A Two-Center Randomized Trial of an Additional Early Dose of Measles Vaccine: Effects on Mortality and Measles Antibody Levels.

Background: In addition to protecting against measles, measles vaccine (MV) may have beneficial nonspecific effects. We tested the effect of an additional early MV on mortality and measles antibody levels. Methods: Children aged 4-7 months at rural health and demographic surveillance sites in Burkina Faso and Guinea-Bissau were randomized 1:1 to an extra early standard dose of MV (Edmonston-Zagreb strain) or no extra MV 4 weeks after the third diphtheria-tetanus-pertussis-hepatitis B-Haemophilus influenzae type b vaccine. All children received routine MV at 9 months. We assessed mortality through home visits and compared mortality from enrollment to age 3 years using Cox proportional hazards models, censoring for subsequent nontrial MV. Subgroups of participants had blood sampled to assess measles antibody levels. Results: Among 8309 children enrolled from 18 July 2012 to 3 December 2015, we registered 145 deaths (mortality rate: 16/1000 person-years). The mortality was lower than anticipated and did not differ by randomization group (hazard ratio, 1.05; 95% confidence interval, 0.75-1.46). At enrollment, 4% (16/447) of children in Burkina Faso and 21% (90/422) in Guinea-Bissau had protective measles antibody levels. By age 9 months, no measles-unvaccinated/-unexposed child had protective levels, while 92% (306/333) of early MV recipients had protective levels. At final follow-up, 98% (186/189) in the early MV group and 97% (196/202) in the control group had protective levels. Conclusions: Early MV did not reduce all-cause mortality. Most children were susceptible to measles infection at age 4-7 months and responded with high antibody levels to early MV. Clinical Trials Registration: NCT01644721.

Whole blood mercury and the risk of cardiovascular disease among the Greenlandic population.

BACKGROUND: Studies have found mercury to be associated with cardiovascular disease (CVD), however, primarily in populations with low exposure. The highest levels, and variations in the levels, of whole blood mercury (WBM) worldwide have been found in Greenland. We prospectively assessed the association between WBM and the risk of developing CVD in the Greenlandic population. METHODS: We assessed the effects of WBM levels on incident CVD among 3083 Greenlandic Inuit, participating in a population-based cohort study conducted from 2005 to 2010. WBM was measured at baseline. Participants were followed in the National Patient Registries for Denmark and Greenland and in the causes of death register for CVD events from inclusion in the study until CVD event, emigration, death or end of follow-up (30/9-2013). Using Cox regression analyses, we calculated the incidence rates and the hazard ratio of CVD events according to WBM levels. Potential interactions with sex were also investigated. RESULTS: The highest levels of WBM were found in men, who had a significantly higher median level (19 µg/L (IQR:1-44)), compared with women (15 µg/L (IQR: 1-32), (p < 0.001)). The crude hazard ratio (HR) for incident CVD was 1.00 (95% CI 1.00-1.00) for 5 µg/l increase in WBM. After adjusting for several potential confounders, there was still no association between WBM and incident CVD (HR 0.99; 95%CI:0.99-1.00). We found no interactions with sex. CONCLUSIONS: In a population with high levels of WBM, we found no association between WBM and the risk of developing CVD in Greenland.

Incidence of psychiatric disorders among accompanied and unaccompanied asylum-seeking children in Denmark: a nation-wide register-based cohort study.

One in four asylum applicants in Europe are children, and 23% of whom are unaccompanied and may be at increased risk of mental illness. This study contributes to the limited evidence base by comparing the incidence of psychiatric disorders among unaccompanied and accompanied refugee children. We linked a cohort of refugee children who obtained right of residency in Denmark between 01 January 1993 and 31 December 2010 to the Danish Psychiatric Central Register, and calculated incidence rates per 100,000 person years and incidence rate ratios of overall psychiatric disorder, psychotic disorders, affective disorders, and neurotic disorders for accompanied and unaccompanied minors using Poisson regression. We adjusted the analyses for sex, age at residency, and age at arrival (aIRR). Stratified analyses were conducted by nationality. Unaccompanied minors had significantly higher rates of any psychiatric disorder (aIRR: 1.38, 95% CI 1.14-1.68) and neurotic disorders (aIRR: 1.67, 95% CI 1.32-2.13) than accompanied minors. Among children from Afghanistan, unaccompanied minors had significantly higher rates of any psychiatric disorder (aIRR: 2.23, 95% CI 1.26-3.93) and neurotic disorders (aIRR: 3.50, 95% CI 1.72-7.11). Among children from Iraq, unaccompanied minors had higher rates of any psychiatric disorder (aIRR: 2.02, 95% CI 1.18-3.45), affective disorders (aIRR: 6.04, 95% CI 2.17-16.8), and neurotic disorders (aIRR: 3.04, 95% CI 1.62-5.70). Unaccompanied children were found to experience a higher incidence of any psychiatric disorder and neurotic disorders. Strategies are needed to address the specific mental health and social needs of unaccompanied minors.

