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1.  Cost-Effectiveness of Early Versus Standard Antiretroviral Therapy in HIV-Infected Adults in Haiti 
PLoS Medicine  2011;8(9):e1001095.
This cost-effectiveness study comparing early versus standard antiretroviral treatment (ART) for HIV, based on randomized clinical trial data from Haiti, reveals that the new WHO guidelines for early ART initiation can be cost-effective in resource-poor settings.
Background
In a randomized clinical trial of early versus standard antiretroviral therapy (ART) in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm3 in Haiti, early ART decreased mortality by 75%. We assessed the cost-effectiveness of early versus standard ART in this trial.
Methods and Findings
Trial data included use of ART and other medications, laboratory tests, outpatient visits, radiographic studies, procedures, and hospital services. Medication, laboratory, radiograph, labor, and overhead costs were from the study clinic, and hospital and procedure costs were from local providers. We evaluated cost per year of life saved (YLS), including patient and caregiver costs, with a median of 21 months and maximum of 36 months of follow-up, and with costs and life expectancy discounted at 3% per annum. Between 2005 and 2008, 816 participants were enrolled and followed for a median of 21 months. Mean total costs per patient during the trial were US$1,381 for early ART and US$1,033 for standard ART. After excluding research-related laboratory tests without clinical benefit, costs were US$1,158 (early ART) and US$979 (standard ART). Early ART patients had higher mean costs for ART (US$398 versus US$81) but lower costs for non-ART medications, CD4 cell counts, clinically indicated tests, and radiographs (US$275 versus US$384). The cost-effectiveness ratio after a maximum of 3 years for early versus standard ART was US$3,975/YLS (95% CI US$2,129/YLS–US$9,979/YLS) including research-related tests, and US$2,050/YLS excluding research-related tests (95% CI US$722/YLS–US$5,537/YLS).
Conclusions
Initiating ART in HIV-infected adults with a CD4 cell count between 200 and 350 cells/mm3 in Haiti, consistent with World Health Organization advice, was cost-effective (US$/YLS <3 times gross domestic product per capita) after a maximum of 3 years, after excluding research-related laboratory tests.
Trial registration
ClinicalTrials.gov NCT00120510
Please see later in the article for the Editors' Summary
Editors' Summary
Background
AIDS has killed more than 25 million people since 1981, and about 33 million people (most of them living in low- and middle-income countries) are now infected with HIV, the virus that causes AIDS. HIV destroys immune system cells (including CD4 cells, a type of lymphocyte), leaving infected individuals susceptible to other infections. Early in the AIDS epidemic, most HIV-infected people died within 10 years of infection. Then, in 1996, highly active antiretroviral therapy (ART) became available and, for people living in affluent countries HIV/AIDS became a chronic condition. However, ART was extremely expensive and so a diagnosis of HIV infection remained a death sentence for people living in developing countries. In 2003, this situation was declared a global health emergency, and governments, international agencies, and funding bodies began to implement plans to increase ART coverage in developing countries. In 2009, more than a third of people in low- and middle-income countries who needed ART were receiving it, on the basis of guidelines that were in place at that time.
Why Was This Study Done?
Until recently, the World Health Organization (WHO) recommended that all HIV-positive patients with CD4 cell count below 200/mm3 blood or an AIDS-defining illness such as Kaposi's sarcoma should be given ART. Then, in 2009, the CIPRA HT-001 randomized clinical trial, which was undertaken in Haiti, reported that patients who started ART when their CD4 cell count was between 200 and 350 cells/mm3 (“early ART”) had a higher survival rate than patients who started ART according to the WHO guidelines (“standard ART”). As a result, WHO now recommends that ART is started in HIV-infected people when their CD4 cell count falls below 350 cells/mm3. But is this new recommendation cost-effective? Do its benefits outweigh its costs? Policy-makers need to know the cost-effectiveness of interventions so that they can allocate their limited resources wisely. A medical intervention is generally considered cost-effective if it costs less than three times a country's per capita gross domestic product (GDP) per year of life saved (YLS). In this study, the researchers assess the cost-effectiveness of early versus standard ART in the CIPRA HT-001 trial.
What Did the Researchers Do and Find?
The researchers used trial data on the use and costs of ART, other medications, laboratory tests, outpatient visits, radiography, procedures, and hospital services to evaluate the costs associated with early ART and standard ART among the 816 CIPRA HT-001 trial participants. The average total costs per patient after a maximum of 3 years treatment were US$1,381 for early ART and US$1,033 for standard ART. These figures dropped to US$1,158 and US$979, respectively, when the costs of research-related tests without clinical benefit were excluded. Patients who received early ART had higher average costs for ART but lower costs for other aspects of their treatment than patients who received standard ART. The incremental cost-effectiveness ratio after 3 years for early ART compared to standard ART was US$3,975/YLS if the costs of research-related tests were included in the calculation. That is, the cost of saving one year of life by starting ART early instead of when the CD4 cell count dropped below 200/mm3 was nearly US$4,000. Importantly, exclusion of the costs of research-related tests reduced the incremental cost-effectiveness ratio of early ART compared to standard ART to US$2,050/YLS.
What Do These Findings Mean?
Because the Haitian GDP per capita is US$785, these findings suggest that, in Haiti, early ART is a cost-effective intervention over a 3-year period. That is, the incremental cost per year of life saved of early ART compared to standard ART after exclusion of research-related tests is less than three times Haiti's per capita GDP. The researchers note that their incremental cost-effectiveness ratios are likely to be conservative because they did not consider the clinical benefits of early ART that continue beyond 3 years—early ART is associated with lower longer-term mortality than standard ART—or the effect of early ART on disability and quality of life. Cost-effectiveness studies now need to be undertaken at different sites to determine whether these findings are generalizable but, for now, this cost-effectiveness study suggests that the new WHO guidelines for ART initiation can be cost-effective in resource-poor settings, information that should help policy-makers in developing countries allocate their limited resources.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001095.
Information is available from the US National Institute of Allergy and infectious diseases on HIV infection and AIDS
HIV InSite has comprehensive information on all aspects of HIV/AIDS
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on the HIV/AIDS in the Caribbean, and on HIV/AIDS treatment and care (in English and Spanish)
WHO provides information about universal access to AIDS treatment (in English, French and Spanish); its 2010 ART guidelines can be downloaded
More information about the CIPRA HT-001 clinical trial is available
Patient stories about living with HIV/AIDS are available through Avert and through the charity website Healthtalkonline
More information about GHESKIO is available from Weill Cornell Global Health
doi:10.1371/journal.pmed.1001095
PMCID: PMC3176754  PMID: 21949643
2.  Cost-effectiveness of a day hospital falls prevention programme for screened community-dwelling older people at high risk of falls 
Age and Ageing  2010;39(6):710-716.
Background: multifactorial falls prevention programmes for older people have been proved to reduce falls. However, evidence of their cost-effectiveness is mixed.
Design: economic evaluation alongside pragmatic randomised controlled trial.
Intervention: randomised trial of 364 people aged ≥70, living in the community, recruited via GP and identified as high risk of falling. Both arms received a falls prevention information leaflet. The intervention arm were also offered a (day hospital) multidisciplinary falls prevention programme, including physiotherapy, occupational therapy, nurse, medical review and referral to other specialists.
Measurements: self-reported falls, as collected in 12 monthly diaries. Levels of health resource use associated with the falls prevention programme, screening (both attributed to intervention arm only) and other health-care contacts were monitored. Mean NHS costs and falls per person per year were estimated for both arms, along with the incremental cost-effectiveness ratio (ICER) and cost effectiveness acceptability curve.
Results: in the base-case analysis, the mean falls programme cost was £349 per person. This, coupled with higher screening and other health-care costs, resulted in a mean incremental cost of £578 for the intervention arm. The mean falls rate was lower in the intervention arm (2.07 per person/year), compared with the control arm (2.24). The estimated ICER was £3,320 per fall averted.
Conclusions: the estimated ICER was £3,320 per fall averted. Future research should focus on adherence to the intervention and an assessment of impact on quality of life.
doi:10.1093/ageing/afq108
PMCID: PMC2956532  PMID: 20833862
cost-effectiveness; accidental falls; screening; comprehensive geriatric assessment; randomised controlled trial; elderly
3.  Falls and mobility in Parkinson's disease: protocol for a randomised controlled clinical trial 
BMC Neurology  2011;11:93.
Background
Although physical therapy and falls prevention education are argued to reduce falls and disability in people with idiopathic Parkinson's disease, this has not yet been confirmed with a large scale randomised controlled clinical trial. The study will investigate the effects on falls, mobility and quality of life of (i) movement strategy training combined with falls prevention education, (ii) progressive resistance strength training combined with falls prevention education, (iii) a generic life-skills social program (control group).
Methods/Design
People with idiopathic Parkinson's disease who live at home will be recruited and randomly allocated to one of three groups. Each person shall receive therapy in an out-patient setting in groups of 3-4. Each group shall be scheduled to meet once per week for 2 hours for 8 consecutive weeks. All participants will also have a structured 2 hour home practice program for each week during the 8 week intervention phase. Assessments will occur before therapy, after the 8 week therapy program, and at 3 and 12 months after the intervention. A falls calendar will be kept by each participant for 12 months after outpatient therapy.
Consistent with the recommendations of the Prevention of Falls Network Europe group, three falls variables will be used as the primary outcome measures: the number of fallers, the number of multiple fallers and the falls rate. In addition to quantifying falls, we shall measure mobility, activity limitations and quality of life as secondary outcomes.
Discussion
This study has the potential to determine whether outpatient movement strategy training combined with falls prevention education or progressive resistance strength training combined with falls prevention education are effective for reducing falls and improving mobility and life quality in people with Parkinson's disease who live at home.
Trial registration
Australia and New Zealand Clinical Trials Register (ANZCTR): ACTRN12606000344594
doi:10.1186/1471-2377-11-93
PMCID: PMC3160881  PMID: 21801451
4.  A Multifaceted Intervention to Improve the Quality of Care of Children in District Hospitals in Kenya: A Cost-Effectiveness Analysis 
PLoS Medicine  2012;9(6):e1001238.
A cost-effective analysis conducted by Edwine Barasa and colleagues estimates that a complex intervention aimed at improving quality of pediatric care would be affordable and cost-effective in Kenya.
Background
To improve care for children in district hospitals in Kenya, a multifaceted approach employing guidelines, training, supervision, feedback, and facilitation was developed, for brevity called the Emergency Triage and Treatment Plus (ETAT+) strategy. We assessed the cost effectiveness of the ETAT+ strategy, in Kenyan hospitals. Further, we estimate the costs of scaling up the intervention to Kenya nationally and potential cost effectiveness at scale.
Methods and Findings
Our cost-effectiveness analysis from the provider's perspective used data from a previously reported cluster randomized trial comparing the full ETAT+ strategy (n = 4 hospitals) with a partial intervention (n = 4 hospitals). Effectiveness was measured using 14 process measures that capture improvements in quality of care; their average was used as a summary measure of quality. Economic costs of the development and implementation of the intervention were determined (2009 US$). Incremental cost-effectiveness ratios were defined as the incremental cost per percentage improvement in (average) quality of care. Probabilistic sensitivity analysis was used to assess uncertainty. The cost per child admission was US$50.74 (95% CI 49.26–67.06) in intervention hospitals compared to US$31.1 (95% CI 30.67–47.18) in control hospitals. Each percentage improvement in average quality of care cost an additional US$0.79 (95% CI 0.19–2.31) per admitted child. The estimated annual cost of nationally scaling up the full intervention was US$3.6 million, approximately 0.6% of the annual child health budget in Kenya. A “what-if” analysis assuming conservative reductions in mortality suggests the incremental cost per disability adjusted life year (DALY) averted by scaling up would vary between US$39.8 and US$398.3.
Conclusion
Improving quality of care at scale nationally with the full ETAT+ strategy may be affordable for low income countries such as Kenya. Resultant plausible reductions in hospital mortality suggest the intervention could be cost-effective when compared to incremental cost-effectiveness ratios of other priority child health interventions.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
According to latest global estimates from UNICEF, 7.6 million children currently die every year before they reach five years of age. Half of these deaths occur in children in sub-Saharan Africa and tragically, most of these deaths are due to a few treatable and preventable diseases, such as pneumonia, malaria, and diarrhea, for which effective interventions are already available. In order to meet the target of the 4th Millennium Development Goal—which aims to reduce the under-five child mortality rate by two-thirds from 1990 levels by 2015—delivering these interventions is essential.
In Kenya, the under-five child mortality rate must be reduced by half from its 2008 level in order to meet the Millennium Development Goal (MDG) target and so improving the management of serious child illness might help achieve this goal. A study published last year in PLoS Medicine described such an approach and included the development and implementation of evidence-based clinical practice guidelines linked to health worker training, follow-up supervision, performance feedback, and facilitation in eight district hospitals in Kenya.
Why Was This Study Done?
In the study mentioned above, the researchers compared the implementation of various processes of care in intervention and control hospitals at baseline and 18 months later and found that performance improved more in the intervention hospitals than in the control hospitals. However, while this strategy was effective at improving the quality of health care, it is unclear whether scaling up the approach would be a good use of limited resources. So in this study, the same researchers performed a cost-effectiveness analysis (which they conducted alongside the original trial) of their quality improvement intervention and estimated the costs and effects of scaling up this approach to cover the entire population of Kenya.
What Did the Researchers Do and Find?
In order to perform the cost part of the analysis, the researchers collected the relevant information on costs by using clinical and accounting record reviews and interviews with those involved in developing and implementing the intervention. The researchers evaluated the effectiveness part of the analysis by comparing the implementation of their improved quality of care strategy as delivered in the intervention hospitals with the partial intervention as delivered in the control hospitals by calculating the mean percentage improvement in the 14 process of care indicators at 18 months. Finally, the researchers calculated the costs of scaling up the intervention by applying their results to the whole of Kenya—121 hospital facilities with an estimated annual child admission rate of 2,000 per facility.
The researchers found that the quality of care (as measured by the process of care indicators) was 25% higher in intervention hospitals than in control hospitals, while the cost per child admission was US$50.74 in intervention hospitals compared to US$31.1 in control hospitals. The researchers calculated that each percentage improvement in the average quality of care was achieved at an additional cost of US$0.79 per admitted child. Extrapolating these results to all of Kenya, the estimated annual cost of scaling up the intervention nationally was US$3.6 million, about 0.6% of the annual child health budget in Kenya.
What Do These Findings Mean?
The findings of this cost-effectiveness analysis suggests that a comprehensive quality improvement intervention is effective at improving standards of care but at an additional cost, which may be relatively cost effective compared with basic care if the improvements observed are associated with decreases in child inpatient mortality. The absolute costs for scaling up are comparable to, or even lower than, costs of other, major child health interventions. As the international community is giving an increasing focus to strengthening health systems, these findings provide a strong case for scaling up this intervention, which improves quality of care and service provision for the major causes of child mortality, in rural hospitals throughout Kenya and other district hospitals in sub-Saharan Africa.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001238.
