc sample size calculations were performed using STATA 10.1.
Quality of Evidence
The quality of each included study was assessed taking into consideration allocation concealment, randomization, blinding, power/sample size, withdrawals/dropouts, and intention-to-treat analyses.
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
NPPV for the Treatment of ARF due to Acute Exacerbations of COPD
NPPV Plus Usual Medical Care Versus Usual Medical Care Alone for First Line Treatment
A total of 1,000 participants were included in 11 RCTs1; the sample size ranged from 23 to 342. The mean age of the participants ranged from approximately 60 to 72 years of age. Based on either the Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPD stage criteria or the mean percent predicted forced expiratory volume in 1 second (FEV1), 4 of the studies included people with severe COPD, and there was inadequate information to classify the remaining 7 studies by COPD severity. The severity of the respiratory failure was classified into 4 categories using the study population mean pH level as follows: mild (pH ≥ 7.35), moderate (7.30 ≤ pH < 7.35), severe (7.25 ≤ pH < 7.30), and very severe (pH < 7.25). Based on these categories, 3 studies included patients with a mild respiratory failure, 3 with moderate respiratory failure, 4 with severe respiratory failure, and 1 with very severe respiratory failure.
The studies were conducted either in the ICU (3 of 11 studies) or general or respiratory wards (8 of 11 studies) in hospitals, with patients in the NPPV group receiving bilevel positive airway pressure (BiPAP) ventilatory support, except in 2 studies, which used pressure support ventilation and volume cycled ventilation, respectively. Patients received ventilation through nasal, facial, or oronasal masks. All studies specified a protocol or schedule for NPPV delivery, but this varied substantially across the studies. For example, some studies restricted the amount of ventilation per day (e.g., 6 hours per day) and the number of days it was offered (e.g., maximum of 3 days); whereas, other studies provided patients with ventilation for as long as they could tolerate it and recommended it for much longer periods of time (e.g., 7 to 10 days). These differences are an important source of clinical heterogeneity between the studies. In addition to NPPV, all patients in the NPPV group also received UMC. Usual medical care varied between the studies, but common medications included supplemental oxygen, bronchodilators, corticosteroids, antibiotics, diuretics, and respiratory stimulators.
The individual quality of the studies ranged. Common methodological issues included lack of blinding and allocation concealment, and small sample sizes.
Need for Endotracheal Intubation
Eleven studies reported the need for endotracheal intubation as an outcome. The pooled results showed a significant reduction in the need for endotracheal intubation in the NPPV plus UMC group compared with the UMC alone group (relative risk [RR], 0.38; 95% confidence interval [CI], 0.28−0.50). When subgrouped by severity of respiratory failure, the results remained significant for the mild, severe, and very severe respiratory failure groups.
GRADE: moderate
Inhospital Mortality
Nine studies reported inhospital mortality as an outcome. The pooled results showed a significant reduction in inhospital mortality in the NPPV plus UMC group compared with the UMC group (RR, 0.53; 95% CI, 0.35−0.81). When subgrouped by severity of respiratory failure, the results remained significant for the moderate and severe respiratory failure groups.
GRADE: moderate
Hospital Length of Stay
Eleven studies reported hospital length of stay (LOS) as an outcome. The pooled results showed a significant decrease in the mean length of stay for the NPPV plus UMC group compared with the UMC alone group (weighted mean difference [WMD], −2.68 days; 95% CI, −4.41 to −0.94 days). When subgrouped by severity of respiratory failure, the results remained significant for the mild, severe, and very severe respiratory failure groups.
GRADE: moderate
Complications
Five studies reported complications. Common complications in the NPPV plus UMC group included pneumonia, gastrointestinal disorders or bleeds, skin abrasions, eye irritation, gastric insufflation, and sepsis. Similar complications were observed in the UMC group including pneumonia, sepsis, gastrointestinal disorders or bleeds, pneumothorax, and complicated endotracheal intubations. Many of the more serious complications in both groups occurred in those patients who required endotracheal intubation. Three of the studies compared complications in the NPPV plus UMC and UMC groups. While the data could not be pooled, overall, the NPPV plus UMC group experienced fewer complications than the UMC group.
