Search

Abstract Background Air pollution poses a significant threat to global public health. While broad mitigation policies exist, an understanding of the economic consequences, both in terms of health benefits and mitigation costs, remains lacking. This study systematically reviewed the existing economic implications of air pollution control strategies worldwide. Methods A predefined search strategy, without limitations on region or study design, was employed to search the PubMed, Scopus, Cochrane Library, Embase, Web of Science, and CEA registry databases for studies from their inception to November 2023 using keywords such as “cost–benefit analyses”, “air pollution”, and “particulate matter”. Focus was placed on studies that specifically considered the health benefits of air pollution control strategies. The evidence was summarized by pollution control strategy and reported using principle economic evaluation measurements such as net benefits and benefit–cost ratios. Results The search yielded 104 studies that met the inclusion criteria. A total of 75, 21, and 8 studies assessed the costs and benefits of outdoor, indoor, and mixed control strategies, respectively, of which 54, 15, and 3 reported that the benefits of the control strategy exceeded the mitigation costs. Source reduction (n = 42) and end-of-pipe treatments (n = 15) were the most commonly employed pollution control methodologies. The association between particulate matter (PM) and mortality was the most widely assessed exposure-effect relationship and had the largest health gains (n = 42). A total of 32 studies employed a broader benefits framework, examining the impacts of air pollution control strategies on the environment, ecology, and society. Of these, 31 studies reported partially or entirely positive economic evidence. However, despite overwhelming evidence in support of these strategies, the studies also highlighted some policy flaws concerning equity, optimization, and uncertainty characterization. Conclusions Nearly 70% of the reviewed studies reported that the economic benefits of implementing air pollution control strategies outweighed the relative costs. This was primarily due to the improved mortality and morbidity rates associated with lowering PM levels. In addition to health benefits, air pollution control strategies were also associated with other environmental and social benefits, strengthening the economic case for implementation. However, future air pollution control strategy designs will need to address some of the existing policy limitations.

Background There is a lack of empirical data on design effects (DEFF) for mortality rate for highly clustered data such as with Ebola virus disease (EVD), along with a lack of documentation of methodological limitations and operational utility of mortality estimated from cluster-sampled studies when the DEFF is high. Objectives The objectives of this paper are to report EVD mortality rate and DEFF estimates, and discuss the methodological limitations of cluster surveys when data are highly clustered such as during an EVD outbreak. Methods We analysed the outputs of two independent population-based surveys conducted at the end of the 2014–2016 EVD outbreak in Bo District, Sierra Leone, in urban and rural areas. In each area, 35 clusters of 14 households were selected with probability proportional to population size. We collected information on morbidity, mortality and changes in household composition during the recall period (May 2014 to April 2015). Rates were calculated for all-cause, all-age, under-5 and EVD-specific mortality, respectively, by areas and overall. Crude and adjusted mortality rates were estimated using Poisson regression, accounting for the surveys sample weights and the clustered design. Results Overall 980 households and 6,522 individuals participated in both surveys. A total of 64 deaths were reported, of which 20 were attributed to EVD. The crude and EVD-specific mortality rates were 0.35/10,000 person-days (95%CI: 0.23–0.52) and 0.12/10,000 person-days (95%CI: 0.05–0.32), respectively. The DEFF for EVD mortality was 5.53, and for non-EVD mortality, it was 1.53. DEFF for EVD-specific mortality was 6.18 in the rural area and 0.58 in the urban area. DEFF for non-EVD-specific mortality was 1.87 in the rural area and 0.44 in the urban area. Conclusion Our findings demonstrate a high degree of clustering; this contributed to imprecise mortality estimates, which have limited utility when assessing the impact of disease. We provide DEFF estimates that can inform future cluster surveys and discuss design improvements to mitigate the limitations of surveys for highly clustered data.

Abstract Background While previously considered a transient condition, with no lasting adverse impact, gestational diabetes mellitus (GDM) is now a well‐established risk factor for developing type 2 diabetes mellitus (T2DM). The risk of developing T2DM appears to be particularly high in the first few years after childbirth, providing a compelling case for early intervention. This review provides an up‐to‐date systematic review and meta‐analysis to assess the effectiveness of interventions to reduce incidence of T2DM in women with a recent history of GDM. Methods The search was conducted on October 20, 2023 with an annual surveillance planned for the next 5 years to maintain a living systematic review. The inclusion criteria were randomized controlled trials of any type in women within 5 years of GDM‐complicated pregnancy that reported outcomes of T2DM diagnosis or measures of dysglycemia with a follow‐up of at least 12 months. Results Seventeen studies met our inclusion criteria and have been included in this review. There were 3 pharmacological and 14 lifestyle interventions. Intervention was not associated with significant reduction in the primary outcome of T2DM (risk ratio, 0.78; 95% confidence interval [CI]: 0.43–1.41; p = 0.41; I2 = 79%) compared with the control group (placebo or usual care). However, meta‐analysis of the four studies reporting hazard ratios suggested a reduction in diabetes incidence (hazard ratio, 0.68; 95% CI: 0.48–0.97; p = 0.03; I2 = 31%). Conclusion This review provides equivocal evidence about the efficacy of interventions to reduce the risk of T2DM in women within 5 years of GDM‐complicated pregnancy and highlights the need for further studies, including pharmacotherapy.

Abstract Background The Victorian Salt Reduction Partnership (VSRP) implemented a media advocacy strategy (intervention) to stimulate food manufacturers to reduce sodium levels across targeted Australian packaged foods between 2017 and 2019. This study assessed changes in sodium levels of targeted and non-targeted packaged foods during the intervention (2017 to 2019) compared to before the intervention (2014 to 2016) in Australia. Methods Annually collected branded-food composition data from 2014 to 2019 were used. Interrupted time series analyses was conducted to compare the trend in sodium levels in packaged foods during the intervention (2017–2019) to the trend in the pre-intervention period (2014–2016). The difference between these trends was derived to estimate the effect of the intervention. Results A total of 90,807 products were included in the analysis, of which 14,743 were targeted by the intervention. The difference in before and during intervention trends between targeted and non-targeted food categories was 2.59 mg/100 g (95% CI: -13.88 to 19.06). There was a difference in the pre-intervention slope (2014, 2015, 2016) and intervention slope (2017, 2018, 2019) for four of 17 targeted food categories. There was a decrease in sodium levels (mg/100 g) in one food category: frozen ready meals (-13.47; 95% CI: -25.40 to -1.53), and an increase in three categories: flat bread (20.46; 95% CI: 9.11 to 31.81), plain dry biscuits (24.53; 95% CI: 5.87 to 43.19), and bacon (44.54; 95% CI: 6.36 to 82.72). For the other 13 targeted categories, the difference in slopes crossed the line of null effect. Conclusions The VSRP’s media advocacy strategy did not result in a meaningful reduction in sodium levels of targeted packaged food products during the intervention years compared to trends in sodium levels before the intervention. Our study suggests media advocacy activities highlighting the differences in sodium levels in packaged food products and industry meetings alone are not sufficient to lower average sodium levels in packaged foods in the absence of government leadership and measurable sodium targets.

