What are the characteristics of participatory surveillance systems for influenza-like-illness?

Background: Seasonal influenza causes significant morbidity and mortality, with an estimated 9.4 million hospitalisations and 290 000-650 000 respiratory related-deaths globally each year. Influenza can also cause mild illness, which is why not all symptomatic persons might necessarily be tested for influenza. To monitor influenza activity, healthcare facility-based syndromic surveillance for influenza-like illness is often implemented. Participatory surveillance systems for influenza-like illness (ILI) play an important role in influenza surveillance and can complement traditional facility-based surveillance systems to provide real-time estimates of influenza-like illness activity. However, such systems differ in designs between countries and contexts, making it necessary to identify their characteristics to better understand how they fit traditional surveillance systems. Consequently, we aimed to investigate the performance of participatory surveillance systems for ILI worldwide. Methods: We systematically searched four databases for relevant articles on influenza participatory surveillance systems for ILI. We extracted data from the included, eligible studies and assessed their quality using the Joanna Briggs Critical Appraisal Tools. We then synthesised the findings using narrative synthesis. Results: We included 39 out of 3797 retrieved articles for analysis. We identified 26 participatory surveillance systems, most of which sought to capture the burden and trends of influenza-like illness and acute respiratory infections among cohorts with risk factors for influenza-like illness. Of all the surveillance system attributes assessed, 52% reported on correlation with other surveillance systems, 27% on representativeness, and 21% on acceptability. Among studies that reported these attributes, all systems were rated highly in terms of simplicity, flexibility, sensitivity, utility, and timeliness. Most systems (87.5%) were also well accepted by users, though participation rates varied widely. However, despite their potential for greater reach and accessibility, most systems (90%) fared poorly in terms of representativeness of the population. Stability was a concern for some systems (60%), as was completeness (50%). Conclusions: The analysis of participatory surveillance system attributes showed their potential in providing timely and reliable influenza data, especially in combination with traditional hospital- and laboratory led-surveillance systems. Further research is needed to design future systems with greater uptake and utility.

Impact of COVID-19 mitigations on anxiety and depression amongst university students: A systematic review and meta-analysis.

Background: While much research has addressed mental health concerns related to the coronavirus disease 2019 (COVID-19) pandemic, there remains a scarcity of studies specifically exploring the changes in anxiety and depression among university students before and after the implementation of COVID-19 mitigation measures. Methods: In this systematic review and meta-analysis, we searched databases including MEDLINE (Ovid), EMBASE (Ovid), PsycINFO (Ovid), CINAHL (EBSCO), ERIC (EBSCO), the WHO COVID-19 database, Scopus, and Science Citation Index (Web of Science) as of 15 February 2023. We included studies that used a validated tool to measure changes in anxiety or depression at two distinct time points - before (T1) and during (T2); during (T2) and after (T3); or before (T1) and after (T3) COVID-19 mitigation. The quality of studies was assessed using an adapted Joanna Briggs Institute Checklist for longitudinal studies. Utilising random-effects models, we synthesised changes in continuous outcomes as standardised mean difference (SMD) with 95% confidence interval (CI) and binary outcomes as risk difference (RD) with 95% CI. Results: In total, 15 studies were included in this review, with eight of moderate and seven of high quality. In most of the included studies (n = 13), the majority of participants were women. Eleven studies analysed mental health outcomes between T1 and T2 of COVID-19 mitigations. Continuous symptom changes were a minimal or small improvement for anxiety (SMD = -0.03, 95% CI = -0.24 to 0.19, I2 = 90%); but worsened for depression (SMD = 0.26, 95% CI = -0.01 to 0.62). However, the proportions of students reporting moderate-to-severe symptoms, defined by specific cut-offs, increased during COVID-19 mitigation measures for both anxiety (RD = 0.17, 95% CI = -0.04 to 0.38, I2 = 95%) and depression (RD = 0.12, 95% CI = 0.03 to 0.22, I2 = 72%). Sensitivity analyses, which distinguished between baseline periods based on awareness of COVID-19, demonstrated an exacerbation of both symptoms when comparing the period before the global awareness of the COVID-19 outbreak (before December 2019) with the period during the implementation of mitigation measures. Conclusions: Mental health outcomes, especially depressive symptoms, were observed to worsen in university students during COVID-19 mitigations. Despite considerable heterogeneity requiring careful interpretation of results, the impact of COVID-19 mitigations on mental health in university students is evident. Registration: PROSPERO (CRD42021266889).

