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Background Pre-gestational diabetes mellitus (PGDM) has been known to be a risk factor for congenital heart defects (CHDs) for decades. However, the associations between maternal PGDM and gestational diabetes mellitus (GDM) and the risk of specific types of CHDs and congenital anomalies (CAs) in other systems remain under debate. We aimed to investigate type-specific CAs in offspring of women with diabetes and to examine the extent to which types of maternal diabetes are associated with increased risk of CAs in offspring. Methods and findings We searched PubMed and Embase from database inception to 15 October 2021 for population-based studies reporting on type-specific CAs in offspring born to women with PGDM (combined type 1 and 2) or GDM, with no limitation on language. Reviewers extracted data for relevant outcomes and performed random effects meta-analyses, subgroup analyses, and multivariable meta-regression. Risk of bias appraisal was performed using the Cochrane Risk of Bias Tool. This study was registered in PROSPERO (CRD42021229217). Primary outcomes were overall CAs and CHDs. Secondary outcomes were type-specific CAs. Overall, 59 population-based studies published from 1990 to 2021 with 80,437,056 participants met the inclusion criteria. Of the participants, 2,407,862 (3.0%) women had PGDM and 2,353,205 (2.9%) women had GDM. The meta-analyses showed increased risks of overall CAs/CHDs in offspring born to women with PGDM (for overall CAs, relative risk [RR] = 1.99, 95% CI 1.82 to 2.17, P < 0.001; for CHDs, RR = 3.46, 95% CI 2.77 to 4.32, P < 0.001) or GDM (for overall CAs, RR = 1.18, 95% CI 1.13 to 1.23, P < 0.001; for CHDs, RR = 1.50, 95% CI 1.38 to 1.64, P < 0.001). The results of the meta-regression analyses showed significant differences in RRs of CAs/CHDs in PGDM versus GDM (all P < 0.001). Of the 23 CA categories, excluding CHD-related categories, in offspring, maternal PGDM was associated with a significantly increased risk of CAs in 21 categories; the corresponding RRs ranged from 1.57 (for hypospadias, 95% CI 1.22 to 2.02) to 18.18 (for holoprosencephaly, 95% CI 4.03 to 82.06). Maternal GDM was associated with a small but significant increase in the risk of CAs in 9 categories; the corresponding RRs ranged from 1.14 (for limb reduction, 95% CI 1.06 to 1.23) to 5.70 (for heterotaxia, 95% CI 1.09 to 29.92). The main limitation of our analysis is that some high significant heterogeneity still persisted in both subgroup and sensitivity analyses. Conclusions In this study, we observed an increased rate of CAs in offspring of women with diabetes and noted the differences for PGDM versus GDM. The RRs of overall CAs and CHDs in offspring of women with PGDM were higher than those in offspring of women with GDM. Screening for diabetes in pregnant women may enable better glycemic control, and may enable identification of offspring at risk for CAs., In a systematic review and meta analysis, Tie-Ning Zhang and colleagues investigate the associations between maternal pre-gestational diabetes and gestational diabetes and congenital heart defects and other congenital anomalies in offspring., Author summary Why was this study done? It is controversial whether maternal pre-gestational or gestational diabetes affects specific types of congenital heart defects (CHDs) and congenital anomalies (CAs) in other systems. Comprehensive estimates of the risks of specific CAs for offspring of women with maternal diabetes are needed to counsel patients and for public health purposes. What did the researchers do and find? To the best of our knowledge, this is the first comprehensive systematic review and meta-analysis of population-based studies of over 80 million participants that demonstrates an increased risk of type-specific CAs, especially CHDs, in offspring born to women with pre-gestational or gestational diabetes. Our study shows that maternal pre-gestational diabetes is associated with a significant increase in the risk of 38 out of 45 categories of CAs in offspring, while maternal gestational diabetes is associated with a small but significant increase in the risk of 16 out of the 45 categories. The corresponding relative risks (RRs) of overall CAs/CHDs in offspring of women with pre-gestational diabetes are higher than those in offspring of women with gestational diabetes, with no overlap in the 95% CIs. What do these findings mean? In this study, we observed that there is an increased rate of CAs in offspring of women with maternal diabetes and noted the differences between pre-gestational and gestational diabetes. Considering the substantial rise in the prevalence of maternal diabetes over recent decades, the expectation that this prevalence will continue to increase, the number of pregnancies worldwide, and the significant individual and global burdens associated with CAs, it is crucial that healthcare providers are aware of this association and can identify women and offspring who are at risk.

Background Pictorial warnings on tobacco products are promising for motivating behavior change, but few studies have examined pictorial warnings for sugary drinks, especially in naturalistic environments. This study aimed to examine the impact of pictorial warnings on parents’ purchases of sugary drinks for their children in a naturalistic store laboratory. Methods and findings Parents of children ages 2 to 12 (n = 325, 25% identifying as Black, 20% Hispanic) completed a shopping task in a naturalistic store laboratory in North Carolina. Participants were randomly assigned to a pictorial warnings arm (sugary drinks displayed pictorial health warnings about type 2 diabetes and heart damage) or a control arm (sugary drinks displayed a barcode label). Parents selected 1 beverage and 1 snack for their child, as well as 1 household good; one of these items was selected for them to purchase and take home. The primary outcome was whether parents purchased a sugary drink for their child. Secondary outcomes included reactions to the trial labels, attitudes toward sugary drinks, and intentions to serve their child sugary drinks. Pictorial warnings led to a 17-percentage point reduction in purchases of sugary drinks (95% CI for reduction: 7% to 27%), with 45% of parents in the control arm buying a sugary drink for their child compared to 28% in the pictorial warning arm (p = 0.002). The impact of pictorial warnings on purchases did not differ by any of the 13 participant characteristics examined (e.g., race/ethnicity, income, education, and age of child). Pictorial warnings also led to lower calories (kcal), purchased from sugary drinks (82 kcal in the control arm versus 52 kcal in the pictorial warnings arm, p = 0.003). Moreover, pictorial warnings led to lower intentions to serve sugary drinks to their child, feeling more in control of healthy eating decisions, greater thinking about the harms of sugary drinks, stronger negative emotional reactions, greater anticipated social interactions, lower perceived healthfulness of sugary drinks for their child, and greater injunctive norms to limit sugary drinks for their child (all p < 0.05). There was no evidence of difference between trial arms on noticing of the labels, appeal of sugary drinks, perceived amount of added sugar in sugary drinks, risk perceptions, or perceived tastiness of sugary drinks (all p > 0.05). Conclusions Pictorial warnings reduced parents’ purchases of sugary drinks for their children in this naturalistic trial. Warnings on sugary drinks are a promising policy approach to reduce sugary drink purchasing in the US. Trial registration The trial design, measures, power calculation, and analytic plan were registered before data collection at www.clinicaltrials.gov NCT04223687., Using a naturalistic store laboratory, Marissa Hall and colleagues examine the impact of pictorial warnings on parents’ purchases of sugary drinks for their children., Author summary Why was this study done? Children in the US consume more than the recommended levels of sugary drinks, increasing their risk of a variety of chronic diseases, including type 2 diabetes and heart disease. Experimental studies of text-only sugary drink warning labels indicate that warnings reduce sugary drink consumption. To our knowledge, studies have not yet examined the effects of pictorial warnings on parents’ purchases of sugary drinks for their children or on purchases in naturalistic settings. What did the researchers do and find? Parents of children aged 2 to 12 years (n = 325) participated in a randomized trial. Participants were randomized to a pictorial warnings arm (sugary drinks displayed pictorial health warnings about type 2 diabetes and heart damage) or a control arm (sugary drinks displayed a barcode label). Participants completed a shopping task in a naturalistic store laboratory, where sugary drinks had the assigned label, and completed a survey. Exposure to pictorial warning labels on sugary drinks led to a 17% absolute reduction in the purchasing of sugary drinks compared to exposure to the barcode control label. What do these findings mean? Pictorial warnings are a promising option for reducing purchases of sugary drinks for children. Implementation of pictorial warning label policies could be an effective strategy for reducing sugary drink purchases and sugary drink–related health outcomes. Future studies should evaluate the long-term effects of warning labels on children’s sugary drink consumption and prevalence of diet-related chronic disease.