The researchers' original article appeared in PLoS Medicine in 2011: Ayieko P, Ntoburi S, Wagai J, Opondo C, Opiyo N, et al. (2011) A Multifaceted Intervention to Implement Guidelines and Improve Admission Paediatric Care in Kenyan District Hospitals: A Cluster Randomised Trial. PLoS Med 8(4): e1001018. doi:10.1371/journal.pmed.1001018
The IDOC Africa provides further information on the ETAT+ strategy
The World Health Organization (WHO) provides information on MDG 4, including strategies to reduce global child mortality) and the WHO pocket-book “Hospital care for children” includes guidelines for the management of common but serious childhood illnesses in resource-limited settings
UNICEF www.unicef.org also publishes information on global child mortality rates and the Countdown to 2015 website tracks coverage levels for health interventions proven to reduce child mortality
doi:10.1371/journal.pmed.1001238
PMCID: PMC3373608  PMID: 22719233
5.  Cost-Effectiveness Study of Three Antimalarial Drug Combinations in Tanzania 
PLoS Medicine  2006;3(10):e373.
Background
As a result of rising levels of drug resistance to conventional monotherapy, the World Health Organization (WHO) and other international organisations have recommended that malaria endemic countries move to combination therapy, ideally with artemisinin-based combinations (ACTs). Cost is a major barrier to deployment. There is little evidence from field trials on the cost-effectiveness of these new combinations.
Methods and Findings
An economic evaluation of drug combinations was designed around a randomised effectiveness trial of combinations recommended by the WHO, used to treat Tanzanian children with non-severe slide-proven malaria. Drug combinations were: amodiaquine (AQ), AQ with sulfadoxine-pyrimethamine (AQ+SP), AQ with artesunate (AQ+AS), and artemether-lumefantrine (AL) in a six-dose regimen. Effectiveness was measured in terms of resource savings and cases of malaria averted (based on parasitological failure rates at days 14 and 28). All costs to providers and to patients and their families were estimated and uncertain variables were subjected to univariate sensitivity analysis. Incremental analysis comparing each combination to monotherapy (AQ) revealed that from a societal perspective AL was most cost-effective at day 14. At day 28 the difference between AL and AQ+AS was negligible; both resulted in a gross savings of approximately US$1.70 or a net saving of US$22.40 per case averted. Varying the accuracy of diagnosis and the subsistence wage rate used to value unpaid work had a significant effect on the number of cases averted and on programme costs, respectively, but this did not change the finding that AL and AQ+AS dominate monotherapy.
Conclusions
In an area of high drug resistance, there is evidence that AL and AQ+AS are the most cost-effective drugs despite being the most expensive, because they are significantly more effective than other options and therefore reduce the need for further treatment. This is not necessarily the case in parts of Africa where recrudescence following SP and AQ treatment (and their combination) is lower so that the relative advantage of ACTs is smaller, or where diagnostic services are not accurate and as a result much of the drug goes to those who do not have malaria.
A randomised effectiveness trial of antimalarial drug combinations used to treat Tanzanian children found artemether-lumefantrine to be the most cost-effective.
Editors' Summary
Background.
For many years, malaria was treated with a course of a single drug. This type of treatment made it easy for malaria parasites to become resistant to antimalarial drugs. This is a major factor contributing to the continuing high death rate from the disease. However, although parasites can easily adapt to resist one drug, adapting to combinations of two or three drugs is much harder. Scientists have therefore developed combinations of antimalarial drugs. One component of these combinations is artemisinin—derived from a Chinese shrub. However, these combination therapies are much more expensive than the older treatments.
The regions worst affected by malaria—Africa and Asia—are also the poorest. And, in these areas, where both individual and government resources are scarce, antimalarial treatments must be cost-effective as well as clinically effective.
Why Was This Study Done?
Most of the estimated 1 million to 3 million people worldwide killed by malaria every year are young children in sub-Saharan Africa. Growing drug resistance, poor prevention programs, and a frequent inability of patients to pay for treatment mean that effective therapy is desperately needed in this part of the world. However, because of differences in drug resistance between regions, a drug combination will not work everywhere. In addition, because of low annual incomes (the average in Tanzania is US$120), heavy subsidies will probably be required to ensure that combination treatments are widely used. With several healthcare problems competing for resources, policymakers are likely to subsidize only the most cost-effective treatments. The researchers wanted to provide policymakers with information on how different combinations of malaria drugs compare in terms of costs, health effects, and cost-effectiveness, so that they can decide which treatment is best for their region.
What Did the Researchers Do and Find?
They compared three combinations that the World Health Organization recommends for countries when making the transition from single-drug therapy. The three combinations—amodiaquine (AQ) and sulfadoxine-pyrimethamine (SP); AQ and artesunate (AS); and artemether-lumefantrine (AL)—were used to treat Tanzanian children. The researchers wanted to find out how many cases of malaria each combination averted (which is also an indication of how much money it saved) and how much the treatment cost. They looked at costs and savings from the perspectives of both healthcare providers and patients.
Compared with no treatment, AL proved to be the most cost-effective; although it cost more for the provider (US$3.01 at day 28 of treatment) than the others, its effectiveness in getting rid of the parasite meant it would save the cost of future treatment. By day 28, AL had averted 382 cases of malaria compared with 279 for AQ+AS, 181 for AQ+SP, and 57 for AQ alone. Also, higher proportions of inaccurate diagnoses of malaria led to lower cost-effectiveness of treatments.
What Do These Findings Mean?
Despite being more expensive, newer drugs can be cost-effective where alternatives fail. Although AL was the most cost-effective in places (such as Tanzania) where the malaria parasites are highly resistant to SP and AQ, the picture is likely to change for other areas. In West Africa, for example, AQ resistance is lower, and AQ+SP and AQ+AS would probably be more cost-effective. And in areas where both these combinations are just as good as AL in preventing recurring disease, they would be more cost-effective than AL. However, since AQ and SP have been used singly for many years, the likelihood is that resistance to these drugs will continue to increase. Accurate diagnosis turns out to be very important for maintaining the cost-effectiveness of combination antimalarial therapies. This will be essential if they are to be incorporated as a sustainable part of local health policies. The researchers also point out that, depending on which perspective is taken (provider or patient), the cost-effectiveness of treatments differs, making it important to compare like with like.
Although investing in costly AL treatments and improving diagnostic capabilities will be a challenge for African governments that currently spend less than US$5 per person per year on healthcare, it will be necessary if they are to seriously tackle the malaria epidemic.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030373
The US enters for Disease Control and Prevention provides malaria information aimed at the general public, physicians, and health workers
The Wellcome Trust; also has malaria information for the general public and covers the science of malaria research, including a downloadable animation of the parasite's life cycle
Medicines for Malaria Venture (MMV) is a charity created to develop new antimalarial drugs through public-private partnerships
doi:10.1371/journal.pmed.0030373
PMCID: PMC1592341  PMID: 17032059
6.  Behavioural Interventions for Urinary Incontinence in Community-Dwelling Seniors 
Executive Summary
In early August 2007, the Medical Advisory Secretariat began work on the Aging in the Community project, an evidence-based review of the literature surrounding healthy aging in the community. The Health System Strategy Division at the Ministry of Health and Long-Term Care subsequently asked the secretariat to provide an evidentiary platform for the ministry’s newly released Aging at Home Strategy.
After a broad literature review and consultation with experts, the secretariat identified 4 key areas that strongly predict an elderly person’s transition from independent community living to a long-term care home. Evidence-based analyses have been prepared for each of these 4 areas: falls and fall-related injuries, urinary incontinence, dementia, and social isolation. For the first area, falls and fall-related injuries, an economic model is described in a separate report.
Please visit the Medical Advisory Secretariat Web site, http://www.health.gov.on.ca/english/providers/program/mas/mas_about.html, to review these titles within the Aging in the Community series.
Aging in the Community: Summary of Evidence-Based Analyses
Prevention of Falls and Fall-Related Injuries in Community-Dwelling Seniors: An Evidence-Based Analysis
Behavioural Interventions for Urinary Incontinence in Community-Dwelling Seniors: An Evidence-Based Analysis
Caregiver- and Patient-Directed Interventions for Dementia: An Evidence-Based Analysis
Social Isolation in Community-Dwelling Seniors: An Evidence-Based Analysis
The Falls/Fractures Economic Model in Ontario Residents Aged 65 Years and Over (FEMOR)
Objective
To assess the effectiveness of behavioural interventions for the treatment and management of urinary incontinence (UI) in community-dwelling seniors.
Clinical Need: Target Population and Condition
Urinary incontinence defined as “the complaint of any involuntary leakage of urine” was identified as 1 of the key predictors in a senior’s transition from independent community living to admission to a long-term care (LTC) home. Urinary incontinence is a health problem that affects a substantial proportion of Ontario’s community-dwelling seniors (and indirectly affects caregivers), impacting their health, functioning, well-being and quality of life. Based on Canadian studies, prevalence estimates range from 9% to 30% for senior men and nearly double from 19% to 55% for senior women. The direct and indirect costs associated with UI are substantial. It is estimated that the total annual costs in Canada are $1.5 billion (Cdn), and that each year a senior living at home will spend $1,000 to $1,500 on incontinence supplies.
Interventions to treat and manage UI can be classified into broad categories which include lifestyle modification, behavioural techniques, medications, devices (e.g., continence pessaries), surgical interventions and adjunctive measures (e.g., absorbent products).
The focus of this review is behavioural interventions, since they are commonly the first line of treatment considered in seniors given that they are the least invasive options with no reported side effects, do not limit future treatment options, and can be applied in combination with other therapies. In addition, many seniors would not be ideal candidates for other types of interventions involving more risk, such as surgical measures.
Note: It is recognized that the terms “senior” and “elderly” carry a range of meanings for different audiences; this report generally uses the former, but the terms are treated here as essentially interchangeable.
Description of Technology/Therapy
Behavioural interventions can be divided into 2 categories according to the target population: caregiver-dependent techniques and patient-directed techniques. Caregiver-dependent techniques (also known as toileting assistance) are targeted at medically complex, frail individuals living at home with the assistance of a caregiver, who tends to be a family member. These seniors may also have cognitive deficits and/or motor deficits. A health care professional trains the senior’s caregiver to deliver an intervention such as prompted voiding, habit retraining, or timed voiding. The health care professional who trains the caregiver is commonly a nurse or a nurse with advanced training in the management of UI, such as a nurse continence advisor (NCA) or a clinical nurse specialist (CNS).
The second category of behavioural interventions consists of patient-directed techniques targeted towards mobile, motivated seniors. Seniors in this population are cognitively able, free from any major physical deficits, and motivated to regain and/or improve their continence. A nurse or a nurse with advanced training in UI management, such as an NCA or CNS, delivers the patient-directed techniques. These are often provided as multicomponent interventions including a combination of bladder training techniques, pelvic floor muscle training (PFMT), education on bladder control strategies, and self-monitoring. Pelvic floor muscle training, defined as a program of repeated pelvic floor muscle contractions taught and supervised by a health care professional, may be employed as part of a multicomponent intervention or in isolation.
Education is a large component of both caregiver-dependent and patient-directed behavioural interventions, and patient and/or caregiver involvement as well as continued practice strongly affect the success of treatment. Incontinence products, which include a large variety of pads and devices for effective containment of urine, may be used in conjunction with behavioural techniques at any point in the patient’s management.
Evidence-Based Analysis Methods
A comprehensive search strategy was used to identify systematic reviews and randomized controlled trials that examined the effectiveness, safety, and cost-effectiveness of caregiver-dependent and patient-directed behavioural interventions for the treatment of UI in community-dwelling seniors (see Appendix 1).
Research Questions
Are caregiver-dependent behavioural interventions effective in improving UI in medically complex, frail community-dwelling seniors with/without cognitive deficits and/or motor deficits?
Are patient-directed behavioural interventions effective in improving UI in mobile, motivated community-dwelling seniors?
Are behavioural interventions delivered by NCAs or CNSs in a clinic setting effective in improving incontinence outcomes in community-dwelling seniors?
Assessment of Quality of Evidence
The quality of the evidence was assessed as high, moderate, low, or very low according to the GRADE methodology and GRADE Working Group. As per GRADE the following definitions apply:
Summary of Findings
Executive Summary Table 1 summarizes the results of the analysis.
The available evidence was limited by considerable variation in study populations and in the type and severity of UI for studies examining both caregiver-directed and patient-directed interventions. The UI literature frequently is limited to reporting subjective outcome measures such as patient observations and symptoms. The primary outcome of interest, admission to a LTC home, was not reported in the UI literature. The number of eligible studies was low, and there were limited data on long-term follow-up.
Summary of Evidence on Behavioural Interventions for the Treatment of Urinary Incontinence in Community-Dwelling Seniors
Prompted voiding
Habit retraining
Timed voiding
Bladder training
PFMT (with or without biofeedback)
Bladder control strategies
Education
Self-monitoring
CI refers to confidence interval; CNS, clinical nurse specialist; NCA, nurse continence advisor; PFMT, pelvic floor muscle training; RCT, randomized controlled trial; WMD, weighted mean difference; UI, urinary incontinence.
Economic Analysis
A budget impact analysis was conducted to forecast costs for caregiver-dependent and patient-directed multicomponent behavioural techniques delivered by NCAs, and PFMT alone delivered by physiotherapists. All costs are reported in 2008 Canadian dollars. Based on epidemiological data, published medical literature and clinical expert opinion, the annual cost of caregiver-dependent behavioural techniques was estimated to be $9.2 M, while the annual costs of patient-directed behavioural techniques delivered by either an NCA or physiotherapist were estimated to be $25.5 M and $36.1 M, respectively. Estimates will vary if the underlying assumptions are changed.
Currently, the province of Ontario absorbs the cost of NCAs (available through the 42 Community Care Access Centres across the province) in the home setting. The 2007 Incontinence Care in the Community Report estimated that the total cost being absorbed by the public system of providing continence care in the home is $19.5 M in Ontario. This cost estimate included resources such as personnel, communication with physicians, record keeping and product costs. Clinic costs were not included in this estimation because currently these come out of the global budget of the respective hospital and very few continence clinics actually exist in the province. The budget impact analysis factored in a cost for the clinic setting, assuming that the public system would absorb the cost with this new model of community care.
Considerations for Ontario Health System
An expert panel on aging in the community met on 3 occasions from January to May 2008, and in part, discussed treatment of UI in seniors in Ontario with a focus on caregiver-dependent and patient-directed behavioural interventions. In particular, the panel discussed how treatment for UI is made available to seniors in Ontario and who provides the service. Some of the major themes arising from the discussions included:
Services/interventions that currently exist in Ontario offering behavioural interventions to treat UI are not consistent. There is a lack of consistency in how seniors access services for treatment of UI, who manages patients and what treatment patients receive.
Help-seeking behaviours are important to consider when designing optimal service delivery methods.
There is considerable social stigma associated with UI and therefore there is a need for public education and an awareness campaign.
The cost of incontinent supplies and the availability of NCAs were highlighted.
Conclusions
There is moderate-quality evidence that the following interventions are effective in improving UI in mobile motivated seniors:
Multicomponent behavioural interventions including a combination of bladder training techniques, PFMT (with or without biofeedback), education on bladder control strategies and self-monitoring techniques.
Pelvic floor muscle training alone.
There is moderate quality evidence that when behavioural interventions are led by NCAs or CNSs in a clinic setting, they are effective in improving UI in seniors.
There is limited low-quality evidence that prompted voiding may be effective in medically complex, frail seniors with motivated caregivers.
There is insufficient evidence for the following interventions in medically complex, frail seniors with motivated caregivers:
habit retraining, and
timed voiding.