A rapid review of COVID-19's global impact on breast cancer screening participation rates and volumes from January to December 2020.

COVID-19 has strained population breast mammography screening programs that aim to diagnose and treat breast cancers earlier. As the pandemic has affected countries differently, we aimed to quantify changes in breast screening volume and uptake during the first year of COVID-19 . We systematically searched Medline, the World Health Organization (WHO) COVID-19 database, and governmental databases. Studies covering January 2020 to March 2022 were included. We extracted and analyzed data regarding study methodology, screening volume, and uptake. To assess for risk of bias, we used the Joanna Briggs Institute (JBI) Critical Appraisal Tool. Twenty-six cross-sectional descriptive studies (focusing on 13 countries/nations) were included out of 935 independent records. Reductions in screening volume and uptake rates were observed among eight countries. Changes in screening participation volume in five nations with national population-based screening ranged from -13 to -31%. Among two countries with limited population-based programs, the decline ranged from -61 to -41%. Within the USA, population participation volumes varied ranging from +18 to -39%, with suggestion of differences by insurance status (HMO, Medicare, and low-income programs). Almost all studies had high risk of bias due to insufficient statistical analysis and confounding factors. The extent of COVID-19-induced reduction in breast screening participation volume differed by region and data suggested potential differences by healthcare setting (e.g., national health insurance vs. private healthcare). Recovery efforts should monitor access to screening and early diagnosis to determine whether prevention services need strengthening to increase the coverage of disadvantaged groups and reduce disparities.

The benefits, challenges, and best practice for patient and public involvement in evidence synthesis: A systematic review and thematic synthesis.

INTRODUCTION: Despite the growing evidence on patient and public involvement (PPI) in health research, little emphasis has been placed on understanding its quality and appropriateness to evidence synthesis (ES) and systematic reviews (SR). This study aimed to synthesise qualitative evidence on the benefits, challenges, and best practices for PPI in ES/SR projects from the perspectives of patients/public and researchers. METHODS: We searched Ovid MEDLINE, Ovid EMBASE, Cochrane Library and CINAHL Plus. We also searched relevant grey literature and conducted hand-searching to identify qualitative studies which report the benefits and challenges of PPI in individual ES/SR projects. Studies were independently screened by two reviewers for inclusion and appraised using the Joanna Briggs Institute's Qualitative Tool. Included studies were synthesised narratively using thematic synthesis. RESULTS: The literature search retrieved 9923 articles, of which eight studies were included in this review. Five themes on benefits emerged: two from patients'/public's perspective-gaining knowledge, and empowerment; and three from researchers' perspective-enhancing relevance, improving quality, and enhancing dissemination of findings. Six themes on challenges were identified: three from patients'/public's perspective-poor communication, time and low self-esteem; and three from researchers' perspective-balancing inputs and managing relations, time, and resources and training. Concerning recommendations for best practice, four themes emerged: provision of sufficient time and resources, developing a clear recruitment plan, provision of sufficient training and support, and the need to foster positive working relationships. CONCLUSION: Highlighting the benefits and challenges of PPI in ES/SR projects from different stakeholder perspectives is essential to understand the process and contextual factors and facilitate meaningful PPI in ES/SR projects. Future research should focus on the utilisation of existing frameworks (e.g., Authors and Consumers Together Impacting on eVidencE [ACTIVE] framework) by researchers to help describe and/or report the best approaches and methods for involving patients/public in ES/SRs projects. PATIENT AND PUBLIC CONTRIBUTION: This review received great contributions from a recognised PPI partner, the Chair of the Cochrane Consumer Network Executive, to inform the final stage of the review (i.e., interpretation, publication and dissemination of findings). The PPI partner has been included as an author of this review.

Risk of serious COVID-19 outcomes among adults and children with moderate-to-severe asthma: a systematic review and meta-analysis.

