Modelling lymphatic filariasis elimination in American Samoa: GEOFIL predicts need for new targets and six rounds of mass drug administration

Background: As part of the global effort to eliminate the debilitating mosquito-borne disease lymphatic filariasis (LF), seven rounds of two-drug (diethylcarbamazine and albendazole) mass drug administration (MDA) were conducted in American Samoa over 2000–2006. However subsequent surveys demonstrated ongoing transmission prompting further rounds of three-drug (diethylcarbamazine, albendazole, and ivermectin) MDA starting in 2018. Methods: We extend GEOFIL, a spatially-explicit agent-based model of LF transmission to predict the probability and timing of the local elimination or resurgence of LF for different MDA scenarios starting in 2018: two-drug vs. three-drug MDA, two to seven annual rounds, and population coverage rates of 55–75%. We developed an interactive visualisation comparing the effect of MDA strategies on different outcomes. Results: At least six annual rounds of three-drug MDA treating 75% of the population were required to achieve LF elimination in American Samoa by 2035 in > 50% of simulations. In scenarios where MDA did not achieve elimination, prevalence doubled approximately every three years, even if MDA reduced antigen prevalence to <1% (the target recommended by the World Health Organisation). Prevalence in six- and seven-year-old children was approximately one quarter of the prevalence in the general population. Conclusion: The three rounds of three-drug MDA conducted in 2018, 2019, and 2021 may have come close to WHO targets but are unlikely to interrupt LF transmission in American Samoa without further interventions. The recommended post-MDA surveillance strategy of testing primarily six and seven-year-old children will delay detection of resurgence compared to population representative surveys. The recommended elimination targets (reducing antigen prevalence below 0.5%, 1%, or 2%) may not be sufficient to interrupt transmission in countries with LF epidemiology like American Samoa. Alternative surveillance strategies and interventions designed to identify and eliminate spatially localized residual transmission may need to be considered. Interactive visualisations may assist decision-makers to choose locally appropriate strategies

GEOFIL: a spatially-explicit agent-based modelling framework for predicting the long-term transmission dynamics of lymphatic filariasis in American Samoa

In this study, a spatially-explicit agent-based modelling framework GEOFIL was developed to predict lymphatic filariasis (LF) transmission dynamics in American Samoa. GEOFIL included individual-level information on age, gender, disease status, household location, household members, workplace/school location and colleagues/schoolmates at each time step during the simulation. In American Samoa, annual mass drug administration from 2000 to 2006 successfully reduced LF prevalence dramatically. However, GEOFIL predicted continual increase in microfilaraemia prevalence in the absence of further intervention. Evidence from seroprevalence and transmission assessment surveys conducted from 2010 to 2016 indicated a resurgence of LF in American Samoa, corroborating GEOFIL’s predictions. The microfilaraemia and antigenaemia prevalence in 6-7-yo children were much lower than in the overall population. Mosquito biting rates were found to be a critical determinant of infection risk. Transmission hotspots are likely to disappear with lower biting rates. GEOFIL highlights current knowledge gaps, such as data on mosquito abundance, biting rates and within-host parasite dynamics, which are important for improving the accuracy of model predictions

Effect of the one-child policy on influenza transmission in China: a stochastic transmission model

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Multiple novel prostate cancer susceptibility signals identified by fine-mapping of known risk loci among Europeans

Genome-wide association studies (GWAS) have identified numerous common prostate cancer (PrCa) susceptibility loci. We have fine-mapped 64 GWAS regions known at the conclusion of the iCOGS study using large-scale genotyping and imputation in 25 723 PrCa cases and 26 274 controls of European ancestry. We detected evidence for multiple independent signals at 16 regions, 12 of which contained additional newly identified significant associations. A single signal comprising a spectrum of correlated variation was observed at 39 regions; 35 of which are now described by a novel more significantly associated lead SNP, while the originally reported variant remained as the lead SNP only in 4 regions. We also confirmed two association signals in Europeans that had been previously reported only in East-Asian GWAS. Based on statistical evidence and linkage disequilibrium (LD) structure, we have curated and narrowed down the list of the most likely candidate causal variants for each region. Functional annotation using data from ENCODE filtered for PrCa cell lines and eQTL analysis demonstrated significant enrichment for overlap with bio-features within this set. By incorporating the novel risk variants identified here alongside the refined data for existing association signals, we estimate that these loci now explain ∼38.9% of the familial relative risk of PrCa, an 8.9% improvement over the previously reported GWAS tag SNPs. This suggests that a significant fraction of the heritability of PrCa may have been hidden during the discovery phase of GWAS, in particular due to the presence of multiple independent signals within the same regio

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Global, regional, and national comparative risk assessment of 84 behavioural, environmental and occupational, and metabolic risks or clusters of risks for 195 countries and territories, 1990–2017 : a systematic analysis for the Global Burden of Disease Study 2017