GRADE: low
Tolerance/Compliance
Eight studies reported patient tolerance or compliance with NPPV as an outcome. NPPV intolerance ranged from 5% to 29%. NPPV tolerance was generally higher for patients with more severe respiratory failure. Compliance with the NPPV protocol was reported by 2 studies, which showed compliance decreases over time, even over short periods such as 3 days.
NPPV Versus IMV for the Treatment of Patients Who Failed Usual Medical Care
A total of 205 participants were included in 2 studies; the sample sizes of these studies were 49 and 156. The mean age of the patients was 71 to 73 years of age in 1 study, and the median age was 54 to 58 years of age in the second study. Based on either the GOLD COPD stage criteria or the mean percent predicted FEV1, patients in 1 study had very severe COPD. The COPD severity could not be classified in the second study. Both studies had study populations with a mean pH less than 7.23, which was classified as very severe respiratory failure in this analysis. One study enrolled patients with ARF due to acute exacerbations of COPD who had failed medical therapy. The patient population was not clearly defined in the second study, and it was not clear whether they had to have failed medical therapy before entry into the study.
Both studies were conducted in the ICU. Patients in the NPPV group received BiPAP ventilatory support through nasal or full facial masks. Patients in the IMV group received pressure support ventilation.
Common methodological issues included small sample size, lack of blinding, and unclear methods of randomization and allocation concealment. Due to the uncertainty about whether both studies included the same patient population and substantial differences in the direction and significance of the results, the results of the studies were not pooled.
Mortality
Both studies reported ICU mortality. Neither study showed a significant difference in ICU mortality between the NPPV and IMV groups, but 1 study showed a higher mortality rate in the NPPV group (21.7% vs. 11.5%) while the other study showed a lower mortality rate in the NPPV group (5.1% vs. 6.4%). One study reported 1-year mortality and showed a nonsignificant reduction in mortality in the NPPV group compared with the IMV group (26.1% vs. 46.1%).
GRADE: low to very low
Intensive Care Unit Length of Stay
Both studies reported LOS in the ICU. The results were inconsistent. One study showed a statistically significant shorter LOS in the NPPV group compared with the IMV group (5 ± 1.35 days vs. 9.29 ± 3 days; P < 0.001); whereas, the other study showed a nonsignificantly longer LOS in the NPPV group compared with the IMV group (22 ± 19 days vs. 21 ± 20 days; P = 0.86).
GRADE: very low
Duration of Mechanical Ventilation
Both studies reported the duration of mechanical ventilation (including both invasive and noninvasive ventilation). The results were inconsistent. One study showed a statistically significant shorter duration of mechanical ventilation in the NPPV group compared with the IMV group (3.92 ± 1.08 days vs. 7.17 ± 2.22 days; P < 0.001); whereas, the other study showed a nonsignificantly longer duration of mechanical ventilation in the NPPV group compared with the IMV group (16 ± 19 days vs. 15 ± 21 days; P = 0.86). GRADE: very low
Complications
Both studies reported ventilator-associated pneumonia and tracheotomies. Both showed a reduction in ventilator-associated pneumonia in the NPPV group compared with the IMV group, but the results were only significant in 1 study (13% vs. 34.6%, P = 0.07; and 6.4% vs. 37.2%, P < 0.001, respectively). Similarly, both studies showed a reduction in tracheotomies in the NPPV group compared with the IMV group, but the results were only significant in 1 study (13% vs. 23.1%, P = 0.29; and 6.4% vs. 34.6%; P < 0.001).