BACKGROUND: The Joint Committee on Vaccination and Immunisation in the United Kingdom requested an evidence synthesis to investigate the relationship between asthma and coronavirus disease 2019 (COVID-19) outcomes. OBJECTIVE: We conducted a systematic review and meta-analysis to summarise evidence on the risk of severe COVID-19 outcomes in people with uncontrolled asthma or markers of asthma severity. METHODS: High-dose inhaled corticosteroids (ICS) or oral corticosteroids (OCS) were used as markers of asthma severity, following international or national asthma guidelines. Risk of bias was assessed using Joanna Briggs Institute tools. Adjusted point estimates were extracted for random-effects meta-analyses and subgroup analyses. RESULTS: After screening, 12 studies (11 in adults and one in children) met the eligibility criteria. Adults using high-dose ICS or OCS had a pooled adjusted hazard ratio (aHR) of 1.33 (95% CI 1.06-1.67, I2=0%) for hospitalisation and an aHR of 1.22 (95% CI 0.90-1.65, I2=70%) for mortality for COVID-19. We found insufficient evidence for associations between markers on COVID-19 mortality in the subgroup analyses. CONCLUSIONS: Adults with severe asthma are at increased risk of COVID-19 hospitalisation compared to nonusers. Our analysis highlighted the dearth of studies in children with asthma investigating serious COVID-19 outcomes.

To what extent is alcohol consumption in social gatherings associated with observance of COVID-19 restrictions? A rapid review.

Background: Pre-pandemic research found a connection between alcohol consumption and reduced physical distancing among strangers. Understanding the association between alcohol consumption at social gatherings and observance of COVID-19 restrictions can help inform policy related to the safe operation of public spaces where alcohol is typically consumed, as well as guidance related to the safe conduct of social events in private spaces. Methods: We conducted a rapid review using adapted systematic review methods to explore the association between alcohol consumption in social gatherings and compliance with COVID-19 public health measures and produced a narrative synthesis of our findings. We ran searches in eleven health-related databases (MEDLINE, PubMed, CINAHL, Scopus, Embase (Ovid), ProQuest Public Health, ProQuest Coronavirus, Global Health (Ovid), WHO COVID-19 literature database, PsycInfo (Ovid) and ASSIA) between July 9, 2021, and July 31, 2021. We assessed methodological quality using the relevant Joanna Briggs Institute (JBI) checklists. This review was conducted and reported in accordance with PRISMA-P guidelines. Results: We identified 7936 studies from the searches. After title, abstract and full-text review, three cross-sectional studies were eligible for inclusion. One study found that people who adhered strongly to physical distancing rules were engaged in about 40% fewer weekly drinks and 60% fewer heavy episodic drinking occasions in a week than people who adhered poorly to physical distancing rules (P < 0.01). One study found that people who reported low-risk alcohol consumption patterns had a higher chance of adhering to hand hygiene measures than those who reported high-risk alcohol consumption (odds ratio (OR) = 4.24, 95% confidence interval (CI) = 1.08-16.64). No other statistically significant results on patterns of alcohol consumption and compliance with individual public health measures or with non-pharmaceutical interventions (NPIs) were found. The direction of effect between alcohol consumption and non-adherence to NPIs and the effect of confounding factors has not been established. The quality of studies found was low to moderate, with risk of recall bias and selection bias due to study design; and the extent to which those studies can be generalised beyond their original settings may be limited. Conclusions: Despite existing evidence suggesting an association between alcohol consumption, reduced physical distancing, and increased social interaction, we found few studies of variable quality exploring the relationship between alcohol consumption and compliance with public health measures. A possible association between higher-risk alcohol behaviours and lower compliance with certain NPIs was suggested, but the direction of effect is unknown, and further studies are required to confirm this finding.

Clinical features of COVID-19 for integration of COVID-19 into influenza surveillance: A systematic review.

