Authorship inequalities in global health research: the IeDEA Southern Africa collaboration.

BACKGROUND: The International epidemiology Databases to Evaluate AIDS conducts research in several regions, including in Southern Africa. We assessed authorship inequalities for the Southern African region, which is led by South African and Swiss investigators. METHODS: We analysed authorships of publications from 2007 to 2020 by gender, country income group, time and citation impact. We used 2020 World Bank categories to define income groups and the relative citation ratio (RCR) to assess citation impact. Authorship parasitism was defined as articles without authors from the countries where the study was conducted. A regression model examined the probability of different authorship positions. RESULTS: We included 313 articles. Of the 1064 contributing authors, 547 (51.4%) were women, and 223 (21.0%) were from 32 low-income/lower middle-income countries (LLMICs), 269 (25.3%) were from 13 upper middle-income countries and 572 (53.8%) were from 25 high-income countries (HICs). Most articles (150/157, 95.5%) reporting data from Southern Africa included authors from all participating countries. Women were more likely to be the first author than men (OR 1.74; 95% CI 1.06 to 2.83) but less likely to be last authors (OR 0.63; 95% CI 0.40 to 0.99). Compared with HIC, LLMIC authors were less likely to publish as first (OR 0.21; 95% CI 0.11 to 0.41) or last author (OR 0.20; 95% CI 0.09 to 0.42). The proportion of women and LLMIC first and last authors increased over time. The RCR tended to be higher, indicating greater impact, if first or last authors were from HIC (p=0.06). CONCLUSIONS: This analysis of a global health collaboration co-led by South African and Swiss investigators showed little evidence of authorship parasitism. There were stark inequalities in authorship position, with women occupying more first and men more last author positions and researchers from LLMIC being 'stuck in the middle' on the byline. Global health research collaborations should monitor, analyse and address authorship inequalities.

Life years lost associated with mental illness: A cohort study of beneficiaries of a South African medical insurance scheme.

BACKGROUND: People with mental illness have a reduced life expectancy, but the extent of the mortality gap and the contribution of natural and unnatural causes to excess mortality among people with mental illness in South Africa are unknown. METHODS: We analysed reimbursement claims from South African medical insurance scheme beneficiaries aged 15-85 years. We estimated excess life years lost (LYL) associated with organic, substance use, psychotic, mood, anxiety, eating, personality, developmental or any mental disorders. RESULTS: We followed 1,070,183 beneficiaries for a median of three years, of whom 282,926 (26.4 %) received mental health diagnoses. Men with a mental health diagnosis lost 3.83 life years (95 % CI 3.58-4.10) compared to men without. Women with a mental health diagnosis lost 2.19 life years (1.97-2.41) compared to women without. Excess mortality varied by sex and diagnosis, from 11.50 LYL (95 % CI 9.79-13.07) among men with alcohol use disorder to 0.87 LYL (0.40-1.43) among women with generalised anxiety disorder. Most LYL were attributable to natural causes (men: 3.42, women: 1.94). A considerable number of LYL were attributable to unnatural causes among men with bipolar (1.52) or substance use (2.45) disorder. LIMITATIONS: Mental diagnoses are based on reimbursement claims. CONCLUSIONS: Premature mortality among South African individuals with mental disorders is high. Our findings support interventions for the prevention, early detection, and treatment of physical comorbidities in this population. Targeted programs for suicide prevention and substance use treatment, particularly among men, can help reduce excess mortality from unnatural causes.

Fungal Endocarditis: Pathophysiology, Epidemiology, Clinical Presentation, Diagnosis, and Management.

Fungal endocarditis accounts for 1% to 3% of all infective endocarditis cases, is associated with high morbidity and mortality (>70%), and presents numerous challenges during clinical care. Candida spp. are the most common causes of fungal endocarditis, implicated in over 50% of cases, followed by Aspergillus and Histoplasma spp. Important risk factors for fungal endocarditis include prosthetic valves, prior heart surgery, and injection drug use. The signs and symptoms of fungal endocarditis are nonspecific, and a high degree of clinical suspicion coupled with the judicious use of diagnostic tests is required for diagnosis. In addition to microbiological diagnostics (e.g., blood culture for Candida spp. or galactomannan testing and PCR for Aspergillus spp.), echocardiography remains critical for evaluation of potential infective endocarditis, although radionuclide imaging modalities such as 18F-fluorodeoxyglucose positron emission tomography/computed tomography are increasingly being used. A multimodal treatment approach is necessary: surgery is usually required and should be accompanied by long-term systemic antifungal therapy, such as echinocandin therapy for Candida endocarditis or voriconazole therapy for Aspergillus endocarditis.