Background We retrospectively data-mined the case records of Reverse Transcription Polymerase Chain Reaction (RT-PCR) confirmed COVID-19 patients hospitalized to a tertiary care centre to derive mortality predictors and formulate a risk score, for prioritizing admission. Methods and findings Data on clinical manifestations, comorbidities, vital signs, and basic lab investigations collected as part of routine medical management at admission to a COVID-19 tertiary care centre in Chengalpattu, South India between May and November 2020 were retrospectively analysed to ascertain predictors of mortality in the univariate analysis using their relative difference in distribution among ‘survivors’ and ‘non-survivors’. The regression coefficients of those factors remaining significant in the multivariable logistic regression were utilised for risk score formulation and validated in 1000 bootstrap datasets. Among 746 COVID-19 patients hospitalised [487 “survivors” and 259 “non-survivors” (deaths)], there was a slight male predilection [62.5%, (466/746)], with a higher mortality rate observed among 40–70 years age group [59.1%, (441/746)] and highest among diabetic patients with elevated urea levels [65.4% (68/104)]. The adjusted odds ratios of factors [OR (95% CI)] significant in the multivariable logistic regression were SaO23; 3.01 (1.61–5.83), Age ≥50 years;2.52 (1.45–4.43), Pulse Rate ≥100/min: 2.02 (1.19–3.47) and coexisting Diabetes Mellitus; 1.73 (1.02–2.95) with hypertension and gender not retaining their significance. The individual risk scores for SaO2Urea ≥50 mg/dl-15, NLR >3–11, Age ≥50 years-9, Pulse Rate ≥100/min-7 and coexisting diabetes mellitus-6, acronymed collectively as ‘OUR-ARDs score’ showed that the sum of scores ≥ 25 predicted mortality with a sensitivity-90%, specificity-64% and AUC of 0.85. Conclusions The ‘OUR ARDs’ risk score, derived from easily assessable factors predicting mortality, offered a tangible solution for prioritizing admission to COVID-19 tertiary care centre, that enhanced patient care but without unduly straining the health system.

The COVID-19 pandemic has been widely spread and affected millions of people and caused hundreds of deaths worldwide, especially in patients with comorbilities and COVID-19. This manuscript aims to present models to predict, firstly, the number of coronavirus cases and secondly, the hospital care demand and mortality based on COVID-19 patients who have been diagnosed with other diseases. For the first part, I present a projection of the spread of coronavirus in Mexico, which is based on a contact tracing model using Bayesian inference. I investigate the health profile of individuals diagnosed with coronavirus to predict their type of patient care (inpatient or outpatient) and survival. Specifically, I analyze the comorbidity associated with coronavirus using Machine Learning. I have implemented two classifiers: I use the first classifier to predict the type of care procedure that a person diagnosed with coronavirus presenting chronic diseases will obtain (i.e. outpatient or hospitalised), in this way I estimate the hospital care demand; I use the second classifier to predict the survival or mortality of the patient (i.e. survived or deceased). I present two techniques to deal with these kinds of unbalanced datasets related to outpatient/hospitalised and survived/deceased cases (which occur in general for these types of coronavirus datasets) to obtain a better performance for the classification.

Background The objective of this study was to evaluate annual heart transplant volumes and 3-year post-transplant outcomes since establishment of United Network for Organ Sharing (UNOS) database stratified by race. Methods The UNOS thoracic transplant database was evaluated for adult patients since 1987. The available database was then stratified by Race: Black, White and Other and era of transplant: group 1(1987–1991), group 2(1992–1996), group 3(1997–2001), group 4(2002–2006), group 5(2007–2011), group 6(2012–2016) and group 7(2017 and later). Demographic and clinical factors were evaluated. Results A total of 105,266 adults have been listed since 1987 and 67,824 have been transplanted. Of the transplanted patients 11,235 were Black, 48,786 White and 6803 were of Other race. The proportion of Black patients listed increased from 7% in 1987 to 13.4% in 1999 and 25% in 2019 and those transplanted increased from 5% in 1987 to 13.4% in 2001 and 26% in 2019. The survival of Black patients gradually improved. Conclusion Historically, fewer Black patients received cardiac transplantation however, their access gradually improved over the years and account for over 25% of cardiac transplantations performed in recent years. The historically poor survival of Black patients has recently improved and became comparable to the rest.

Background The effect of fasting on immunity is unclear. Prolonged fasting is thought to increase the risk of infection due to dehydration. This study describes antibiotic prescribing patterns before, during, and after Ramadan in a primary care setting within the Pakistani and Bangladeshi populations in the UK, most of whom are Muslims, compared to those who do not observe Ramadan. Method Retrospective controlled interrupted time series analysis of electronic health record data from primary care practices. The study consists of two groups: Pakistanis/Bangladeshis and white populations. For each group, we constructed a series of aggregated, daily prescription data from 2007 to 2017 for the 30 days preceding, during, and after Ramadan, respectively. Findings Controlling for the rate in the white population, there was no evidence of increased antibiotic prescription in the Pakistani/Bangladeshi population during Ramadan, as compared to before Ramadan (IRR: 0.994; 95% CI: 0.988–1.001, p = 0.082) or after Ramadan (IRR: 1.006; 95% CI: 0.999–1.013, p = 0.082). Interpretation In this large, population-based study, we did not find any evidence to suggest that fasting was associated with an increased susceptibility to infection.