Background: In November 2020, the World Health Organization (WHO) created interim guidance on how to integrate testing for SARS-CoV-2 into existing influenza surveillance systems. Influenza-like illness (ILI) and severe acute respiratory illness (SARI) case definitions have been used to specify the case definition of COVID-19 for surveillance purposes. This review aims to assess whether the common clinical features of COVID-19 have changed to the point that the criteria used to identify both COVID-19 and influenza in surveillance programs needs to be altered. Methods: A systematic review of reviews following PRISMA-P guidelines was conducted using the "COVID-19 evidence review" database from August 19, 2020, to August 19, 2021. Reviews providing pooled estimates of the prevalence of clinical features of COVID-19 within the general population, diagnosed by polymerase chain reaction or rapid diagnostic test, were included. These were critically appraised and sensitivity analysis was undertaken to examine potential causes of bias. Results: Fourteen reviews were identified, including three on adults only and three on children only. For all reviews, combined fever (median prevalence = 73.0%, IQR = 58.3-78.7) and cough (45.1%, IQR = 28.9-54.0) were the most common features. These were followed by loss of taste or smell (45.1%, IQR = 28.9-54.0), hypoxemia (33%, one review), fatigue (26.4%, IQR = 9.0-39.4) and expectoration (23.9%, IQR = 23.3-25.5). Fever and cough continued to be the most prevalent features for adults and children, with subsequent symptoms being similar for adults only. However, the pattern differed for children, with headache (34.3%, IQR = 18-50.7) and nasal congestion (20%, one review) being the third and fourth commonest symptoms. Conclusions: The prevalent features found in this recent review were the same as the ones identified at the beginning of the pandemic. Therefore, the current approach of using the ILI and SARI criteria which incorporate fever and cough will identify COVID-19 cases in addition to influenza. Interestingly, children may present with different features, as headaches and nasal congestion were more common in this group. Future research could examine this further and investigate whether symptomology changes with new variants of COVID-19.

Prevalence and characteristics associated with diabetes mellitus and impaired fasting glucose among people aged 15 to 64 years in rural and urban Rwanda: secondary data analysis of World Health Organization surveillance data.

Introduction: diabetes mellitus is an increasing public health burden in developing countries. The magnitude of diabetes association with traditional risk factors for diabetes have been given less attention in rural population. This study aims to determine the prevalence of diabetes and impaired fasting glucose and to assess associated characteristics to hyperglycemia in rural and urban Rwanda. Methods: this is a secondary analysis of data from a population-based cross-sectional study of 7240 people describing risk factors for non-communicable diseases using the WHO stepwise methods (STEPS). Relative frequencies of variables of interest were compared in rural and urban residence using Pearson chi-square tests. Diabetes and impaired fasting glucose were combined in a single hyperglycemia variable and odds ratios with 95% confidence intervals were used to explore associations between hyperglycemia, socio-demographic and health factors in urban and rural populations. Results: the prevalence in rural and urban areas was 7.5% and 9.7% (p.005) for diabetes and 5.0% and 6.2% for impaired fasting glucose (p.079) respectively. Obesity (AOR 2.57: CI: 0.86-7.9), high total cholesterol (AOR 3.83: CI: 2.03-7.208), hypertension (AOR 1.18: CI: 0.69-2.00), increasing age were associated with hyperglycemia in urban participants but only high total cholesterol and low high density lipoproteins (HDL) cholesterol were risk factors for hyperglycemia in rural participants. Conclusion: approximately one in six people in Rwanda have hyperglycemia. The magnitude of the association with traditional risk factors for diabetes differ in rural and urban settings. Different approaches to primary and secondary prevention of diabetes may be needed in rural populations.

The effects of mobile health on emergency care in low- and middle-income countries: A systematic review and narrative synthesis.

BACKGROUND: In resource-constrained settings, mobile health (mHealth) has varied applications. While there is strong evidence for its use in chronic disease management, the applications of mHealth for management of acute illness in low- and middle-income countries (LMICs) are not as well described. This review systematically explores current available evidence on the effectiveness of mHealth interventions at improving health outcomes in emergency care settings in LMICs. METHODS: A systematic search of the literature was performed in accordance with PRISMA guidelines, utilizing seven electronic databases and manual searches to identify peer-reviewed literature containing each of three search elements: mHealth, emergency care (EC), and LMICs. Articles quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) criteria. RESULTS: After removing duplicates, 6498 studies met initial search criteria; 108 were eligible for full text review and 46 met criteria for inclusion. Thirty-six pertained to routine emergency care, and 10 involved complex humanitarian emergencies. Based on the GRADE criteria, 15 studies were rated as "Very Low" quality, 24 as "Low" quality, 6 as "Moderate" quality, and 1 as "High" quality. Eight studied data collection, 9 studied decision support, 15 studied direct patient care, and 14 studied health training. All 46 studies reported positive impacts of mHealth on EC in LMICs. CONCLUSIONS: Mobile health interventions can be effective in improving provider-focused and patient-centered outcomes in both routine and complex EC settings. Future investigations focusing on patient-centered outcomes are needed to further validate these findings.

Which factors influence the extent of indoor transmission of SARS-CoV-2? A rapid evidence review.