PMCID: PMC3377527  PMID: 23074508
7.  Economic Appraisal of Ontario's Universal Influenza Immunization Program: A Cost-Utility Analysis 
PLoS Medicine  2010;7(4):e1000256.
Beate Sander and colleagues assess the cost-effectiveness of the program that provides free seasonal influenza vaccines to the entire population of Ontario, Canada.
Background
In July 2000, the province of Ontario, Canada, initiated a universal influenza immunization program (UIIP) to provide free seasonal influenza vaccines for the entire population. This is the first large-scale program of its kind worldwide. The objective of this study was to conduct an economic appraisal of Ontario's UIIP compared to a targeted influenza immunization program (TIIP).
Methods and Findings
A cost-utility analysis using Ontario health administrative data was performed. The study was informed by a companion ecological study comparing physician visits, emergency department visits, hospitalizations, and deaths between 1997 and 2004 in Ontario and nine other Canadian provinces offering targeted immunization programs. The relative change estimates from pre-2000 to post-2000 as observed in other provinces were applied to pre-UIIP Ontario event rates to calculate the expected number of events had Ontario continued to offer targeted immunization. Main outcome measures were quality-adjusted life years (QALYs), costs in 2006 Canadian dollars, and incremental cost-utility ratios (incremental cost per QALY gained). Program and other costs were drawn from Ontario sources. Utility weights were obtained from the literature. The incremental cost of the program per QALY gained was calculated from the health care payer perspective. Ontario's UIIP costs approximately twice as much as a targeted program but reduces influenza cases by 61% and mortality by 28%, saving an estimated 1,134 QALYs per season overall. Reducing influenza cases decreases health care services cost by 52%. Most cost savings can be attributed to hospitalizations avoided. The incremental cost-effectiveness ratio is Can$10,797/QALY gained. Results are most sensitive to immunization cost and number of deaths averted.
Conclusions
Universal immunization against seasonal influenza was estimated to be an economically attractive intervention.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Annual outbreaks (epidemics) of influenza—a viral disease of the nose, throat, and airways—make millions of people ill and kill about 500,000 individuals every year. In doing so, they impose a considerable economic burden on society in terms of health care costs and lost productivity. Influenza epidemics occur because small but frequent changes in the viral proteins to which the immune system responds mean that an immune response produced one year by exposure to an influenza virus provides only partial protection against influenza the next year. Annual immunization with a vaccine that contains killed influenza viruses of the major circulating strains can boost this natural immunity and greatly reduce a person's chances of catching influenza. Consequently, many countries run seasonal influenza vaccine programs. These programs usually target people at high risk of complications from influenza and individuals likely to come into close contact with them, and people who provide essential community services. So, for example, in most Canadian provinces, targeted influenza immunization programs (TIIPs) offer free influenza vaccinations to people aged 65 years or older, to people with chronic medical conditions, and to health care workers.
Why Was This Study Done?
Some experts argue, however, that universal vaccination might provide populations with better protection from influenza. In 2000, the province of Ontario in Canada decided, therefore, to introduce a universal influenza immunization program (UIIP) to provide free influenza vaccination to everyone older than 6 months, the first large program of this kind in the world. A study published in 2008 showed that, following the introduction of the UIIP, vaccination rates in Ontario increased more than in other Canadian provinces. In addition, deaths from influenza and influenza-related use of health care facilities decreased more in Ontario than in provinces that continued to offer a TIIP. But is universal influenza vaccination good value for money? In this study, the researchers evaluate the cost-effectiveness of the Ontario UIIP by comparing the health outcomes and costs associated with its introduction with the health outcomes and costs associated with a hypothetical continuation of targeted influenza immunization.
What Did the Researchers Do and Find?
The researchers used data on TIIP and UIIP vaccine uptake, physician visits, emergency department visits, hospitalizations for influenza, and deaths from influenza between 1997 and 2004 in Ontario and in nine Canadian states offering TIIPs, and Ontario cost data, in their “cost-utility” analysis. This type of analysis estimates the additional cost required to generate a year of perfect health (a quality-adjusted life-year or QALY) through the introduction of an intervention. QALYs are calculated by multiplying the time spent in a certain health state by a measure of the quality of that health state. The researchers report that the cost of Ontario's UIIP was about twice as much as the cost of a TIIP for the province. However, the introduction of the UIIP reduced the number of influenza cases by nearly two-thirds and reduced deaths from influenza by more than a quarter compared with what would have been expected had the province continued to offer a TIIP, an overall saving of 1,134 QALYs. Furthermore, the reduction in influenza cases halved influenza-related health care costs, mainly because of reductions in hospitalization. Overall, this means that the additional cost to Ontario of saving one QALY through the introduction of the UIIP was Can$10,797, an “incremental cost-effectiveness ratio” of $10,797 per QALY gained.
What Do These Findings Mean?
In Canada, an intervention is considered cost-effective from the point of view of a health care purchaser if it costs less than Canadian $50,000 to gain one QALY. These findings indicate, therefore, that for Ontario the introduction of the UIIP is economically attractive. Indeed, the researchers calculate that even if the costs of the UIIP were to double, the additional cost of saving one QALY by introducing universal immunization would remain below $50,000. Other “sensitivity” analyses undertaken by the researchers also indicate that universal immunization is likely to be effective and cost-effective in Ontario if other key assumptions and/or data included in the calculations are varied within reasonable limits. Given these findings, the researchers suggest that a UIIP might be an appealing intervention in other Canadian provinces and in other high-income countries where influenza transmission and health-care costs are broadly similar to those in Ontario.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000256.
A PLoS Medicine Research Article by Kwong and colleagues describes how the introduction of universal influenza immunization in Ontario altered influenza-related health care use and deaths in the province
Wikipedia pages are available on QALYs and on cost-utility analysis (note that Wikipedia is a free online encyclopedia that anyone can edit; available in several languages)
Bandolier, an independent online journal about evidence-based health-care, provides information about QALYs and their use in cost-utility analysis
The UK National Institute for Health and Clinical Excellence has a webpage on Measuring effectiveness and cost-effectiveness: the QALY
doi:10.1371/journal.pmed.1000256
PMCID: PMC2850382  PMID: 20386727
8.  Exercise therapy for prevention of falls in people with Parkinson's disease: A protocol for a randomised controlled trial and economic evaluation 
BMC Neurology  2009;9:4.
Background
People with Parkinson's disease are twice as likely to be recurrent fallers compared to other older people. As these falls have devastating consequences, there is an urgent need to identify and test innovative interventions with the potential to reduce falls in people with Parkinson's disease. The main objective of this randomised controlled trial is to determine whether fall rates can be reduced in people with Parkinson's disease using exercise targeting three potentially remediable risk factors for falls (reduced balance, reduced leg muscle strength and freezing of gait). In addition we will establish the cost effectiveness of the exercise program from the health provider's perspective.
Methods/Design
230 community-dwelling participants with idiopathic Parkinson's disease will be recruited. Eligible participants will also have a history of falls or be identified as being at risk of falls on assessment. Participants will be randomly allocated to a usual-care control group or an intervention group which will undertake weight-bearing balance and strengthening exercises and use cueing strategies to address freezing of gait. The intervention group will choose between the home-based or support group-based mode of the program. Participants in both groups will receive standardized falls prevention advice. The primary outcome measure will be fall rates. Participants will record falls and medical interventions in a diary for the duration of the 6-month intervention period. Secondary measures include the Parkinson's Disease Falls Risk Score, maximal leg muscle strength, standing balance, the Short Physical Performance Battery, freezing of gait, health and well being, habitual physical activity and positive and negative affect schedule.
Discussion
No adequately powered studies have investigated exercise interventions aimed at reducing falls in people with Parkinson's disease. This trial will determine the effectiveness of the exercise intervention in reducing falls and its cost effectiveness. This pragmatic program, if found to be effective, has the potential to be implemented within existing community services.
Trial registration
The protocol for this study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12608000303347).
doi:10.1186/1471-2377-9-4
PMCID: PMC2637228  PMID: 19161631
9.  Protocol for a home-based integrated physical therapy program to reduce falls and improve mobility in people with Parkinson’s disease 
BMC Neurology  2012;12:54.
Background
The high incidence of falls associated with Parkinson’s disease (PD) increases the risk of injuries and immobility and compromises quality of life. Although falls education and strengthening programs have shown some benefit in healthy older people, the ability of physical therapy interventions in home settings to reduce falls and improve mobility in people with Parkinson’s has not been convincingly demonstrated.
Methods/design
180 community living people with PD will be randomly allocated to receive either a home-based integrated rehabilitation program (progressive resistance strength training, movement strategy training and falls education) or a home-based life skills program (control intervention). Both programs comprise one hour of treatment and one hour of structured homework per week over six weeks of home therapy. Blinded assessments occurring before therapy commences, the week after completion of therapy and 12 months following intervention will establish both the immediate and long-term benefits of home-based rehabilitation. The number of falls, number of repeat falls, falls rate and time to first fall will be the primary measures used to quantify outcome. The economic costs associated with injurious falls, and the costs of running the integrated rehabilitation program from a health system perspective will be established. The effects of intervention on motor and global disability and on quality of life will also be examined.
Discussion
This study will provide new evidence on the outcomes and cost effectiveness of home-based movement rehabilitation programs for people living with PD.
Trial registration
The trial is registered on the Australian and New Zealand Clinical Trials Registry (ACTRN12608000390381).
doi:10.1186/1471-2377-12-54
PMCID: PMC3436761  PMID: 22799601
Parkinson’s disease; Accidental falls; Randomized controlled trial; Falls prevention
10.  Optimal Uses of Antiretrovirals for Prevention in HIV-1 Serodiscordant Heterosexual Couples in South Africa: A Modelling Study 
PLoS Medicine  2011;8(11):e1001123.
Hallett et al use a mathematical model to examine the long-term impact and cost-effectiveness of different pre-exposure prophylaxis (PrEP) strategies for HIV prevention in serodiscordant couples.
Background
Antiretrovirals have substantial promise for HIV-1 prevention, either as antiretroviral treatment (ART) for HIV-1–infected persons to reduce infectiousness, or as pre-exposure prophylaxis (PrEP) for HIV-1–uninfected persons to reduce the possibility of infection with HIV-1. HIV-1 serodiscordant couples in long-term partnerships (one member is infected and the other is uninfected) are a priority for prevention interventions. Earlier ART and PrEP might both reduce HIV-1 transmission in this group, but the merits and synergies of these different approaches have not been analyzed.
Methods and Findings
We constructed a mathematical model to examine the impact and cost-effectiveness of different strategies, including earlier initiation of ART and/or PrEP, for HIV-1 prevention for serodiscordant couples. Although the cost of PrEP is high, the cost per infection averted is significantly offset by future savings in lifelong treatment, especially among couples with multiple partners, low condom use, and a high risk of transmission. In some situations, highly effective PrEP could be cost-saving overall. To keep couples alive and without a new infection, providing PrEP to the uninfected partner could be at least as cost-effective as initiating ART earlier in the infected partner, if the annual cost of PrEP is <40% of the annual cost of ART and PrEP is >70% effective.
Conclusions
Strategic use of PrEP and ART could substantially and cost-effectively reduce HIV-1 transmission in HIV-1 serodiscordant couples. New and forthcoming data on the efficacy of PrEP, the cost of delivery of ART and PrEP, and couples behaviours and preferences will be critical for optimizing the use of antiretrovirals for HIV-1 prevention.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Every year, about 2.5 million people become infected with HIV, the virus that causes AIDS. HIV is usually transmitted through unprotected sex with an HIV-infected partner. It destroys immune system cells (including CD4 cells, a type of lymphocyte), leaving infected individuals susceptible to other infections. There is no cure for AIDS, although HIV can be held in check with antiretroviral therapy (ART), and there is no vaccine that protects against HIV infection. So, to halt the AIDS epidemic, other ways of preventing the spread of HIV are needed. Antiretroviral drugs could potentially be used in two ways to reduce HIV transmission. First, ART could be given to HIV-infected people before they need it for their own health to reduce their infectiousness; the World Health Organization currently recommends that HIV-positive people initiate ART when their CD4 count drops below 350 cells/µl blood but in many African countries ART is only initiated when CD4 counts fall below 200 cells/µl. Second, ART could be given to HIV-uninfected people to reduce acquisition of the virus. This approach—preexposure prophylaxis (PrEP)—has provided protection against HIV transmission in some but not all clinical trials.
Why Was This Study Done?
Couples in long-term relationships where one partner is HIV-positive and the other is HIV-negative (HIV serodiscordant couples) are a priority group for prevention interventions. In sub-Saharan Africa, where most new HIV infections occur, 10%–20% of stable partnerships are serodiscordant and condom use is often low, not least because such couples may want children. Earlier ART or PrEP might reduce HIV transmission in this group but the merits of different approaches have not been analyzed. In this study, the researchers use a mathematical model to examine the long-term impact and cost-effectiveness of different PrEP and ART strategies for HIV prevention in serodiscordant couples.
What Did the Researchers Do and Find?
The researchers constructed a model to simulate HIV infection and disease progression among hypothetical HIV serodiscordant stable heterosexual couples. The model incorporated data from South Africa on couple characteristics, disease progression, ART use, pregnancies, frequency of sex, and contact with other sexual partners, as well as estimates of the effectiveness of PrEP from clinical trials. The researchers used the model to compare the impact on HIV transmission, survival and quality of life, and the cost-effectiveness of no PrEP with four PrEP strategies—always use PrEP after diagnosis of HIV serodiscordancy, use PrEP up to and for a year after ART initiation by the HIV-infected partner (at a CD4 count of ≤200 cells/µl or ≤350 cells/µl), use PrEP only up to ART initiation by the infected partner, and use PrEP only while trying for a baby and during pregnancy. The model predicts, for example, that the cost per infection averted of PrEP used before ART initiation will be offset by future savings in lifelong treatment, particularly among couples with multiple partners, low condom use, and a high risk of transmission. To keep couples alive without the HIV-uninfected partner becoming infected, it could be more cost-effective to provide PrEP to the uninfected partner than to initiate ART earlier in the infected partner, provided the annual cost of PrEP is less than 40% of the annual cost of ART and PrEP is more than 70% effective. Finally, if PREP is 30%–60% effective, the most cost-effective strategy for couples could be to use PrEP in the uninfected partner prior to ART initiation in the infected partner at a CD4 count ≤350 cells/µl.
What Do These Findings Mean?
These findings suggest that the strategic use of PrEP and ART could cost-effectively reduce HIV transmission in HIV serodiscordant stable heterosexual couples in sub-Saharan Africa. The accuracy of these findings depends on the assumptions included in the mathematical model and on the data fed into it. In particular, the interpretation of these results is complicated by uncertainties in the likely cost of PrEP and the “real-world” effectiveness of PrEP. Nevertheless, these findings suggest that PrEP may become a valuable addition in some settings to existing approaches for HIV prevention such as condom promotion and male circumcision programs. Moreover, additional simulations with this mathematical model using more accurate information on the costs and effectiveness of PrEP could assist in future policy making decisions.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001123.