GRADE: very low
Other Outcomes
One of the studies followed patients for 12 months. At the end of follow-up, patients in the NPPV group had a significantly lower rate of needing de novo oxygen supplementation at home. In addition, the IMV group experienced significant increases in functional limitations due to COPD, while no increase was seen in the NPPV group. Finally, no significant differences were observed for hospital readmissions, ICU readmissions, and patients with an open tracheotomy, between the NPPV and IMV groups.
NPPV for Weaning COPD Patients From IMV
A total of 80 participants were included in the 2 RCTs; the sample sizes of the studies were 30 and 50 patients. The mean age of the participants ranged from 58 to 69 years of age. Based on either the GOLD COPD stage criteria or the mean percent predicted FEV1, both studies included patients with very severe COPD. Both studies also included patients with very severe respiratory failure (mean pH of the study populations was less than 7.23). Chronic obstructive pulmonary disease patients receiving IMV were enrolled in the study if they failed a T-piece weaning trial (spontaneous breathing test), so they could not be directly extubated from IMV.
Both studies were conducted in the ICU. Patients in the NPPV group received weaning using either BiPAP or pressure support ventilation NPPV through a face mask, and patients in the IMV weaning group received pressure support ventilation. In both cases, weaning was achieved by tapering the ventilation level.
The individual quality of the studies ranged. Common methodological problems included unclear randomization methods and allocation concealment, lack of blinding, and small sample size.
Mortality
Both studies reported mortality as an outcome. The pooled results showed a significant reduction in ICU mortality in the NPPV group compared with the IMV group (RR, 0.47; 95% CI, 0.23−0.97; P = 0.04).
GRADE: moderate
Intensive Care Unit Length of Stay
Both studies reported ICU LOS as an outcome. The pooled results showed a nonsignificant reduction in ICU LOS in the NPPV group compared with the IMV group (WMD, −5.21 days; 95% CI, −11.60 to 1.18 days).
GRADE: low
Duration of Mechanical Ventilation
Both studies reported duration of mechanical ventilation (including both invasive and noninvasive ventilation) as an outcome. The pooled results showed a nonsignificant reduction in duration of mechanical ventilation (WMD, −3.55 days; 95% CI, −8.55 to 1.44 days).
GRADE: low
Nosocomial Pneumonia
Both studies reported nosocominal pneumonia as an outcome. The pooled results showed a significant reduction in nosocomial pneumonia in the NPPV group compared with the IMV group (RR, 0.14; 95% CI, 0.03−0.71; P = 0.02).
GRADE: moderate
Weaning Failure
One study reported a significant reduction in weaning failure in the NPPV group compared with the IMV group, but the results were not reported in the publication. In this study, 1 of 25 patients in the NPPV group and 2 of 25 patients in the IMV group could not be weaned after 60 days in the ICU.
NPPV After Extubation of COPD Patients From IMV
The literature was reviewed to identify studies examining the effectiveness of NPPV compared with UMC in preventing recurrence of ARF after extubation from IMV or treating acute ARF which has recurred after extubation from IMV. No studies that included only COPD patients or reported results for COPD patients separately were identified for the prevention of ARF postextubation.
One study was identified for the treatment of ARF in COPD patients that recurred within 48 hours of extubation from IMV. This study included 221 patients, of whom 23 had COPD. A post hoc subgroup analysis was conducted examining the rate of reintubation in the COPD patients only. A nonsignificant reduction in the rate of reintubation was observed in the NPPV group compared with the UMC group (7 of 14 patients vs. 6 of 9 patients, P = 0.67). GRADE: low
Conclusions
NPPV Plus UMC Versus UMC Alone for First Line Treatment of ARF due to Acute Exacerbations of COPD
Moderate quality of evidence showed that compared with UMC, NPPV plus UMC significantly reduced the need for endotracheal intubation, inhospital mortality, and the mean length of hospital stay.
Low quality of evidence showed a lower rate of complications in the NPPV plus UMC group compared with the UMC group.
NPPV Versus IMV for the Treatment of ARF in Patients Who Have Failed UMC
Due to inconsistent and low to very low quality of evidence, there was insufficient evidence to draw conclusions on the comparison of NPPV versus IMV for patients who failed UMC.