Every person diagnosed with diabetes mellitus (T2DM) is at risk of developing Diabetic retinopathy (DR). Thus, DR is one of the major chronic microvascular complications of T2DM. However, in Malaysia, research about DR is still scarce. This study aimed to determine the prevalence of DR among diabetic patients across 46 primary healthcare clinics in Sabah, Malaysia. Secondly, it purported to identify the factors influencing the development of DR. This cross-sectional study involved a total of 22,345 Type 2 diabetes mellitus (T2DM) patients in the Sabah Diabetic Registry from 2008 to 2015. Of the 22,345 T2DM patients, 13.5% (n = 3,029) of them were diagnosed with DR. Multiple logistic regression revealed seven major risk factors of DR, i.e. patients with diabetic foot ulcer [aOR: 95% CI 3.08 (1.96–4.85)], patients with diabetic nephropathy [aOR: 95% CI 2.47 (2.13–2.86)], hypertension [aOR: 95% CI 1.63 (1.43–1.87)], dyslipidaemia [aOR: 95% CI 1.30 (1.17–1.44)], glycated haemoglobin [(HbA1c) > 6.5 (aOR: 95% CI 1.25 (1.14–1.38)], duration of diabetes mellitus (T2DM) [aOR: 95% CI 1.06 (1.05–1.07)] and age of patient [aOR: 95% CI 1.01 (1.00–1.02)] respectively. DR is a preventable complication. The effective glycaemic control is crucial in preventing DR. In minimizing the prevalence of DR, the healthcare authorities should institute programmes to induce awareness on the management of DR’s risk factors among patient and practitioner.

Funder: NIHR Cambridge Biomedical Research Centre, Clustering genetic variants based on their associations with different traits can provide insight into their underlying biological mechanisms. Existing clustering approaches typically group variants based on the similarity of their association estimates for various traits. We present a new procedure for clustering variants based on their proportional associations with different traits, which is more reflective of the underlying mechanisms to which they relate. The method is based on a mixture model approach for directional clustering and includes a noise cluster that provides robustness to outliers. The procedure performs well across a range of simulation scenarios. In an applied setting, clustering genetic variants associated with body mass index generates groups reflective of distinct biological pathways. Mendelian randomization analyses support that the clusters vary in their effect on coronary heart disease, including one cluster that represents elevated body mass index with a favourable metabolic profile and reduced coronary heart disease risk. Analysis of the biological pathways underlying this cluster identifies inflammation as potentially explaining differences in the effects of increased body mass index on coronary heart disease.

The PERSIAN Kavar cohort study (PKCS) aims to investigate the prevalence, trends, and relevant prognostic risk factors of non-communicable diseases in participants aged 35–70 years living in the urban area of Kavar County. Kavar County is located at the center of Fars province in the southwest of Iran. Overall, 5236 adults aged 35–70 years old were invited to participate in the PKCS. From whom, 4997 people comprising 2419 men and 2578 women met the inclusion criteria and were recruited in the study (participation rate: 95.4%). This study is aimed to follow participants for at least 10 years; it is designed to perform all procedures similar to the primary phase including biological sampling, laboratory tests, physical examinations, and collecting general, nutritional, and medical data at the 5th and 10th years of follow-up. In addition, participants are annually followed-up by phone to acquire data on the history of hospitalization, any major diagnosis or death. At the enrollment phase, trained interviewers were responsible for obtaining general, nutritional, and medical data utilizing a 482-item questionnaire. The results of the baseline phase of this study show that the overweight category was the most prevalent BMI category among the registered participants (n = 2005, 40.14%). Also, almost one-third of Kavar adult population suffered from metabolic syndrome at the baseline phase (n = 1664, 33.30%). The rate of eighteen-month follow-up response was 100% in the PKCS. Hypertension (n = 116, 2.32%), cardiovascular outcomes (n = 33, 0.66%), and diabetes (n = 32, 0.64%) were the most prevalent new-onset NCDs during eighteen months of follow-up in the participants.

Background Hypertension and diabetes are risk factors for severe cardiovascular disease and are prevalent comorbidities. No studies have examined the associations of various risk factors related to anthropometry, bone mineral density and body composition of specific body regions with hypertension and diabetes comorbidity (HDC). This study explored the association between HDC and various risk factors related to specific body regions. Method A total of 7,978 subjects (3,451 men and 4,527 women) aged ≥ 50 years were included in the analysis. A binary logistic regression analysis based on complex sample data analysis was conducted to examine associations between the normal and diabetes groups, between the normal and hypertension groups, and between the normal and HDC groups. Results Among Korean adults aged ≥ 50 years, 11.27% of men and 10.05% of women had both diabetes and hypertension. The HDC prevalence was higher in men than in women. In men, waist-to-height ratio (WHtR, adjusted OR = 1.63 [1.22–2.18], adjusted p Discussion HDC was more strongly associated with fat and lean mass than diabetes and hypertension. The association between HDC and body fat variables was more robust in women than in men.

Aim Heart failure with preserved ejection fraction (HFpEF) is a major cause of death worldwide with no approved treatment. Left ventricular hypertrophy (LVH) and diastolic dysfunction represent the structural and functional components of HFpEF, respectively. Endothelial dysfunction is prevalent in HFpEF and predicts cardiovascular events. We investigated if SAR247799, a G-protein-biased sphingosine-1-phosphate receptor 1 (S1P1) agonist with endothelial-protective properties, could improve cardiac and renal functions in a rat model of metabolic syndrome LVH and diastolic function. Methods 31- and 65-week-old obese ZSF1 (Ob-ZSF1) rats, representing adult and aged animals with LVH and diastolic dysfunction, were randomized to a chow diet containing 0.025% (w/w) of SAR247799, or control (CTRL) chow for 4 weeks. Age-matched lean ZSF1 (Le-ZSF1) rats were fed control chow. Echocardiography, telemetry, biochemical and histological analysis were performed to evaluate the effect of SAR247799. Results Echocardiography revealed that Ob-ZSF1 rats, in contrast to Le-ZSF1 rats, developed progressive diastolic dysfunction and cardiac hypertrophy with age. SAR247799 blunted the progression of diastolic dysfunction in adult and aged animals: in adult animals E/e’ was evaluated at 21.8 ± 1.4 for Ob-ZSF1-CTRL, 19.5 ± 1.2 for Ob-ZSF1-SAR247799 p1 desensitization. Conclusions These experimental findings suggest that S1P1 activation with SAR247799 may be considered as a new therapeutic approach for LVH and diastolic dysfunction, major components of HFpEF.