The Swiss neighbourhood index of socioeconomic position: update and re-validation.

BACKGROUND: The widely used Swiss neighbourhood index of socioeconomic position (Swiss-SEP 1) was based on data from the 2000 national census on rent, household head education and occupation, and crowding. It may now be out of date. METHODS: We created a new index (Swiss-SEP 2) based on the 2012-2015 yearly micro censuses that have replaced the decennial house-to-house census in Switzerland since 2010. We used principal component analysis on neighbourhood-aggregated variables and standardised the index. We also created a hybrid version (Swiss-SEP 3), with updated values for neighbourhoods centred on buildings constructed after the year 2000 and original values for the remaining neighbourhoods. RESULTS: A total of 1.54 million neighbourhoods were included. With all three indices, the mean yearly equivalised household income increased from around 52,000 to 90,000 CHF from the lowest to the highest index decile. Analyses of mortality were based on 33.6 million person-years of follow-up. The age- and sex-adjusted hazard ratios of all-cause mortality comparing areas in the lowest Swiss-SEP decile with areas of the highest decile were 1.39 (95% confidence interval [CI] 1.36-1.41), 1.31 (1.29-1.33) and 1.34 (1.32-1.37) using the old, new and hybrid indices, respectively. DISCUSSION: The Swiss-SEP indices capture area-based SEP at a high resolution and allow the study of SEP when individual-level SEP data are missing or area-level effects are of interest. The hybrid version (Swiss-SEP 3) maintains high spatial resolution while adding information on new neighbourhoods. The index will continue to be useful for Switzerland's epidemiological and public health research.

Diagnosis and treatment of opioid-related disorders in a South African private sector medical insurance scheme: A cohort study.

BACKGROUND: The use of opioids is increasing globally, but data from low- and middle-income countries on opioid-related mental and behavioural disorders (hereafter referred to as opioid-related disorders) are scarce. This study examines the incidence of opioid-related disorders, opioid agonist use, and excess mortality among persons with opioid-related disorders in South Africa's private healthcare sector. METHODS: We analysed longitudinal data of beneficiaries (≥ 11 years) of a South African medical insurance scheme using reimbursement claims from Jan 1, 2011, to Jul 1, 2020. Beneficiaries were classified as having an opioid-related disorder if they received an opioid agonist (buprenorphine or methadone) or an ICD-10 diagnosis for harmful opioid use (F11.1), opioid dependence or withdrawal (F11.2-4), or an unspecified or other opioid-related disorder (F11.0, F11.5-9). We calculated adjusted hazard ratios (aHR) for factors associated with opioid-related disorders, estimated the cumulative incidence of opioid agonist use after receiving an ICD-10 diagnosis for opioid dependence or withdrawal, and examined excess mortality among beneficiaries with opioid-related disorders. RESULTS: Of 1,251,458 beneficiaries, 1286 (0.1%) had opioid-related disorders. Between 2011 and 2020, the incidence of opioid-related disorders increased by 12% (95% CI 9%-15%) per year. Men, young adults in their twenties, and beneficiaries with co-morbid mental health or other substance use disorders were at increased risk of opioid-related disorders. The cumulative incidence of opioid agonist use among beneficiaries who received an ICD-10 diagnosis for opioid dependence or withdrawal was 18.0% (95% CI 14.0-22.4) 3 years after diagnosis. After adjusting for age, sex, year, medical insurance coverage, and population group, opioid-related disorders were associated with an increased risk of mortality (aHR 2.28, 95% CI 1.84-2.82). Opioid-related disorders were associated with a 7.8-year shorter life expectancy. CONCLUSIONS: The incidence of people diagnosed with or treated for an opioid-related disorder in the private sector is increasing rapidly. People with opioid-related disorders are a vulnerable population with substantial psychiatric comorbidity who often die prematurely. Evidence-based management of opioid-related disorders is urgently needed to improve the health outcomes of people with opioid-related disorders.