Seasonal variation in child mortality in rural Guinea-Bissau.

OBJECTIVES: In many African countries, child mortality is higher in the rainy season than in the dry season. We investigated the effect of season on child mortality by time periods, sex and age in rural Guinea-Bissau. METHODS: Bandim health project follows children under-five in a health and demographic surveillance system in rural Guinea-Bissau. We compared the mortality in the rainy season (June to November) between 1990 and 2013 with the mortality in the dry season (December to May) in Cox proportional hazards models providing rainy vs. dry season mortality rate ratios (r/d-mrr). Seasonal effects were estimated in strata defined by time periods with different frequency of vaccination campaigns, sex and age (<1 month, 1-11 months, 12-59 months). Verbal autopsies were interpreted using InterVa-4 software. RESULTS: From 1990 to 2013, overall mortality was declined by almost two-thirds among 81 292 children (10 588 deaths). Mortality was 51% (95% ci: 45-58%) higher in the rainy season than in the dry season throughout the study period. The seasonal difference increased significantly with age, the r/d-mrr being 0.94 (0.86-1.03) among neonates, 1.57 (1.46-1.69) in post-neonatal infants and 1.83 (1.72-1.95) in under-five children (P for same effect <0.001). According to the InterVa, malaria deaths were the main reason for the seasonal mortality difference, causing 50% of all deaths in the rainy season, but only if the InterVa included season of death, making the argument self-confirmatory. CONCLUSION: The mortality declined throughout the study, yet rainy season continued to be associated with 51% higher overall mortality.

Cardiovascular disease incidence and survival: Are migrants always worse off?

Studies on cardiovascular disease (CVD) incidence and survival show varying results between different ethnic groups. Our aim was to add a new dimension by exploring the role of migrant status in combination with ethnic background on incidence of-and survival from-CVD and more specifically acute myocardial infarction (AMI) and stroke. We conducted a historically prospective cohort study comprising all newly-arrived migrants to Denmark between 1.1.1993 and 31.12.2010 (n = 114,331), matched 1:6 to Danish-born by age and sex. CVD incidence was retrieved from the National Patient Registry and differences in incidence were assessed by Poisson regression and stratified by sex. Survival differences were assessed by Cox regression using all-cause and cause-specific mortality as outcome. Male refugees had significantly lower incidence of CVD (RR = 0.89; 95 % CI 0.85-0.93) and stroke (IRR = 0.62; 95 % CI 0.56-0.69) compared to Danish-born, but significantly higher incidence of AMI (IRR = 1.12; 95 % CI 1.02-1.24). Female refugees had similar rates of CVD and AMI, but significantly lower incidence of stroke (RR = 0.76; 95 % CI 0.67-0.85). Both male and female family-reunified immigrants had significantly lower incidence of CVD, AMI and stroke. All-cause and cause-specific survival after CVD, AMI and stroke was similar or significantly better for migrants compared to Danish-born, regardless of type of migrant (refugee vs. family-reunified) or country of origin. Refugees are disadvantaged in terms of some types of cardiovascular disease compared to Danish-born. Family-reunified migrants on the other hand had lower rates of CVD. All migrants had better survival than Danish-born indicating that migrants may not always be disadvantaged in health.

Somatic comorbidity among migrants with posttraumatic stress disorder and depression - a prospective cohort study.