Abstract Background Consumption of ultra-processed foods is associated with increased risk of obesity and non-communicable diseases. Little is known about current patterns of ultra-processed foods intake in Australia. The aim of this study was to examine the amount and type of ultra-processed foods purchased by Australian households in 2019 and determine whether purchases differed by socio-economic status (SES). We also assessed whether purchases of ultra-processed foods changed between 2015 and 2019. Methods We used grocery purchase data from a nationally representative consumer panel in Australia to assess packaged and unpackaged grocery purchases that were brought home between 2015 to 2019. Ultra-processed foods were identified according to the NOVA system, which classifies foods according to the nature, extent and purpose of industrial food processing. Purchases of ultra-processed foods were calculated per capita, using two outcomes: grams/day and percent of total energy. The top food categories contributing to purchases of ultra-processed foods in 2019 were identified, and differences in ultra-processed food purchases by SES (Index of Relative Social Advantage and Disadvantage) were assessed using survey-weighted linear regression. Changes in purchases of ultra-processed foods between 2015 to 2019 were examined overall and by SES using mixed linear models. Results In 2019, the mean ± SD total grocery purchases made by Australian households was 881.1 ± 511.9 g/d per capita. Of this, 424.2 ± 319.0 g/d per capita was attributable to purchases of ultra-processed foods, which represented 56.4% of total energy purchased. The largest food categories contributing to total energy purchased included mass-produced, packaged breads (8.2% of total energy purchased), chocolate and sweets (5.7%), biscuits and crackers (5.7%) and ice-cream and edible ices (4.3%). In 2019, purchases of ultra-processed foods were significantly higher for the lowest SES households compared to all other SES quintiles (P

Abstract Background Monitoring salt consumption in children is essential for informing and implementing public health interventions to reduce children’s salt intake. However, collection of 24-hour urines, considered as the most reliable approach, can be especially challenging to school children. This study aimed to assess the agreement between 24-hour urine (24hrU) and 24-hour food recall (24hrFR) in: (1) estimating salt intake in children; (2) classifying salt intakes above the recommended upper level set for children, and; (3) estimating change in mean salt intake over time. Methods This study utilised data from two cross-sectional surveys of school children aged 8 to 12 years living in the state of Victoria, Australia. A single 24hrU and 24hrFR were collected from each participant. Suspected inaccurate urine collections and implausible energy intakes were excluded based on pre-defined criteria. The agreement between the two methods was assessed using Bland-Altman methodology, the intraclass correlation coefficient (ICC), and the kappa statistic. The difference between the measured change in salt intake over time using 24hrU and 24hrFR was derived using mixed effects linear regression analysis. Results A total of 588 participants provided a 24hrU and 24hrFR. Overall, there was no meaningful difference in mean estimated salt intake between the two methods (− 0.2 g/day, 95% CI − 0.5 to 0.1). The Bland-Altman plot showed wide 95% limits of agreement (− 7.2 to 6.8). The ICC between the two methods was 0.13 (95% CI 0.05 to 0.21). There was poor interrater reliability in terms of classifying salt intake above the recommended upper level for children, with an observed agreement of 63% and kappa statistic of 0.11. The change in mean salt intake over time was 0.2 g/day (− 0.4 to 0.7) based on 24hrU, and 0.5 g/day (− 0.0 to 1.1) based on 24hrFR, with a difference-in-differences of 0.4 g/day (− 0.3 to 1.1). Conclusions 24hrFR appears to provide a reasonable estimate of mean salt intake as measured by 24hrU in Australian school children. However, similar to previous observations in adults, and of studies exploring other alternative methods for estimating salt intake, 24hrFR is a poor predictor of individual-level salt intake in children.

Objectives To systematically investigate the associations between vision impairment and risk of motor vehicle crash (MVC) involvement, and evaluate vision-related interventions to reduce MVCs.Design Medline (Ovid), EMBASE and Global Health electronic databases were systematically searched from inception to March 2022 for observational and interventional English-language studies. Screening, data extraction and appraisals using the Joanna Briggs Institute appraisal tools were completed by two reviewers independently. Where appropriate, measures of association were converted into risk ratios (RRs) or ORs for meta-analysis.Participants Drivers of four-wheeled vehicles of all ages with no cognitive declines.Primary and secondary outcomes MVC involvement (primary) and driving cessation (secondary).Results 101 studies (n=778 052) were included after full-text review. 57 studies only involved older drivers (≥65 years) and 85 were in high-income settings. Heterogeneity in the data meant that most meta-analyses were underpowered as only 25 studies, further split into different groups of eye diseases and measures of vision, could be meta-analysed. The limited evidence from the meta-analyses suggests that visual field defects (four studies; RR 1.51 (95% CI 1.23, 1.85); p

Introduction: The extensive spread of COVID-19 meant action to address the pandemic took precedence over routine service delivery, thus impacting access to care for many health conditions, including the effects of snakebite.Method: We prospectively collected facility-level data from several health facilities in India, including number of snakebite admissions and snakebite envenoming admissions on modality of transport to reach the health facility. To analyse the effect of a health facility being in cluster-containment zone, we used negative binomial regression analysis.Results: Our findings suggest that that health facilities located within a COVID containment zone saw a significant decrease in total snakebite admissions (incidence rate ratio 0.64 (0.43-0.94), standard error 0.13, p≤0.02)) and envenoming snakebite admissions (incidence rate ratio 0.43 (0.23-0.81), standard error 0.14, p≤0.01) compared to when health facilities were not within a COVID containment zone. There was no statistically significant difference in non-envenoming admissions and modalities of transport used to reach health facilities.Conclusion: This article provides the first quantitative estimate of the impact of COVID-19 containment measures on access to snakebite care. More research is needed to understand how containment measures altered care-seeking pathways and the nature of snake-human-environment conflict. Primary healthcare systems need to be safeguarded for snakebite care to mitigate effects of cluster-containment measures. Keywords: COVID-19, health system, India, pandemic, snake-human conflict, snakebite.

Two recent large trials showed the potential of single pill combinations (SPCs) with ≥3 low-dose components among people with hypertension who were untreated or receiving monotherapy. In both trials, these ‘hypertension polypills’ were superior to usual care, achieving >80% BP control without increasing withdrawal due to side effects. However, there are no such products available for prescribers. To address this unmet need, George Medicines developed GMRx2 with telmisartan/amlodipine/indapamide in three strengths (mg): 10/1.25/0.625, 20/2.5/1.25; 40/5/2.5. Two pivotal trials are ongoing to support FDA submission for the treatment of hypertension, including initial treatment. These assess efficacy and safety of GMRx2 compared to: placebo, and each of the three possible dual combinations. Regulatory submissions are planned for 2024, with the aim of providing access to GMRx2 in developed and developing regions. Wider implementation of GMRx2-based treatment strategies will be guided by further research to inform access and appropriate scale up.