Anthropometry is a Greek word that consists of the two words “Anthropo” meaning human species and “metery” meaning measurement. It is a science that deals with the size of the body including the dimensions of different parts, the field of motion and the strength of the muscles of the body. Specific individual dimensions such as heights, widths, depths, distances, environments and curvatures are usually measured. In this article, we investigate the anthropometric characteristics of patients with chronic diseases (diabetes, hypertension, cardiovascular disease, heart attacks and strokes) and find the factors affecting these diseases and the extent of the impact of each to make the necessary planning. We have focused on cohort studies for 10047 qualified participants from Ravansar County. Machine learning provides opportunities to improve discrimination through the analysis of complex interactions between broad variables. Among the chronic diseases in this cohort study, we have used three deep neural network models for diagnosis and prognosis of the risk of type 2 diabetes mellitus (T2DM) as a case study. Usually in Artificial Intelligence for medicine tasks, Imbalanced data is an important issue in learning and ignoring that leads to false evaluation results. Also, the accuracy evaluation criterion was not appropriate for this task, because a simple model that is labeling all samples negatively has high accuracy. So, the evaluation criteria of precession, recall, AUC, and AUPRC were considered. Then, the importance of variables in general was examined to determine which features are more important in the risk of T2DM. Finally, personality feature was added, in which individual feature importance was examined. Performing by Shapley Values, the model is tuned for each patient so that it can be used for prognosis of T2DM risk for that patient. In this paper, we have focused and implemented a full pipeline of Data Creation, Data Preprocessing, Handling Imbalanced Data, Deep Learning model, true Evaluation method, Feature Importance and Individual Feature Importance. Through the results, the pipeline demonstrated competence in improving the Diagnosis and Prognosis the risk of T2DM with personalization capability.

We aimed to assess the epidemiological, clinical, and laboratory characteristics associated with mortality among hospitalized Egyptian patients with COVID-19. A multicenter, retrospective study was conducted on all polymerase chain reaction (PCR)-confirmed COVID-19 cases admitted through the period from April to July 2020. A generalized linear model was reconstructed with covariates based on predictor’s statistical significance and clinically relevance. The odds ratio (OR) was calculated by using stepwise logistic regression modeling. A total of 3712 hospitalized patients were included; of them, 900 deaths were recorded (24.2%). Compared to survived patients, non-survived patients were more likely to be older than 60 years (65.7%), males (53.6%) diabetic (37.6%), hypertensive (37.2%), and had chronic renal insufficiency (9%). Non-survived patients were less likely to receive azithromycin (p 60 years, comorbidities, tachycardia, hypoxemia, and altered consciousness level are independent predictors of mortality among Egyptian hospitalized patients with COVID-19. On the other hand, the use of anticoagulants and azithromycin is associated with reduced mortality.

In the last four decades, the problem of income inequality has gradually become one of the most serious social problems in China at both the regional and individual levels. Recently, the central government announced that the main social contradiction is that between people’s growing need for a better life and unbalanced and insufficient economic development. In this study, we analyse the effects of income distribution on individuals’ health using a series of indicators of income distribution and different measures of individuals’ health status. By utilizing data from the China Health and Nutrition Survey (CHNS) from 1989 to 2015, our empirical findings show that self-reported health (SRH), activities of daily living (ADLs), and diabetes mellitus appear to be negatively related to the income share of rich people when average income is equalized among counties, which indicates that individuals’ health will deteriorate as the income share of rich people increases. In addition, our results show that there is an inverted U-shaped relationship between income inequality, as measured by the county-level Gini coefficient, and individuals’ health status. We also find that income inequality affects health through the accessibility of healthcare facilities and public infrastructures and through hazardous health behaviours such as smoking and alcohol use. These findings suggest that reducing income inequality could be an important means of improving the overall health of China’s population.

Background Chronic kidney disease is often asymptomatic in its early stages but constitutes a severe burden for patients and causes major healthcare systems costs worldwide. While models for assessing the cost-effectiveness of screening were proposed in the past, they often presented only a limited view. This study aimed to develop a simulation-based German Albuminuria Screening Model (S-GASM) and present some initial applications. Methods The model consists of an individual-based simulation of disease progression, considering age, gender, body mass index, systolic blood pressure, diabetes, albuminuria, glomerular filtration rate, and quality of life, furthermore, costs of testing, therapy, and renal replacement therapy with parameters based on published evidence. Selected screening scenarios were compared in a cost-effectiveness analysis. Results Compared to no testing, a simulation of 10 million individuals with a current age distribution of the adult German population and a follow-up until death or the age of 90 shows that a testing of all individuals with diabetes every two years leads to a reduction of the lifetime prevalence of renal replacement therapy from 2.5% to 2.3%. The undiscounted costs of this intervention would be 1164.10 € / QALY (quality-adjusted life year). Considering saved costs for renal replacement therapy, the overall undiscounted costs would be—12581.95 € / QALY. Testing all individuals with diabetes or hypertension and screening the general population reduced the lifetime prevalence even further (to 2.2% and 1.8%, respectively). Both scenarios were cost-saving (undiscounted, - 7127.10 €/QALY and—5439.23 €/QALY). Conclusions The S-GASM can be used for the comparison of various albuminuria testing strategies. The exemplary analysis demonstrates cost savings through albuminuria testing for individuals with diabetes, diabetes or hypertension, and for population-wide screening.

This study aimed to investigate the survival and efficacy indicators of human thyroid tissue transplantation into a retrievable, prevascularized implanted Sernova Corp Cell Pouch™ (CP) device. Thyroid tissue from human donors was transplanted subcutaneously into the pre-implanted CP device or into the subcutaneous (SC) space alone as a control in a nude Mus musculus model. Transplanted M. musculus were monitored for human serum thyroglobulin (TG) levels for 3 months until the transplants were removed for histological assessment. Human thyroid tissue survived and continued to produce TG in transplanted nude M. musculus in the CP, with no adverse events. CP transplants exhibited more persistent and robust production of human TG than tissue placed in the SC space alone from 3 to 13 weeks post transplantation. Fresh thyroid transplants had better survival and function compared to cryopreserved transplants. Thyroid transplant viability correlated with TG levels at 3 months post-transplant (p = 0.03). Immunofluorescence staining of transplants for TG and TPO localized in thyroid follicles. Human thyroid tissue transplanted into the subcutaneously implanted pre-vascularized CP in nude M. musculus survived and continued to produce robust and persistent human TG and warrants further investigation as a treatment for postoperative hypothyroidism.

