Cost-effectiveness of a structured medication review approach for multimorbid older adults: Within-trial analysis of the OPERAM study.

BACKGROUND: Inappropriate polypharmacy has been linked with adverse outcomes in older, multimorbid adults. OPERAM is a European cluster-randomized trial aimed at testing the effect of a structured pharmacotherapy optimization intervention on preventable drug-related hospital admissions in multimorbid adults with polypharmacy aged 70 years or older. Clinical results of the trial showed a pattern of reduced drug-related hospital admissions, but without statistical significance. In this study we assessed the cost-effectiveness of the pharmacotherapy optimisation intervention. METHODS: We performed a pre-planned within-trial cost-effectiveness analysis (CEA) of the OPERAM intervention, from a healthcare system perspective. All data were collected within the trial apart from unit costs. QALYs were computed by applying the crosswalk German valuation algorithm to EQ-5D-5L-based quality of life data. Considering the clustered structure of the data and between-country heterogeneity, we applied Generalized Structural Equation Models (GSEMs) on a multiple imputed sample to estimate costs and QALYs. We also performed analyses by country and subgroup analyses by patient and morbidity characteristics. RESULTS: Trial-wide, the intervention was numerically dominant, with a potential cost-saving of CHF 3'588 (95% confidence interval (CI): -7'716; 540) and gain of 0.025 QALYs (CI: -0.002; 0.052) per patient. Robustness analyses confirmed the validity of the GSEM model. Subgroup analyses suggested stronger effects in people at higher risk. CONCLUSION: We observed a pattern towards dominance, potentially resulting from an accumulation of multiple small positive intervention effects. Our methodological approaches may inform other CEAs of multi-country, cluster-randomized trials facing presence of missing values and heterogeneity between centres/countries.

Drug prescription patterns, polypharmacy and potentially inappropriate medication in Swiss nursing homes: a descriptive analysis based on claims data.

BACKGROUND: To date, comprehensive data on drug utilisation in Swiss nursing homes are lacking. OBJECTIVE: To describe drug prescription patterns, polypharmacy and potentially inappropriate medication (PIM) in Swiss nursing home residents (NHR). METHODS: Using administrative claims data provided by the Swiss health insurance company Helsana, we assessed drug claims and drug costs in 2016 in individuals aged ≥65 years and insured with Helsana, who were either NHR or living in the community (reference group, RG). In particular, we analysed the prevalence of polypharmacy (≥5 claims for different drugs during a 3-month period) and PIM use according to the 2015 Beers criteria and the PRISCUS list. We standardised the results to the Swiss population. RESULTS: In 2016, NHR had on average nearly twice as many drug claims per capita as individuals in the RG (NHR 58.8; RG 30.8). The average per capita drug costs per day for NHR were low, but higher than in the RG (NHR CHF 8.55; RG CHF 5.45). The same pattern applied to the prevalence of polypharmacy (NHR 85.5%; RG 50.4%). Standardisation by age and sex did not materially alter these observations. Overall, 79.1% of NHR received ≥1 PIM, and 56.2% were long-term users (≥3 claims) of at least one PIM (based on the combined PRISCUS list and Beers criteria). Among all PIMs in nursing homes, quetiapine (antipsychotic agent), lorazepam (anxiolytic agent) and zolpidem (hypnotic agent) were the most prevalent (22.4, 20.2 and 13.0%, respectively). CONCLUSIONS: The high prevalence of polypharmacy and PIM in Swiss nursing homes may indicate a need for interventions aiming at de-prescribing drugs with an unfavourable benefit-risk profile.

A longitudinal review of national HIV policy and progress made in health facility implementation in Eastern Zimbabwe.