BACKGROUND: In a cohort of migrants in Denmark, we compared somatic disease incidence among migrants diagnosed with posttraumatic stress disorder (PTSD) and depression with migrants without a diagnosed psychiatric disorder. METHODS: The study builds on a unique cohort of migrants who obtained residence permit in Denmark from 1993 to 2010 (N = 92,104). The association with somatic disease was explored via register linkage. We used Poisson regression to model incidence rate ratios (IRR) adjusted for age, sex, income and region of origin. The Danish Data Protection Agency granted authorisation for the implementation of the project (No 2012-41-0065). RESULTS: Our results showed that migrants diagnosed with PTSD and depression had significantly higher rates of somatic diseases compared with migrants without diagnosed psychiatric disorders - especially, infectious disease (IRR, 1.89; 95% CI, 1.45-2.48; p < 0.01), neurological disease (IRR, 2.35; 95% CI, 1.91-2.91; p < 0.01) and pulmonary disease (IRR, 1.69; 95% CI, 1.37-2.00; p < 0.01). We further saw differences in the IRRs according to region of origin. CONCLUSION: Migrants with PTSD and depression had a significantly higher rates of somatic comorbidity compared with migrants without a diagnosed psychiatric disorder. The rates were especially high for infectious, neurological and pulmonary diseases. Our results further suggest difference in the rates of somatic comorbidity according to region of. Preventive and treatment services should pay special attention to improve the overall health of migrants with PTSD and depression.

Duration of residence and disease occurrence among refugees and family reunited immigrants: test of the 'healthy migrant effect' hypothesis.

OBJECTIVES: The 'healthy migrant effect' (HME) hypothesis postulates that health selection has a positive effect on migrants' health outcomes, especially in the first years after migration. We examined the potential role of the HME by assessing the association between residence duration and disease occurrence. METHODS: We performed a historical prospective cohort study. We included migrants who obtained residence permits in Denmark between 1 January 1993 and 31 December 2010 (n = 114,331). Occurrence of severe conditions was identified through linkage to the Danish National Patient Register. Hazard Ratios (HRs) were modelled for disease incidence by residence duration since arrival (0-5 years; 0-10 years; 0-18 years) adjusting for age and sex. RESULTS: Compared with Danish-born individuals, refugees and family reunited immigrants had lower HRs of stroke and breast cancer within 5 years after arrival; however, HRs increased at longer follow-up. For example, HRs of stroke among refugees increased from 0.77 (95% CI: 0.66; 0.91) to 0.96 (95% CI: 0.88; 1.05). For ischaemic heart disease (IHD) and diabetes, refugees and family reunited migrants had higher HRs within 5 years after arrival, and most HRs had increased by end of follow-up. For example, HRs of IHD among family reunited migrants increased from 1.29 (95% CI: 1.17; 1.42) to 1.43 (95% CI: 1.39; 1.52). In contrast, HRs for TB and HIV/AIDS showed a consistent decrease over time. CONCLUSION: Our analyses of the effect of duration of residence on disease occurrence among migrants imply that, when explaining migrants' advantageous health outcomes, the ruling theory of the HME should be used with caution, and other explanatory models should be included.

BCG coverage and barriers to BCG vaccination in Guinea-Bissau: an observational study.

BACKGROUND: BCG vaccination is recommended at birth in low-income countries, but vaccination is often delayed. Often 20-dose vials of BCG are not opened unless at least ten children are present for vaccination ("restricted vial-opening policy"). BCG coverage is usually reported as 12-month coverage, not disclosing the delay in vaccination. Several studies show that BCG at birth lowers neonatal mortality. We assessed BCG coverage at different ages and explored reasons for delay in BCG vaccination in rural Guinea-Bissau. METHODS: Bandim Health Project (BHP) runs a health and demographic surveillance system covering women and their children in 182 randomly selected village clusters in rural Guinea-Bissau. BCG coverage was assessed for children born in 2010, when the restricted vial-opening policy was universally implemented, and in 2012-2013, where BHP provided BCG to all children at monthly visits in selected intervention regions. Factors associated with delayed BCG vaccination were evaluated using logistic regression models. Coverage between intervention and control regions were evaluated in log-binomial regression models providing prevalence ratios. RESULTS: Among 3951 children born in 2010, vaccination status was assessed for 84%. BCG coverage by 1 week of age was 11%, 38% by 1 month, and 92% by 12 months. If BCG had been given at first contact with the health system, 1-week coverage would have been 35% and 1-month coverage 54%. When monthly visits were introduced in intervention regions, 1-month coverage was higher in intervention regions (88%) than in control regions (51%), the prevalence ratio being 1.74 (1.53-2.00). Several factors, including socioeconomic factors, were associated with delayed BCG vaccination in the 2010-birth cohort. When BCG was available at monthly visits these factors were no longer associated with delayed BCG vaccination, only region of residence was associated with delayed BCG vaccination. CONCLUSION: BCG coverage during the first months of life is low in Guinea-Bissau. Providing BCG at monthly vaccination visits removes the risk factors associated with delayed BCG vaccination.