Information is available from the US National Institute of Allergy and infectious diseases on HIV infection and AIDS
NAM/aidsmap provides basic information about HIV/AIDS, summaries of recent research findings on HIV care and treatment, and a section on PrEP
Information is available from Avert, an international AIDS charity on many aspects of HIV/AIDS, including information on all aspects of HIV prevention, and on HIV/AIDS in Africa (in English and Spanish)
AVAC Global Advocacy for HIV Prevention provides up-to-date information on all aspects of HIV prevention, including PrEP
The US Centers for Disease Control and Prevention also has information on PrEP
WHO provides information about antiretroviral therapy
Patient stories about living with HIV/AIDS are available through Avert and through the charity website Healthtalkonline
doi:10.1371/journal.pmed.1001123
PMCID: PMC3217021  PMID: 22110407
11.  Population Health Impact and Cost-Effectiveness of Tuberculosis Diagnosis with Xpert MTB/RIF: A Dynamic Simulation and Economic Evaluation 
PLoS Medicine  2012;9(11):e1001347.
Nicolas Menzies and colleagues investigate the potential impact and cost-effectiveness of implementing Xpert MTB/RIF for diagnosing tuberculosis in five southern African countries.
Background
The Xpert MTB/RIF test enables rapid detection of tuberculosis (TB) and rifampicin resistance. The World Health Organization recommends Xpert for initial diagnosis in individuals suspected of having multidrug-resistant TB (MDR-TB) or HIV-associated TB, and many countries are moving quickly toward adopting Xpert. As roll-out proceeds, it is essential to understand the potential health impact and cost-effectiveness of diagnostic strategies based on Xpert.
Methods and Findings
We evaluated potential health and economic consequences of implementing Xpert in five southern African countries—Botswana, Lesotho, Namibia, South Africa, and Swaziland—where drug resistance and TB-HIV coinfection are prevalent. Using a calibrated, dynamic mathematical model, we compared the status quo diagnostic algorithm, emphasizing sputum smear, against an algorithm incorporating Xpert for initial diagnosis. Results were projected over 10- and 20-y time periods starting from 2012. Compared to status quo, implementation of Xpert would avert 132,000 (95% CI: 55,000–284,000) TB cases and 182,000 (97,000–302,000) TB deaths in southern Africa over the 10 y following introduction, and would reduce prevalence by 28% (14%–40%) by 2022, with more modest reductions in incidence. Health system costs are projected to increase substantially with Xpert, by US$460 million (294–699 million) over 10 y. Antiretroviral therapy for HIV represents a substantial fraction of these additional costs, because of improved survival in TB/HIV-infected populations through better TB case-finding and treatment. Costs for treating MDR-TB are also expected to rise significantly with Xpert scale-up. Relative to status quo, Xpert has an estimated cost-effectiveness of US$959 (633–1,485) per disability-adjusted life-year averted over 10 y. Across countries, cost-effectiveness ratios ranged from US$792 (482–1,785) in Swaziland to US$1,257 (767–2,276) in Botswana. Assessing outcomes over a 10-y period focuses on the near-term consequences of Xpert adoption, but the cost-effectiveness results are conservative, with cost-effectiveness ratios assessed over a 20-y time horizon approximately 20% lower than the 10-y values.
Conclusions
Introduction of Xpert could substantially change TB morbidity and mortality through improved case-finding and treatment, with more limited impact on long-term transmission dynamics. Despite extant uncertainty about TB natural history and intervention impact in southern Africa, adoption of Xpert evidently offers reasonable value for its cost, based on conventional benchmarks for cost-effectiveness. However, the additional financial burden would be substantial, including significant increases in costs for treating HIV and MDR-TB. Given the fundamental influence of HIV on TB dynamics and intervention costs, care should be taken when interpreting the results of this analysis outside of settings with high HIV prevalence.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
In 2010, about 9 million people developed tuberculosis (TB)—a contagious bacterial disease that usually infects the lungs—and about 1.5 million people died from the disease. Most of these deaths were in low- and middle-income countries, and a quarter were in HIV-positive individuals, who are particularly susceptible to TB. Mycobacterium tuberculosis, the bacterium that causes TB, is spread in airborne droplets when people with active disease cough or sneeze. The characteristic symptoms of TB are a persistent cough, weight loss, fever, and night sweats. Diagnostic tests for TB include sputum smear analysis (microscopic examination of mucus coughed up from the lungs for the presence of M. tuberculosis) and mycobacterial liquid culture (growth of M. tuberculosis from sputum and determination of its drug sensitivity). TB can be cured by taking several antibiotics daily for at least six months, although the recent emergence of multidrug-resistant TB (MDR-TB) is making the disease increasingly hard to treat.
Why Was This Study Done?
To reduce the global TB burden, active disease must be diagnosed quickly and accurately. In most high-burden settings, however, TB diagnosis relies on sputum smear analysis, which fails to identify some people (especially HIV-infected individuals) who have TB. Mycobacterial culture correctly identifies more infected people but is slow and costly, and many high-burden settings lack the infrastructure for high-volume culture diagnosis of TB. Faced with these diagnostic inadequacies, the World Health Organization (WHO) recently recommended the use of Xpert MTB/RIF for initial diagnosis in patients suspected of having MDR-TB or HIV-associated TB. This new, automated DNA test detects M. tuberculosis and DNA differences that make the bacteria resistant to the drug rifampicin (an indicator of MDR-TB) within two hours. Many countries are moving toward adopting Xpert for TB diagnosis, so it is essential to understand the population health impact and cost-effectiveness of diagnostic strategies based on this test. Here, the researchers use a calibrated, dynamic mathematical model of TB to investigate the consequences of Xpert MTB/RIF implementation in five southern African countries where both TB-HIV coinfection and MDR-TB are common.
What Did the Researchers Do and Find?
The researchers used their mathematical model, which simulates the movement of individuals through different stages of TB infection, to investigate the potential health and economic consequences of implementing Xpert for initial TB diagnosis in Botswana, Lesotho, Namibia, South Africa, and Swaziland. In the modeled scenarios, compared to an diagnostic approach based on sputum smear (the “status quo”), implementation of Xpert averted an estimated 132,000 TB cases and 182,000 TB deaths in southern Africa over the ten years following its introduction, reduced the proportion of the population with TB by 28%, and increased health service costs by US$460 million. Much of this cost increase reflected increased antiretroviral therapy costs for TB/HIV-infected individuals who survived TB infection because of better case-finding and treatment. Finally, relative to the status quo, over ten years, Xpert implementation in southern Africa cost US$959 for every DALY (disability-adjusted life-year) averted. Cost-effectiveness ratios in individual countries ranged from US$792 per DALY averted in Swaziland to US$1,257 per DALY averted in Botswana.
What Do These Findings Mean?
These findings suggest that Xpert implementation in southern Africa could substantially reduce TB illness and death through improved case-finding and treatment, but that the impact of Xpert on long-term transmission dynamics may be more limited. Although the additional financial burden associated with Xpert roll-out is likely to be substantial, these findings suggest that using Xpert for TB diagnosis offers reasonable value given its cost. WHO considers any intervention with a cost-effectiveness ratio less than the per-capita gross domestic product (GDP) highly cost-effective—in 2010, the per-capita GDP ranged from US$7,000 in South Africa and Botswana to US$982 in Lesotho.
These findings may not be generalizable to regions with different HIV infection rates, and their accuracy is likely to be affected by the quality of the data fed into the mathematical model and by the structure of the model. Thus, it is essential that the impact of Xpert-based TB diagnosis be carefully evaluated as the approach is rolled out, and that the information generated by these evaluations be used to improve the accuracy of model-based estimates of the long-term effects of this new strategy for TB diagnosis.
Additional Information
Please access these websites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001347.
WHO provides information (in several languages) on all aspects of tuberculosis, including general information on tuberculosis diagnostics and specific information on the roll-out of the Xpert MTB/RIF test; further information about WHO's endorsement of Xpert MTB/RIF is included in a recent Strategic and Technical Advisory Group for Tuberculosis report; WHO also provides information about tuberculosis and HIV
The Stop TB Partnership is working towards tuberculosis elimination; patient stories about TB-HIV coinfection are available
The US Centers for Disease Control and Prevention has information about tuberculosis, and about TB diagnosis
The US National Institute of Allergy and Infectious Diseases also has detailed information on all aspects of tuberculosis
The Tuberculosis Survival Project, which aims to raise awareness of tuberculosis and provide support for people with tuberculosis, provides personal stories about treatment for tuberculosis; the Tuberculosis Vaccine Initiative also provides personal stories about dealing with tuberculosis
MedlinePlus has links to further information about tuberculosis (in English and Spanish)
doi:10.1371/journal.pmed.1001347
PMCID: PMC3502465  PMID: 23185139
12.  Caregiver- and Patient-Directed Interventions for Dementia 
Executive Summary
In early August 2007, the Medical Advisory Secretariat began work on the Aging in the Community project, an evidence-based review of the literature surrounding healthy aging in the community. The Health System Strategy Division at the Ministry of Health and Long-Term Care subsequently asked the secretariat to provide an evidentiary platform for the ministry’s newly released Aging at Home Strategy.
After a broad literature review and consultation with experts, the secretariat identified 4 key areas that strongly predict an elderly person’s transition from independent community living to a long-term care home. Evidence-based analyses have been prepared for each of these 4 areas: falls and fall-related injuries, urinary incontinence, dementia, and social isolation. For the first area, falls and fall-related injuries, an economic model is described in a separate report.
Please visit the Medical Advisory Secretariat Web site, http://www.health.gov.on.ca/english/providers/program/mas/mas_about.html, to review these titles within the Aging in the Community series.
Aging in the Community: Summary of Evidence-Based Analyses
Prevention of Falls and Fall-Related Injuries in Community-Dwelling Seniors: An Evidence-Based Analysis
Behavioural Interventions for Urinary Incontinence in Community-Dwelling Seniors: An Evidence-Based Analysis
Caregiver- and Patient-Directed Interventions for Dementia: An Evidence-Based Analysis
Social Isolation in Community-Dwelling Seniors: An Evidence-Based Analysis
The Falls/Fractures Economic Model in Ontario Residents Aged 65 Years and Over (FEMOR)
This report features the evidence-based analysis on caregiver- and patient-directed interventions for dementia and is broken down into 4 sections:
Introduction
Caregiver-Directed Interventions for Dementia
Patient-Directed Interventions for Dementia
Economic Analysis of Caregiver- and Patient-Directed Interventions for Dementia
Caregiver-Directed Interventions for Dementia
Objective
To identify interventions that may be effective in supporting the well-being of unpaid caregivers of seniors with dementia living in the community.
Clinical Need: Target Population and Condition
Dementia is a progressive and largely irreversible syndrome that is characterized by a loss of cognitive function severe enough to impact social or occupational functioning. The components of cognitive function affected include memory and learning, attention, concentration and orientation, problem-solving, calculation, language, and geographic orientation. Dementia was identified as one of the key predictors in a senior’s transition from independent community living to admission to a long-term care (LTC) home, in that approximately 90% of individuals diagnosed with dementia will be institutionalized before death. In addition, cognitive decline linked to dementia is one of the most commonly cited reasons for institutionalization.
Prevalence estimates of dementia in the Ontario population have largely been extrapolated from the Canadian Study of Health and Aging conducted in 1991. Based on these estimates, it is projected that there will be approximately 165,000 dementia cases in Ontario in the year 2008, and by 2010 the number of cases will increase by nearly 17% over 2005 levels. By 2020 the number of cases is expected to increase by nearly 55%, due to a rise in the number of people in the age categories with the highest prevalence (85+). With the increase in the aging population, dementia will continue to have a significant economic impact on the Canadian health care system. In 1991, the total costs associated with dementia in Canada were $3.9 billion (Cdn) with $2.18 billion coming from LTC.
Caregivers play a crucial role in the management of individuals with dementia because of the high level of dependency and morbidity associated with the condition. It has been documented that a greater demand is faced by dementia caregivers compared with caregivers of persons with other chronic diseases. The increased burden of caregiving contributes to a host of chronic health problems seen among many informal caregivers of persons with dementia. Much of this burden results from managing the behavioural and psychological symptoms of dementia (BPSD), which have been established as a predictor of institutionalization for elderly patients with dementia.
It is recognized that for some patients with dementia, an LTC facility can provide the most appropriate care; however, many patients move into LTC unnecessarily. For individuals with dementia to remain in the community longer, caregivers require many types of formal and informal support services to alleviate the stress of caregiving. These include both respite care and psychosocial interventions. Psychosocial interventions encompass a broad range of interventions such as psychoeducational interventions, counseling, supportive therapy, and behavioural interventions.
Assuming that 50% of persons with dementia live in the community, a conservative estimate of the number of informal caregivers in Ontario is 82,500. Accounting for the fact that 29% of people with dementia live alone, this leaves a remaining estimate of 58,575 Ontarians providing care for a person with dementia with whom they reside.
Description of Interventions
The 2 main categories of caregiver-directed interventions examined in this review are respite care and psychosocial interventions. Respite care is defined as a break or relief for the caregiver. In most cases, respite is provided in the home, through day programs, or at institutions (usually 30 days or less). Depending on a caregiver’s needs, respite services will vary in delivery and duration. Respite care is carried out by a variety of individuals, including paid staff, volunteers, family, or friends.
Psychosocial interventions encompass a broad range of interventions and have been classified in various ways in the literature. This review will examine educational, behavioural, dementia-specific, supportive, and coping interventions. The analysis focuses on behavioural interventions, that is, those designed to help the caregiver manage BPSD. As described earlier, BPSD are one of the most challenging aspects of caring for a senior with dementia, causing an increase in caregiver burden. The analysis also examines multicomponent interventions, which include at least 2 of the above-mentioned interventions.
Methods of Evidence-Based Analysis
A comprehensive search strategy was used to identify systematic reviews and randomized controlled trials (RCTs) that examined the effectiveness of interventions for caregivers of dementia patients.
Questions
Section 2.1
Are respite care services effective in supporting the well-being of unpaid caregivers of seniors with dementia in the community?
Do respite care services impact on rates of institutionalization of these seniors?
Section 2.2
Which psychosocial interventions are effective in supporting the well-being of unpaid caregivers of seniors with dementia in the community?
Which interventions reduce the risk for institutionalization of seniors with dementia?
Outcomes of Interest
any quantitative measure of caregiver psychological health, including caregiver burden, depression, quality of life, well-being, strain, mastery (taking control of one’s situation), reactivity to behaviour problems, etc.;
rate of institutionalization; and
cost-effectiveness.
Assessment of Quality of Evidence
The quality of the evidence was assessed as High, Moderate, Low, or Very low according to the GRADE methodology and GRADE Working Group. As per GRADE the following definitions apply:
Summary of Findings
Conclusions in Table 1 are drawn from Sections 2.1 and 2.2 of the report.
Summary of Conclusions on Caregiver-Directed Interventions
There is limited evidence from RCTs that respite care is effective in improving outcomes for those caring for seniors with dementia.
There is considerable qualitative evidence of the perceived benefits of respite care.
Respite care is known as one of the key formal support services for alleviating caregiver burden in those caring for dementia patients.
Respite care services need to be tailored to individual caregiver needs as there are vast differences among caregivers and patients with dementia (severity, type of dementia, amount of informal/formal support available, housing situation, etc.)
There is moderate- to high-quality evidence that individual behavioural interventions (≥ 6 sessions), directed towards the caregiver (or combined with the patient) are effective in improving psychological health in dementia caregivers.
There is moderate- to high-quality evidence that multicomponent interventions improve caregiver psychosocial health and may affect rates of institutionalization of dementia patients.
RCT indicates randomized controlled trial.