Introduction Relationships between glycemic-lowering effects of sodium glucose co-transporter 2 inhibitors and impact on kidney and cardiovascular outcomes are uncertain.Research design and methods We analyzed 4395 individuals with prebaseline and postbaseline hemoglobin A1c (HbA1c) randomized to canagliflozin (n=2193) or placebo (n=2202) in The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation trial. Effects on HbA1c were assessed using mixed models. Mediation of treatment effects by achieved glycemic control was analyzed using proportional hazards regression with and without adjustment for achieved HbA1c. End points included combined kidney or cardiovascular death, end-stage kidney disease or doubling of serum creatinine (primary trial outcome), and individual end point components.Results HbA1c lowering was modified by baseline estimated glomerular filtration rate (eGFR). For baseline eGFR 60–90, 45–59, and 30–44 mL/min/1.73 m2, overall HbA1c (canagliflozin vs placebo) decreased by −0.24%, −0.14%, and −0.08% respectively and likelihood of >0.5% decrease in HbA1c decreased with ORs of 1.47 (95% CI 1.27 to 1.67), 1.12 (0.94 to 1.33) and 0.99 (0.83 to 1.18), respectively. Adjustment for postbaseline HbA1c marginally attenuated canagliflozin effects on primary and kidney composite outcomes: unadjusted HR 0.67 (95% CI 0.57 to 0.80) and 0.66 (95% CI 0.53 to 0.81); adjusted for week 13 HbA1c, HR 0.71 (95% CI 0.060 to 0.84) and 0.68 (95% CI 0.55 to 0.83). Results adjusted for time-varying HbA1c or HbA1c as a cubic spline were similar and consistent with preserved clinical benefits across a range of excellent and poor glycemic control.Conclusions The glycemic effects of canagliflozin are attenuated at lower eGFR but effects on kidney and cardiac end points are preserved. Non-glycemic effects may be primarily responsible for the kidney and cardioprotective benefits of canagliflozin.22

Objective: To assess whether inter-professional, bidirectional collaboration between general practitioners (GPs) and pharmacists has an impact on improving cardiovascular risk outcomes among patients in the primary care setting. It also aimed to understand the different types of collaborative care models used. Study design: Systematic review and Hartung-Knapp-Sidik-Jonkman random effects meta-analyses of randomised control trials (RCTs) in inter-professional bidirectional collaboration between GP and pharmacists assessing a change of patient cardiovascular risk in the primary care setting. Data sources: MEDLINE, EMBASE, Cochrane, CINAHL and International Pharmaceutical Abstracts, scanned reference lists of relevant studies, hand searched key journals and key papers until August 2021. Data synthesis: Twenty-eight RCTs were identified. Collaboration was associated with significant reductions in systolic and diastolic blood pressure (23 studies, 5,620 participants) of –6.42 mmHg (95% confidence interval (95%CI) –7.99 to –4.84) and –2.33 mmHg (95%CI –3.76 to –0.91), respectively. Changes in other cardiovascular risk factors included total cholesterol (6 studies, 1,917 participants) –0.26 mmol/L (95%CI –0.49 to –0.03); low-density lipoprotein (8 studies, 1,817 participants) –0.16 mmol/L (95%CI –0.63 to 0.32); high-density lipoprotein (7 studies, 1,525 participants) 0.02 mmol/L (95%CI –0.02 to 0.07). Reduction in haemoglobin A1c (HbA1C) (10 studies, 2,025 participants), body mass index (8 studies, 1,708 participants) and smoking cessation (1 study, 132 participants) was observed with GP-pharmacist collaboration. Meta-analysis was not conducted for these changes. Various models of collaborative care included verbal communication (via phone calls or face to face), and written communication (emails, letters). We found that co-location was associated with positive changes in cardiovascular risk factors. Conclusion: Although it is clear that collaborative care is ideal compared to usual care, greater details in the description of the collaborative model of care in studies is required for a core comprehensive evaluation of the different models of collaboration.

Uncertainties about the efficacy of influenza vaccination for populations with heart failure (HF) in preventing cardiovascular outcomes, as well as lack of effective vaccination strategies, may contribute to low vaccine coverage rate (VCR) in China and globally. We assessed the feasibility of a strategy to promote influenza vaccines in patients hospitalized with acute HF in China and to inform the design of a hybrid effectiveness-implementation cluster randomized trial to evaluate this strategy on mortality and hospital re-admission. We conducted a cluster randomized pilot trial involving 11 hospitals in Henan Province in China, with mixed-methods evaluation between December 2020 and April 2021. A process evaluation involved interviews with 51 key informants (patients, health professionals, policy makers). The intervention included education about influenza vaccination and availability of free vaccines administered prior to hospital discharge for HF patients, while usual care included attending community-based points of vaccination (PoV) for screening and vaccination. Implementation outcomes focused on reach, fidelity, adoption, and acceptability. Recruitment rates were assessed for trial feasibility. Effectiveness outcomes were influenza VCR, HF-specific rehospitalizations and mortality at 90 days. A total of 518 HF patients were recruited from 7 intervention and 4 usual care hospitals (mean of 45 participants per hospital per month). VCR was 89.9% (311/346, 86.1-92.8%) in the intervention group and 0.6% (1/172, 0.0-3.7%) in the control group. The process evaluation demonstrated reach to patients with lower socioeconomic and education status. There was good fidelity of the intervention components, with education and PoV set up processes being adapted to local hospital workflow and workforce capacity. Intervention was acceptable and adopted by patients and health professionals. However, outside of a trial setting, concerns were raised around vaccination reimbursement costs, workforce accountability and capacity. The intervention strategy appears feasible and acceptable for improving VCR in HF patients at county-level hospitals in China. Trial registration: This pilot trial is registered with the acronym PANDA II Pilot (Population Assessment of Influenza and Disease Activity) at ChiCTR.org.cn (ChiCTR2000039081).

Introduction: This systematic review aims to (1) investigate the associations between vision impairment and driving performance, and (2) evaluate the effectiveness of vision-related interventions to improve driving performance. Method: Medline (Ovid), EMBASE and Global Health electronic databases were searched from their inception to March 2022 for observational and interventional English-language studies. The population of focus were licensed drivers of all ages of four-wheeled motorised vehicles. The primary outcome was measures of driving performance from naturalistic driving and/or on-road closed circuits. All screening, data extraction and critical appraisals were completed independently by two authors. Results: 27 studies (n = 6358 participants) from the 4281 identified in the search were included in this review. All but one study, an RCT, were observational. Only 2 cross-sectional studies were rated as high risk of bias. The majority of papers (80 %) were limited to older drivers. There were 33 different performance measures reported. Poor driving performance was associated with glaucoma, AMD and monocularity, and measures of vision function including contrast sensitivity, visual acuity and visual fields. From the vision-related interventions identified only cataract surgery and toric refractive correction for astigmatism were shown to improve driving performance on selected measures. Conclusion: Despite differences in outcome measures, there is consistent evidence for associations between vision impairments and poor driving performance. This review highlights the importance vision has on an individual’s ability to safely drive and complete common manoeuvres. Early detection and management of eye conditions may help decrease the likelihood of crashing and road traffic injuries.