NPPV for Weaning COPD Patients From IMV
Moderate quality of evidence showed that weaning COPD patients from IMV using NPPV results in significant reductions in mortality, nosocomial pneumonia, and weaning failure compared with weaning with IMV.
Low quality of evidence showed a nonsignificant reduction in the mean LOS and mean duration of mechanical ventilation in the NPPV group compared with the IMV group.
NPPV for the Treatment of ARF in COPD Patients After Extubation From IMV
Low quality of evidence showed a nonsignificant reduction in the rate of reintubation in the NPPV group compared with the UMC group; however, there was inadequate evidence to draw conclusions on the effectiveness of NPPV for the treatment of ARF in COPD patients after extubation from IMV
PMCID: PMC3384377  PMID: 23074436
23.  Update in Palliative Care - 2011 
ABSTRACT
INTRODUCTION
The aim of this update is to summarize scientifically rigorous articles published in 2010 that serve to advance the field of palliative medicine and have an impact on clinical practice.
METHOD
We conducted two separate literature searches for articles published between January 1, 2010 and December 31, 2010. We reviewed title pages from the Annals of Internal Medicine, British Medical Journal, Journal of the American Geriatrics Society, JAMA, Journal of Clinical Oncology, JGIM, Journal of Pain and Symptom Management, Journal of Palliative Medicine, Lancet, New England Journal of Medicine, PC-FACS (Fast Article Critical Summaries for Clinicians in Palliative Care). We also conducted a Medline search with the key words "palliative," "hospice," and "terminal" care. Each author presented approximately 20 abstracts to the group. All authors reviewed these abstracts, and when needed, full text publications. We focused on articles relevant to general internists. We rated the articles individually, eliminating by consensus those that were not deemed of highest priority, and discussed the final choices as a group.
RESULTS
We first identified 126 articles with potential relevance. We presented 20 at the annual SGIM update session, and discuss 11 in this paper.
doi:10.1007/s11606-011-1929-9
PMCID: PMC3326102  PMID: 22127796
palliative; end-of-life; communication; pain
24.  Statistical validation of a global model for the distribution of the ultimate number of citations accrued by papers published in a scientific journal 
A central issue in evaluative bibliometrics is the characterization of the citation distribution of papers in the scientific literature. Here, we perform a large-scale empirical analysis of journals from every field in Thomson Reuters’ Web of Science database. We find that only 30 of the 2,184 journals have citation distributions that are inconsistent with a discrete lognormal distribution at the rejection threshold that controls the False Discovery Rate at 0.05. We find that large, multidisciplinary journals are over-represented in this set of 30 journals, leading us to conclude that, within a discipline, citation distributions are lognormal. Our results strongly suggest that the discrete lognormal distribution is a globally accurate model for the distribution of “eventual impact” of scientific papers published in single-discipline journal in a single year that is removed sufficiently from the present date.
doi:10.1002/asi.21335
PMCID: PMC3158611  PMID: 21858251
25.  How to Select a Journal to Submit and Publish Your Biomedical Paper? 
BioImpacts : BI  2012;2(1):61-68.
SUMMARY
Introduction
journal selection for publication purposes is one of the concerns of biomedi-cal researchers. They apply various criteria for choosing appropriate journal. Here, we have tried to collect main criteria biomedical researchers use to select a journal to submit their works.
Methods
we collected these criteria through focus group conversations with researchers during our careers, feedbacks from participants of our scientific writing work-shops and non-systematic review of some related literature.
Results
we have presented a summative and informative guidance in the selection of journals for biomedical paper submission and publication.
Conclusion
Categorized criteria as a mnemonic tool for au-thors may help the authors in journal selection process.
doi:10.5681/bi.2012.008
PMCID: PMC3648921  PMID: 23678443
Journal Selection Criteria; Submission and Publication; Biomedical Papers

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