Patient-Directed Interventions for Dementia
Objective
The section on patient-directed interventions for dementia is broken down into 4 subsections with the following questions:
3.1 Physical Exercise for Seniors with Dementia – Secondary Prevention
What is the effectiveness of physical exercise for the improvement or maintenance of basic activities of daily living (ADLs), such as eating, bathing, toileting, and functional ability, in seniors with mild to moderate dementia?
3.2 Nonpharmacologic and Nonexercise Interventions to Improve Cognitive Functioning in Seniors With Dementia – Secondary Prevention
What is the effectiveness of nonpharmacologic interventions to improve cognitive functioning in seniors with mild to moderate dementia?
3.3 Physical Exercise for Delaying the Onset of Dementia – Primary Prevention
Can exercise decrease the risk of subsequent cognitive decline/dementia?
3.4 Cognitive Interventions for Delaying the Onset of Dementia – Primary Prevention
Does cognitive training decrease the risk of cognitive impairment, deterioration in the performance of basic ADLs or instrumental activities of daily living (IADLs),1 or incidence of dementia in seniors with good cognitive and physical functioning?
Clinical Need: Target Population and Condition
Secondary Prevention2
Exercise
Physical deterioration is linked to dementia. This is thought to be due to reduced muscle mass leading to decreased activity levels and muscle atrophy, increasing the potential for unsafe mobility while performing basic ADLs such as eating, bathing, toileting, and functional ability.
Improved physical conditioning for seniors with dementia may extend their independent mobility and maintain performance of ADL.
Nonpharmacologic and Nonexercise Interventions
Cognitive impairments, including memory problems, are a defining feature of dementia. These impairments can lead to anxiety, depression, and withdrawal from activities. The impact of these cognitive problems on daily activities increases pressure on caregivers.
Cognitive interventions aim to improve these impairments in people with mild to moderate dementia.
Primary Prevention3
Exercise
Various vascular risk factors have been found to contribute to the development of dementia (e.g., hypertension, hypercholesterolemia, diabetes, overweight).
Physical exercise is important in promoting overall and vascular health. However, it is unclear whether physical exercise can decrease the risk of cognitive decline/dementia.
Nonpharmacologic and Nonexercise Interventions
Having more years of education (i.e., a higher cognitive reserve) is associated with a lower prevalence of dementia in crossectional population-based studies and a lower incidence of dementia in cohorts followed longitudinally. However, it is unclear whether cognitive training can increase cognitive reserve or decrease the risk of cognitive impairment, prevent or delay deterioration in the performance of ADLs or IADLs or reduce the incidence of dementia.
Description of Interventions
Physical exercise and nonpharmacologic/nonexercise interventions (e.g., cognitive training) for the primary and secondary prevention of dementia are assessed in this review.
Evidence-Based Analysis Methods
A comprehensive search strategy was used to identify systematic reviews and RCTs that examined the effectiveness, safety and cost effectiveness of exercise and cognitive interventions for the primary and secondary prevention of dementia.
Questions
Section 3.1: What is the effectiveness of physical exercise for the improvement or maintenance of ADLs in seniors with mild to moderate dementia?
Section 3.2: What is the effectiveness of nonpharmacologic/nonexercise interventions to improve cognitive functioning in seniors with mild to moderate dementia?
Section 3.3: Can exercise decrease the risk of subsequent cognitive decline/dementia?
Section 3.4: Does cognitive training decrease the risk of cognitive impairment, prevent or delay deterioration in the performance of ADLs or IADLs, or reduce the incidence of dementia in seniors with good cognitive and physical functioning?
Assessment of Quality of Evidence
The quality of the evidence was assessed as High, Moderate, Low, or Very low according to the GRADE methodology. As per GRADE the following definitions apply:
Summary of Findings
Table 2 summarizes the conclusions from Sections 3.1 through 3.4.
Summary of Conclusions on Patient-Directed Interventions*
Previous systematic review indicated that “cognitive training” is not effective in patients with dementia.
A recent RCT suggests that CST (up to 7 weeks) is effective for improving cognitive function and quality of life in patients with dementia.
Regular leisure time physical activity in midlife is associated with a reduced risk of dementia in later life (mean follow-up 21 years).
Regular physical activity in seniors is associated with a reduced risk of cognitive decline (mean follow-up 2 years).
Regular physical activity in seniors is associated with a reduced risk of dementia (mean follow-up 6–7 years).
Evidence that cognitive training for specific functions (memory, reasoning, and speed of processing) produces improvements in these specific domains.
Limited inconclusive evidence that cognitive training can offset deterioration in the performance of self-reported IADL scores and performance assessments.
1° indicates primary; 2°, secondary; CST, cognitive stimulation therapy; IADL, instrumental activities of daily living; RCT, randomized controlled trial.
Benefit/Risk Analysis
As per the GRADE Working Group, the overall recommendations consider 4 main factors:
the trade-offs, taking into account the estimated size of the effect for the main outcome, the confidence limits around those estimates, and the relative value placed on the outcome;
the quality of the evidence;
translation of the evidence into practice in a specific setting, taking into consideration important factors that could be expected to modify the size of the expected effects such as proximity to a hospital or availability of necessary expertise; and
uncertainty about the baseline risk for the population of interest.
The GRADE Working Group also recommends that incremental costs of health care alternatives should be considered explicitly alongside the expected health benefits and harms. Recommendations rely on judgments about the value of the incremental health benefits in relation to the incremental costs. The last column in Table 3 reflects the overall trade-off between benefits and harms (adverse events) and incorporates any risk/uncertainty (cost-effectiveness).
Overall Summary Statement of the Benefit and Risk for Patient-Directed Interventions*
Economic Analysis
Budget Impact Analysis of Effective Interventions for Dementia
Caregiver-directed behavioural techniques and patient-directed exercise programs were found to be effective when assessing mild to moderate dementia outcomes in seniors living in the community. Therefore, an annual budget impact was calculated based on eligible seniors in the community with mild and moderate dementia and their respective caregivers who were willing to participate in interventional home sessions. Table 4 describes the annual budget impact for these interventions.
Annual Budget Impact (2008 Canadian Dollars)
Assumed 7% prevalence of dementia aged 65+ in Ontario.
Assumed 8 weekly sessions plus 4 monthly phone calls.
Assumed 12 weekly sessions plus biweekly sessions thereafter (total of 20).
Assumed 2 sessions per week for first 5 weeks. Assumed 90% of seniors in the community with dementia have mild to moderate disease. Assumed 4.5% of seniors 65+ are in long-term care, and the remainder are in the community. Assumed a rate of participation of 60% for both patients and caregivers and of 41% for patient-directed exercise. Assumed 100% compliance since intervention administered at the home. Cost for trained staff from Ministry of Health and Long-Term Care data source. Assumed cost of personal support worker to be equivalent to in-home support. Cost for recreation therapist from Alberta government Website.
Note: This budget impact analysis was calculated for the first year after introducing the interventions from the Ministry of Health and Long-Term Care perspective using prevalence data only. Prevalence estimates are for seniors in the community with mild to moderate dementia and their respective caregivers who are willing to participate in an interventional session administered at the home setting. Incidence and mortality rates were not factored in. Current expenditures in the province are unknown and therefore were not included in the analysis. Numbers may change based on population trends, rate of intervention uptake, trends in current programs in place in the province, and assumptions on costs. The number of patients was based on patients likely to access these interventions in Ontario based on assumptions stated below from the literature. An expert panel confirmed resource consumption.
PMCID: PMC3377513  PMID: 23074509
13.  Cost-Effectiveness of Male Circumcision for HIV Prevention in a South African Setting  
PLoS Medicine  2006;3(12):e517.
Background
Consistent with observational studies, a randomized controlled intervention trial of adult male circumcision (MC) conducted in the general population in Orange Farm (OF) (Gauteng Province, South Africa) demonstrated a protective effect against HIV acquisition of 60%. The objective of this study is to present the first cost-effectiveness analysis of the use of MC as an intervention to reduce the spread of HIV in sub-Saharan Africa.
Methods and Findings
Cost-effectiveness was modeled for 1,000 MCs done within a general adult male population. Intervention costs included performing MC and treatment of adverse events. HIV prevalence was estimated from published estimates and incidence among susceptible subjects calculated assuming a steady-state epidemic. Effectiveness was defined as the number of HIV infections averted (HIA), which was estimated by dynamically projecting over 20 years the reduction in HIV incidence observed in the OF trial, including secondary transmission to women. Net savings were calculated with adjustment for the averted lifetime duration cost of HIV treatment. Sensitivity analyses examined the effects of input uncertainty and program coverage. All results were discounted to the present at 3% per year.
For Gauteng Province, assuming full coverage of the MC intervention, with a 2005 adult male prevalence of 25.6%, 1,000 circumcisions would avert an estimated 308 (80% CI 189–428) infections over 20 years. The cost is $181 (80% CI $117–$306) per HIA, and net savings are $2.4 million (80% CI $1.3 million to $3.6 million). Cost-effectiveness is sensitive to the costs of MC and of averted HIV treatment, the protective effect of MC, and HIV prevalence. With an HIV prevalence of 8.4%, the cost per HIA is $551 (80% CI $344–$1,071) and net savings are $753,000 (80% CI $0.3 million to $1.2 million). Cost-effectiveness improves by less than 10% when MC intervention coverage is 50% of full coverage.
Conclusions
In settings in sub-Saharan Africa with high or moderate HIV prevalence among the general population, adult MC is likely to be a cost-effective HIV prevention strategy, even when it has a low coverage. MC generates large net savings after adjustment for averted HIV medical costs.
Based on data from a trial of adult male circumcision to reduce the spread of HIV, a modeling study shows this intervention to be a cost-effective strategy.
Editors' Summary
Background.
Preventing the spread of HIV is an enormous challenge of great importance worldwide. In 2005, HIV/AIDS was responsible for around 3 million deaths, of which approximately one-third were in sub-Saharan Africa. HIV is spread from one person to another in three main ways: through unprotected sex; through contaminated blood or blood products (for example when shared needles are used); and from mother to child (during pregnancy, labor, and breastfeeding). Many strategies for preventing HIV focus on reducing risky behaviors. For example, condoms used correctly are effective at preventing HIV infection, and many countries now aim to promote condom use, together with other approaches that will reduce the risk of getting HIV. However, it is unlikely that strategies involving large-scale changes in behavior will ever be completely effective. Recently, much attention has focused on the possibility that circumcision might provide men with some protection against getting HIV. The results of a trial carried out in South Africa, the ANRS 1265 trial (published in PLoS Medicine in October 2005) seem to support this theory, and additional trials are being carried out in Kenya and Uganda. The results from these further trials will help determine whether, and to what extent, the effect of circumcision seen in the South African trial is true more generally.
Why Was This Study Done?
The investigators who had carried out the South African circumcision trial wanted to find out how the economic aspects of this prevention strategy would compare with other strategies for prevention of HIV. Specifically, they wanted to know how much male circumcision would cost overall, per HIV infection prevented, as compared with the cost of other strategies. They also wanted to understand whether circumcision would be “cost-saving.” In other words, would the cost of performing the operation (together with the cost of treating any adverse effects suffered by the men who were circumcised) be offset by the costs of treatment for HIV infections that the intervention prevented? Getting this information is crucial before health policy makers can decide what strategies for preventing HIV are most appropriate for their country.
What Did the Researchers Do and Find?
In this study, the researchers carried out a set of mathematical calculations, using the results from the ANRS 1265 trial, together with some other data and background assumptions. Their model was based on a hypothetical group of 1,000 men, all of whom would be circumcised. The researchers calculated that in such a hypothetical group, the cost of providing male circumcision, per HIV infection prevented, would be around $180. Overall, this procedure seemed to be cost-saving when the cost of HIV treatment was also factored in; around $2.4 million would be saved for the 1,000 men circumcised.
What Do These Findings Mean?
These results suggest that, assuming the results of the South African trial are generally true, male circumcision would reduce the cost of health care in South Africa, mainly through savings on the cost of HIV treatment. The overall cost of male circumcision, per HIV infection prevented, is reasonable as compared to the costs of other strategies for prevention of HIV. There would also be implications for HIV prevention programs in other African countries. However, these estimates are based on the data from one trial only. The World Health Organization does not currently recommend the promotion of male circumcision for prevention of HIV. Meanwhile, proven strategies for preventing HIV exist, and more information is available from the links below.
Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030517.
The World Health Organization has an HIV/AIDS program site providing comprehensive information on the HIV/AIDS epidemic worldwide
General information and resources from the US Centers for Disease Control and Prevention on preventing HIV/AIDS
Fact sheet from the Joint United Nations Programme on HIV/AIDS about male circumcision and HIV
Results of the ANRS 1265 Trial evaluating male circumcision for HIV prevention were published in PLoS Medicine in October 2005; two related “Perspective” articles were also published in the same issue by Nandi Siegfried and Peter Cleaton-Jones
doi:10.1371/journal.pmed.0030517
PMCID: PMC1716193  PMID: 17194197
14.  Falls prevention for the elderly 
Background
An ageing population, a growing prevalence of chronic diseases and limited financial resources for health care underpin the importance of prevention of disabling health disorders and care dependency in the elderly. A wide variety of measures is generally available for the prevention of falls and fall-related injuries. The spectrum ranges from diagnostic procedures for identifying individuals at risk of falling to complex interventions for the removal or reduction of identified risk factors. However, the clinical and economic effectiveness of the majority of recommended strategies for fall prevention is unclear. Against this background, the literature analyses in this HTA report aim to support decision-making for effective and efficient fall prevention.
Research questions
The pivotal research question addresses the effectiveness of single interventions and complex programmes for the prevention of falls and fall-related injuries. The target population are the elderly (> 60 years), living in their own housing or in long term care facilities. Further research questions refer to the cost-effectiveness of fall prevention measures, and their ethical, social and legal implications.
Methods
Systematic literature searches were performed in 31 databases covering the publication period from January 2003 to January 2010. While the effectiveness of interventions is solely assessed on the basis of randomised controlled trials (RCT), the assessment of the effectiveness of diagnostic procedures also considers prospective accuracy studies. In order to clarify social, ethical and legal aspects all studies deemed relevant with regard to content were taken into consideration, irrespective of their study design. Study selection and critical appraisal were conducted by two independent assessors. Due to clinical heterogeneity of the studies no meta-analyses were performed.
Results
Out of 12,000 references retrieved by literature searches, 184 meet the inclusion criteria. However, to a variable degree the validity of their results must be rated as compromised due to different biasing factors. In summary, it appears that the performance of tests or the application of parameters to identify individuals at risk of falling yields little or no clinically relevant information. Positive effects of exercise interventions may be expected in relatively young and healthy seniors, while studies indicate opposite effects in the fragile elderly. For this specific vulnerable population the modification of the housing environment shows protective effects. A low number of studies, low quality of studies or inconsistent results lead to the conclusion that the effectiveness of the following interventions has to be rated unclear yet: correction of vision disorders, modification of psychotropic medication, vitamin D supplementation, nutritional supplements, psychological interventions, education of nursing personnel, multiple and multifactorial programs as well as the application of hip protectors.
For the context of the German health care system the economic evaluations of fall prevention retrieved by the literature searches yield very few useful results. Cost-effectiveness calculations of fall prevention are mostly based on weak effectiveness data as well as on epidemiological and cost data from foreign health care systems.