Introduction Shared treatment decision-making and planning of care are fundamental in advanced chronic kidney disease (CKD) management. There are limited data on several key outcomes for the elderly population including survival, quality of life, symptom burden, changes in physical functioning and experienced burden of healthcare. Patients, caregivers and clinicians consequently face significant uncertainty when making life-impacting treatment decisions. The Elderly Advanced CKD Programme includes quantitative and qualitative studies to better address challenges in treatment decision-making and planning of care among this increasingly prevalent elderly cohort.Methods and analysis The primary component is OUTcomes of Older patients with Kidney failure (OUTLOOK), a multicentre prospective observational cohort study that will enrol 800 patients ≥75 years with kidney failure (estimated glomerular filtration rate ≤15 mL/min/1.73 m2) across a minimum of six sites in Australia. Patients entered are in the decision-making phase or have recently made a decision on preferred treatment (dialysis, conservative kidney management or undecided). Patients will be prospectively followed until death or a maximum of 4 years, with the primary outcome being survival. Secondary outcomes are receipt of short-term acute dialysis, receipt of long-term maintenance dialysis, changes in biochemistry and end-of-life care characteristics. Data will be used to formulate a risk prediction tool applicable for use in the decision-making phase. The nested substudies Treatment modalities for the InfirM ElderLY with end stage kidney disease (TIMELY) and Caregivers of The InfirM ElderLY with end stage kidney disease (Co-TIMELY) will longitudinally assess quality of life, symptom burden and caregiver burden among 150 patients and 100 caregivers, respectively. CONsumer views of Treatment options for Elderly patieNts with kiDney failure (CONTEND) is an additional qualitative study that will enrol a minimum of 20 patients and 20 caregivers to explore experiences of treatment decision-making and care.Ethics and dissemination Ethics approval was obtained through Sydney Local Health District Human Research Ethics Committee (2019/ETH07718, 2020/ETH02226, 2021/ETH01020, 2019/ETH07783). OUTLOOK is approved to have waiver of individual patient consent. TIMELY, Co-TIMELY and CONTEND participants will provide written informed consent. Final results will be disseminated through peer-reviewed journals and presented at scientific meetings.

This article details a correction to: Li J-W, Guo Y-T, Di Tanna GL, Neal B, Chen Y-D, Schutte AE. Vital Signs During the COVID-19 Outbreak: A Retrospective Analysis of 19,960 Participants in Wuhan and Four Nearby Capital Cities in China. Global Heart. 2021;16(1):47. DOI: http://doi.org/10.5334/gh.913.

Background Published randomized controlled trials are underpowered for binary clinical end points to assess the safety and efficacy of renin‐angiotensin system inhibitors (RASi) in adults with COVID‐19. We therefore performed a meta‐analysis to assess the safety and efficacy of RASi in adults with COVID‐19. Methods and Results MEDLINE, EMBASE, ClinicalTrials.gov, and the Cochrane Controlled Trial Register were searched for randomized controlled trials that randomly assigned patients with COVID‐19 to RASi continuation/commencement versus no RASi therapy. The primary outcome was all‐cause mortality at ≤30 days. A total of 14 randomized controlled trials met the inclusion criteria and enrolled 1838 participants (aged 59 years, 58% men, mean follow‐up 26 days). Of the trials, 11 contributed data. We found no effect of RASi versus control on all‐cause mortality (7.2% versus 7.5%; relative risk [RR], 0.95; [95% CI, 0.69–1.30]) either overall or in subgroups defined by COVID‐19 severity or trial type. Network meta‐analysis identified no difference between angiotensin‐converting enzyme inhibitors versus angiotensin II receptor blockers. RASi users had a nonsignificant reduction in acute myocardial infarction (2.1% versus 3.6%; RR, 0.59; [95% CI, 0.33–1.06]), but increased risk of acute kidney injury (7.0% versus 3.6%; RR, 1.82; [95% CI, 1.05–3.16]), in trials that initiated and continued RASi. There was no increase in need for dialysis or differences in congestive cardiac failure, cerebrovascular events, venous thromboembolism, hospitalization, intensive care admission, inotropes, or mechanical ventilation. Conclusions This meta‐analysis of randomized controlled trials evaluating angiotensin‐converting enzyme inhibitors/angiotensin II receptor blockers versus control in patients with COVID‐19 found no difference in all‐cause mortality, a borderline decrease in myocardial infarction, and an increased risk of acute kidney injury with RASi. Our findings provide strong evidence that RASi can be used safely in patients with COVID‐19.

BackgroundDigital health interventions have significant potential to improve safety, efficacy, and quality of care, reducing waste in healthcare costs. Despite these premises, the evidence regarding cost and effectiveness of digital tools in health is scarce and limited.ObjectivesThe aim of this systematic review is to summarize the evidence on the cost-effectiveness of digital health interventions and to assess whether the studies meet the established quality criteria.MethodsWe queried PubMed, Scopus and Web of Science databases for articles in English published from January 1, 2016 to December 31, 2020 that performed economic evaluations of digital health technologies. The methodological rigorousness of studies was assessed with the Consolidated Health Economic Evaluation Reporting Standards (CHEERS). The review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) 2009 checklist.ResultsSearch identified 1,476 results, 552 of which were selected for abstract and 35 were included in this review. The studies were heterogeneous by country (mostly conducted in upper and upper-middle income countries), type of eHealth intervention, method of implementation, and reporting perspectives. The qualitative analysis identified the economic and effectiveness evaluation of six different types of interventions: (1) seventeen studies on new video-monitoring service systems; (2) five studies on text messaging interventions; (3) five studies on web platforms and digital health portals; (4) two studies on telephone support; (5) three studies on new mobile phone-based systems and applications; and (6) three studies on digital technologies and innovations.ConclusionFindings on cost-effectiveness of digital interventions showed a growing body of evidence and suggested a generally favorable effect in terms of costs and health outcomes. However, due to the heterogeneity across study methods, the comparison between interventions still remains difficult. Further research based on a standardized approach is needed in order to methodically analyze incremental cost-effectiveness ratios, costs, and health benefits.