Mathematical Models for Evaluating Effectiveness and Cost-Effectiveness of Cervical Cancer Control Policies in Populations Including Women Living With Human Immunodeficiency Virus: A Scoping Review.

OBJECTIVES: Mathematical modeling is increasingly used to inform cervical cancer control policies, and model-based evaluations of such policies in women living with human immunodeficiency virus (HIV) are an emerging research area. We did a scoping review of published literature to identify research gaps and inform future work in this field. METHODS: We systematically searched literature up to April 2022 and included mathematical modeling studies evaluating the effectiveness or cost-effectiveness of cervical cancer prevention strategies in populations including women living with HIV. We extracted information on prevention strategies and modeling approaches. RESULTS: We screened 1504 records and included 22 studies, almost half of which focused on South Africa. We found substantial between-study heterogeneity in terms of strategies assessed and modeling approaches used. Fourteen studies evaluated cervical cancer screening strategies, 7 studies assessed human papillomavirus vaccination (with or without screening), and 1 study evaluated the impact of HIV control measures on cervical cancer incidence and mortality. Thirteen conducted cost-effectiveness analyses. Markov cohort state-transition models were used most commonly (n = 12). Most studies (n = 17) modeled the effect of HIV by creating HIV-related health states. Thirteen studies performed model calibration, but 11 did not report the calibration methods used. Only 1 study stated that model code was available upon request. CONCLUSIONS: Few model-based evaluations of cervical cancer control strategies have specifically considered women living with HIV. Improvements in model transparency, by sharing information and making model code publicly available, could facilitate the utility of these evaluations for other high disease-burden countries, where they are needed for assisting policy makers.

Regression discontinuity analysis demonstrated varied effect of Treat-All on CD4 testing among Southern African countries.

OBJECTIVE: To determine whether Treat-All policy impacted laboratory testing practices of antiretroviral therapy (ART) programs in Southern Africa. STUDY DESIGN AND SETTING: We used HIV cohort data from Lesotho, Malawi, Mozambique, South Africa, Zambia and Zimbabwe in a regression discontinuity design to estimate changes in pre-ART CD4 testing and viral load monitoring following national Treat-all adoption that occurred during 2016 to 2017. This study included more than 230,000 ART-naïve people living with HIV (PLHIV) aged five years or older who started ART within two years of national Treat-All adoption. RESULTS: We found pre-ART CD4 testing decreased following adoption of Treat-All recommendations in Malawi (-21.4 percentage points (pp), 95% confidence interval, CI: -26.8, -16.0) and in Mozambique (-8.8pp, 95% CI: -14.9, -2.8), but increased in Zambia (+2.7pp, 95% CI: +0.4, +5.1). Treat-All policy had no effect on viral load monitoring, except among females in South Africa (+7.1pp, 95% CI: +1.1, +13.0). CONCLUSION: Treat-All policy expanded ART eligibility, but led to reductions in pre-ART CD4 testing in some countries that may weaken advanced HIV disease management. Continued and expanded support of CD4 and viral load laboratory capacity is needed to further improve treatment successes and allow for uniform evaluation of ART implementation across Southern Africa.

Socioeconomic position and the COVID-19 care cascade from testing to mortality in Switzerland: a population-based analysis.