The use of artificial intelligence to assess diabetic eye disease among the Greenlandic population.

Background: Retina fundus images conducted in Greenland are telemedically assessed for diabetic retinopathy by ophthalmological nurses in Denmark. Applying an AI grading solution, in a Greenlandic setting, could potentially improve the efficiency and cost-effectiveness of DR screening.Method: We developed an AI model using retina fundus photos, performed on persons registered with diabetes in Greenland and Denmark, using Optos® ultra wide-field scanning laser ophthalmoscope, graded according to ICDR.Using the ResNet50 network we compared the model's ability to distinguish between different images of ICDR severity levels in a confusion matrix.Results: Comparing images with ICDR level 0 to images of ICDR level 4 resulted in an accuracy of 0.9655, AUC of 0.9905, sensitivity and specificity of 96.6%.Comparing ICDR levels 0,1,2 with ICDR levels 3,4, we achieved a performance with an accuracy of 0.8077, an AUC of 0.8728, a sensitivity of 84.6% and a specificity of 78.8%. For the other comparisons, we achieved a modest performance.Conclusion: We developed an AI model using Greenlandic data, to automatically detect DR on Optos retina fundus images. The sensitivity and specificity were too low for our model to be applied directly in a clinical setting, thus optimising the model should be prioritised.

The HIV care continuum of Guinea-Bissau; Progress towards the UNAIDS 90-90-90 targets for HIV-1 and HIV-2.

OBJECTIVE: In the 2020 UNAIDS HIV treatment goals, 90% of people living with HIV (PLHIV) should be diagnosed, 90% of these should receive antiretroviral treatment (ART) and 90% of these should be virally suppressed. We aimed to evaluate whether Guinea-Bissau fulfills the 2020 treatment goals for both for HIV-1 and HIV-2. DESIGN: By combining data from a general population survey, treatment records from HIV clinics across Guinea-Bissau and a biobank from patients attending the largest HIV clinics in Bissau, we estimated each column of the 90-90-90 cascade. METHOD: 2601 participated in the survey and were used to estimate the proportion of PLHIV who knew their HIV status and the proportion of PLHIV on ART. Answers given in the survey was verified with treatment records from HIV clinics. We measured viral load from biobank materials from HIV patients and estimated the proportion of virally suppressed PLHIV. RESULT: 19.1% of PLHIV indicated to be aware of their HIV status. Of these, 48.5% received ART, and 76.4% of these were virally suppressed. For HIV-1 and HIV-1/2 the results were 21.2%, 40.9% and 75.1%. For HIV-2 the results were 15.9%, 63.6% and 80.7%. 26.9% of all HIV-1 infected in the survey were virologically suppressed, indicating that a much higher number of HIV-1 infected were aware of their status and on treatment. CONCLUSION: Guinea-Bissau lags severely behind both the global and regional progress. Improvement in both testing and treating HIV is necessary to improve the quality of care.

Factors Associated With Nonattendance in a Nationwide Screening Program for Diabetic Retinopathy: A Register-Based Cohort Study.