Ethical analysis demonstrates ambivalent views of the target population concerning fall risk and the necessity of fall prevention. The willingness to take up preventive measures depends on a variety of personal factors, the quality of information, guidance and decision-making, the prevention program itself and social support.
The analysis of papers regarding legal issues shows three main challenges: the uncertainty of which standard of care has to be expected with regard to fall prevention, the necessity to consider the specific conditions of every single case when measures for fall prevention are applied, and the difficulty to balance the rights to autonomous decision making and physical integrity.
Discussion and conclusions
The assessment of clinical effectiveness of interventions for fall prevention is complicated by inherent methodological problems (esp. absence of blinding) and meaningful clinical heterogeneity of available studies. Therefore meta-analyses are not appropriate, and single study results are difficult to interpret. Both problems also impair the informative value of economic analyses. With this background it has to be stated that current recommendations regarding fall prevention in the elderly are not fully supported by scientific evidence. In particular, for the generation of new recommendations the dependency of probable effects on specific characteristics of the target populations or care settings should be taken into consideration. This also applies to the variable factors influencing the willingness of the target population to take up and pursue preventive measures.
In the planning of future studies equal weight should be placed on methodological rigour (freedom from biases) and transferability of results into routine care. Economic analyses require input of German data, either in form of a “piggy back study“ or in form of a modelling study that reflects the structures of the German health care system and is based on German epidemiological and cost data.
doi:10.3205/hta000099
PMCID: PMC3334922  PMID: 22536299
accidental falls; accidents, home/*; activities of daily living; aged/*; aged/*psychology; adjustment of the living environment; cataract surgery; correction of the visual acuity; customisation of the living environment; diagnosis; dietary supplements; dose-response relationship, drug; EBM; economic evaluation; elderly; environment design; evidence-based medicine; exercise program; exercise/physiology; eye test; eyesight; eyesight test; fall; fall prevention; fall prophylaxis; fall risk; fall risk factors; falling consequences; falling danger; fall-related injuries; fracture; freedom/*; freedom-depriving measures; geriatric nursing home; health technology assessment; hip fracture; hip fractures; hip protectors; homes for the aged; HTA; humans; interventions; medical adjustment; meta-analysis as topic; motor activity; motor activity/drug effects; motor skills; motor function; multi-factorial programs; multimodal programs; nursing homes; peer review; power of movement; prevention; primary prevention; private domesticity; prophylaxis; randomized controlled trial; randomized controlled trials as topic; RCT; review literature as topic; risk assessment; risk factors; risk reduction behavior; seniors; sight; stabilized; systematic review; technology assessment, biomedical; training program; visual acuity; Vitamin D/administration & dosage
15.  Event Rates, Hospital Utilization, and Costs Associated with Major Complications of Diabetes: A Multicountry Comparative Analysis 
PLoS Medicine  2010;7(2):e1000236.
Philip Clarke and colleagues examined patient-level data for over 11,000 participants with type 2 diabetes from 20 countries and find that major complications of diabetes significantly increased hospital use and costs across settings.
Background
Diabetes imposes a substantial burden globally in terms of premature mortality, morbidity, and health care costs. Estimates of economic outcomes associated with diabetes are essential inputs to policy analyses aimed at prevention and treatment of diabetes. Our objective was to estimate and compare event rates, hospital utilization, and costs associated with major diabetes-related complications in high-, middle-, and low-income countries.
Methods and Findings
Incidence and history of diabetes-related complications, hospital admissions, and length of stay were recorded in 11,140 patients with type 2 diabetes participating in the Action in Diabetes and Vascular Disease (ADVANCE) study (mean age at entry 66 y). The probability of hospital utilization and number of days in hospital for major events associated with coronary disease, cerebrovascular disease, congestive heart failure, peripheral vascular disease, and nephropathy were estimated for three regions (Asia, Eastern Europe, and Established Market Economies) using multiple regression analysis. The resulting estimates of days spent in hospital were multiplied by regional estimates of the costs per hospital bed-day from the World Health Organization to compute annual acute and long-term costs associated with the different types of complications. To assist, comparability, costs are reported in international dollars (Int$), which represent a hypothetical currency that allows for the same quantities of goods or services to be purchased regardless of country, standardized on purchasing power in the United States. A cost calculator accompanying this paper enables the estimation of costs for individual countries and translation of these costs into local currency units. The probability of attending a hospital following an event was highest for heart failure (93%–96% across regions) and lowest for nephropathy (15%–26%). The average numbers of days in hospital given at least one admission were greatest for stroke (17–32 d across region) and heart failure (16–31 d) and lowest for nephropathy (12–23 d). Considering regional differences, probabilities of hospitalization were lowest in Asia and highest in Established Market Economies; on the other hand, lengths of stay were highest in Asia and lowest in Established Market Economies. Overall estimated annual hospital costs for patients with none of the specified events or event histories ranged from Int$76 in Asia to Int$296 in Established Market Economies. All complications included in this analysis led to significant increases in hospital costs; coronary events, cerebrovascular events, and heart failure were the most costly, at more than Int$1,800, Int$3,000, and Int$4,000 in Asia, Eastern Europe, and Established Market Economies, respectively.
Conclusions
Major complications of diabetes significantly increase hospital use and costs across various settings and are likely to impose a high economic burden on health care systems.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Worldwide, nearly 250 million people have diabetes, and this number is increasing rapidly. Diabetes is characterized by dangerous amounts of sugar (glucose) in the blood. Blood sugar levels are normally controlled by insulin, a hormone produced by the pancreas. Blood sugar control fails in people with diabetes because they make no insulin (type 1 diabetes) or, more commonly, because the fat and muscle cells that usually respond to insulin by removing excess sugar from the blood have become insulin insensitive (type 2 diabetes). Type 2 diabetes can be prevented and controlled by eating a healthy diet and exercising regularly. It can also be treated with drugs that help the pancreas make more insulin or that increase insulin sensitivity. Major long-term complications of diabetes include kidney failure and an increased risk of cardiovascular problems such as heart attacks, heart failure, stroke, and problems with the blood vessels in the arms and legs. Because of these complications, the life expectancy of people with diabetes is about ten years shorter than that of people without diabetes.
Why Was This Study Done?
Diabetes imposes considerable demands on health care systems but little is known about the direct medical costs associated with treating this chronic disease in low- and middle-income countries where more than three-quarters of affected people live. In particular, although estimates have been made of the overall resources devoted to the treatment of diabetes, very little is known about how the different long-term complications of diabetes contribute to health care costs in different countries. Public-health experts and governments need this information to help them design effective and sustainable policies for the prevention and treatment of diabetes. In this study, the researchers estimate the resource use associated with diabetes-related complications in three economic regions using information collected in the Action in Diabetes and Vascular Disease (ADVANCE) study. This multinational clinical trial is investigating how drugs that control blood pressure and blood sugar levels affect the long-term complications of diabetes.
What Did the Researchers Do and Find?
The researchers recorded diabetes-related complications, hospital admissions for these complications, and length of hospital stays in 11,140 patients with severe diabetes from 20 countries who participated in the ADVANCE study. They used “multiple regression analysis” to estimate the number of days spent in hospital for diabetes-related complications in Asia, Eastern Europe, and the Established Market Economies (Canada, Australia, New Zealand, and several Western European countries). Finally, they calculated the economic costs of each complication using regional estimates of the costs per bed-day from the World Health Organization's CHOICE project (CHOosing Interventions that are Cost Effective). Nearly everyone in the study who developed heart failure attended a hospital, but only 15%–26% of people attended a hospital for kidney problems. The chances of hospitalization for any complication were lowest in Asia and highest in the Established Market Economies; conversely, lengths of stay were longest in Asia and shortest in the Established Market Economies. Finally, the estimated annual hospital costs for patients who had a coronary event, stroke, or heart failure were more than Int$1,800, Int$3,000, and Int$4,000 in Asia, Eastern Europe, and the Established Market Economies, respectively (the international dollar, Int$, is a hypothetical currency that has the same purchasing power in all countries), compared to Int$76, Int$156, and Int$296 for patients who experienced none of these events.
What Do These Findings Mean?
Because the ADVANCE trial had strict entry criteria, the findings of this study may not be generalizable to the broader population of people with diabetes. Nevertheless, given the lack of information about the costs associated with diabetes-related complications in low- and middle-income countries, these findings provide important new information about the patterns of hospital resource use and costs in these countries. Specifically, these findings show that the major complications of diabetes greatly increase hospital use and costs in all three economic regions considered and impose a high economic burden on health care systems that is likely to increase as the diabetes epidemic develops. Importantly, these findings should help policy makers anticipate the future health care costs associated with diabetes and should help them evaluate which therapies aimed at preventing diabetes-related complications will reduce these costs most effectively.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000236.
The International Diabetes Federation provides information about all aspects of diabetes
The US National Diabetes Information Clearinghouse provides detailed information about diabetes for patients, health care professionals, and the general public (in English and Spanish)
The UK National Health Service also provides information for patients and caregivers about type 2 diabetes (in several languages)
Information about the ADVANCE study is available
The World Health Organization's CHOICE Web site provides information about the analysis of the cost effectiveness of health care interventions
doi:10.1371/journal.pmed.1000236
PMCID: PMC2826379  PMID: 20186272
16.  An exercise intervention to prevent falls in Parkinson’s: an economic evaluation 
Background
People with Parkinson’s (PwP) experience frequent and recurrent falls. As these falls may have devastating consequences, there is an urgent need to identify cost-effective interventions with the potential to reduce falls in PwP. The purpose of this economic evaluation is to compare the costs and cost-effectiveness of a targeted exercise programme versus usual care for PwP who were at risk of falling.
Methods
One hundred and thirty participants were recruited through specialist clinics, primary care and Parkinson’s support groups and randomised to either an exercise intervention or usual care. Health and social care utilisation and health-related quality of life (EQ-5D) were assessed over the 20 weeks of the study (ten-week intervention period and ten-week follow up period), and these data were complete for 93 participants. Incremental cost per quality adjusted life year (QALY) was estimated. The uncertainty around costs and QALYs was represented using cost-effectiveness acceptability curves.
Results
The mean cost of the intervention was £76 per participant. Although in direction of favour of exercise intervention, there was no statistically significant differences between groups in total healthcare (−£128, 95% CI: -734 to 478), combined health and social care costs (£-35, 95% CI: -817 to 746) or QALYs (0.03, 95% CI: -0.02 to 0.03) at 20 weeks. Nevertheless, exploration of the uncertainty surrounding these estimates suggests there is more than 80% probability that the exercise intervention is a cost-effective strategy relative to usual care.
Conclusion
Whilst we found no difference between groups in total healthcare, total social care cost and QALYs, analyses indicate that there is high probability that the exercise intervention is cost-effective compared with usual care. These results require confirmation by larger trial-based economic evaluations and over the longer term.
doi:10.1186/1472-6963-12-426
PMCID: PMC3560229  PMID: 23176532
Economic evaluation; Cost effectiveness; Parkinson’s; Falls prevention; Rehabilitation
17.  Cost-Effectiveness of Interventions to Promote Physical Activity: A Modelling Study 
PLoS Medicine  2009;6(7):e1000110.
Linda Cobiac and colleagues model the costs and health outcomes associated with interventions to improve physical activity in the population, and identify specific interventions that are likely to be cost-saving.
Background
Physical inactivity is a key risk factor for chronic disease, but a growing number of people are not achieving the recommended levels of physical activity necessary for good health. Australians are no exception; despite Australia's image as a sporting nation, with success at the elite level, the majority of Australians do not get enough physical activity. There are many options for intervention, from individually tailored advice, such as counselling from a general practitioner, to population-wide approaches, such as mass media campaigns, but the most cost-effective mix of interventions is unknown. In this study we evaluate the cost-effectiveness of interventions to promote physical activity.
Methods and Findings
From evidence of intervention efficacy in the physical activity literature and evaluation of the health sector costs of intervention and disease treatment, we model the cost impacts and health outcomes of six physical activity interventions, over the lifetime of the Australian population. We then determine cost-effectiveness of each intervention against current practice for physical activity intervention in Australia and derive the optimal pathway for implementation. Based on current evidence of intervention effectiveness, the intervention programs that encourage use of pedometers (Dominant) and mass media-based community campaigns (Dominant) are the most cost-effective strategies to implement and are very likely to be cost-saving. The internet-based intervention program (AUS$3,000/DALY), the GP physical activity prescription program (AUS$12,000/DALY), and the program to encourage more active transport (AUS$20,000/DALY), although less likely to be cost-saving, have a high probability of being under a AUS$50,000 per DALY threshold. GP referral to an exercise physiologist (AUS$79,000/DALY) is the least cost-effective option if high time and travel costs for patients in screening and consulting an exercise physiologist are considered.
Conclusions
Intervention to promote physical activity is recommended as a public health measure. Despite substantial variability in the quantity and quality of evidence on intervention effectiveness, and uncertainty about the long-term sustainability of behavioural changes, it is highly likely that as a package, all six interventions could lead to substantial improvement in population health at a cost saving to the health sector.
Please see later in the article for Editors' Summary
Editors' Summary
Background
The human body needs regular physical activity throughout life to stay healthy. Physical activity—any bodily movement produced by skeletal muscles that uses energy—helps to maintain a healthy body weight and to prevent or delay heart disease, stroke, type 2 diabetes, colon cancer, and breast cancer. In addition, physically active people feel better and live longer than physically inactive people. For an adult, 30 minutes of moderate physical activity—walking briskly, gardening, swimming, or cycling—at least five times a week is sufficient to promote and maintain health. But at least 60% of the world's population does not do even this modest amount of physical activity. The daily lives of people in both developed and developing countries are becoming increasingly sedentary. People are sitting at desks all day instead of doing manual labor; they are driving to work in cars instead of walking or cycling; and they are participating less in physical activities during their leisure time.
Why Was This Study Done?
In many countries, the chronic diseases that are associated with physical inactivity are now a major public-health problem; globally, physical inactivity causes 1.9 million deaths per year. Clearly, something has to be done about this situation. Luckily, there is no shortage of interventions designed to promote physical activity, ranging from individual counseling from general practitioners to mass-media campaigns. But which intervention or package of interventions will produce the optimal population health benefits relative to cost? Although some studies have examined the cost-effectiveness of individual interventions, different settings for analysis and use of different methods and assumptions make it difficult to compare results and identify which intervention approaches should be give priority by policy makers. Furthermore, little is known about the cost-effectiveness of packages of interventions. In this study, the researchers investigate the cost-effectiveness in Australia (where physical inactivity contributes to 10% of deaths) of a package of interventions designed to promote physical activity in adults using a standardized approach (ACE-Prevention) to the assessment of the cost-effectiveness of health-care interventions.
What Did the Researchers Do and Find?
The researchers selected six interventions for their study: general practitioner “prescription” of physical activity; general practitioner referral to an exercise physiologist; a mass-media campaign to promote physical activity; the TravelSmart car use reduction program; a campaign to encourage the use of pedometers to increase physical activity; and an internet-based program. Using published data on the effects of physical activity on the amount of illness and death caused by breast and colon cancer, heart disease, stroke, and type 2 diabetes and on the effectiveness of each intervention, the researchers calculated the health outcomes of each intervention in disability-adjusted life years (DALY; a year of healthy life lost because of premature death or disability) averted over the lifetime of the Australian population. They also calculated the costs associated with each intervention offset by the costs associated with the five conditions listed above. These analyses showed that the pedometer program and the mass-media campaign were likely to be the most cost-effective interventions. These interventions were also most likely to be cost-saving. Referral to an exercise physiologist was the least cost-effective intervention. The other three interventions, though unlikely to be cost-saving, were likely to be cost-effective. Finally, a package of all six interventions would be cost-effective and would avert 61,000 DALYs, a third of what could be achieved if every Australian did 30 minutes of physical activity five times a week.