BACKGROUND: This rapid evidence review identifies and integrates evidence from epidemiology, microbiology and fluid dynamics on the transmission of SARS-CoV-2 in indoor environments. METHODS: Searches were conducted in May 2020 in PubMed, medRxiv, arXiv, Scopus, WHO COVID-19 database, Compendex & Inspec. We included studies reporting data on any indoor setting except schools, any indoor activities and any potential means of transmission. Articles were screened by a single reviewer, with rejections assessed by a second reviewer. We used Joanna Briggs Institute and Critical Appraisal Skills Programme tools for evaluating epidemiological studies and developed bespoke tools for the evaluation of study types not covered by these instruments. Data extraction and quality assessment were conducted by a single reviewer. We conducted a meta-analysis of secondary attack rates in household transmission. Otherwise, data were synthesised narratively. RESULTS: We identified 1573 unique articles. After screening and quality assessment, fifty-eight articles were retained for analysis. Experimental evidence from fluid mechanics and microbiological studies demonstrates that aerosolised transmission is theoretically possible; however, we found no conclusive epidemiological evidence of this occurring. The evidence suggests that ventilation systems have the potential to decrease virus transmission near the source through dilution but to increase transmission further away from the source through dispersal. We found no evidence for faecal-oral transmission. Laboratory studies suggest that the virus survives for longer on smooth surfaces and at lower temperatures. Environmental sampling studies have recovered small amounts of viral RNA from a wide range of frequently touched objects and surfaces; however, epidemiological studies are inconclusive on the extent of fomite transmission. We found many examples of transmission in settings characterised by close and prolonged indoor contact. We estimate a pooled secondary attack rate within households of 11% (95% confidence interval (CI) = 9, 13). There were insufficient data to evaluate the transmission risks associated with specific activities. Workplace challenges related to poverty warrant further investigation as potential risk factors for workplace transmission. Fluid mechanics evidence on the physical properties of droplets generated by coughing, speaking and breathing reinforce the importance of maintaining 2 m social distance to reduce droplet transmission. CONCLUSIONS: This review provides a snap-shot of evidence on the transmission of SARS-CoV-2 in indoor environments from the early months of the pandemic. The overall quality of the evidence was low. As the quality and quantity of available evidence grows, it will be possible to reach firmer conclusions on the risk factors for and mechanisms of indoor transmission.

Socio-demographic and clinical characteristics of diabetes mellitus in rural Rwanda: time to contextualize the interventions? A cross-sectional study.

BACKGROUND: Existing prevention and treatment strategies target the classic types of diabetes yet this approach might not always be appropriate in some settings where atypical phenotypes exist. This study aims to assess the socio-demographic and clinical characteristics of people with diabetes in rural Rwanda compared to those of urban dwellers. METHODS: A cross-sectional, clinic-based study was conducted in which individuals with diabetes mellitus were consecutively recruited from April 2015 to April 2016. Demographic and clinical data were collected from patient interviews, medical files and physical examinations. Chi-square tests and T-tests were used to compare proportions and means between rural and urban residents. RESULTS: A total of 472 participants were recruited (mean age 40.2 ± 19.1 years), including 295 women and 315 rural residents. Compared to urban residents, rural residents had lower levels of education, were more likely to be employed in low-income work and to have limited access to running water and electricity. Diabetes was diagnosed at a younger age in rural residents (mean ± SD 32 ± 18 vs 41 ± 17 years; p < 0.001). Physical inactivity, family history of diabetes and obesity were significantly less prevalent in rural than in urban individuals (44% vs 66, 14.9% vs 28.7 and 27.6% vs 54.1%, respectively; p < 0.001). The frequency of fruit and vegetable consumption was lower in rural than in urban participants. High waist circumference was more prevalent in urban than in rural women and men (75.3% vs 45.5 and 30% vs 6%, respectively; p < 0.001). History of childhood under-nutrition was more frequent in rural than in urban individuals (22.5% vs 6.4%; p < 0.001). CONCLUSIONS: Characteristics of people with diabetes in rural Rwanda appear to differ from those of individuals with diabetes in urban settings, suggesting that sub-types of diabetes exist in Rwanda. Generic guidelines for diabetes prevention and management may not be appropriate in different populations.

The association of malaria infection and gestational hypertension in Africa: Systematic review and meta-analysis.