Objective We investigated prevalence and predictors of glucose metabolism disorders (GMDs) among People Living with HIV (PLWH) on efavirenz- and atazanavir/ritonavir-based combination antiretroviral therapy (cART). Methods This cross-sectional study involved adult PLWH on efavirenz- (n = 240) and atazanavir/ritonavir-based (n = 111) cART. The prevalence of GMDs was determined by fasting serum glucose, insulin, and homeostasis model assessment. A logistic regression model was used to determine predictors. Results The overall prevalence of GMDs for all regimens was 27.6% (97/351) [95% CI 23.0–32.6%] s, with 31.1% (75/240) [95% CI 25.4–37.5%] for efavirenz-based and 19.8% (22/111) [95% CI 12.9–28.5%)] for atazanavir/ritonavir-based cART group. The prevalence of impaired fasting glycemia was significantly higher (p = 0.026) in the efavirenz- [(15.4%) (37/240); 95%CI (11.1–20.6%)] than atazanavir/ritonavir-based [(7.2%) (8/111), (95%CI (3.2–13.7%)] cART. However, no significant difference was observed in the prevalence of diabetes mellitus and insulin resistance between the two regimens. Age ≥46 years old and specific type of ARV contained in cART, such as TDF, were independent predictors of GMD in both groups. Whereas the male gender and BMI category were predictors of GMDs among EFV-based cART group, AZT- and ABC- containing regimens and triglyceride levels were predictors in the ATV/r-based group. Conclusions GMDs were highly prevalent among adults on EFV- than ATV/r-based cARTs. Age ≥46 years and TDF-containing cARTs are common predictors in both regimens. Close monitoring for impaired fasting glucose during long-term EFV-based cART is recommended for early diagnosis of type-2 diabetes and management.

d-allulose is a rare sugar that has been reported to possess anti-hyperglycemic effects. In the present study, we hypothesized that d-allulose is effective in attenuating the progression of diabetic nephropathy in the Otsuka Long-Evans Tokushima Fatty (OLETF) rat model of type 2 diabetes mellitus. Drinking water with or without 3% d-allulose was administered to OLETF rats for 13 weeks. Long-Evans Tokushima Otsuka rats that received drinking water without d-allulose were used as non-diabetic control rats. d-allulose significantly attenuated the increase in blood glucose levels and progressive mesangial expansion in the glomerulus, which is regarded as a characteristic of diabetic nephropathy, in OLETF rats. d-allulose also attenuated the significant increases in renal IL-6 and tumor necrosis factor-α mRNA levels in OLETF rats, which is a proinflammatory parameter. Additionally, we showed that d-allulose suppresses mesangial matrix expansion, but its correlation with suppressing renal inflammation in OLETF rats should be investigated further. Collectively, our results support the hypothesis that d-allulose can prevent diabetic nephropathy in rats.

Introduction We aimed to evaluate the association between the phase angle and muscle mass, muscle strength, physical performance tests, quality-of-life scales, mood scales, or patient and hospitalization-free survival rates in hemodialysis (HD) patients. Methods We included 83 HD patients. The patients were divided into tertiles based on phase angle value. The phase angle was measured using a bioimpedance analysis machine. Thigh muscle area per height squared (TMA/Ht2), handgrip strength (HGS), nutritional indicators, physical performance, quality-of-life, depression or anxiety status, and the presence of hospitalization or death regardless of cause were evaluated. Results In our study, no significant differences were observed in the serum albumin level and body mass index according to tertiles of phase angle. The phase angle tertiles were associated with TMA/Ht2 and HGS. The phase angle was also associated with physical performance measurements and depression or anxiety status. Subgroup analyses according to sex, age, and diabetes mellitus showed similar trends to those of the total cohort. Furthermore, the hospitalization-free survival rate and patient survival rate were favorable in patients with high values for the phase angle. Conclusion The present study demonstrated that the phase angle is associated with muscle mass, strength, physical performance, quality-of-life scale, and hospitalization-free survival in maintenance HD patients.

Background While conventional medicine (CM) is commonly used to treat non-communicable diseases (NCDs), complementary and alternative medicine (CAM) is gaining popularity as a healthcare option in Bangladesh. We aimed to investigate the prevalence and factors associated with using CAM solely and using CAM in conjunction with CM for chronic illness treatment among NCD patients in Bangladesh. Methods A multicenter cross-sectional study was conducted, including 549 adults with a confirmed chronic illness diagnosis from three tertiary care hospitals in Dhaka city. Interviews were used to gather socio-demographic data, while medical records were used to get information on chronic illnesses. A multinomial logistic regression model was used to determine the associated factors of utilizing CAM primarily and CAM use in conjunction with CM to manage the chronic disease. Results Out of 549 NCD patients (282 women [51.4%], mean [standard deviation] age 45.4 [12.8] years), 180 (32.8%) ever used CAM for the treatment of chronic illness. Also, 15.3% of patients exclusively used CAM among the NCD patients, while 17.5% used CAM in conjunction with CM. Homeopathy medicine was the most prevalent type of treatment among CAM users (52.2%). Furthermore, 55.5% of CAM users said they used it due to its less adverse effects, and 41.6% trusted its effectiveness for chronic illness. Elderly patients (≥60 years) preferred CAM in complementary with CM, but they did not rely only on CAM. According to the multinomial regression analysis, unmarried patients, predominantly in the younger age group, adopted CAM significantly for chronic illness treatment (Relative risk ratio, RRR = 0.29, 95% CI = 0.12–0.71, reference = Unmarried). Patients in the high-income group used CAM in conjunction with CM (RRR = 6.26, 95% CI = 1.35–18.90, reference: low-income), whereas patients in the high-income group did not rely on CAM alone (RRR = 0.99, 95% CI = 0.34–2.85). Conclusion Although CM remains the mainstream of health care in Bangladesh, CAM services play an essential role in people’s health care, particularly in treating chronic illnesses. Physicians of Bangladesh should be aware that their patients may be using other services and be prepared to ask and answer questions regarding the risks and benefits of using CAM in addition to regular medical care. Thus, clinicians required to follow best-practice guidelines, which are currently not practiced in Bangladesh, when disseminating information regarding integrative techniques that combine CM and CAM approaches.