What Do These Findings Mean?
As in all modeling studies, these findings depend on the quality of the data and on the assumptions included by the researchers in their calculations. Unfortunately, there was substantial variability in the quantity and quality of evidence on the effectiveness of each intervention and uncertainty about the long-term effects of each intervention. Nevertheless, the findings presented in this study suggest that the assessment of the cost-effectiveness of a combination of interventions designed to promote physical activity might provide policy makers with some guidance about the best way to reduce the burden of disease caused by physical inactivity. More specifically, for Australia, these findings suggest that the package of the six interventions considered here is likely to provide a cost-effective way to substantially improve the health of the nation.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000110.
The World Health Organization provides information about physical activity and health (in several languages); it also provides an explanation of DALYs
The US Centers for Disease Control and Prevention provides information on physical activity for different age groups and for health professionals
The UK National Health Service information source Choices also explains the benefits of regular physical activity
MedlinePlus has links to other resources about exercise and physical fitness (in English and Spanish)
The University of Queensland Web site has more information on ACE-Prevention (Assessing Cost-Effectiveness Prevention)
doi:10.1371/journal.pmed.1000110
PMCID: PMC2700960  PMID: 19597537
18.  Economic evaluation of a community based exercise programme to prevent falls 
OBJECTIVE—To assess the incremental costs and cost effectiveness of implementing a home based muscle strengthening and balance retraining programme that reduced falls and injuries in older women.
DESIGN—An economic evaluation carried out within a randomised controlled trial with two years of follow up. Participants were individually prescribed an exercise programme (exercise group, n=116) or received usual care and social visits (control group, n=117).
SETTING—17 general practices in Dunedin, New Zealand.
PARTICIPANTS—Women aged 80 years and older living in the community and invited by their general practitioner to take part.
MAIN OUTCOME MEASURES—Number of falls and injuries related to falls, costs of implementing the intervention, healthcare service costs resulting from falls and total healthcare service costs during the trial. Cost effectiveness was measured as the incremental cost of implementing the exercise programme per fall event prevented.
MAIN RESULTS—27% of total hospital costs during the trial were related to falls. However, there were no significant differences in health service costs between the two groups. Implementing the exercise programme for one and two years respectively cost $314 and $265 (1995 New Zealand dollars) per fall prevented, and $457 and $426 per fall resulting in a moderate or serious injury prevented.
CONCLUSIONS—The costs resulting from falls make up a substantial proportion of the hospital costs for older people. Despite a reduction in falls as a result of this home exercise programme there was no significant reduction in healthcare costs. However, the results reported will provide information on the cost effectiveness of the programme for those making decisions on falls prevention strategies.


Keywords: falls; exercise; elderly
doi:10.1136/jech.55.8.600
PMCID: PMC1731948  PMID: 11449021
19.  Can social dancing prevent falls in older adults? a protocol of the Dance, Aging, Cognition, Economics (DAnCE) fall prevention randomised controlled trial 
BMC Public Health  2013;13:477.
Background
Falls are one of the most common health problems among older people and pose a major economic burden on health care systems. Exercise is an accepted stand-alone fall prevention strategy particularly if it is balance training or regular participation in Tai chi. Dance shares the ‘holistic’ approach of practices such as Tai chi. It is a complex sensorimotor rhythmic activity integrating multiple physical, cognitive and social elements. Small-scale randomised controlled trials have indicated that diverse dance styles can improve measures of balance and mobility in older people, but none of these studies has examined the effect of dance on falls or cognition. This study aims to determine whether participation in social dancing: i) reduces the number of falls; and ii) improves cognitive functions associated with fall risk in older people.
Methods/design
A single-blind, cluster randomised controlled trial of 12 months duration will be conducted. Approximately 450 participants will be recruited from 24 self-care retirement villages that house at least 60 residents each in Sydney, Australia. Village residents without cognitive impairment and obtain medical clearance will be eligible. After comprehensive baseline measurements including physiological and cognitive tests and self-completed questionnaires, villages will be randomised to intervention sites (ballroom or folk dance) or to a wait-listed control using a computer randomisation method that minimises imbalances between villages based on two baseline fall risk measures. Main outcome measures are falls, prospectively measured, and the Trail Making cognitive function test. Cost-effectiveness and cost-utility analyses will be performed.
Discussion
This study offers a novel approach to balance training for older people. As a community-based approach to fall prevention, dance offers older people an opportunity for greater social engagement, thereby making a major contribution to healthy ageing. Providing diversity in exercise programs targeting seniors recognises the heterogeneity of multicultural populations and may further increase the number of taking part in exercise.
Trial registration
Australian New Zealand Clinical Trials Registry ACTRN12612000889853
The trial is now in progress with 12 villages already have been randomised.
doi:10.1186/1471-2458-13-477
PMCID: PMC3691670  PMID: 23675705
20.  Rapid Diagnosis of Tuberculosis with the Xpert MTB/RIF Assay in High Burden Countries: A Cost-Effectiveness Analysis 
PLoS Medicine  2011;8(11):e1001120.
A cost-effectiveness study by Frank Cobelens and colleagues reveals that Xpert MTB/RIF is a cost-effective method of tuberculosis diagnosis that is suitable for use in low- and middle-income settings.
Background
Xpert MTB/RIF (Xpert) is a promising new rapid diagnostic technology for tuberculosis (TB) that has characteristics that suggest large-scale roll-out. However, because the test is expensive, there are concerns among TB program managers and policy makers regarding its affordability for low- and middle-income settings.
Methods and Findings
We estimate the impact of the introduction of Xpert on the costs and cost-effectiveness of TB care using decision analytic modelling, comparing the introduction of Xpert to a base case of smear microscopy and clinical diagnosis in India, South Africa, and Uganda. The introduction of Xpert increases TB case finding in all three settings; from 72%–85% to 95%–99% of the cohort of individuals with suspected TB, compared to the base case. Diagnostic costs (including the costs of testing all individuals with suspected TB) also increase: from US$28–US$49 to US$133–US$146 and US$137–US$151 per TB case detected when Xpert is used “in addition to” and “as a replacement of” smear microscopy, respectively. The incremental cost effectiveness ratios (ICERs) for using Xpert “in addition to” smear microscopy, compared to the base case, range from US$41–$110 per disability adjusted life year (DALY) averted. Likewise the ICERS for using Xpert “as a replacement of” smear microscopy range from US$52–$138 per DALY averted. These ICERs are below the World Health Organization (WHO) willingness to pay threshold.
Conclusions
Our results suggest that Xpert is a cost-effective method of TB diagnosis, compared to a base case of smear microscopy and clinical diagnosis of smear-negative TB in low- and middle-income settings where, with its ability to substantially increase case finding, it has important potential for improving TB diagnosis and control. The extent of cost-effectiveness gain to TB programmes from deploying Xpert is primarily dependent on current TB diagnostic practices. Further work is required during scale-up to validate these findings.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Tuberculosis (TB) is a bacterial disease that infects one-third of the world's population. The disease is caused by Mycobacterium tuberculosis, a bacterium that most commonly infects the lungs (known as pulmonary TB) and is transmitted from person to person when an infected individual coughs, sneezes, or talks. The symptoms of TB include chest pain, weight loss, fever, and a persistent cough that sometimes contains blood. Only 5%–10% of people who are infected with TB become sick or infectious, but people with weakened immune systems, such as individuals who are HIV-positive, are more likely to develop the disease. TB is estimated to have killed 1.7 million people in 2009 and is currently the leading cause of death among people infected with HIV.
Why Was This Study Done?
Although TB can be treated with a six-month course of antibiotics, effectively diagnosing TB is not always straightforward and drug resistance is becoming an increasing problem. One of the most common and simple methods to diagnose TB is a technique called sputum smear microscopy, which involves examining matter from the lungs under a microscope for the presence of TB-causing bacteria. However, despite being cheap and relatively simple, the test does not always detect active TB (smear-negative) and cannot determine whether the TB-causing bacteria are resistant to antibiotics. The World Health Organization has recently endorsed a new rapid test, called Xpert MTB/RIF (referred to as Xpert), for the initial diagnosis of TB. The test uses DNA amplification methods to reliably and quickly detect TB and whether infecting bacteria are resistant to the antibiotic rifampicin. The new test is expensive so there are concerns that the test might not be cost-effective in low- and middle-income countries.
What Did the Researchers Do and Find?
The researchers used a technique called modeling to simulate the outcome of 10,000 individuals with suspected TB as they went through a hypothetical diagnostic and treatment pathway. The model compared the costs associated with the introduction of Xpert to a base case for two different scenarios. In the base case all individuals with suspected TB had two sputum smear microscopy examinations followed by clinical diagnosis if they were smear-negative. For the different scenarios Xpert was either used in addition to the two sputum smear microscopy examinations (if the patient was smear-negative) or Xpert was used as a replacement for sputum smear microscopy for all patients. Different input parameters, based on country-specific estimates, were applied so that the model reflected the implementation of Xpert in India, South Africa, and Uganda.
In the researcher's model the introduction of Xpert increased the proportion of TB-infected patients who were correctly diagnosed with TB in any of the settings. However, the cost per TB case detected increased by approximately US$100 in both scenarios. Although the cost of detection increased significantly, the cost of treatment increased only moderately because the number of false-positive cases was reduced. For example, the percentage of treatment costs spent on false-positive diagnoses in India was predicted to fall from 22% to 4% when Xpert was used to replace sputum smear microscopy. The model was used to calculate incremental cost effectiveness ratios (ICERs—the additional cost of each disability-adjusted life year [DALY] averted) for the different scenarios of Xpert implementation in the different settings. In comparison to the base case, introducing Xpert in addition to sputum smear microscopy produced ICERs ranging from US$41 to US$110 per DALY averted, while introducing Xpert instead of sputum smear microscopy yielded ICERs ranging from US$52 to US$138 per DALY averted.
What Do These Findings Mean?
The findings suggest that the implementation of Xpert in addition to, or instead of, sputum smear microscopy will be cost-effective in low- and middle-income countries. The calculated ICERs are below the World Health Organization's “willingness to pay threshold” for all settings. That is the incremental cost of each DALY averted by introduction of Xpert is below the gross domestic product per capita for each country ($1,134 for India, $5,786 South Africa, and $490 for Uganda in 2010). However, the authors note that achieving ICERs below the “willingness to pay threshold” does not necessarily mean that countries have the resources to implement the test. The researchers also note that there are limitations to their study; additional unknown costs associated with the scale-up of Xpert and some parameters, such as patient costs, were not included in the model. Although the model strongly suggests that Xpert will be cost-effective, the researchers caution that initial roll-out of Xpert should be carefully monitored and evaluated before full scale-up.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1001120.
The World Health Organization provides information on all aspects of tuberculosis, including tuberculosis diagnostics and the Stop TB Partnership (some information is in several languages)
The US Centers for Disease Control and Prevention has information about tuberculosis, including information on the diagnosis of tuberculosis disease
MedlinePlus has links to further information about tuberculosis (in English and Spanish)
doi:10.1371/journal.pmed.1001120
PMCID: PMC3210757  PMID: 22087078
21.  Cost-Effectiveness of Treating Multidrug-Resistant Tuberculosis 
PLoS Medicine  2006;3(7):e241.
Background
Despite the existence of effective drug treatments, tuberculosis (TB) causes 2 million deaths annually worldwide. Effective treatment is complicated by multidrug-resistant TB (MDR TB) strains that respond only to second-line drugs. We projected the health benefits and cost-effectiveness of using drug susceptibility testing and second-line drugs in a lower-middle-income setting with high levels of MDR TB.
Methods and Findings
We developed a dynamic state-transition model of TB. In a base case analysis, the model was calibrated to approximate the TB epidemic in Peru, a setting with a smear-positive TB incidence of 120 per 100,000 and 4.5% MDR TB among prevalent cases. Secondary analyses considered other settings. The following strategies were evaluated: first-line drugs administered under directly observed therapy (DOTS), locally standardized second-line drugs for previously treated cases (STR1), locally standardized second-line drugs for previously treated cases with test-confirmed MDR TB (STR2), comprehensive drug susceptibility testing and individualized treatment for previously treated cases (ITR1), and comprehensive drug susceptibility testing and individualized treatment for all cases (ITR2). Outcomes were costs per TB death averted and costs per quality-adjusted life year (QALY) gained. We found that strategies incorporating the use of second-line drug regimens following first-line treatment failure were highly cost-effective compared to strategies using first-line drugs only. In our base case, standardized second-line treatment for confirmed MDR TB cases (STR2) had an incremental cost-effectiveness ratio of $720 per QALY ($8,700 per averted death) compared to DOTS. Individualized second-line drug treatment for MDR TB following first-line failure (ITR1) provided more benefit at an incremental cost of $990 per QALY ($12,000 per averted death) compared to STR2. A more aggressive version of the individualized treatment strategy (ITR2), in which both new and previously treated cases are tested for MDR TB, had an incremental cost-effectiveness ratio of $11,000 per QALY ($160,000 per averted death) compared to ITR1. The STR2 and ITR1 strategies remained cost-effective under a wide range of alternative assumptions about treatment costs, effectiveness, MDR TB prevalence, and transmission.
Conclusions
Treatment of MDR TB using second-line drugs is highly cost-effective in Peru. In other settings, the attractiveness of strategies using second-line drugs will depend on TB incidence, MDR burden, and the available budget, but simulation results suggest that individualized regimens would be cost-effective in a wide range of situations.
Editors' Summary
  Background.
Tuberculosis (TB) remains one of the most entrenched diseases on the planet—an estimated one in three people worldwide are infected with Mycobacterium tuberculosis, which causes the disease. Although effective drugs exist, a major reason for the failure to stem the spread of TB lies in the rise of drug-resistant strains of the bacterium. Some strains are resistant to several drugs; patients with this sort of infection are said to have multidrug-resistant (MDR) TB. The development of drug-resistant strains is fostered when health-care workers do not follow treatment guidelines or fail to ensure that patients take the whole treatment course. The World Health Organization recommends an approach to TB control called “DOTS,” which has been adopted by many countries. (See the link below for an explanation of what DOTS involves.) The antibiotics that are used in DOTS are described as “first-line” treatment drugs. They are highly effective against non-resistant TB but much less so against MDR TB. There are other, more expensive, “second-line” antibiotics that perform better against MDR TB.
  Why Was This Study Done?
Despite the worrying rise in MDR TB cases, the much higher cost of using second-line drugs is prompting some policy-makers to question the merits of introducing them in poor countries with limited resources. However, with MDR TB accounting for nearly a third of TB cases in some countries, first-line therapies seem unlikely to be sufficient in the long term. Second-line strategies, or “DOTS-Plus” strategies, are either standardized for a particular region or are chosen for individual patients on the basis of drug susceptibility tests. The researchers wanted to investigate whether standardized or individualized second-line regimens could save lives and be cost-effective in poor countries.
  What Did the Researchers Do and Find?