BACKGROUND: The World Health Organisation (WHO) estimates that hypertensive disorders of pregnancy (HDP) contribute 14% to global maternal mortality. HDP encompasses several subcategories, including gestational hypertension (GH) and pre-eclampsia. These two conditions are both characterised by a rise in blood pressure, with an onset from 20 weeks of gestation. They also share some common risk factors. The current definition of pre-eclampsia includes raised blood pressure in the absence of proteinuria, thus presenting the two conditions as a spectrum. In this article, we refer to both conditions as gestational hypertension, which is our outcome of interest. The aetiology of GH is not yet clearly understood. Observational studies have suggested that malaria may be associated with GH. However, the evidence from these small studies has been inconclusive. Having a better understanding of the association between malaria and GH may help inform prevention strategies to reduce maternal and infant mortality and morbidity. METHODS: In assessing the association between malaria infection and GH we explored open access articles published in the English language on Medline, Embase, WHO GIM and Google scholar. The subject related articles were retrieved and processed according to preferred reporting items in systematic reviews and meta-analyses (PRISMA) guidelines. Search date was 9th week of 2018. Inverse variance weighting method in Revman 5 software (Cochrane Collaboration, London, United Kingdom) was used to aggregate evidence by computing the pooled odds ratio to show the nature and strength of the relationship between malaria and GH. RESULTS: Using critical appraisal skills program (CASP) checklist tool we identified four good quality case-control studies. The total sample size was 1281 women out of which 518 were cases. These studies together show malaria is associated with GH with an overall odds ratio of 2.67, 95% confidence interval (CI) = 1.58-4.53. Heterogeneity of the individual studies supported fixed effect modelling assumptions (I2 = 0%). Malaria infection may have a constant effect on GH across different African populations. The funnel plot did not suggest publication bias however, the four studies involved in the meta-analysis were insufficient to rule it out. CONCLUSIONS: Our findings provide evidence of an association between malaria infection and gestational hypertension; this underscores the need to control malaria especially during pregnancy.

A systematic review and meta-analysis to assess the association between urogenital schistosomiasis and HIV/AIDS infection.

BACKGROUND: Urogenital schistosomiasis and HIV/AIDS infections are widespread in sub-Saharan Africa (SSA) leading to substantial morbidity and mortality. The co-occurrence of both diseases has led to the possible hypothesis that urogenital schistosomiasis leads to increased risk of acquiring HIV infection. However, the available evidence concerning this association is inconsistent. The aim of this study was to systematically review and quantitatively synthesize studies that investigated the association between urogenital schistosomiasis and HIV/AIDS infection. METHODS: A systematic review basing on PRISMA guidelines was conducted. It is registered with PROSPERO, number CRD42018116648. We searched four databases, MEDLINE, EMBASE, Global Health and Global Index Medicus for studies investigating the association between urogenital schistosomiasis and HIV infection. Only studies published in English were considered. Results of the association were summarised by gender. A meta-analysis was performed for studies on females using random-effects model and a pooled OR with 95% confidence interval was reported. RESULTS: Of the 993 studies screened, only eight observational studies met the inclusion criteria. Across all studies, the reported unadjusted OR ranged from 0.78 to 3.76. The pooled estimate of unadjusted OR among females was 1.31 (95% CI: 0.87-1.99). Only four of the eight studies reported an adjusted OR. A separate meta-analysis done in the three studies among females that reported an adjusted OR showed that the pooled estimate was 1.85 (95% CI: 1.17-2.92). There were insufficient data to pool results for association between urogenital schistosomiasis and HIV infection in the males. CONCLUSION: Our investigation supports the hypothesis of an association between urogenital schistosomiasis with HIV/AIDS infection in females. Due to insufficient evidence, no conclusion could be drawn in males with urogenital schistosomiasis. Large-scale prospective studies are needed in future.

Atypical forms of diabetes mellitus in Africans and other non-European ethnic populations in low- and middle-income countries: a systematic literature review.