BACKGROUND: In recent years, WHO has made major changes to its guidance on the provision of HIV care and treatment services. We conducted a longitudinal study from 2013 to 2015 to establish how these changes have been translated into national policy in Zimbabwe and to measure progress in implementation within local health facilities. METHODS: National HIV programme policy guidelines published between 2003 and 2013 (n = 9) and 2014 and 2015 (n = 5) were reviewed to assess adoption of WHO recommendations on HIV testing services, prevention of mother-to-child transmission (PMTCT) of HIV, and provision of antiretroviral therapy (ART). Changes in local implementation of these policies over time were measured in two rounds of a survey conducted at 36 health facilities in Eastern Zimbabwe in 2013 and 2015. RESULTS: High levels of adoption of WHO guidance into national policy were recorded, including adoption of new recommendations made in 2013-2015 to introduce PMTCT Option B+ and to increase the threshold for ART initiation from CD4 ≤ 350 cells/mm3 to ≤ 500 cells/mm3. New strategies to implement national HIV policies were introduced such as the decentralisation of ART services from hospitals to clinics and task-shifting of care from doctors to nurses. The proportions of health facilities offering free HIV testing and counselling, PMTCT (including Option B+) and ART services increased substantially from 2013 to 2015, despite reductions in numbers of health workers. Provision of provider-initiated HIV testing remained consistently high. At least one test-kit stock-out in the prior year was reported in most facilities (2013: 69%; 2015: 61%; p = 0.44). Stock-outs of first-line ART and prophylactic drugs for opportunistic infections remained low. Repeat testing for HIV-negative individuals within 3 months decreased (2013: 97%; 2015: 72%; p = 0.01). Laboratory testing remained low across both survey rounds, despite policy and operational guidelines to expand coverage of diagnostic services. CONCLUSIONS: Good progress has been made in implementing international guidance on HIV service delivery in Zimbabwe. Further novel implementation strategies may be needed to achieve the latest targets for universal ART eligibility.

Spatial patterns of HIV prevalence and service use in East Zimbabwe: implications for future targeting of interventions.

INTRODUCTION: Focusing resources for HIV control on geographic areas of greatest need in countries with generalized epidemics has been recommended to increase cost-effectiveness. However, socioeconomic inequalities between areas of high and low prevalence could raise equity concerns and have been largely overlooked. We describe spatial patterns in HIV prevalence in east Zimbabwe and test for inequalities in accessibility and uptake of HIV services prior to the introduction of spatially-targeted programmes. METHODS: 8092 participants in an open-cohort study were geo-located to 110 locations. HIV prevalence and HIV testing and counselling (HTC) uptake were mapped with ordinary kriging. Clusters of high or low HIV prevalence were detected with Kulldorff statistics, and the socioeconomic characteristics and sexual risk behaviours of their populations, and levels of local HIV service availability (measured in travel distance) and uptake were compared. Kulldorff statistics were also determined for HTC, antiretroviral therapy (ART), and voluntary medical male circumcision (VMMC) uptake. RESULTS: One large and one small high HIV prevalence cluster (relative risk [RR] = 1.78, 95% confidence interval [CI] = 1.53-2.07; RR = 2.50, 95% CI = 2.08-3.01) and one low-prevalence cluster (RR = 0.70, 95% CI = 0.60-0.82) were detected. The larger high-prevalence cluster was urban with a wealthier population and more high-risk sexual behaviour than outside the cluster. Despite better access to HIV services, there was lower HTC uptake in the high-prevalence cluster (odds ratio [OR] of HTC in past three years: OR = 0.80, 95% CI = 0.66-0.97). The low-prevalence cluster was predominantly rural with a poorer population and longer travel distances to HIV services; however, uptake of HIV services was not reduced. CONCLUSION: High-prevalence clusters can be identified to which HIV control resources could be targeted. To date, poorer access to HIV services in the poorer low-prevalence areas has not resulted in lower service uptake, whilst there is significantly lower uptake of HTC in the high-prevalence cluster where health service access is better. Given the high levels of risky sexual behaviour and lower uptake of HTC services, targeting high-prevalence clusters may be cost-effective in this setting. If spatial targeting is introduced, inequalities in HIV service uptake may be avoided through mobile service provision for lower prevalence areas.

Spatial distribution of schistosomiasis and treatment needs in sub-Saharan Africa: a systematic review and geostatistical analysis.

BACKGROUND: Schistosomiasis affects more than 200 million individuals, mostly in sub-Saharan Africa, but empirical estimates of the disease burden in this region are unavailable. We used geostatistical modelling to produce high-resolution risk estimates of infection with Schistosoma spp and of the number of doses of praziquantel treatment needed to prevent morbidity at different administrative levels in 44 countries. METHODS: We did a systematic review to identify surveys including schistosomiasis prevalence data in sub-Saharan Africa via PubMed, ISI Web of Science, and African Journals Online, from inception to May 2, 2014, with no restriction of language, survey date, or study design. We used Bayesian geostatistical meta-analysis and rigorous variable selection to predict infection risk over a grid of 1 155 818 pixels at 5 × 5 km, on the basis of environmental and socioeconomic predictors and to calculate the number of doses of praziquantel needed for prevention of morbidity. FINDINGS: The literature search identified Schistosoma haematobium and Schistosoma mansoni surveys done in, respectively, 9318 and 9140 unique locations. Infection risk decreased from 2000 onwards, yet estimates suggest that 163 million (95% Bayesian credible interval [CrI] 155 million to 172 million; 18·5%, 17·6-19·5) of the sub-Saharan African population was infected in 2012. Mozambique had the highest prevalence of schistosomiasis in school-aged children (52·8%, 95% CrI 48·7-57·8). Low-risk countries (prevalence among school-aged children lower than 10%) included Burundi, Equatorial Guinea, Eritrea, and Rwanda. The numbers of doses of praziquantel needed per year were estimated to be 123 million (95% CrI 121 million to 125 million) for school-aged children and 247 million (239 million to 256 million) for the entire population. INTERPRETATION: Our results will inform policy makers about the number of treatments needed at different levels and will guide the spatial targeting of schistosomiasis control interventions. FUNDING: European Research Council, China Scholarship Council, UBS Optimus Foundation, and Swiss National Science Foundation.