Background: Acute appendicitis (AA) is one of the most common emergencies in general surgery worldwide. During the pandemic, a significant decrease in the number of accesses to the emergency department for AA has been recorded in different countries. A systematic review of the current literature sought to determine the impact of Coronavirus Disease 2019 (COVID-19) on hospital admissions and complications of AA. Method: A systematic search was undertaken to identify repeated cross-sectional studies reporting the management of AA during the COVID-19 pandemic (index period) as compared to the previous year, or at the turn of lockdown (reference period). Data were abstracted on article (country of origin) and patients characteristics (adults, children [i.e. non adults,

Abstract Background Little is known about the capacity of overnight and spot urine samples to estimate changes in mean salt intake over time. The objective of this review was to compare the estimates of change in mean population salt intake based on 24-h urine and overnight/spot urine samples. Methods Studies were systematically identified through searches of peer-reviewed databases (Medline, Embase, Global Health, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews) and grey literature. Studies that reported estimates of mean salt intake for at least two time points based on both 24-h and overnight/spot urines were deemed eligible. The capacity of overnight/spot urine samples to estimate the change in mean salt intake was assessed both at the individual-study level and overall through random-effects meta-analyses. The level of heterogeneity was assessed through the I2 statistic. Subgroup and sensitivity analyses were conducted to explore possible sources of heterogeneity, and check the robustness of the findings from the primary analysis. Results A total of 1244 records were identified, 50 were assessed as full text, and 14 studies met the criteria, capturing data on 7291 participants from seven countries. Nine and five studies collected overnight and spot urines, respectively. The comparison of the change in mean salt intake between 24-h and overnight/spot urines showed some inconsistencies at the individual study-level. The pooled mean change in salt intake was − 0.43 g/day (95% CI − 1.16 to 0.30; I2 = 95%) using 24-h urines, and − 0.22 g/day (− 0.65 to 0.20; I2 = 87%) using overnight/spot urines, with a pooled difference-in-differences between the two methods of 0.27 g/day (− 0.23 to 0.77; I2 = 89%). Subgroup analyses showed substantial heterogeneity for most subgroups. Sensitivity analyses did not change the effect observed in the primary analysis. Conclusion The evidence for the capacity of overnight/spot urines to estimate changes in mean salt intake over time is uncertain. More research where overnight/spot urines are collected in parallel with 24-h urines is needed to enable a more in-depth evaluation of these alternative approaches to estimating change in mean salt intake.

IntroductionThe World Health Organization and International Union against Tuberculosis (TB) recommends screening patients with TB for Diabetes Mellitus (DM) at the initiation of treatment. There are few pilot studies which screen TB patients for DM, but none of them have documented the feasibility of managing TB patients with DM in the Indian healthcare setting. Operational research is needed to determine the best way to manage individuals with both conditions. This pilot study aimed to develop, and field test an integrated, multidisciplinary program addressing the management of individuals with TB and DM and other associated chronic conditions in the Indian primary healthcare setting.MethodsThis pilot study used a randomized controlled trial design with mixed-methods evaluation and was conducted in Guntur district of Andhra Pradesh, a southern state of India. All the 120 patients newly diagnosed with TB from 10 participating villages were screened for DM and associated cardiovascular risk factors. Non-physician health workers were trained to follow-up patients for a period of 8 months to encourage treatment adherence, monitor treatment response including blood glucose levels and provide lifestyle advice.ResultsThe intervention was well-accepted by the providers and patients. However, there were no statistically significant variations observed for mean blood glucose levels (mean [SD]: 5.3 [−23.3 to 33.8]) of patients for both intervention and control group participants in this feasibility study. Awareness about diabetes and tuberculosis comorbidity and cardiovascular risk increased among the non-physician health workers in the intervention arm of the study.DiscussionThe co-management of TB-DM is acceptable to both the health providers and patients. With appropriate training, availability of infrastructure and planned intervention implementation, it is feasible to co-manage TB-DM within the existing primary health care system in India.

Introduction Influenza virus infection is known to increase the risk of cardiovascular events, especially in populations with pre-existing cardiovascular disease (CVD). Considering that influenza is vaccine preventable, international guidelines recommend high-risk populations with CVD receive an influenza vaccine every year. However, there are various classifications of recommendations and levels of evidence. Previous systematic reviews concluded uncertain evidence on influenza vaccine efficacy for preventing cardiovascular events in the general population or in populations with pre-existing CVD. Limited safety data of influenza vaccines were reported for populations with pre-existing CVD. Randomised controlled trials with larger sample sizes relative to previous studies are emerging, the findings of these trials are likely to be highly influential on summary efficacy estimates.Methods and analysis We aim to perform a living systematic review and a prospective meta-analysis to evaluate the efficacy and safety of influenza vaccines compared with no vaccines or placebo for preventing mortality or CVD events in the general population and in populations with pre-existing CVD. Any types of randomised controlled trial and observational study meeting the Population, Intervention, Comparator, Outcome and Study design criteria for the research question will be selected for inclusion. The living systematic review status will be maintained for 3 years with an update for every 6 months. Mainstream medical literature databases will be independently searched by two authors with predefined strategies. Two authors will perform the risk of bias assessment with consensus. Narrative synthesis and meta-analyses will be performed to summarise the results.Ethics and dissemination Formal ethical review is not required as this study does not involve primary data collection. We will publish results of the living systematic review and prospective meta-analysis in a peer-reviewed journal. Findings will also be presented at relevant meetings.PROSPERO registration number CRD42021222519.

Background. The fracture pathophysiology associated with type 2 diabetes and chronic kidney disease (CKD) is incompletely understood. We examined individual fracture predictors and prediction sets based on different pathophysiological hypotheses, testing whether any of the sets improved prediction beyond that based on traditional osteoporotic risk factors. Methods. Within the CREDENCE cohort with adjudicated fracture outcomes, we assessed the association of individual factors with fracture using Cox regression models. We used the Akaike information criteria (AIC) and Schwartz Bayes Criterion (SBC) to assess six separate variable sets based on hypothesized associations with fracture, namely, traditional osteoporosis, exploratory general population findings, cardiovascular risk, CKD-mineral and bone disorder, diabetic osteodystrophy, and an all-inclusive set containing all variables. Results. Fracture occurred in 135 (3.1%) participants over a median 2.35 [1.88–2.93] years. Independent fracture predictors were older age (hazard ratio [HR] 1.04, confidence interval [CI] 1.01–1.06), female sex (HR 2.49, CI 1.70–3.65), previous fracture (HR 2.30, CI 1.58–3.34), Asian race (HR 1.74, CI 1.09–2.78), vitamin D therapy requirement (HR 2.05, CI 1.31–3.21), HbA1c (HR 1.14, CI 1.00–1.32), prior cardiovascular event (HR 1.60, CI 1.10–2.33), and serum albumin (HR 0.41, CI 0.23–0.74) (lower albumin associated with greater risk). The goodness of fit of the various hypothesis sets was similar (AIC range 1870.92–1849.51, SBC range 1875.60–1948.04). Conclusion. Independent predictors of fracture were identified in the CREDENCE participants with type 2 diabetes and CKD. Fracture prediction was not improved by models built on alternative pathophysiology hypotheses compared with traditional osteoporosis predictors.