Glycation process refers to reactions between reduction sugars and amino acids that can lead to formation of advanced glycation end products (AGEs) which are related to changes in chemical and functional properties of biological structures that accumulate during aging and diseases. The aim of this study was to perform and analyze in vitro glycation by fructose and methylglyoxal (MGO) using salivary fluid, albumin, lysozyme, and salivary α-amylase (sAA). Glycation effect was analyzed by biochemical and spectroscopic methods. The results were obtained by fluorescence analysis, infrared spectroscopy (total attenuated reflection—Fourier transform, ATR-FTIR) followed by multivariate analysis of principal components (PCA), protein profile, immunodetection, enzymatic activity and oxidative damage to proteins. Fluorescence increased in all glycated samples, except in saliva with fructose. The ATR-FTIR spectra and PCA analysis showed structural changes related to the vibrational mode of glycation of albumin, lysozyme, and salivary proteins. Glycation increased the relative molecular mass (Mr) in protein profile of albumin and lysozyme. Saliva showed a decrease in band intensity when glycated. The analysis of sAA immunoblotting indicated a relative reduction in intensity of its correspondent Mr after sAA glycation; and a decrease in its enzymatic activity was observed. Carbonylation levels increased in all glycated samples, except for saliva with fructose. Thiol content decreased only for glycated lysozyme and saliva with MGO. Therefore, glycation of salivary fluid and sAA may have the potential to identify products derived by glycation process. This opens perspectives for further studies on the use of saliva, an easy and non-invasive collection fluid, to monitor glycated proteins in the aging process and evolution of diseases.

Background Increasing global diabetes incidence has profound implications for health systems and for people living with diabetes. Guidelines have established clinical targets but there may be variation in clinical outcomes including HbA1c, based on location and practice size. Investigating this variation may help identify factors amenable to systemic improvement interventions. The aims of this study were to identify centre-specific and patient-specific factors associated with variation in HbA1c levels and to determine how these associations contribute to variation in performance across diabetes centres. Methods This cross-sectional study analysed data for 5,872 people with type 1 (n = 1,729) or type 2 (n = 4,143) diabetes mellitus collected through the Australian National Diabetes Audit (ANDA). A linear mixed-effects model examined centre-level and patient-level factors associated with variation in HbA1c levels. Results Mean age was: 43±17 years (type 1), 64±13 (type 2); median disease duration: 18 years (10,29) (type 1), 12 years (6,20) (type 2); female: 52% (type 1), 45% (type 2). For people with type 1 diabetes, volume of patients was associated with increases in HbA1c (p = 0.019). For people with type 2 diabetes, type of centre was associated with reduction in HbA1c (p Conclusions Centre-level and patient-level factors were associated with variation in HbA1c, but patient-level factors had greater impact. Interventions targeting patient-level factors conducted at a centre level including sick-day management, smoking cessation programs and culturally appropriate diabetes education for and Aboriginal and Torres Strait Islander peoples may be more important for improving glycaemic control than targeting factors related to the Centre itself.

Introduction Non-Communicable Diseases (NCDs) have become the leading public health problems worldwide and the cardiovascular diseases (CVDs) is one of the major NCDs. Female Community Health Volunteers (FCHVs) in Nepal are the key drivers to implementing frontline health services. We explored the potential for engaging FCHVs for CVD risk screening at the community level in Nepal. Methods We used multiple approaches (quantitative and qualitative) for data collection. The trained FCHVs administered CVD risk screening questionnaire among 491 adults in rural and urban areas and calculated the CVD risk scores. To maintain consistency and quality, a registered medical doctor also, using the same risk scoring chart, independently calculated the CVD risk scores. Kappa statistics and concordance coefficient were used to compare these two sets of risk screening results. Sensitivity and specificity analyses were conducted. Two focus group discussions among the FCHVs were conducted to determine their experiences with CVD risk screening and willingness to engage with CVD prevention and control efforts. Results The mean level of agreement between two sets of risk screening results was 94.5% (Kappa = 0.77, P Conclusion We conclude that there is a potential for engaging FCHVs to use simple CVD risk screening tools at the community level. The findings are promising, however, further studies engaging larger number of FCHVs and larger population would warrant feasibility of such tools within the existing healthcare systems in Nepal.

Carotid plaque is a subclinical measure of atherosclerosis. We have previously shown measures of carotid plaque to be heritable in a sample of 100 Dominican families and found evidence for linkage and association of common variants (CVs) on 7q36, 11p15, 14q32 and 15q23 with plaque presence. Our current study aimed to refine these regions further and identify rare variants (RVs) influencing plaque presence. Therefore, we performed targeted sequencing of the one LOD unit down region on 7q36, 11p15, 14q32 and 15q23 in 12 Dominican families with evidence for linkage to plaque presence. Gene-based RV analyses were performed using the Sequence Association Test for familial data (F-SKAT) under two filtering algorithms; 1. all exonic RVs and 2. non-synonymous RVs. Replication analyses were performed using a sample of 22 Dominican families and 556 unrelated Dominicans with Exome Array data. To identify additional non-synonymous RVs influencing plaque, we looked for co-segregation of RVs with plaque in each of the sequenced families. Our most strongly associated gene with evidence for replication was AMPD3 which showed suggestive association with plaque presence in the sequenced families (exonic RV p = 0.003, nonsynonymous RV p = 0.005) and replication families (exonic RV p = 0.04, nonsynonymous RV p = 0.02). Examination of the sequenced family pedigrees revealed two missense variants on chromosome 11 which co-segregated with plaque presence in one of our families; rs61751342 (located in DENND2B), and rs61760882 (located in RNF141). The rs61751342 missense variant is an eQTL for SCUBE2 in the atrial appendage. Notably, SCUBE2 encodes a protein which interacts with vascular endothelial growth factor (VEGF) receptor 2 to regulate VEGF-induced angiogenesis, thus providing biologic plausibility for this gene in atherosclerosis. In conclusion, using targeted sequencing of previously-identified linkage regions, we have identified suggestive evidence for the role of RVs in carotid plaque pathogenesis.

Background Suboptimal glycemic control among patients with type 2 diabetes mellitus (DM) is a significant public health problem, particularly among people living with poor education and economic statuses, including those with a unique dietary culture. This study aimed to estimate the prevalence and identify the factors associated with suboptimal glycemic control among patients with type 2 DM during the coronavirus disease-2019 (COVID-19) pandemic. Methods A hospital-based cross-sectional study was used to elicit information from DM patients attending six hospitals located in Chiang Rai Province, northern Thailand, between February and May 2021. A validated questionnaire and 5 mL blood specimens were used as the research tools. Glycated hemoglobin (HbA1c) greater than 7.0% among DM patients at least two years after diagnosis was defined as suboptimal glycemic control. Chi-square tests and logistic regression were used to identify the associations between variables at the significance level α = 0.05. Results A total of 967 patients were recruited for this study; 54.8% 530 had suboptimal glycemic control, 58.8% were female, 66.5% were aged 50-69 years, and 78.5% were married (78.5%). Six variables were found to be associated with suboptimal glycemic control in multivariable logistic regression. Participants aged Conclusion Effective health interventions to control blood glucose among DM patients during ongoing treatment are urgently required. The interventions should focus on patients aged less than 69 years, marital status, forgetting to take their medication, and a longer time since diagnosis, including reducing their sticky rice consumption. The effects of copayments should also be considered.