BACKGROUND: The inverse care law states that disadvantaged populations need more health care than advantaged populations but receive less. Gaps in COVID-19-related health care and infection control are not well understood. We aimed to examine inequalities in health in the care cascade from testing for SARS-CoV-2 to COVID-19-related hospitalisation, intensive care unit (ICU) admission, and death in Switzerland, a wealthy country strongly affected by the pandemic. METHODS: We analysed surveillance data reported to the Swiss Federal Office of Public Health from March 1, 2020, to April 16, 2021, and 2018 population data. We geocoded residential addresses of notifications to identify the Swiss neighbourhood index of socioeconomic position (Swiss-SEP). The index describes 1·27 million small neighbourhoods of approximately 50 households each on the basis of rent per m2, education and occupation of household heads, and crowding. We used negative binomial regression models to calculate incidence rate ratios (IRRs) with 95% credible intervals (CrIs) of the association between ten groups of the Swiss-SEP index defined by deciles (1=lowest, 10=highest) and outcomes. Models were adjusted for sex, age, canton, and wave of the epidemic (before or after June 8, 2020). We used three different denominators: the general population, the number of tests, and the number of positive tests. FINDINGS: Analyses were based on 4 129 636 tests, 609 782 positive tests, 26 143 hospitalisations, 2432 ICU admissions, 9383 deaths, and 8 221 406 residents. Comparing the highest with the lowest Swiss-SEP group and using the general population as the denominator, more tests were done among people living in neighbourhoods of highest SEP compared with lowest SEP (adjusted IRR 1·18 [95% CrI 1·02-1·36]). Among tested people, test positivity was lower (0·75 [0·69-0·81]) in neighbourhoods of highest SEP than of lowest SEP. Among people testing positive, the adjusted IRR was 0·68 (0·62-0·74) for hospitalisation, was 0·54 (0·43-0·70) for ICU admission, and 0·86 (0·76-0·99) for death. The associations between neighbourhood SEP and outcomes were stronger in younger age groups and we found heterogeneity between areas. INTERPRETATION: The inverse care law and socioeconomic inequalities were evident in Switzerland during the COVID-19 epidemic. People living in neighbourhoods of low SEP were less likely to be tested but more likely to test positive, be admitted to hospital, or die, compared with those in areas of high SEP. It is essential to continue to monitor testing for SARS-CoV-2, access and uptake of COVID-19 vaccination and outcomes of COVID-19. Governments and health-care systems should address this pandemic of inequality by taking measures to reduce health inequalities in response to the SARS-CoV-2 pandemic. FUNDING: Swiss Federal Office of Public Health, Swiss National Science Foundation, EU Horizon 2020, Branco Weiss Foundation.

Face-to-face panel meetings versus remote evaluation of fellowship applications: simulation study at the Swiss National Science Foundation.

OBJECTIVES: To trial a simplified, time and cost-saving method for remote evaluation of fellowship applications and compare this with existing panel review processes by analysing concordance between funding decisions, and the use of a lottery-based decision method for proposals of similar quality. DESIGN: The study involved 134 junior fellowship proposals for postdoctoral research ('Postdoc.Mobility'). The official method used two panel reviewers who independently scored the application, followed by triage and discussion of selected applications in a panel. Very competitive/uncompetitive proposals were directly funded/rejected without discussion. The simplified procedure used the scores of the two panel members, with or without the score of an additional, third expert. Both methods could further use a lottery to decide on applications of similar quality close to the funding threshold. The same funding rate was applied, and the agreement between the two methods analysed. SETTING: Swiss National Science Foundation (SNSF). PARTICIPANTS: Postdoc.Mobility panel reviewers and additional expert reviewers. PRIMARY OUTCOME MEASURE: Per cent agreement between the simplified and official evaluation method with 95% CIs. RESULTS: The simplified procedure based on three reviews agreed in 80.6% (95% CI: 73.9% to 87.3%) of applicants with the official funding outcome. The agreement was 86.6% (95% CI: 80.6% to 91.8%) when using the two reviews of the panel members. The agreement between the two methods was lower for the group of applications discussed in the panel (64.2% and 73.1%, respectively), and higher for directly funded/rejected applications (range: 96.7%-100%). The lottery was used in 8 (6.0%) of 134 applications (official method), 19 (14.2%) applications (simplified, three reviewers) and 23 (17.2%) applications (simplified, two reviewers). With the simplified procedure, evaluation costs could have been halved and 31 hours of meeting time saved for the two 2019 calls. CONCLUSION: Agreement between the two methods was high. The simplified procedure could represent a viable evaluation method for the Postdoc.Mobility early career instrument at the SNSF.

Author Correction: A global mass budget for positively buoyant macroplastic debris in the ocean.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

CINeMA: Software for semiautomated assessment of the confidence in the results of network meta-analysis.