Background: The implications of city lockdown on vital signs during the COVID-19 outbreak are unknown. Objective: We longitudinally tracked vital signs using data from wearable sensors and determined associations with anxiety and depression. Methods: We selected all participants in the HUAWEI Heart Study from Wuhan and four nearby large provincial capital cities (Guangzhou, Chongqing, Hangzhou, Zhengzhou) and extracted all data from 26 December 2019 (one month before city lockdown) to 21 February 2020. Sleep duration and quality, daily steps, oxygen saturation and heart rate were collected on a daily basis. We compared the vital signs before and after the lockdown using segmented regression analysis of the interrupted time series. The depression and anxiety cases were defined as scores ≥8 on the Hospital Anxiety and Depression Scale depression and anxiety subscales [HADS-D and HADS-A] in 727 participants who finished the survey. Results: We included 19,960 participants (mean age 36 yrs, 90% men). Compared with pre-lockdown, resting heart rate dropped immediately by 1.1 bpm after city lockdown (95% confidence interval [CI]: –1.8, –0.4). Sleep duration increased by 0.5 hour (95% CI: 0.3, 0.8) but deep sleep ratio decreased by 0.9% (95% CI: –1.2, –0.6). Daily steps decreased by 3352 steps (95% CI: –4333, –2370). Anxiety and depression existed in 26% and 17% among 727 available participants, respectively, and associated with longer sleep duration (0.2 and 0.1 hour, both p < 0.001). Conclusions: Lockdown of Wuhan in China was associated with an adverse vital signs profile (reduced physical activity, heart rate, and sleep quality, but increased sleep duration). Wearable devices in combination with mobile-based apps may be useful to monitor both physical and mental health. Clinical trial registration: The trial is registered at Chinese Clinical Trial Registry (ChiCTR) website (ChiCTR-OOC-17014138).

OBJECTIVES:. To investigate the association between plasma sodium concentrations and 6-month neurologic outcome in critically ill patients with aneurysmal subarachnoid hemorrhage. DESIGN:. Prospective cohort study. SETTING:. Eleven ICUs in Australia and New Zealand. PARTICIPANTS:. Three-hundred fifty-six aneurysmal subarachnoid hemorrhage patients admitted to ICU between March 2016 and June 2018. The exposure variable was daily measured plasma sodium. INTERVENTIONS:. None. MEASUREMENTS AND MAIN RESULTS:. Six-month neurologic outcome as measured by the modified Rankin Scale. A poor outcome was defined as a modified Rankin Scale greater than or equal to 4. The mean age was 57 years (± 12.6 yr), 68% were female, and 32% (n = 113) had a poor outcome. In multivariable analysis, including age, illness severity, and process of care measures as covariates, higher mean sodium concentrations (odds ratio, 1.17; 95% CI, 1.05–1.29), and greater overall variability—as measured by the sd (odds ratio, 1.53; 95% CI, 1.17–1.99)—were associated with a greater likelihood of a poor outcome. Multivariable generalized additive modeling demonstrated, specifically, that a high initial sodium concentration, followed by a gradual decline from day 3 onwards, was also associated with a poor outcome. Finally, greater variability in sodium concentrations was associated with a longer ICU and hospital length of stay: mean ICU length of stay ratio (1.13; 95% CI, 1.07–1.20) and mean hospital length of stay ratio (1.08; 95% CI, 1.01–1.15). CONCLUSIONS:. In critically ill aneurysmal subarachnoid hemorrhage patients, higher mean sodium concentrations and greater variability were associated with worse neurologic outcomes at 6 months, despite adjustment for known confounders. Interventional studies would be required to demonstrate a causal relationship.

Abstract Background Cost-effectiveness analyses in patients with migraine require estimates of patients’ utility values and how these relate to monthly migraine days (MMDs). This analysis examined four different modelling approaches to assess utility values as a function of MMDs. Methods Disease-specific patient-reported outcomes from three erenumab clinical studies (two in episodic migraine [NCT02456740 and NCT02483585] and one in chronic migraine [NCT02066415]) were mapped to the 5-dimension EuroQol questionnaire (EQ-5D) as a function of the Migraine-Specific Quality of Life Questionnaire (MSQ) and the Headache Impact Test (HIT-6™) using published algorithms. The mapped utility values were used to estimate generic, preference-based utility values suitable for use in economic models. Four models were assessed to explain utility values as a function of MMDs: a linear mixed effects model with restricted maximum likelihood (REML), a fractional response model with logit link, a fractional response model with probit link and a beta regression model. Results All models tested showed very similar fittings. Root mean squared errors were similar in the four models assessed (0.115, 0.114, 0.114 and 0.114, for the linear mixed effect model with REML, fractional response model with logit link, fractional response model with probit link and beta regression model respectively), when mapped from MSQ. Mean absolute errors for the four models tested were also similar when mapped from MSQ (0.085, 0.086, 0.085 and 0.085) and HIT-6 and (0.087, 0.088, 0.088 and 0.089) for the linear mixed effect model with REML, fractional response model with logit link, fractional response model with probit link and beta regression model, respectively. Conclusions This analysis describes the assessment of longitudinal approaches in modelling utility values and the four models proposed fitted the observed data well. Mapped utility values for patients treated with erenumab were generally higher than those for individuals treated with placebo with equivalent number of MMDs. Linking patient utility values to MMDs allows utility estimates for different levels of MMD to be predicted, for use in economic evaluations of preventive therapies. Trial registration ClinicalTrials.gov numbers of the trials used in this study: STRIVE, NCT02456740 (registered May 14, 2015), ARISE, NCT02483585 (registered June 12, 2015) and NCT02066415 (registered Feb 17, 2014).

Abstract Background Health economic models are critical tools to inform reimbursement agencies on health care interventions. Many clinical trials report outcomes using the frequency of an event over a set period of time, for example, the primary efficacy outcome in most clinical trials of migraine prevention is mean change in the frequency of migraine days (MDs) per 28 days (monthly MDs [MMD]) relative to baseline for active treatment versus placebo. Using these cohort-level endpoints in economic models, accounting for variation among patients is challenging. In this analysis, parametric models of change in MMD for migraine preventives were assessed using data from erenumab clinical studies. Methods MMD observations from the double-blind phases of two studies of erenumab were used: one in episodic migraine (EM) (NCT02456740) and one in chronic migraine (CM) (NCT02066415). For each trial, two longitudinal regression models were fitted: negative binomial and beta binomial. For a thorough comparison we also present the fitting from the standard multilevel Poisson and the zero inflated negative binomial. Results Using the erenumab study data, both the negative binomial and beta-binomial models provided unbiased estimates relative to observed trial data with well-fitting distribution at various time points. Conclusions This proposed methodology, which has not been previously applied in migraine, has shown that these models may be suitable for estimating MMD frequency. Modelling MMD using negative binomial and beta-binomial distributions can be advantageous because these models can capture intra- and inter-patient variability so that trial observations can be modelled parametrically for the purposes of economic evaluation of migraine prevention. Such models have implications for use in a wide range of disease areas when assessing repeated measured utility values.