Objective The aim of the present study was to investigate the associations between breastfeeding and the prevalence of metabolic syndrome in community-dwelling parous women and to clarify whether the associations depend on age. Methods The present cross-sectional study included 11,118 women, aged 35–69 years. Participants’ longest breastfeeding duration for one child and their number of breastfed children were assessed using a self-administered questionnaire, and their total breastfeeding duration was approximated as a product of the number of breastfed children and the longest breastfeeding duration. The longest and the total breastfeeding durations were categorized into none and tertiles above 0 months. Metabolic syndrome and cardiovascular risk factors (obesity, hypertension, dyslipidemia, and hyperglycemia) were defined as primary and secondary outcomes, respectively. Associations between breastfeeding history and metabolic syndrome or each cardiovascular risk factor were assessed using multivariable unconditional logistic regression analysis. Results Among a total of 11,118 women, 10,432 (93.8%) had ever breastfed, and 1,236 (11.1%) had metabolic syndrome. In participants aged Conclusions Breastfeeding history may be related to lower prevalence of metabolic syndrome in middle-aged parous women.

Introduction Diabetes mellitus (DM), hypertension and pulmonary tuberculosis (PTB) are catastrophic illnesses that collectively lead to increased mortality and premature death. However, the size of the problem and the appropriate approach to deal with the burden is still unclear. We aimed to evaluate the yield, number needed to screen (NNS) to prevent one death or adverse event for screening DM and hypertension and assess the prevalence and contributors to DM and/or hypertension. Methods Based on PTB contact tracing, a cross-sectional study was conducted among 801 PTB index cases and 972 household contacts from April 2019 to October 2020 in Guizhou, China. All the participants were screened for DM and hypertension. The yield was calculated as the proportion of newly detected cases among the study subjects, excluding known cases. The NNS was computed by dividing the number needed to treat for risk factors by the prevalence of the unrecognized diseases. The univariate and multivariate logistic regression analyses were applied to determine the independent predictors of DM and/or hypertension. Results Of the 1,773 participants, the prevalence of DM and hypertension was 8.7% (70/801) and 15.2% (122/801) in the PTB patients, 3.2% (31/972) and 14.0% (136/972) in the contacts, respectively. The prevalence of DM and/or hypertension was 21.2% (170/801) among the PTB patients and 15.4% (150/972) among their contacts. The screening yields to detect new cases of DM and hypertension among PTB patients were 1.9% and 5.2%, and that in the contacts were 0.8% and 4.8%, respectively. The NNS for DM was 359 for the PTB cases and 977 for the contacts, 299 for PTB cases and 325 for hypertension, respectively. Older age, under or overweight and obesity, family history hypertension and earlier diagnosis of other chronic conditions were the independent predictors for DM and/or hypertension among both PTB cases and their contacts. Conclusion Screening for DM and hypertension should be mandated in PTB patients and their household contacts to disclose undetected cases of these two conditions during TB contact tracing, which might reduce the potential cardiovascular disease deaths.

Background Clinical pathways are changing to incorporate support and appropriate follow-up for people to achieve remission of type 2 diabetes, but there is limited understanding of the prevalence of remission in current practice or patient characteristics associated with remission. Methods and findings We carried out a cross-sectional study estimating the prevalence of remission of type 2 diabetes in all adults in Scotland aged ≥30 years diagnosed with type 2 diabetes and alive on December 31, 2019. Remission of type 2 diabetes was assessed between January 1, 2019 and December 31, 2019. We defined remission as all HbA1c values, Mireille Captieux and co-workers report on population-level evidence for remission of type 2 diabetes in Scotland., Author summary Why was this study done? Feasibility of diabetes remission has been demonstrated in research settings and after bariatric surgery, but we do not know how many people in the general population achieve remission of type 2 diabetes. Informed decisions need to be made about which people are most likely to achieve and maintain remission; to do this, we need to better understand the characteristics of people who are currently in remission. Estimating the prevalence of remission of type 2 diabetes in Scotland in 2019 creates a baseline to evaluate the impact of future initiatives to support remission and for future studies of duration of remission and effect on risk of complications of diabetes. What did the researchers do and find? We calculated how many people were in remission of type 2 diabetes in 2019 in Scotland from a national type 2 diabetes register. This register contains 99% of people with diabetes in Scotland. We described the characteristics of people who were in remission of type 2 diabetes compared to people who were not in remission and created a mathematical model that shows the probability of achieving remission in 2019 based on these characteristics. We found that about 1 in 20 of people with type 2 diabetes in the study population were in remission of type 2 diabetes. Compared to people who did not achieve remission, people in remission of type 2 diabetes tended to be older; have a lower HbA1c at diagnosis; have never taken any glucose-lowering medication; have lost weight since the diagnosis of diabetes; and have had bariatric surgery. What do these findings mean? There is a sizeable proportion of people who achieve remission of type 2 diabetes outside research trials and without bariatric surgery. These people should be recognised and coded appropriately so they can be supported by their clinicians. The clinical progress of these people can now be followed by researchers. People who have not yet been prescribed drugs to treat diabetes may be the most appropriate group for clinicians to initiate discussions around remission and weight management options. Guidelines for supporting people who achieve remission of diabetes must recognise differences between people that lose weight intentionally and those that lose weight because of severe illness. Clinicians also need greater clarity on how to manage older or frailer people who achieve remission criteria.

Background Some earlier studies have found indications of significant changes in cardiometabolic risk factors in children born after assisted reproductive technology (ART). Most of these studies are based on small cohorts with high risk of selection bias. In this study, we compared the risk of cardiovascular disease, obesity, and type 2 diabetes between singleton children born after ART and singleton children born after spontaneous conception (SC). Methods and findings This was a large population-based cohort study of individuals born in Norway, Sweden, Finland, and Denmark between 1984 and 2015. Data were obtained from national ART and medical birth registers and cross-linked with data from national patient registers and other population-based registers in the respective countries. In total, 122,429 children born after ART and 7,574,685 children born after SC were included. Mean (SD) maternal age was 33.9 (4.3) years for ART and 29.7 (5.2) for SC, 67.7% versus 41.8% were primiparous, and 45.2% versus 32.1% had more than 12 years of education. Preterm birth (p = 0.02), obesity (HR 1.13; 95% CI 1.05–1.23; p = 0.002), and type 2 diabetes (HR 1.71; 95% CI 1.08–2.73; p = 0.02). After adjustment, there was no significant difference between children born after ART and children born after SC for any cardiovascular disease (adjusted HR [aHR]1.02; 95% CI 0.86–1.22; p = 0.80) or type 2 diabetes (aHR 1.31; 95% CI 0.82–2.09; p = 0.25). For any cardiovascular disease, the 95% CI was reasonably narrow, excluding effects of a substantial magnitude, while the 95% CI for type 2 diabetes was wide, not excluding clinically meaningful effects. For obesity, there was a small but significant increased risk among children born after ART (aHR 1.14; 95% CI 1.06–1.23; p = 0.001). Important limitations of the study were the relatively short follow-up time, the limited number of events for some outcomes, and that the outcome obesity is often not considered as a disease and therefore not caught by registers, likely leading to an underestimation of obesity in both children born after ART and children born after SC. Conclusions In this study, we observed no difference in the risk of cardiovascular disease or type 2 diabetes between children born after ART and children born after SC. For obesity, there was a small but significant increased risk for children born after ART. Trial registration number ISRCTN11780826.