Network meta-analysis (NMA) compares several interventions that are linked in a network of comparative studies and estimates the relative treatment effects between all treatments, using both direct and indirect evidence. NMA is increasingly used for decision making in health care, however, a user-friendly system to evaluate the confidence that can be placed in the results of NMA is currently lacking. This paper is a tutorial describing the Confidence In Network Meta-Analysis (CINeMA) web application, which is based on the framework developed by Salanti et al (2014, PLOS One, 9, e99682) and refined by Nikolakopoulou et al (2019, bioRxiv). Six domains that affect the level of confidence in the NMA results are considered: (a) within-study bias, (b) reporting bias, (c) indirectness, (d) imprecision, (e) heterogeneity, and (f) incoherence. CINeMA is freely available and open-source and no login is required. In the configuration step users upload their data, produce network plots and define the analysis and effect measure. The dataset should include assessments of study-level risk of bias and judgments on indirectness. CINeMA calls the netmeta routine in R to estimate relative effects and heterogeneity. Users are then guided through a systematic evaluation of the six domains. In this way reviewers assess the level of concerns for each relative treatment effect from NMA as giving rise to "no concerns," "some concerns," or "major concerns" in each of the six domains, which are graphically summarized on the report page for all effect estimates. Finally, judgments across the domains are summarized into a single confidence rating ("high," "moderate," "low," or "very low"). In conclusion, the user-friendly web-based CINeMA platform provides a transparent framework to evaluate evidence from systematic reviews with multiple interventions.

Cervical cancer risk in women living with HIV across four continents: A multicohort study.

We compared invasive cervical cancer (ICC) incidence rates in Europe, South Africa, Latin and North America among women living with HIV who initiated antiretroviral therapy (ART) between 1996 and 2014. We analyzed cohort data from the International Epidemiology Databases to Evaluate AIDS (IeDEA) and the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord. We used flexible parametric survival models to determine regional ICC rates and risk factors for incident ICC. We included 64,231 women from 45 countries. During 320,141 person-years (pys), 356 incident ICC cases were diagnosed (Europe 164, South Africa 156, North America 19 and Latin America 17). Raw ICC incidence rates per 100,000 pys were 447 in South Africa (95% confidence interval [CI]: 382-523), 136 in Latin America (95% CI: 85-219), 76 in North America (95% CI: 48-119) and 66 in Europe (95% CI: 57-77). Compared to European women ICC rates at 5 years after ART initiation were more than double in Latin America (adjusted hazard ratio [aHR]: 2.43, 95% CI: 1.27-4.68) and 11 times higher in South Africa (aHR: 10.66, 95% CI: 6.73-16.88), but similar in North America (aHR: 0.79, 95% CI: 0.37-1.71). Overall, ICC rates increased with age (>50 years vs. 16-30 years, aHR: 1.57, 95% CI: 1.03-2.40) and lower CD4 cell counts at ART initiation (per 100 cell/µl decrease, aHR: 1.25, 95% CI: 1.15-1.36). Improving access to early ART initiation and effective cervical cancer screening in women living with HIV should be key parts of global efforts to reduce cancer-related health inequities.

A global mass budget for positively buoyant macroplastic debris in the ocean.

Predicted global figures for plastic debris accumulation in the ocean surface layer range on the order of hundreds of thousands of metric tons, representing only a few percent of estimated annual emissions into the marine environment. The current accepted explanation for this difference is that positively buoyant macroplastic objects do not persist on the ocean surface. Subject to degradation into microplastics, the major part of the mass is predicted to have settled below the surface. However, we argue that such a simple emission-degradation model cannot explain the occurrence of decades-old objects collected by oceanic expeditions. We show that debris circulation dynamics in coastal environments may be a better explanation for this difference. The results presented here suggest that there is a significant time interval, on the order of several years to decades, between terrestrial emissions and representative accumulation in offshore waters. Importantly, our results also indicate that the current generation of secondary microplastics in the global ocean is mostly a result of the degradation of objects produced in the 1990s and earlier. Finally, we propose a series of future emission scenarios until 2050, discussing the necessity to rapidly reduce emissions and actively remove waste accumulated in the environment to mitigate further microplastic contamination in the global ocean.

Diagnosis and clinical outcomes of extrapulmonary tuberculosis in antiretroviral therapy programmes in low- and middle-income countries: a multicohort study.