BACKGROUND:The ability to predict risk allows healthcare providers to propose which patients might benefit most from certain therapies, and is relevant to payers' demands to justify clinical and economic value. To understand the robustness of risk prediction models for heart failure (HF), we conducted a systematic literature review to (1) identify HF risk-prediction models, (2) assess statistical approach and extent of validation, (3) identify common variables, and (4) assess risk of bias (ROB). METHODS:Literature databases were searched from March 2013 to May 2018 to identify risk prediction models conducted in an out-of-hospital setting in adults with HF. Distinct risk prediction variables were ranked according to outcomes assessed and incorporation into the studies. ROB was assessed using Prediction model Risk Of Bias ASsessment Tool (PROBAST). RESULTS:Of 4720 non-duplicated citations, 40 risk-prediction publications were deemed relevant. Within the 40 publications, 58 models assessed 55 (co)primary outcomes, including all-cause mortality (n = 17), cardiovascular death (n = 9), HF hospitalizations (n = 15), and composite endpoints (n = 14). Few publications reported detail on handling missing data (n = 11; 28%). The discriminatory ability for predicting all-cause mortality, cardiovascular death, and composite endpoints was generally better than for HF hospitalization. 105 distinct predictor variables were identified. Predictors included in >5 publications were: N-terminal prohormone brain-natriuretic peptide, creatinine, blood urea nitrogen, systolic blood pressure, sodium, NYHA class, left ventricular ejection fraction, heart rate, and characteristics including male sex, diabetes, age, and BMI. Only 11/58 (19%) models had overall low ROB, based on our application of PROBAST. In total, 26/58 (45%) models discussed internal validation, and 14/58 (24%) external validation. CONCLUSIONS:The majority of the 58 identified risk-prediction models for HF present particular concerns according to ROB assessment, mainly due to lack of validation and calibration. The potential utility of novel approaches such as machine learning tools is yet to be determined. REGISTRATION NUMBER:The SLR was registered in Prospero (ID: CRD42018100709).

[This corrects the article DOI: 10.1371/journal.pone.0224135.].

Abstract Background Despite the biological plausibility of hotspots fueling malaria transmission, the evidence to support this concept has been mixed. If transmission spreads from high burden to low burden households in a consistent manner, then this could have important implications for control and elimination program development. Methods Data from a longitudinal cohort in The Gambia was analyzed. All consenting individuals residing in 12 villages across the country were sampled monthly from June (dry season) to December 2013 (wet season), in April 2014 (mid dry season), and monthly from June to December 2014. A study nurse stationed within each village recorded passively detected malaria episodes between visits. Plasmodium falciparum infections were determined by polymerase chain reaction and analyzed using a geostatistical model. Results Household-level observed monthly incidence ranged from 0 to 0.50 infection per person (interquartile range = 0.02–0.10) across the sampling months, and high burden households exist across all study villages. There was limited evidence of a spatio-temporal pattern at the monthly timescale irrespective of transmission intensity. Within-household transmission was the most plausible hypothesis examined to explain the observed heterogeneity in infections. Conclusions Within-village malaria transmission patterns are concentrated in a small proportion of high burden households, but patterns are stochastic regardless of endemicity. Our findings support the notion of transmission occurring at the household and village scales but not the use of a targeted approach to interrupt spreading of infections from high to low burden areas within villages in this setting.

Abstract Background Little is understood of Ebola virus disease (EVD) transmission dynamics and community compliance with control measures over time. Understanding these interactions is essential if interventions are to be effective in future outbreaks. We conducted a mixed-methods study to explore these factors in a rural village that experienced sustained EVD transmission in Kailahun District, Sierra Leone. Methods We reconstructed transmission dynamics using a cross-sectional survey conducted in April 2015, and cross-referenced our results with surveillance, burial, and Ebola Management Centre (EMC) data. Factors associated with EVD transmission were assessed with Cox proportional hazards regression. Following the survey, qualitative semi-structured interviews explored views of community informants and households. Results All households (n = 240; 1161 individuals) participated in the survey. 29 of 31 EVD probable/confirmed cases died (93·5% case fatality rate); six deaths (20·6%) had been missed by other surveillance systems. Transmission over five generations lasted 16 weeks. Although most households had ≤5 members there was a significant increase in risk of Ebola in households with > 5 members. Risk of EVD was also associated with older age. Cases were spatially clustered; all occurred in 15 households. EVD transmission was better understood when the community experience started to concord with public health messages being given. Perceptions of contact tracing changed from invading privacy and selling people to ensuring community safety. Burials in plastic bags, without female attendants or prayer, were perceived as dishonourable. Further reasons for low compliance were low EMC survival rates, family perceptions of a moral duty to provide care to relatives, poor communication with the EMC, and loss of livelihoods due to quarantine. Compliance with response measures increased only after the second generation, coinciding with the implementation of restrictive by-laws, return of the first survivor, reduced contact with dead bodies, and admission of patients to the EMC. Conclusions Transmission occurred primarily in a few large households, with prolonged transmission and a high death toll. Return of a survivor to the village and more effective implementation of control strategies coincided with increased compliance to control measures, with few subsequent cases. We propose key recommendations for management of EVD outbreaks based on this experience.

Abstract Background Laparoscopic ventral mesh rectopexy (LVMR) is an established treatment for external full-thickness rectal prolapse. However, its clinical efficacy in patients with internal prolapse is uncertain due to the lack of high-quality evidence. Methods An individual level, stepped-wedge randomised trial has been designed to allow observer-blinded data comparisons between patients awaiting LVMR with those who have undergone surgery. Adults with symptomatic internal rectal prolapse, unresponsive to prior conservative management, will be eligible to participate. They will be randomised to three arms with different delays before surgery (0, 12 and 24 weeks). Efficacy outcome data will be collected at equally stepped time points (12, 24, 36 and 48 weeks). The primary objective is to determine clinical efficacy of LVMR compared to controls with reduction in the Patient Assessment of Constipation Quality of Life (PAC-QOL) at 24 weeks serving as the primary outcome. Secondary objectives are to determine: (1) the clinical effectiveness of LVMR to 48 weeks to a maximum of 72 weeks; (2) pre-operative determinants of outcome; (3) relevant health economics for LVMR; (4) qualitative evaluation of patient and health professional experience of LVMR and (5) 30-day morbidity and mortality rates. Discussion An individual-level, stepped-wedge, randomised trial serves the purpose of providing an untreated comparison for the active treatment group, while at the same time allowing the waiting-listed participants an opportunity to obtain the intervention at a later date. In keeping with the basic ethical tenets of this design, the average waiting time for LVMR (12 weeks) will be shorter than that for routine services (24 weeks). Trial registration ISRCTN registry, ISRCTN11747152. Registered on 30 September 2015. The trial was prospectively registered (first patient enrolled on 21 March 2016).