OBJECTIVE: The aim of the study was to identify factors associated with nonattendance in a Danish nationwide screening program for diabetic retinopathy among people with type 2 diabetes. RESEARCH DESIGN AND METHODS: A retrospective observational study linking individual-level register data was performed. First, we compared characteristics of 156,878 people with type 2 diabetes divided into attenders and never-attenders on the basis of their screening history over a 6-year period. Second, we assessed 230,173 screening intervals within the same 6-year period. Mixed-effects models were used to investigate the effect of sociodemographic and health-related factors on the likelihood of having a nonattender interval (i.e., failing to attend screening within the recommended interval). RESULTS: A total of 42,068 (26.8%) people were identified as never-attenders, having no registered eye screening over a 6-year period. Compared with attenders, never-attenders were more frequently divorced/widowed, lived in the Capital Region of Denmark, and had poorer health. A total of 62,381 (27.1%) screening intervals were identified as nonattender intervals. Both sociodemographic and health-related factors were significantly associated with the likelihood of having a nonattender interval. The largest odds ratios for nonattendance were seen for mental illness, nonwestern descent, divorce, comorbidity, and place of residence. CONCLUSIONS: Our findings suggest that never- and nonattendance of screening for diabetic retinopathy are more common among people who are divorced/widowed and of poorer health. Additionally, nonattendance is more frequent among people of nonwestern decent. These population subgroups may benefit from targeted interventions aimed at increasing participation in diabetic retinopathy screening.

Twins in Guinea-Bissau have a 'thin-fat' body composition compared to singletons.

The 'thrifty phenotype' hypothesis proposed that fetal undernutrition increases risk of diabetes in later life. Undernourished low birthweight Indian babies are paradoxically more adipose compared to well-nourished European babies, and are at higher risk of diabetes in later life. Twin pregnancies are an example of in utero growth restrictive environment due to shared maternal nutrition. There are few studies of body composition in twins. We performed secondary analysis of anthropometric body composition of twins and singletons in Guinea-Bissau, an economically deprived African country.Anthropometric data were available on 7-34 year-old twins (n = 209, 97 males) and singletons (n = 182, 86 males) in the Guinea-Bissau Twin Registry at the Bandim Health Project. Twins had lower birthweight (2420 vs 3100 g, p < 0.001); and at follow-up, lower height (HAZ mean Z-score difference, -0.21, p = 0.055), weight (WAZ -0.73, p = 0.024) and BMI (BAZ -0.22, p = 0.079) compared to singletons but higher adiposity (skinfolds: +0.33 SD, p = 0.001). Twins also had higher fasting (+0.38 SD, p < 0.001) and 2-hour OGTT glucose concentrations (+0.29 SD, p < 0.05). Linear mixed-effect model accounting for intrapair correlations and interactions confirmed that twins were thinner but fatter across the age range. Data on maternal morbidity and prematurity were not available in this cohort.African populations are known to have a muscular (less adipose) body composition. Demonstration of a thin-fat phenotype in twins in a low socio-economic African country supports the thesis that it could be a manifestation of early life undernutrition and not exclusive to Indians. This phenotype could increase risk of diabetes and related conditions.

The Greenland population health survey 2018 - methods of a prospective study of risk factors for lifestyle related diseases and social determinants of health amongst Inuit.

Since 1993, regular population health surveys in Greenland have supported and monitored the public health strategy of Greenland and have monitored cardiometabolic and lung diseases. The most recent of these surveys included 2539 persons aged 15+ from 20 communities spread over the whole country. The survey instruments included personal interviews, self-administered questionnaires, blood sampling, anthropometric measurements, blood pressure, ECG, oral glucose test, pulmonary function, hand grip strength and chair stand test. Blood samples were analysed for glucose, glycated haemoglobin (HbA1c), insulin, incretin hormones, cholesterol, kidney function, fatty acids in erythrocyte membranes and mercury, urine for albumin-creatinine ratio, and aliquots were stored at -80°C for future use. Data were furthermore collected for studies of the gut microbiome and diabetes complications. Survey participants were followed up with register data. The potential of the study is to contribute to the continued monitoring of risk factors and health conditions as part of Greenland's public health strategy and to study the epidemiology of cardiometabolic diseases and other chronic diseases and behavioural risk factors. The next population health survey is planned for 2024. The emphasis of the article is on the methods of the study and results will be presented in other publications.

Effect of early two-dose measles vaccination on childhood mortality and modification by maternal measles antibody in Guinea-Bissau, West Africa: A single-centre open-label randomised controlled trial.