Mapping and prediction of schistosomiasis in Nigeria using compiled survey data and Bayesian geospatial modelling.

Schistosomiasis prevalence data for Nigeria were extracted from peer-reviewed journals and reports, geo-referenced and collated in a nationwide geographical information system database for the generation of point prevalence maps. This exercise revealed that the disease is endemic in 35 of the country's 36 states, including the federal capital territory of Abuja, and found in 462 unique locations out of 833 different survey locations. Schistosoma haematobium, the predominant species in Nigeria, was found in 368 locations (79.8%) covering 31 states, S. mansoni in 78 (16.7%) locations in 22 states and S. intercalatum in 17 (3.7%) locations in two states. S. haematobium and S. mansoni were found to be co-endemic in 22 states, while co-occurrence of all three species was only seen in one state (Rivers). The average prevalence for each species at each survey location varied between 0.5% and 100% for S. haematobium, 0.2% to 87% for S. mansoni and 1% to 10% for S. intercalatum. The estimated prevalence of S. haematobium, based on Bayesian geospatial predictive modelling with a set of bioclimatic variables, ranged from 0.2% to 75% with a mean prevalence of 23% for the country as a whole (95% confidence interval (CI): 22.8-23.1%). The model suggests that the mean temperature, annual precipitation and soil acidity significantly influence the spatial distribution. Prevalence estimates, adjusted for school-aged children in 2010, showed that the prevalence is <10% in most states with a few reaching as high as 50%. It was estimated that 11.3 million children require praziquantel annually (95% CI: 10.3-12.2 million).

Determining treatment needs at different spatial scales using geostatistical model-based risk estimates of schistosomiasis.

BACKGROUND: After many years of neglect, schistosomiasis control is going to scale. The strategy of choice is preventive chemotherapy, that is the repeated large-scale administration of praziquantel (a safe and highly efficacious drug) to at-risk populations. The frequency of praziquantel administration is based on endemicity, which usually is defined by prevalence data summarized at an arbitrarily chosen administrative level. METHODOLOGY: For an ensemble of 29 West and East African countries, we determined the annualized praziquantel treatment needs for the school-aged population, adhering to World Health Organization guidelines. Different administrative levels of prevalence aggregation were considered; country, province, district, and pixel level. Previously published results on spatially explicit schistosomiasis risk in the selected countries were employed to classify each area into distinct endemicity classes that govern the frequency of praziquantel administration. PRINCIPAL FINDINGS: Estimates of infection prevalence adjusted for the school-aged population in 2010 revealed that most countries are classified as moderately endemic for schistosomiasis (prevalence 10-50%), while four countries (i.e., Ghana, Liberia, Mozambique, and Sierra Leone) are highly endemic (>50%). Overall, 72.7 million annualized praziquantel treatments (50% confidence interval (CI): 68.8-100.7 million) are required for the school-aged population if country-level schistosomiasis prevalence estimates are considered, and 81.5 million treatments (50% CI: 67.3-107.5 million) if estimation is based on a more refined spatial scale at the provincial level. CONCLUSIONS/SIGNIFICANCE: Praziquantel treatment needs may be over- or underestimated depending on the level of spatial aggregation. The distribution of schistosomiasis in Ethiopia, Liberia, Mauritania, Uganda, and Zambia is rather uniform, and hence country-level risk estimates are sufficient to calculate treatment needs. On the other hand, countries like Burkina Faso, Mali, Mozambique, Sudan, and Tanzania show large spatial heterogeneity in schistosomiasis risk, which should be taken into account for calculating treatment requirements.