Abstract Background Dengue fever is rapidly expanding geographically, with about half of the world’s population now at risk. Among the various diagnostic options, rapid diagnostic tests (RDTs) are convenient and prompt, but limited in terms of accuracy and availability. Methods A systematic review was conducted of published data on the use of RDTs for dengue with respect to their economic impact. The search was conducted with combinations of key search terms, including “((Dengue[Title]) AND cost/economic)” and “rapid diagnostic test/assay (or point-of-care)”. Articles with insufficient report on cost/economic aspect of dengue RDTs, usually on comparison of different RDTs or assessment of novel rapid diagnostic tools, were excluded. This review has been registered in the PROSPERO International prospective register of systematic reviews (registry #: CRD42015017775). Results Eleven articles were found through advanced search on Pubmed. From Embase and Web of Science, two and 14 articles were obtained, respectively. After removal of duplicate items, title screening was done on 21 published works and 12 titles, including 2 meeting abstracts, were selected for abstract review. For full-text review, by two independent reviewers, 5 articles and 1 meeting abstract were selected. Among these, the abstract was referring to the same study results as one of the articles. After full text review, two studies (two articles and one abstract) were found to report on cost-wise or economic benefits of dengue RDTs and were selected for data extraction. One study found satisfactory performance of IgM-based Panbio RDT, concluding that it would be cost-effective in endemic settings. The second study was a modeling analysis and showed that a dengue RDT would not be advantageous in terms of cost and effectiveness compared to current practice of antibiotics prescription for acute febrile illness. Conclusions Despite growing use of RDTs in research and clinical settings, there were limited data to demonstrate an economic impact. The available two studies reached different conclusions on the cost-effectiveness of dengue RDTs, although only one of the two studies reported outcomes from cost-effectiveness analysis of dengue and the other was considering febrile illness more generally. Evidence of such an impact would require further quantitative economic studies.

Abstract Background Cluster randomised trials (CRTs) often use geographical areas as the unit of randomisation, however explicit consideration of the location and spatial distribution of observations is rare. In many trials, the location of participants will have little importance, however in some, especially against infectious diseases, spillover effects due to participants being located close together may affect trial results. This review aims to identify spatial analysis methods used in CRTs and improve understanding of the impact of spatial effects on trial results. Methods A systematic review of CRTs containing spatial methods, defined as a method that accounts for the structure, location, or relative distances between observations. We searched three sources: Ovid/Medline, Pubmed, and Web of Science databases. Spatial methods were categorised and details of the impact of spatial effects on trial results recorded. Results We identified ten papers which met the inclusion criteria, comprising thirteen trials. We found that existing approaches fell into two categories; spatial variables and spatial modelling. The spatial variable approach was most common and involved standard statistical analysis of distance measurements. Spatial modelling is a more sophisticated approach which incorporates the spatial structure of the data within a random effects model. Studies tended to demonstrate the importance of accounting for location and distribution of observations in estimating unbiased effects. Conclusions There have been a few attempts to control and estimate spatial effects within the context of human CRTs, but our overall understanding is limited. Although spatial effects may bias trial results, their consideration was usually a supplementary, rather than primary analysis. Further work is required to evaluate and develop the spatial methodologies relevant to a range of CRTs.

Background: Asymptomatic low-density gametocyte carriers represent the majority of malaria-infected individuals. However, the impact of recommended treatment with single low dose of primaquine and an artemisinin-based combination therapy to reduce transmission in this group is unknown. Methods: This was a four-arm, open label, randomized controlled trial comparing the effect of dihydroartemisinin-piperaquine (DHAP) alone or combined with single dose of primaquine (PQ) at 0.20 mg/kg, 0.40 mg/kg, or 0.75 mg/kg on Plasmodium falciparum gametocytaemia, infectiousness to mosquitoes and hemoglobin change in asymptomatic, malaria-infected, glucose-6-phosphate dehydrogenase (G6PD) normal individuals. Randomization was done using a computer-generated sequence of uneven block sizes with codes concealed in sequentially numbered opaque envelopes. The primary endpoint was the prevalence of P. falciparum gametocytemia at day 7 of follow-up determined by quantitative nucleic acid sequence based assay and analysis was by intention to treat. The trial has been concluded (registration number: NCT01838902; https://clinicaltrials.gov/ct2/show/NCT01838902). Results: A total of 694 asymptomatic, malaria-infected individuals were enrolled. Gametocyte prevalence at day 7 was 37.0% (54/146; 95% CI 29.2–45.4), 19.0% (27/142; 95% CI 12.9–26.4), 17.2% (25/145; 95% CI 11.0–23.5) and 10.6% (15/141; 95% CI 6.1–16.9) in the DHAP alone, 0.20 mg/kg, 0.40 mg/kg, and 0.75 mg/kg PQ arms, respectively. The main adverse events reported include headache (130/471, 27.6%), cough (73/471, 15.5%), history of fever (61/471, 13.0%) and abdominal pain (57/471, 12.1%). There were five serious adverse events however, none was related to the interventions. Interpretation: A single course of PQ significantly reduces gametocyte carriage in malaria-infected asymptomatic, G6PD-normal individuals without increasing the risk of clinical anemia. The limited number of successful mosquito infections suggests that post-treatment transmission potential in this asymptomatic population is low.

Over the last decades, malaria has declined substantially in The Gambia but its transmission has not been interrupted. In order to better target control interventions, it is essential to understand the dynamics of residual transmission. This prospective cohort study was conducted between June 2013 and April 2014 in six pairs of villages across The Gambia. Blood samples were collected monthly during the transmission season (June-December) from all residents aged ≥6 months (4,194 individuals) and then in April (dry season). Entomological data were collected monthly throughout the malaria transmission season. Ownership of Long-Lasting Insecticidal Nets was 71.5% (2766/3869). Incidence of malaria infection and clinical disease varied significantly across the country, with the highest values in eastern (1.7/PYAR) than in central (0.2 /PYAR) and western (0.1/PYAR) Gambia. Malaria infection at the beginning of the transmission season was significantly higher in individuals who slept outdoors (HR = 1.51, 95% CI: 1.02-2.23, p = 0.04) and in those who had travelled outside the village (HR = 2.47, 95% CI: 1.83-3.34, p

Aim: The Child-Oral Impacts on Daily Performance (OIDP) assesses the impacts of oral health problems on the daily activities ofchildren. Objectives of this study were to cross-culturally adapt the Child-OIDP for use among Italian children and provide initialevidence on its reliability and validity in a sample of 10-11 year-olds. Materials and Method: The Italian Child-OIDP was administered to a convenience sample of 10-11-year-old 5th graders of“Giò Leonardo di Bona” Public School in Cutro (Italy). Informed positive consent was sought and obtained from the participants’parents. Analyses were performed using SAS statistical package; reliability testing referred to internal consistency that was evaluatedusing the Cronbach’s alpha, alpha if item deleted, and inter-item and item-total correlation coefficients. Result: To provide initial evidence for the evaluation of the psychometric properties of the Italian Child-OIDP, we invited 103 10-11-year-old schoolchildren and 97 participated in the study (response rate = 94.2%), 50 boys (51.5%) and 47 girls (48.5%).Almost all children (95.87%) reported that they had experienced at least one problem with their teeth or mouth in the past 3months. All item-total correlation were above 0.20 and Cronbach's alpha was 0.59. Higher Child-OIDP scores were significantlyassociated with worse perceptions in terms of oral health, general health and satisfaction with oral health status, but not withperceived dental treatment needs. Analyses were performed using SAS statistical package; reliability testing referred to internalconsistency that was evaluated using the Cronbach’s alpha, alpha if item deleted, and inter-item and item-total correlationcoefficients. Conclusion: Child-OIDP index is a measure of oral health-related quality of life that can be applied to Italian children. Initialevidence of its psychometric properties was promising, but future studies should be conducted to fully evaluate its psychometricproperties in a population based epidemiological study.