Background: Early 2-dose measles vaccine (MV) at 4 and 9 months of age vs. the WHO strategy of MV at 9 months of age reduced all-cause child mortality in a previous trial. We aimed to test two hypotheses: 1) a 2-dose strategy reduces child mortality between 4 and 60 months of age by 30%; 2) receiving early MV at 4 months in the presence versus absence of maternal measles antibodies (MatAb) reduces child mortality by 35%. Methods: Single-centre open-label community-based randomised controlled trial in Guinea-Bissau, with 2:1 block-randomisation by sex to a 2-dose (4 + 9 months) vs. 1-dose (9 months) MV strategy. Healthy children were eligible 4 weeks after the 3rd diphtheria-tetanus-pertussis-containing vaccine. Before randomisation a blood sample was collected to determine MatAb level. The primary outcome was all-cause mortality. Hazard ratios (HR) were derived from Cox regression in the per protocol population. We tested for interactions with national campaigns with oral polio vaccine (C-OPV). Trial registration: NCT01486355. Findings: Between August 2011-April 17th 2015, 6,636 children were enroled, 6,598[n2-dose=4,397; n1-dose=2,201] were included in the analysis of the primary outcome, The HR(2-dose/1-dose) between 4 and 60 months was 1.38 (95%CI: 0.92-2.06) [deaths: n2-dose=90; n1-dose=33]. Before the 9-month MV and the HR(1-dose/no dose) was 0.94 (0.45-1.96) [deaths: n2-dose=21; n1-dose=11]. The HR(2-dose/1-dose) was 0.81 (0.29-2.22) for children, who received no C-OPV [deaths/children: n2-dose=10/2,801; n1-dose=6/1,365], and 4.73 (1.44-15.6) for children, who received C-OPV before and after enrolment (p for interaction=0.027) [deaths/children: n2-dose=27/1,602; n1-dose=3/837]. In the 2-dose group receiving early MV at 4 months, mortality was 50% (20-68%) lower for those vaccinated in the presence of MatAb vs. the absence of MatAb [deaths/children: nMatAb=51/3,132; nnoMatAb=31/1,028]. Interpretation: The main result contrasts with previous findings but may, though based on a small number of events, be explained by frequent OPV campaigns that reduced the mortality rate, but apparently interacted negatively with early MV. The beneficial non-specific effects of MV in the presence of MatAb should be investigated further. Funding: ERC, Danish National Research Foundation, the Danish Council for Development Research, Ministry of Foreign Affairs, Novo Nordisk Foundation, European Union and the Lundbeck Foundation.

HbA1c variability and the development of nephropathy in individuals with type 1 diabetes mellitus from Rwanda.

AIM: To estimate the incidence and prevalence of nephropathy and investigate whether high and fluctuating HbA1c levels were associated with development of nephropathy among T1 diabetes individuals in Rwanda. METHODS: From 2009 to 2018, 471 T1 diabetes individuals from Rwanda were assessed for nephropathy (albumin-creatinine ratio (ACR) ≥ 30 mg/g). We calculated the mean HbA1c (HbA1c-MEAN) and two measures of HbA1c variability, i.e. A): intra-individual standard deviation (HbA1c-SD), adjusted for HbA1c assessments (HbA1c-AdjSD) and coefficient of variation (HbA1c-CV) and B): (number of HbA1c variability measures > 11 mmol/mol between two measures/number of comparisons between measurements)*100. We followed individuals from first ACR-measurement (baseline) until nephropathy, death or last ACR-measurement (end-of-follow-up), and calculated HRs for developing nephropathy using Cox-regression. RESULTS: The incidence and prevalence of nephropathy were 25% and 40%, respectively. All HbA1c variability measures were associated with lower HRs of developing nephropathy, i.e. individuals with HbA1c-AdjSD levels of 0.8-1.5%, 1.5-2.1% and > 4.1% had 53% (95 %CI:0.26;0.86), 55% (95 %CI:0.25;0.82) and 53% (95 %CI:0.26;0.84) lower HRs, respectively, of nephropathy compared to individuals with HbA1c-AdjSD < 0.8%. Results did not change after adjustments, though some estimates were no longer significant. Individuals with adjusted HbA1c-MEAN 9.9-11.4% and > 11.4% had HRs of 1.7 (95 %CI: 0.87;3.32) and 1.8 (95 %CI: 0.94;3.50) compared to individuals with HbA1c-MEAN of 4.9-8.5%. CONCLUSION: The incidence and prevalence of nephropathy was high. Higher mean HbA1c was associated with higher HRs of developing nephropathy whereas higher HbA1c variability was associated with lower HRs of nephropathy. This indicates that higher HbA1c levels rather than fluctuating HbA1c levels is a risk factor for developing nephropathy.