INTRODUCTION: Extrapulmonary tuberculosis (EPTB) is difficult to confirm bacteriologically and requires specific diagnostic capacities. Diagnosis can be especially challenging in under-resourced settings. We studied diagnostic modalities and clinical outcomes of EPTB compared to pulmonary tuberculosis (PTB) among HIV-positive adults in antiretroviral therapy (ART) programmes in low- and middle-income countries (LMIC). METHODS: We collected data from HIV-positive TB patients (≥16 years) in 22 ART programmes participating in the International Epidemiology Databases to Evaluate AIDS (IeDEA) consortium in sub-Saharan Africa, Asia-Pacific, and Caribbean, Central and South America regions between 2012 and 2014. We categorized TB as PTB or EPTB (EPTB included mixed PTB/EPTB). We used multivariable logistic regression to assess associations with clinical outcomes. RESULTS AND DISCUSSION: We analysed 2695 HIV-positive TB patients. Median age was 36 years (interquartile range (IQR) 30 to 43), 1102 were female (41%), and the median CD4 count at TB treatment start was 114 cells/µL (IQR 40 to 248). Overall, 1930 had PTB (72%), and 765 EPTB (28%). Among EPTB patients, the most frequently involved sites were the lymph nodes (24%), pleura (15%), abdomen (11%) and meninges (6%). The majority of PTB (1123 of 1930, 58%) and EPTB (582 of 765, 76%) patients were diagnosed based on clinical criteria. Bacteriological confirmation (using positive smear microscopy, culture, Xpert MTB/RIF, or other nucleic acid amplification tests result) was obtained in 897 of 1557 PTB (52%) and 183 of 438 EPTB (42%) patients. EPTB was not associated with higher mortality compared to PTB (adjusted odd ratio (aOR) 1.0, 95% CI 0.8 to 1.3), but TB meningitis was (aOR 1.9, 95% CI 1.0 to 3.1). Bacteriological confirmation was associated with reduced mortality among PTB patients (aOR 0.7, 95% CI 0.6 to 0.8) and EPTB patients (aOR 0.3 95% CI 0.1 to 0.8) compared to TB patients with a negative test result. CONCLUSIONS: Diagnosis of EPTB and PTB at ART programmes in LMIC was mainly based on clinical criteria. Greater availability and usage of TB diagnostic tests would improve the diagnosis and clinical outcomes of both EPTB and PTB.

Extending Visit Intervals for Clinically Stable Patients on Antiretroviral Therapy: Multicohort Analysis of HIV Programs in Southern Africa.

BACKGROUND: The World Health Organization recommends differentiated antiretroviral therapy (ART) delivery with longer visit intervals for clinically stable patients. We examined time trends in visit frequency and associations between criteria for clinical stability and visit frequency in ART programs in Southern Africa. METHODS: We included adults on ART from 4 programs with viral-load monitoring, 2 programs with CD4 monitoring, and 4 programs with clinical monitoring of ART. We classified patients as clinically stable based on virological (viral load <1000 copies/mL), immunological (CD4 >200 cells/µL), or clinical (no current tuberculosis) criteria. We used Poisson regression and survival models to examine associations between criteria for clinical stability and the rate of clinic visits. RESULTS: We included 180,837 patients. There were trends toward fewer visits in more recent years and with longer ART duration. In all ART programs, clinically stable patients were seen less frequently than patients receiving failing ART, but the strength of the association varied. Adjusted incidence rate ratios comparing visit rates for stable patients with patients on failing ART were 0.82 (95% confidence interval: 0.73 to 0.90) for patients classified based on the virological criterion, 0.81 (0.69 to 0.93) for patients classified based on the clinical criterion, and 0.90 (0.85 to 0.96) for patients classified based on the immunological criterion for stability. CONCLUSION: Differences in visit rates between stable patients and patients failing ART were variable and modest overall. Larger differences were seen in programs using virological criteria for clinical stability than in programs using immunological criteria. Greater access to routine viral-load monitoring may increase scale-up of differentiated ART delivery.

The use of mathematical modeling studies for evidence synthesis and guideline development: A glossary.

Mathematical modeling studies are increasingly recognised as an important tool for evidence synthesis and to inform clinical and public health decision-making, particularly when data from systematic reviews of primary studies do not adequately answer a research question. However, systematic reviewers and guideline developers may struggle with using the results of modeling studies, because, at least in part, of the lack of a common understanding of concepts and terminology between evidence synthesis experts and mathematical modellers. The use of a common terminology for modeling studies across different clinical and epidemiological research fields that span infectious and non-communicable diseases will help systematic reviewers and guideline developers with the understanding, characterisation, comparison, and use of mathematical modeling studies. This glossary explains key terms used in mathematical modeling studies that are particularly salient to evidence synthesis and knowledge translation in clinical medicine and public health.

Planning a future randomized clinical trial based on a network of relevant past trials.