Background: The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2017 comparative risk assessment (CRA) is a comprehensive approach to risk factor quantification that offers a useful tool for synthesising evidence on risks and risk outcome associations. With each annual GBD study, we update the GBD CRA to incorporate improved methods, new risks and risk outcome pairs, and new data on risk exposure levels and risk outcome associations. Methods: We used the CRA framework developed for previous iterations of GBD to estimate levels and trends in exposure, attributable deaths, and attributable disability-adjusted life-years (DALYs), by age group, sex, year, and location for 84 behavioural, environmental and occupational, and metabolic risks or groups of risks from 1990 to 2017. This study included 476 risk outcome pairs that met the GBD study criteria for convincing or probable evidence of causation. We extracted relative risk and exposure estimates from 46 749 randomised controlled trials, cohort studies, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. Using the counterfactual scenario of theoretical minimum risk exposure level (TMREL), we estimated the portion of deaths and DALYs that could be attributed to a given risk. We explored the relationship between development and risk exposure by modelling the relationship between the Socio-demographic Index (SDI) and risk-weighted exposure prevalence and estimated expected levels of exposure and risk-attributable burden by SDI. Finally, we explored temporal changes in risk-attributable DALYs by decomposing those changes into six main component drivers of change as follows: (1) population growth; (2) changes in population age structures; (3) changes in exposure to environmental and occupational risks; (4) changes in exposure to behavioural risks; (5) changes in exposure to metabolic risks; and (6) changes due to all other factors, approximated as the risk-deleted death and DALY rates, where the risk-deleted rate is the rate that would be observed had we reduced the exposure levels to the TMREL for all risk factors included in GBD 2017. Findings: In 2017,34.1 million (95% uncertainty interval [UI] 33.3-35.0) deaths and 121 billion (144-1.28) DALYs were attributable to GBD risk factors. Globally, 61.0% (59.6-62.4) of deaths and 48.3% (46.3-50.2) of DALYs were attributed to the GBD 2017 risk factors. When ranked by risk-attributable DALYs, high systolic blood pressure (SBP) was the leading risk factor, accounting for 10.4 million (9.39-11.5) deaths and 218 million (198-237) DALYs, followed by smoking (7.10 million [6.83-7.37] deaths and 182 million [173-193] DALYs), high fasting plasma glucose (6.53 million [5.23-8.23] deaths and 171 million [144-201] DALYs), high body-mass index (BMI; 4.72 million [2.99-6.70] deaths and 148 million [98.6-202] DALYs), and short gestation for birthweight (1.43 million [1.36-1.51] deaths and 139 million [131-147] DALYs). In total, risk-attributable DALYs declined by 4.9% (3.3-6.5) between 2007 and 2017. In the absence of demographic changes (ie, population growth and ageing), changes in risk exposure and risk-deleted DALYs would have led to a 23.5% decline in DALYs during that period. Conversely, in the absence of changes in risk exposure and risk-deleted DALYs, demographic changes would have led to an 18.6% increase in DALYs during that period. The ratios of observed risk exposure levels to exposure levels expected based on SDI (O/E ratios) increased globally for unsafe drinking water and household air pollution between 1990 and 2017. This result suggests that development is occurring more rapidly than are changes in the underlying risk structure in a population. Conversely, nearly universal declines in O/E ratios for smoking and alcohol use indicate that, for a given SDI, exposure to these risks is declining. In 2017, the leading Level 4 risk factor for age-standardised DALY rates was high SBP in four super-regions: central Europe, eastern Europe, and central Asia; north Africa and Middle East; south Asia; and southeast Asia, east Asia, and Oceania. The leading risk factor in the high-income super-region was smoking, in Latin America and Caribbean was high BMI, and in sub-Saharan Africa was unsafe sex. O/E ratios for unsafe sex in sub-Saharan Africa were notably high, and those for alcohol use in north Africa and the Middle East were notably low. Interpretation: By quantifying levels and trends in exposures to risk factors and the resulting disease burden, this assessment offers insight into where past policy and programme efforts might have been successful and highlights current priorities for public health action. Decreases in behavioural, environmental, and occupational risks have largely offset the effects of population growth and ageing, in relation to trends in absolute burden. Conversely, the combination of increasing metabolic risks and population ageing will probably continue to drive the increasing trends in non-communicable diseases at the global level, which presents both a public health challenge and opportunity. We see considerable spatiotemporal heterogeneity in levels of risk exposure and risk-attributable burden. Although levels of development underlie some of this heterogeneity, O/E ratios show risks for which countries are overperforming or underperforming relative to their level of development. As such, these ratios provide a benchmarking tool to help to focus local decision making. Our findings reinforce the importance of both risk exposure monitoring and epidemiological research to assess causal connections between risks and health outcomes, and they highlight the usefulness of the GBD study in synthesising data to draw comprehensive and robust conclusions that help to inform good policy and strategic health planning