BACKGROUND: Atypical presentations of diabetes mellitus (DM) have been reported in non-European ethnic populations under various names. It is unclear whether those names are used for the same or different clinical phenotypes. Unclear terminology may lead to inappropriate treatment and an underestimation of the burden caused by atypical diabetes phenotypes overlapping with classic types of diabetes. This review aimed to describe the terms used for atypical forms of diabetes and to investigate whether the terms are used for similar or different phenotypes. METHODS: PubMed and Scopus were searched for relevant publications in French or English available before 15 September 2015 using the terms: "Atypical diabetes", "Malnutrition Related Diabetes Mellitus (MRDM)", "Fibro-calculus pancreatic diabetes (FCPD)", Protein deficient Pancreatic Diabetes (PDPD)", "African diabetes", "Ketosis prone-type 2 diabetes", "tropical diabetes", "Flatbush diabetes", "J-type diabetes". Titles, abstracts screening and quality assessment were performed by two independent authors. Observational studies addressing atypical diabetes in humans aged 14 years and above were included. One author extracted data from selected articles. RESULTS: 22 articles among 350 identified articles were retained for data extraction. Two atypical diabetes phenotypes were identified, each of them with a variety of names but similar definitions. One phenotype occurred in very thin people less than 30 years of age, typically from poor socio-economic backgrounds and requires insulin for life. It differs from type 1 diabetes in the tolerance of high blood glucose without ketosis in the absence of exogenous insulin. The second phenotype resembles type1 diabetes as it presents with ketosis at onset but responds well, as type2 diabetes, to oral hypoglycemic drugs after initial stabilization with insulin. It occurs in individuals who are usually over 30 years of age, with normal or overweight and absence of auto antibodies mainly found in type 1 diabetes. CONCLUSION: The scarce existing literature used various terms for similar diabetes phenotypes. Agreement on nomenclature for the various forms of diabetes using the above reported characteristics are needed in populations where atypical forms of diabetes exist as well as better characterization of phenotypes and genotypes to inform evidence based treatment.

Farming, Foreign Holidays, and Vitamin D in Orkney.

Orkney, north of mainland Scotland, has the world's highest prevalence of multiple sclerosis (MS); vitamin D deficiency, a marker of low UV exposure, is also common in Scotland. Strong associations have been identified between vitamin D deficiency and MS, and between UV exposure and MS independent of vitamin D, although causal relationships remain to be confirmed. We aimed to compare plasma 25-hydroxyvitamin D levels in Orkney and mainland Scotland, and establish the determinants of vitamin D status in Orkney. We compared mean vitamin D and prevalence of deficiency in cross-sectional study data from participants in the Orkney Complex Disease Study (ORCADES) and controls in the Scottish Colorectal Cancer Study (SOCCS). We used multivariable regression to identify factors associated with vitamin D levels in Orkney. Mean (standard deviation) vitamin D was significantly higher among ORCADES than SOCCS participants (35.3 (18.0) and 31.7 (21.2), respectively). Prevalence of severe vitamin D deficiency was lower in ORCADES than SOCCS participants (6.6% to 16.2% p = 1.1 x 10(-15)). Older age, farming occupations and foreign holidays were significantly associated with higher vitamin D in Orkney. Although mean vitamin D levels are higher in Orkney than mainland Scotland, this masks variation within the Orkney population which may influence MS risk.

A general approach for haplotype phasing across the full spectrum of relatedness.

Many existing cohorts contain a range of relatedness between genotyped individuals, either by design or by chance. Haplotype estimation in such cohorts is a central step in many downstream analyses. Using genotypes from six cohorts from isolated populations and two cohorts from non-isolated populations, we have investigated the performance of different phasing methods designed for nominally 'unrelated' individuals. We find that SHAPEIT2 produces much lower switch error rates in all cohorts compared to other methods, including those designed specifically for isolated populations. In particular, when large amounts of IBD sharing is present, SHAPEIT2 infers close to perfect haplotypes. Based on these results we have developed a general strategy for phasing cohorts with any level of implicit or explicit relatedness between individuals. First SHAPEIT2 is run ignoring all explicit family information. We then apply a novel HMM method (duoHMM) to combine the SHAPEIT2 haplotypes with any family information to infer the inheritance pattern of each meiosis at all sites across each chromosome. This allows the correction of switch errors, detection of recombination events and genotyping errors. We show that the method detects numbers of recombination events that align very well with expectations based on genetic maps, and that it infers far fewer spurious recombination events than Merlin. The method can also detect genotyping errors and infer recombination events in otherwise uninformative families, such as trios and duos. The detected recombination events can be used in association scans for recombination phenotypes. The method provides a simple and unified approach to haplotype estimation, that will be of interest to researchers in the fields of human, animal and plant genetics.