BACKGROUND: The important role of network meta-analysis of randomized clinical trials in health technology assessment and guideline development is increasingly recognized. This approach has the potential to obtain conclusive results earlier than with new standalone trials or conventional, pairwise meta-analyses. METHODS: Network meta-analyses can also be used to plan future trials. We introduce a four-step framework that aims to identify the optimal design for a new trial that will update the existing evidence while minimizing the required sample size. The new trial designed within this framework does not need to include all competing interventions and comparisons of interest and can contribute direct and indirect evidence to the updated network meta-analysis. We present the method by virtually planning a new trial to compare biologics in rheumatoid arthritis and a new trial to compare two drugs for relapsing-remitting multiple sclerosis. RESULTS: A trial design based on updating the evidence from a network meta-analysis of relevant previous trials may require a considerably smaller sample size to reach the same conclusion compared with a trial designed and analyzed in isolation. Challenges of the approach include the complexity of the methodology and the need for a coherent network meta-analysis of previous trials with little heterogeneity. CONCLUSIONS: When used judiciously, conditional trial design could significantly reduce the required resources for a new study and prevent experimentation with an unnecessarily large number of participants.

Death at no cost? Persons with no health insurance claims in the last year of life in Switzerland.

BACKGROUND: Lack of health insurance claims (HIC) in the last year of life might indicate suboptimal end-of-life care, but reasons for no HIC are not fully understood because information on causes of death is often missing. We investigated association of no HIC with characteristics of individuals and their place of residence. METHODS: We analysed HIC of persons who died between 2008 and 2010, which were obtained from six providers of mandatory Swiss health insurance. We probabilistically linked these persons to death certificates to get cause of death information and analysed data using sex-stratified, multivariable logistic regression. Supplementary analyses looked at selected subgroups of persons according to the primary cause of death. RESULTS: The study population included 113,277 persons (46% males). Among these persons, 1199 (proportion 0.022, 95% CI: 0.021-0.024) males and 803 (0.013, 95% CI: 0.012-0.014) females had no HIC during the last year of life. We found sociodemographic and health differentials in the lack of HIC at the last year of life among these 2002 persons. The likelihood of having no HIC decreased steeply with older age. Those who died of cancer were more likely to have HIC (adjusted odds ratio for males 0.17, 95% CI: 0.13-0.22; females 0.19, 95% CI: 0.12-0.28) whereas those dying of mental and behavioural disorders (AOR males 1.83, 95% CI:1.42-2.37; females 1.65, 95% CI: 1.27-2.14), and males dying of suicide (AOR 2.15, 95% CI: 1.72-2.69) and accidents (AOR 2.41, 95% CI: 1.96-2.97) were more likely to have none. Single, widowed, and divorced persons also were more likely to have no HIC (AORs in range of 1.29-1.80). There was little or no association between the lack of HIC and characteristics of region of residence. Patterns of no HIC differed across main causes of death. Associations with age and civil status differed in particular for persons who died of cancer, suicide, accidents and assaults, and mental and behavioural disorders. CONCLUSIONS: Particular groups might be more likely to not seek care or not report health insurance costs to insurers. Researchers should be aware of this aspect of health insurance data and account for persons who lack HIC.

Suicide in adolescents: findings from the Swiss National cohort.

Suicide in adolescents is the second most common cause of death in this age group and an important public health problem. We examined sociodemographic factors associated with suicide in Swiss adolescents and analysed time trends in youth suicide in the Swiss National Cohort (SNC). The SNC is a longitudinal study of the whole Swiss resident population, based on linkage of census and mortality records. We identified suicides in adolescents aged 10-18 years from 1991 to 2013. A total of 2.396 million adolescents were included and 592 suicides were recorded, corresponding to a rate of 3.7 per 100,000 [95% confidence interval (CI) 3.4-4.0]. Rates increased with age from 0.0 per 100,000 at age 10 years to 14.8 per 100,000 (95% CI 12.6-17.5) at 18 years in boys, and from 0.0 to 5.4 per 100,000 (4.1-7.2) in girls. Being a boy, living in a single parent household, being an only or middle-born child, and living in rural regions were factors associated with a higher rate of suicide. Hanging was the most common method in boys, and railway suicides were most frequent in girls. There was no clear evidence for an increase or decrease over calendar time. We conclude that familial and socioeconomic factors including type of household, birth order and urbanity are associated with youth suicide in Switzerland. These factors should be considered when designing prevention programmes for youth suicide.