The mortality effects of disregarding the strategy to save doses of measles vaccine: a cluster-randomised trial in Guinea-Bissau.

INTRODUCTION: Measles vaccine (MV) may improve health beyond measles protection. To avoid wastage from multi-dose vials, children in Guinea-Bissau are only measles vaccinated when aged 9-11 months and when six or more children are present. We assessed health impacts of providing MV to all measles-unvaccinated children 9-35 months. METHODS: We cluster-randomised 182 village clusters under demographic surveillance in rural Guinea-Bissau to an 'MV-for-all-policy' arm where we offered MV regardless of age and number of children present at our bi-annual village visits, or a 'Restrictive-MV-policy' arm where we followed national policy. Measles-unvaccinated children aged 9-35 months were eligible for enrolment and followed to 5 years of age. In intention-to-treat analyses, we compared mortality using Cox regression analyses with age as underlying timescale. The primary analysis was for children aged 12-35 months at eligibility assessment. Interactions with several background factors were explored. RESULTS: Between 2011 and 2016, we followed 2778 children in the primary analysis. MV coverage by 3 years was 97% among children eligible for enrolment under the MV-for-all-policy, and 48% under the Restrictive-MV-policy. Mortality was 59% lower than anticipated and did not differ by trial arm (MV-for-all-policy: 45/1405: Restrictive-MV-policy: 44/1373; HR: 0.95 (95% CI 0.64 to 1.43)). The effect of MV-for-all changed over time: The HR was 0.53 (95% CI 0.27 to 1.07) during the first 1½ years of enrolment but 1.47 (95% CI 0.87 to 2.50) later (p=0.02, test of interaction). Explorative analyses indicated that the temporal change may be related to interactions with other childhood interventions. CONCLUSION: The MV-for-all-policy increased MV coverage but had no overall effect on overall mortality. TRIAL REGISTRATION NUMBER: NCT01306006.

Quality assessment of a screening algorithm for diabetic retinopathy: prolongation of screening intervals with minimal effect of HbA1c and arterial hypertension on the length of intervals.

PURPOSE: At Steno Diabetes Center Copenhagen (SDCC), diabetic retinopathy (DR) screening intervals are based on quantification of retinal lesions. Screening intervals are, for the milder forms of DR, prolonged to 2-3 years. The purpose of the present study was to evaluate the effect of the prolongation on developing unexpected events and to evaluate the effect of HbA1c and arterial hypertension. METHODS: We assessed 18 972 screening intervals from 6000 patients from 1/1-2003 to 1/5-2017 for occurrence of unexpected events, defined as: (1) DR progression requiring treatment, at the following screening date, and (2) DR-related hospital contact within the planned interval. We modelled the effect of several risk factors for developing unexpected events in a Cox regression. Furthermore, we assessed the risk of unexpected events in a logistic regression analysis using cubic splines to model the effect of HbA1c , stratified by arterial hypertension status. RESULTS: 16 283 (86%) intervals followed the planned interval and among those, only 86 (0.5%) experienced unexpected events. Intervals of dysregulated patients (86% of all intervals) did not experience more unexpected events, compared with well-regulated patient intervals (Hazard Ratio: 1.12, 95% CI: 0.55-2.27). We found a nonlinear effect of HbA1c on the risk of unexpected events which peaked around HbA1c levels of 80 mmol/mol. Having arterial hypertension slightly increased the risk of unexpected events. CONCLUSIONS: The present study supports the validity of the current algorithm. We found no increased risk of unexpected events among dysregulated intervals but a nonlinear effect of HbA1c . Age, diabetes duration and diabetes type were significantly associated with unexpected events.

Low prevalence of retinopathy among Greenland Inuit.

