Corrigendum: A systematic review and economic evaluation of bisphosphonates for the prevention of fragility fractures

Abstract Background Fragility fractures are fractures that result from mechanical forces that would not ordinarily result in fracture. Objectives To evaluate the clinical effectiveness and safety of bisphosphonates [alendronic acid (Fosamax® and Fosamax® Once Weekly, Merck Sharp & Dohme Ltd), risedronic acid (Actonel® and Actonel Once a Week®, Warner Chilcott UK Ltd), ibandronic acid (Bonviva®, Roche Products Ltd) and zoledronic acid (Aclasta®, Novartis Pharmaceuticals UK Ltd)] for the prevention of fragility fracture and to assess their cost-effectiveness at varying levels of fracture risk. Data sources For the clinical effectiveness review, six electronic databases and two trial registries were searched: MEDLINE, EMBASE, The Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Web of Science and BIOSIS Previews, Clinicaltrials.gov and World Health Organization International Clinical Trials Registry Platform. Searches were limited by date from 2008 until September 2014. Review methods A systematic review and network meta-analysis (NMA) of effectiveness studies were conducted. A review of published economic analyses was undertaken and a de novo health economic model was constructed. Discrete event simulation was used to estimate lifetime costs and quality-adjusted life-years (QALYs) for each bisphosphonate treatment strategy and a strategy of no treatment for a simulated cohort of patients with heterogeneous characteristics. The model was populated with effectiveness evidence from the systematic review and NMA. All other parameters were estimated from published sources. A NHS and Personal Social Services perspective was taken, and costs and benefits were discounted at 3.5% per annum. Fracture risk was estimated from patient characteristics using the QFracture® (QFracture-2012 open source revision 38, Clinrisk Ltd, Leeds, UK) and FRAX® (web version 3.9, University of Sheffield, Sheffield, UK) tools. The relationship between fracture risk and incremental net benefit (INB) was estimated using non-parametric regression. Probabilistic sensitivity analysis (PSA) and scenario analyses were used to assess uncertainty. Results Forty-six randomised controlled trials (RCTs) were included in the clinical effectiveness systematic review, with 27 RCTs providing data for the fracture NMA and 35 RCTs providing data for the femoral neck bone mineral density (BMD) NMA. All treatments had beneficial effects on fractures versus placebo, with hazard ratios varying from 0.41 to 0.92 depending on treatment and fracture type. The effects on vertebral fractures and percentage change in BMD were statistically significant for all treatments. There was no evidence of a difference in effect on fractures between bisphosphonates. A statistically significant difference in the incidence of influenza-like symptoms was identified from the RCTs for zoledronic acid compared with placebo. Reviews of observational studies suggest that upper gastrointestinal symptoms are frequently reported in the first month of oral bisphosphonate treatment, but pooled analyses of placebo-controlled trials found no statistically significant difference. A strategy of no treatment was estimated to have the maximum INB for patients with a 10-year QFracture risk under 1.5%, whereas oral bisphosphonates provided maximum INB at higher levels of risk. However, the PSA suggested that there is considerable uncertainty regarding whether or not no treatment is the optimal strategy until the QFracture score is around 5.5%. In the model using FRAX, the mean INBs were positive for all oral bisphosphonate treatments across all risk categories. Intravenous bisphosphonates were estimated to have lower INBs than oral bisphosphonates across all levels of fracture risk when estimated using either QFracture or FRAX. Limitations We assumed that all treatment strategies are viable alternatives across the whole population. Conclusions Bisphosphonates are effective in preventing fragility fractures. However, the benefit-to-risk ratio in the lowest-risk patients may be debatable given the low absolute QALY gains and the potential for adverse events. We plan to extend the analysis to include non-bisphosphonate therapies. Study registration This study is registered as PROSPERO CRD42013006883. Funding The National Institute for Health Research Health Technology Assessment programme

Antiretroviral treatment coverage in a rural district in Tanzania--a modeling study using empirical data.

BACKGROUND: The Tanzanian Government started scaling up its antiretroviral treatment (ART) program from referral, regional and district hospitals to primary health care facilities in October 2004. In 2010, most ART clinics were decentralized to primary health facilities. ART coverage, i.e. people living with HIV (PLHIV) on combination treatment as a proportion of those in need of treatment, provides the basis for evaluating the efficiency of ART programs at national and district level. We aimed to evaluate adult ART and pre-ART care coverage by age and sex at CD4 < 200, < 350 and all PLHIV in the Rufiji district of Tanzania from 2006 to 2010. METHODS: The numbers of people on ART and pre-ART care were obtained from routinely aggregated, patient-level, cohort data from care and treatment centers in the district. We used ALPHA model to predict the number in need of pre-ART care and ART by age and sex at CD4 < 200 and < 350. RESULTS: Adult ART coverage among PLHIV increased from 2.9% in 2006 to 17.6% in 2010. In 2010, coverage was 20% for women and 14.8% for men. ART coverage was 30.2% and 38.7% in 2010 with reference to CD4 criteria of 350 and 200 respectively. In 2010, ART coverage was 0 and 3.4% among young people aged 15-19 and 20-24 respectively. ART coverage among females aged 35-39 and 40-44 was 30.6 and 35% respectively in 2010. Adult pre-ART care coverage for PLHIV of CD4 < 350 increased from 5% in 2006 to 37.7% in 2010. The age-sex coverage patterns for pre-ART care were similar to ART coverage for both CD4 of 200 and 350 over the study period. CONCLUSIONS: ART coverage in the Rufiji district is unevenly distributed and far from the universal coverage target of 80%, in particular among young men. The findings in 2010 are close to the most recent estimates of ART coverage in 2013. To strive for universal coverage, both the recruitment of new eligible individuals to pre-ART and ART and the successful retention of those already on ART in the program need to be prioritized

Improving the quality of drug error reporting

NoBackground: Drug errors are a common and persistent problem in health care and are also associated with serious adverse events. Reporting has become the cornerstone of learning from errors, but is not without its imperfections. Aim: The aim of this study is to improve reporting and learning from drug errors through investigating the contributory factors in drug errors and quality of reporting in an acute hospital. Methods: A retrospective, random sample of 991 drug error reports from 1999 to 2003 were subjected to quantitative and qualitative analysis. This was followed by 40 qualitative interviews with a volunteer, multi‐disciplinary sample of health professionals. The combined analysis has been used to develop a knowledge base for improved drug error reporting. Results: The quality of reports varied considerably, and 27% of reports lacked any contributory factors. Documentary analysis revealed a focus on individuals, sometimes culminating in blame without obvious justification. Doctors submitted few reports, and there were notable differences in reporting according to clinical location. Communication difficulties commonly featured in causation, and high workload and interruptions were predominant contributory factors in the interview data. Interviewees viewed causation as multifactorial, including cognitive and psychosocial factors. Organizational orientation to error was predominantly perceived by interviewees as individual rather than systems‐based. Staff felt obliged to report but rarely received feedback. Implications and conclusio: Drug errors are multifactorial in causation. Current reporting schemes lack a theoretical basis, and are unlikely to capture the information required to ensure learning about causation. Health professionals have reporting fatigue and some remain concerned that reporting promotes individual blame rather than an examination of systems factors. Reporting can be strengthened by human error theory, redesigned to capture a range of contributory factors, facilitate learning and foster supportive actions. It can also be feasible in routine practice. Such an approach should be examined through multi‐centred evaluation