Local exome sequences facilitate imputation of less common variants and increase power of genome wide association studies.

The analysis of less common variants in genome-wide association studies promises to elucidate complex trait genetics but is hampered by low power to reliably detect association. We show that addition of population-specific exome sequence data to global reference data allows more accurate imputation, particularly of less common SNPs (minor allele frequency 1-10%) in two very different European populations. The imputation improvement corresponds to an increase in effective sample size of 28-38%, for SNPs with a minor allele frequency in the range 1-3%.

Inference of identity by descent in population isolates and optimal sequencing studies.

In an isolated population, individuals are likely to share large genetic regions inherited from common ancestors. Identity by descent (IBD) can be inferred from SNP genotypes, which is useful in a number of applications, including identifying genetic variants influencing complex disease risk, and planning efficient cohort-sequencing strategies. We present ANCHAP--a method for detecting IBD in isolated populations. We compare accuracy of the method against other long-range and local phasing methods, using parent-offspring trios. In our experiments, we show that ANCHAP performs similarly as the other long-range method, but requires an order-of-magnitude less computational resources. A local phasing model is able to achieve similar sensitivity, but only at the cost of higher false discovery rates. In some regions of the genome, the studied individuals share haplotypes particularly often, which hints at the history of the populations studied. We demonstrate the method using SNP genotypes from three isolated island populations, as well as in a cohort of unrelated individuals. In samples from three isolated populations of around 1000 individual each, an average individual shares a haplotype at a genetic locus with 9-12 other individuals, compared with only 1 individual within the non-isolated population. We describe an application of ANCHAP to optimally choose samples in resequencing studies. We find that with sample sizes of 1000 individuals from an isolated population genotyped using a dense SNP array, and with 20% of these individuals sequenced, 65% of sequences of the unsequenced subjects can be partially inferred.

Evidence of inbreeding depression on human height.

Stature is a classical and highly heritable complex trait, with 80%-90% of variation explained by genetic factors. In recent years, genome-wide association studies (GWAS) have successfully identified many common additive variants influencing human height; however, little attention has been given to the potential role of recessive genetic effects. Here, we investigated genome-wide recessive effects by an analysis of inbreeding depression on adult height in over 35,000 people from 21 different population samples. We found a highly significant inverse association between height and genome-wide homozygosity, equivalent to a height reduction of up to 3 cm in the offspring of first cousins compared with the offspring of unrelated individuals, an effect which remained after controlling for the effects of socio-economic status, an important confounder (χ(2) = 83.89, df = 1; p = 5.2 × 10(-20)). There was, however, a high degree of heterogeneity among populations: whereas the direction of the effect was consistent across most population samples, the effect size differed significantly among populations. It is likely that this reflects true biological heterogeneity: whether or not an effect can be observed will depend on both the variance in homozygosity in the population and the chance inheritance of individual recessive genotypes. These results predict that multiple, rare, recessive variants influence human height. Although this exploratory work focuses on height alone, the methodology developed is generally applicable to heritable quantitative traits (QT), paving the way for an investigation into inbreeding effects, and therefore genetic architecture, on a range of QT of biomedical importance.

Genome-wide homozygosity and multiple sclerosis in Orkney and Shetland Islanders.

There is strong evidence for both genetic and environmental risk factors comprising the aetiology of multiple sclerosis (MS). While much progress has been made in recent years in identifying common genetic variants using genome-wide association studies, alternative approaches have remained relatively neglected. The prevalence of MS in Orkney and Shetland is among the highest in the world. Previous studies have suggested that a higher degree of parental relatedness in these isolated communities may contribute to the high rates of MS, indicating that recessive effects have an important role in MS aetiology. The Northern Isles Multiple Sclerosis (NIMS) study investigated the potential role of genome-wide homozygosity in MS risk by genotyping 88 MS patients, 89 controls matched by age, sex and ancestry, and a further 89 controls matched for sex and ancestry, but passed the majority of lifetime risk of developing MS (>70 years of age). Three participants were removed on the basis of pedigree-genomic anomalies (n=263). Three measures of genome-wide homozygosity were generated for each individual, and association with MS was assessed using logistic regression models. No effect of genome-wide homozygosity was detected, indicating that inbreeding and consanguinity are not risk factors for MS in this population.