The researchers used a method called modeling. They took information already available about TB in Peru, where for every 100,000 people there are 120 new TB infections every year, and 4.5% of existing cases are MDR TB. The researchers then calculated what might happen over the next 30 years, comparing the likely effects of five alternative strategies. In four, new cases were given first-line drugs for 6 months. Those who were not cured were then treated in different ways. In DOTS, they were retreated with a second course of the same drugs; in STR1 they were given an 18-month standardized course of second-line and first-line drugs; in STR2, only confirmed MDR TB patients were given an 18-month standardized course of second-line and first-line drugs; and in ITR1, confirmed MDR TB patients were given a personalized regimen of second-line drugs. The fifth strategy, ITR2, tested all patients for drug susceptibility at the outset of treatment, and those with MDR TB were given an individualized course; those not cured were tested again and given another individualized course.
  Compared with DOTS, both the STR1 and STR2 strategies averted 4.8 deaths per 100,000 population, at a cost of $8,700 per averted death—with STR2 being a better value for money since it treated only confirmed MDR TB cases with the more expensive, second-line drugs. Of the individualized treatments, ITR1 averted an extra 0.9 deaths at a cost of $12,000 per averted death; ITR2 averted a further 1.2 deaths but at a much higher $160,000 per saved life.
  What Do These Findings Mean?
Despite the slightly higher cost of ITR1, the extra number of lives it would save compared with STR2 makes it a good approach for treatment in Peru. However, cost-effectiveness varies with other factors. If the difference in cost between the two strategies became higher than $9,500 per patient, STR would be preferable. And, if MDR TB were present in 10% of all TB cases, ITR2—with comprehensive drug susceptibility testing for all TB patients—would be best.
  The findings are of interest not just in Peru but in other developing countries where MDR TB is a growing problem. The researchers maintain that, in areas where DOTS has not yet been fully implemented, it would be more efficient to expand DOTS than to introduce DOTS-Plus. But they add that it would be beneficial to expand DOTS as well as implement DOTS-Plus. Individualized treatment after drug susceptibility testing is likely to be cost-effective even in the poorest of countries, which should give impetus to governments and organizations in those countries where MDR TB is a growing concern to modify their approach to treatment.
  Additional Information.
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0030241.
• Basic information about tuberculosis can be found on the Web site of the US National Institute of Allergy and Infectious Diseases
• The Web site of the World Health Organization's Stop TB department outlines both the DOTS and DOTS-Plus strategies
•  TB Alert, a UK-based charity that promotes TB awareness worldwide, has information on TB in several European, African, and Asian languages
Resch and colleagues found that treatment of MDR TB using second-line drugs is highly cost-effective in Peru.
doi:10.1371/journal.pmed.0030241
PMCID: PMC1483913  PMID: 16796403
22.  Multifactorial evaluation and treatment of persons with a high risk of recurrent falling was not cost-effective 
Osteoporosis International  2010;22(7):2187-2196.
Summary
This study evaluated the cost-effectiveness of multifactorial evaluation and treatment of fall risk factors in community-dwelling older persons at high risk of falling. The intervention and usual care groups did not differ in fall risk or costs. The multifactorial approach was not cost-effective compared to usual care in this group.
Introduction
International guidelines recommend multifactorial evaluation and tailored treatment of risk factors to reduce falling in older persons. The cost-effectiveness may be enhanced in high-risk persons. Our study evaluates the cost-effectiveness of multifactorial evaluation and treatment of fall risk factors in community-dwelling older persons at high risk of recurrent falling.
Methods
An economic evaluation was conducted alongside a randomised controlled trial. Participants (≥65 years) with a high risk of recurrent falling were randomised into an intervention (n = 106) and usual care group (n = 111). The intervention consisted of multifactorial assessment and treatment of fall risk factors. Clinical outcomes were proportions of fallers and utility during 1 year. Costs were measured using questionnaires at 3, 6 and 12 months after baseline and valued using cost prices, if available, and guideline prices. Differences in costs and cost-effectiveness were analysed using bootstrapping. Cost-effectiveness planes and acceptability curves were presented.
Results
During 1 year, 52% and 56% of intervention and usual care participants reported at least one fall, respectively. The clinical outcome measures did not differ between the two groups. The mean costs were Euro 7,740 (SD 9,129) in the intervention group and Euro 6,838 (SD 8,623) in the usual care group (mean difference Euro 902, bootstrapped 95% CI: −1,534 to 3,357). Cost-effectiveness planes and acceptability curves indicated that multifactorial evaluation and treatment of fall risk factors was not cost-effective compared with usual care.
Conclusions
Multifactorial evaluation and treatment of persons with a high risk of recurrent falling was not cost-effective compared to usual care.
doi:10.1007/s00198-010-1438-4
PMCID: PMC3106152  PMID: 20959965
Accidental falls; Cost-effectiveness; Multifactorial intervention; Prevention
23.  Preventing panic disorder: cost-effectiveness analysis alongside a pragmatic randomised trial 
Background
Panic disorder affects many people, is associated with a formidable disease burden, and imposes costs on society. The annual influx of new cases of panic disorder is substantial. From the public health perspective it may therefore be a sound policy to reduce the influx of new cases, to maintain the quality of life in many people, and to avoid the economic costs associated with the full-blown disorder. For this purpose, prevention is needed. Here we present the first economic evaluation of such an intervention.
Methods
Randomised trial of 117 people with panic disorder symptoms not meeting the diagnostic criteria of DSM-IV panic disorder. The interventions were time-limited cognitive-behavioural therapy v care-as-usual. The central clinical endpoint was DSM-IV panic disorder-free survival over 3 months. Costs were calculated from the societal perspective. Using the bootstrap method, incremental cost-effectiveness ratios were obtained, placed in 95% confidence intervals, projected on the cost-effectiveness plane, and presented as acceptability curves.
Results
The median incremental cost-effectiveness ratio is €6,198 (95% CI 2,435 – 60,731) per PD-free survival gained, which has a likelihood of 75.2% of being more acceptable from a cost-effectiveness point of view than care-as-usual when a willingness-to-pay ceiling is assumed of €10,000 per PD-free survival. The most significant cost driver was therapists' time. A sensitivity analysis indicated that cost-effectiveness improves when the number of therapist hours is reduced.
Conclusion
This is the first economic evaluation alongside a prevention trial in panic disorder. The small sample (n = 117) and the short time horizon of 3 months preclude firm conclusions, but our findings suggest that the intervention may be acceptable from a cost-effectiveness point of view, especially when therapist involvement can be kept minimal. Nevertheless, our results must await replication in a larger trial with longer follow-up times before we can confidently recommend implementation of the intervention on a broad scale. In the light of our findings and given the burden of panic disorder, such a new trial is well worth the effort.
Trial registration
Current Controlled Trials ISRCTN33407455.
doi:10.1186/1478-7547-7-8
PMCID: PMC2680812  PMID: 19393084
24.  Cost effectiveness of patient education for the prevention of falls in hospital: economic evaluation from a randomized controlled trial 
BMC Medicine  2013;11:135.
Background
Falls are one of the most frequently occurring adverse events that impact upon the recovery of older hospital inpatients. Falls can threaten both immediate and longer-term health and independence. There is need to identify cost-effective means for preventing falls in hospitals. Hospital-based falls prevention interventions tested in randomized trials have not yet been subjected to economic evaluation.
Methods
Incremental cost-effectiveness analysis was undertaken from the health service provider perspective, over the period of hospitalization (time horizon) using the Australian Dollar (A$) at 2008 values. Analyses were based on data from a randomized trial among n = 1,206 acute and rehabilitation inpatients. Decision tree modeling with three-way sensitivity analyses were conducted using burden of disease estimates developed from trial data and previous research. The intervention was a multimedia patient education program provided with trained health professional follow-up shown to reduce falls among cognitively intact hospital patients.
Results
The short-term cost to a health service of one cognitively intact patient being a faller could be as high as A$14,591 (2008). The education program cost A$526 (2008) to prevent one cognitively intact patient becoming a faller and A$294 (2008) to prevent one fall based on primary trial data. These estimates were unstable due to high variability in the hospital costs accrued by individual patients involved in the trial. There was a 52% probability the complete program was both more effective and less costly (from the health service perspective) than providing usual care alone. Decision tree modeling sensitivity analyses identified that when provided in real life contexts, the program would be both more effective in preventing falls among cognitively intact inpatients and cost saving where the proportion of these patients who would otherwise fall under usual care conditions is at least 4.0%.
Conclusions
This economic evaluation was designed to assist health care providers decide in what circumstances this intervention should be provided. If the proportion of cognitively intact patients falling on a ward under usual care conditions is 4% or greater, then provision of the complete program in addition to usual care will likely both prevent falls and reduce costs for a health service.
Trial registration
Australia and New Zealand Clinical Trials Register: ACTRN12608000015347.
doi:10.1186/1741-7015-11-135
PMCID: PMC3668305  PMID: 23692953
Accidental falls; Cost effectiveness; Economic evaluation; Hospital; Prevention
25.  Clinical Benefits, Costs, and Cost-Effectiveness of Neonatal Intensive Care in Mexico 
PLoS Medicine  2010;7(12):e1000379.
Joshua Salomon and colleagues performed a cost-effectiveness analysis using health and economic outcomes following preterm birth in Mexico and showed that neonatal intensive care provided high value for the money in this setting.
Background
Neonatal intensive care improves survival, but is associated with high costs and disability amongst survivors. Recent health reform in Mexico launched a new subsidized insurance program, necessitating informed choices on the different interventions that might be covered by the program, including neonatal intensive care. The purpose of this study was to estimate the clinical outcomes, costs, and cost-effectiveness of neonatal intensive care in Mexico.
Methods and Findings
A cost-effectiveness analysis was conducted using a decision analytic model of health and economic outcomes following preterm birth. Model parameters governing health outcomes were estimated from Mexican vital registration and hospital discharge databases, supplemented with meta-analyses and systematic reviews from the published literature. Costs were estimated on the basis of data provided by the Ministry of Health in Mexico and World Health Organization price lists, supplemented with published studies from other countries as needed. The model estimated changes in clinical outcomes, life expectancy, disability-free life expectancy, lifetime costs, disability-adjusted life years (DALYs), and incremental cost-effectiveness ratios (ICERs) for neonatal intensive care compared to no intensive care. Uncertainty around the results was characterized using one-way sensitivity analyses and a multivariate probabilistic sensitivity analysis. In the base-case analysis, neonatal intensive care for infants born at 24–26, 27–29, and 30–33 weeks gestational age prolonged life expectancy by 28, 43, and 34 years and averted 9, 15, and 12 DALYs, at incremental costs per infant of US$11,400, US$9,500, and US$3,000, respectively, compared to an alternative of no intensive care. The ICERs of neonatal intensive care at 24–26, 27–29, and 30–33 weeks were US$1,200, US$650, and US$240, per DALY averted, respectively. The findings were robust to variation in parameter values over wide ranges in sensitivity analyses.
Conclusions
Incremental cost-effectiveness ratios for neonatal intensive care imply very high value for money on the basis of conventional benchmarks for cost-effectiveness analysis.
Please see later in the article for the Editors' Summary
Editors' Summary
Background
Most pregnancies last about 40 weeks but increasing numbers of babies are being born preterm, before they reach 37 weeks of gestation (the period during which a baby develops in its mother). In developed countries and some middle-income countries such as Mexico, improvements in the care of newborn babies (neonatal intensive care) mean that more preterm babies survive now than in the past. Nevertheless, preterm birth is still a major cause of infant death worldwide that challenges attainment of Target 5 of Millennium Development Goal 4—the reduction of the global under-five mortality rate by two-thirds of the 1990 rate by 2015 (the Millennium Development Goals, which were agreed by world leaders in 2000, aim to reduce world poverty). Furthermore, many preterm babies who survive have long-term health problems and disabilities such as cerebral palsy, deafness, or learning difficulties. The severity of these disabilities and their long-term costs to families and to society depend on the baby's degree of prematurity.
Why Was This Study Done?
Mexico recently reformed its health system in an effort to improve access to care, particularly for the poorest sections of its population, and to improve the quality of its health care. The central component of this health care reform is the System of Social Protection of Health (SSPH). The SSPH contains a family health insurance program—Seguro Popular—that aims to provide the 50 million uninsured people living in Mexico with free access to an explicit set of health care interventions. As with any insurance program, decisions have to be made about which interventions Seguro Poplar should cover. Should neonatal intensive care be covered, for example? Do the benefits of this intervention (increased survival of babies) outweigh the costs of neonatal care and of long-term care for survivors with disabilities? In other words, is neonatal intensive care cost-effective? In this study, the researchers investigate this question by estimating the clinical benefits, costs, and cost-effectiveness of neonatal intensive care in Mexico.
What Did the Researchers Do and Find?
The researchers built a decision analytic model, a mathematical model that combines evidence on the outcomes and costs of alternative treatments to help inform decisions about health care policy. They gathered data about the health outcomes of preterm births in Mexico from registers of births and deaths and from hospital discharge databases, and estimated the costs of neonatal intensive care and long-term care for disabled survivors using data from the Mexican Ministry of Health and the World Health Organization. They then applied their model, which estimates changes in parameters such as life expectancy, lifetime costs, disability-adjusted life years (DALYs; one DALY represents the loss of a year of healthy life), and incremental cost-effectiveness ratios (ICERs; the additional cost expended for each DALY averted) for neonatal intensive care compared to no intensive care, to a group of 2 million infants. Neonatal intensive care for infants born at 24–26, 27–29, and 30–33 weeks gestation prolonged life expectancy by 28, 43, and 34 years and averted 9, 15, and 12 DALYs at incremental costs of US$11,000, US$10,000, and US$3000, respectively, compared to no intensive care. The ICERs of neonatal intensive care for babies born at these times were US$1200, US$700, and US$300 per DALY averted, respectively.
What Do These Findings Mean?
Interventions with ICERs of less than a country's per capita gross domestic product (GDP) are highly cost-effective; those with ICERs of 1–3 times the per capita GDP are potentially cost-effective. Mexico's per capita GDP in 2005 was approximately US$8,200. Thus, neonatal intensive care could provide exceptional value for money in Mexico (and maybe in other middle-income countries), even for very premature babies. The accuracy of these findings inevitably depends on the assumptions used to build the decision analytic model and on the accuracy of the data fed into it, but the findings were little changed by a wide range of alterations that the researchers made to the model. Importantly, however, this cost-effectiveness analysis focuses on health and economic consequences of different intervention choices, and does not capture all aspects of well-being. Decisions regarding neonatal intensive care will need to be based on a full consideration of all relevant factors, including ethical issues, and cost-effectiveness analyses should continue to be updated as new data emerge on health outcomes and costs associated with neonatal intensive care.
Additional Information
Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.1000379.
The March of Dimes, a nonprofit organization for pregnancy and baby health, provides information on preterm birth (in English and Spanish)
The Nemours Foundation, another nonprofit organization for child health, also provides information on premature babies (in English and Spanish)
MedlinePlus provides links to other information on premature babies (in English and Spanish)
The United Nations Childrens Fund (UNICEF) works for children's rights, survival, development and protection around the world; it provides information on Millennium Development Goal 4 and its Childinfo website provides detailed statistics about child survival and health (some information in several languages)
A PLoS Medicine Policy Forum by Núria Homedes and Antonio Ugalde discusses health care reforms in Mexico
doi:10.1371/journal.pmed.1000379
PMCID: PMC3001895  PMID: 21179496

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