To assess the prevalence of diabetic retinopathy (DR) among persons with diabetes and prediabetes participating in the 2018 Population Health Survey in Greenland (B2018), a follow-up survey of three previous health surveys. Participants were invited to a diabetes complication screening. We assessed the prevalence of DR using Optos Daytona Ultra-wide field fundus camera and assessed differences in prevalence according to demographic and clinical characteristics using chi square test and a t-test and assessed DR based on ethnicity. The overall prevalence of DR was 2% (10/483). Among participants with HbA1c ≥48 mmol/mol (6.5%) DR prevalence was 9% (9/91), compared with <1% (1/382) among participants with HbA1c <48 mmol/mol (6.5%). All participants with DR lived in towns. The mean Inuit genetic admixture was lower among participants with DR. The prevalence of DR is low in Greenland and almost non-existent among persons with HbA1c below the diabetes threshold.

Normative data on cardiovascular autonomic function in Greenlandic Inuit.

INTRODUCTION: Diabetes is increasing among Greenlandic Inuit; however, the prevalence of cardiovascular autonomic neuropathy (CAN) is yet unknown. The assessment of CAN requires an ability to differentiate between normal and abnormal. The aim was to establish normative reference data of cardiovascular autonomic function in Greenlandic Inuit. RESEARCH DESIGN AND METHODS: In this cross-sectional study, cardiovascular autonomic function was evaluated in participants without diabetes during the Greenlandic Population Study 2018 and in the town Qasigiannguit in 2020. Assessment included cardiovascular autonomic reflex tests (CARTs) and power spectral analysis of heart rate variability (HRV). Normative reference limits were estimated by applying piecewise linear quantile regression models at the fifth percentile. Models were adjusted for age and sex. RESULTS: Based on examinations of 472 participants (61.7% females), normative reference data was established for all outcomes. Mean age was 54 years (SD 13.1). Higher age was inversely associated with all outcomes of CARTs and HRV. A linear fall in cardiovascular autonomic function tended to level off beyond age of 60 or 70 years for supine-to-upright position ratio and low frequency power. However, the number of observations in subjects older than 60 or 70 years was limited, which may have caused a flattening of the curve around that age. No other associations were found. CONCLUSIONS: The general level of the CARTs and HRV for all age groups is notably lower than in previous studies from other nationalities. We speculate that sociodemographic and cultural aspects of the Greenlandic Inuit population including body mass index, smoking, physical activity and alcohol consumption may have affected the cardiovascular autonomic function.

Disregarding the restrictive vial-opening policy for BCG vaccine in Guinea-Bissau: impact and cost-effectiveness for tuberculosis mortality and all-cause mortality in children aged 0-4 years.

OBJECTIVE: BCG vaccination is frequently delayed in low-income countries. Restrictive vial-opening policies, where a vial of BCG vaccine is not opened for few children, are a major reason for delay. During delays, children are unprotected against tuberculosis (TB) and deprived of non-specific effects of BCG. We assessed the potential effect and cost-effectiveness of disregarding the restrictive vial-opening policy, on TB and all-cause mortality, in children aged 0-4 years in Guinea-Bissau. METHODS: Using static mathematical models, we estimated the absolute and percentage change in TB and all-cause deaths, in children aged 0-4 years, between the current BCG vaccine restrictive-opening policy scenario, and a non-restrictive policy scenario where all children were vaccinated in the first health-facility contact. Incremental cost-effectiveness was estimated by integration of vaccine and treatment costs. FINDINGS: Disregarding the restrictive BCG vial-opening policy was estimated to reduce TB deaths by 11.0% (95% uncertainty range (UR):0.5%-28.8%), corresponding to 4 (UR:0-15) TB deaths averted per birth cohort in Guinea-Bissau, resulting in incremental cost-effectiveness of US$ 911 per discounted life-year gained (LYG) (UR:145-9142). For all-cause deaths, the estimated reduction was 8.1% (UR: 3.3%-12.7%) corresponding to 392 (UR:158-624) fewer all-cause deaths and an incremental cost-effectiveness of US$ 9 (UR:5-23) per discounted LYG. CONCLUSIONS: Disregarding the restrictive BCG vial-opening policy was associated with reductions in TB deaths and all-cause deaths and low cost-effectiveness ratios. Our results suggest that it would be cost-effective to disregard the restrictive vial-opening policy. Other settings with similar practice are also likely to gain from disregarding this policy.