Nurse experiences of medication administration to people with swallowing difficulties living in aged care facilities: a systematic review of qualitative evidence

To identify nurses' experiences of administering oral medications to residents of aged care facilities (ACFs) with swallowing difficulties.Administering medicines to older people with swallowing difficulties is a challenging task. Nurses frequently modify oral medications e.g. by crushing/splitting tablets or opening capsules, to facilitate the administration process. These practices are associated with an increased risk of medication administration errors. However, the reasons for these practices from the nurse's perspective are not well understood.The review investigated studies on the experiences of nurses of any level with the responsibility of medication administration in ACFs in terms of problems and challenges they encountered when administering oral medicines to aged care residents with swallowing difficulties. Aged care facilities providing all levels of care were considered for inclusion. Qualitative studies including, but not limited to, phenomenology, grounded theory, ethnography and action research designs as well as mixed methods studies and text and opinion papers were considered.A comprehensive database search of PubMed, CINAHL, Embase and Scopus was conducted between October and December 2016. MedNar and ProQuest Dissertations and Theses were used to search for gray literature. No date limitation was applied. The Joanna Briggs Institute Qualitative Assessment and Review Instrument critical appraisal tool (JBI-QARI) was used to assess the quality of the papers. The JBI-QARI data extraction instrument was used to extract qualitative findings. Data synthesis was not applicable in the final analysis due to the inclusion of only one article.The initial search resulted in 1681 unique titles for screening. A total of 202 abstracts were screened, after which a full-text review conducted for 19 articles. After the full-text review, only one article was eligible to be included in the final report. The included study scored highly in terms of methodological quality. The findings highlighted issues around time constraints, complexity of medication administration process to residents of ACFs with swallowing difficulties, cost and resources for alternative strategies, inefficient information flow and communication among healthcare professionals, and nurses' knowledge and training needs.The limited findings of this systematic review indicate that further research is necessary to provide evidence of nurses' experiences with regards to administering oral medications to older people with swallowing difficulties living in ACFs. A comprehensive understanding of these experiences may lead to organizational system changes to support nurses and older people with swallowing difficulties in ACFs

Dosage form modification and oral drug delivery in older people

Many people cannot swallow whole tablets and capsules. The cause ranges from difficulties overriding the natural instinct to chew solids/foodstuff before swallowing, to a complex disorder of swallowing function affecting the ability to manage all food and fluid intake. Older people can experience swallowing difficulties because of co-morbidities, age-related physiological changes, and polypharmacy. To make medicines easier to swallow, many people will modify the medication dosage form e.g. split or crush tablets, and open capsules. Some of the challenges associated with administering medicines to older people, and issues with dosage form modification will be reviewed. Novel dosage forms in development are promising and may help overcome some of the issues. However, until these are more readily available, effective interdisciplinary teams, and improving patient health literacy will help reduce the risk of medication misadventures in older people

Maternal diabetes and risk of attention-deficit/hyperactivity disorder in offspring in a multinational cohort of 3.6 million mother–child pairs

Previous studies report an association between maternal diabetes mellitus (MDM) and attention-deficit/hyperactivity disorder (ADHD), often overlooking unmeasured confounders such as shared genetics and environmental factors. We therefore conducted a multinational cohort study with linked mother–child pairs data in Hong Kong, New Zealand, Taiwan, Finland, Iceland, Norway and Sweden to evaluate associations between different MDM (any MDM, gestational diabetes mellitus (GDM) and pregestational diabetes mellitus (PGDM)) and ADHD using Cox proportional hazards regression. We included over 3.6 million mother–child pairs between 2001 and 2014 with follow-up until 2020. Children who were born to mothers with any type of diabetes during pregnancy had a higher risk of ADHD than unexposed children (pooled hazard ratio (HR) = 1.16, 95% confidence interval (CI) = 1.08-1.24). Higher risks of ADHD were also observed for both GDM (pooled HR = 1.10, 95% CI = 1.04-1.17) and PGDM (pooled HR = 1.39, 95% CI = 1.25-1.55). However, siblings with discordant exposure to GDM in pregnancy had similar risks of ADHD (pooled HR = 1.05, 95% CI = 0.94-1.17), suggesting potential confounding by unmeasured, shared familial factors. Our findings indicate that there is a small-to-moderate association between MDM and ADHD, whereas the association between GDM and ADHD is unlikely to be causal. This finding contrast with previous studies, which reported substantially higher risk estimates, and underscores the need to reevaluate the precise roles of hyperglycemia and genetic factors in the relationship between MDM and ADHD