Objective To assess the healthcare utilization, economic burden, and long-term neurological complications and mortality of an adult population with Japanese encephalitis (JE). Methods This study utilized two nationwide datasets in Taiwan: the Notifiable Disease Dataset of confirmed cases from the Centers for Disease Control to identify JE patients, and the National Health Insurance Research Database to obtain patients’ healthcare utilization. Survival analyses were performed to identify prognostic factors associated with the all-cause mortality of patients. Results This study included 352 adult cases with JE (aged≥20 years). The mean age of JE patients was 45 years. Stroke (event rate: 3.49/100 person-years) was the most common neurological complication, followed by epilepsy/convulsions (3.13/100 person-years), encephalopathy/delirium (2.20/100 person-years), and parkinsonism (1.97/100 person-years). Among the 336 hospitalized patients at JE diagnosis, 58.33% required intensive care. Among 79 patients who died following JE diagnosis, 48.84% of death events occurred within the year of diagnosis. The medical costs increased considerably at JE diagnosis and subsequent-year costs remained significantly higher than the costs before diagnosis (p, Author summary The epidemiology of adulthood Japanese encephalitis (JE) remains limited, and data on the economic burden associated with JE is lacking. This study is the first to comprehensively examine the healthcare burden (i.e., healthcare utilization and costs, neurological complications, all-cause mortality) of an adult population with JE, utilizing a nationwide cohort of JE-infected adults with up to 16 years of follow-up. In the first 6 months following JE diagnosis, a higher rate of neurological disorders was found, compared to the years after the diagnosis, with stroke being the most common neurological complication, followed by epilepsy/convulsions. The healthcare utilization of JE patients was higher in the first 6 months after the diagnosis compared to the years following the diagnosis. Medical costs increased considerably at JE diagnosis and subsequent-year costs after diagnosis remained higher than the cost before diagnosis. Having comorbid diabetes or incident epilepsy/convulsion events was a significant risk factor for mortality of adults with JE. Being born after 1976 in Taiwan, and thus likely receiving a four-dose schedule of vaccination, was associated with reduced mortality. Therefore, special attention is required for JE patients with comorbid diabetes or incident epilepsy/convulsion events, and JE vaccination should be considered to prevent this sporadic but lethal viral infection.

Background Some earlier studies have found indications of significant changes in cardiometabolic risk factors in children born after assisted reproductive technology (ART). Most of these studies are based on small cohorts with high risk of selection bias. In this study, we compared the risk of cardiovascular disease, obesity, and type 2 diabetes between singleton children born after ART and singleton children born after spontaneous conception (SC). Methods and findings This was a large population-based cohort study of individuals born in Norway, Sweden, Finland, and Denmark between 1984 and 2015. Data were obtained from national ART and medical birth registers and cross-linked with data from national patient registers and other population-based registers in the respective countries. In total, 122,429 children born after ART and 7,574,685 children born after SC were included. Mean (SD) maternal age was 33.9 (4.3) years for ART and 29.7 (5.2) for SC, 67.7% versus 41.8% were primiparous, and 45.2% versus 32.1% had more than 12 years of education. Preterm birth (, Emma Norrman and co-workers study the health of children born with and without assisted reproductive technology., Author summary Why was this study done? Earlier studies have found indications of alterations in cardiometabolic risk factors in children born after assisted reproductive technology (ART). Most earlier studies are based on small cohorts with high risk of selection bias. Furthermore, most earlier studies have measured markers and risk factors for disease instead of clinical diseases. In this study we wanted to compare the risk of cardiovascular disease, obesity, and type 2 diabetes between singleton children born after ART and singleton children born after spontaneous conception (SC). What did the researchers do and find? By combining high-quality Nordic registers, we included singleton children born after ART (n = 122,429) and SC (n = 7,574,685) between 1984 and 2015 in Norway, Sweden, Finland, and Denmark. The findings showed that children born after ART had no increased risk of cardiovascular disease or type 2 diabetes after adjustment for measured confounders. For any cardiovascular disease, the 95% CI was reasonably narrow, excluding effects of a substantial magnitude, while the 95% CI for type 2 diabetes was wide, not excluding clinically meaningful effects. We observed a slightly increased risk of obesity in children born after ART. What do these findings mean? Since type 2 diabetes and most of the cardiovascular diseases had a limited number of events, the ART population is relatively young, and there was a slightly increased risk of obesity in children born after ART, there is a need for further studies with longer follow-up in this area.

Background Dengue infections are on the rise in Sri Lanka and are spreading to all areas in the country. Here, we discuss the changes in dengue epidemiology in Sri Lanka in relation to changes in age distribution, changes in seroprevalence rates over time, and possible reasons contributing to such changes. Methods and findings Although the incidence of dengue increased 20-fold from the year 2000 to 2012 and a further 3-fold from 2012 to 2019, this increase is not reflected in a similar increase in the age-stratified seropositivity rates for dengue. For instance, the annual seroconversion rates were 0.76% in 2013 and 0.91% in 2017. The annual seroconversion rates in the 6 to 17 age group were 1.5% per year in 2003, 3.9% in 2013, and 4.1% in 2017. In addition, although a 13-fold increase in dengue was seen in those who were, Author summary Dengue infections are on the rise in Sri Lanka and are spreading throughout the country. Although the incidence of dengue increased 20-fold from the year 2000 to 2012 and a further 3-fold from 2012 to 2019, this increase is not reflected in a similar increase in the age-stratified seropositivity rates for dengue, with the annual seroconversion rates being 0.76% in 2013 and 0.91% in 2017. In addition, although a 13-fold increase in dengue was seen in those who were

Background Angiotensin receptor blockers (ARBs) may have protective effects against dementia occurrence in patients with hypertension (HTN). However, whether telmisartan, an ARB with peroxisome proliferator-activated receptor γ (PPAR-γ)–modulating effects, has additional benefits compared to other ARBs remains unclear. Methods and findings Between 1997 and 2013, 2,166,944 type 2 diabetes mellitus (T2DM) patients were identified from the National Health Insurance Research Database of Taiwan. Patients with HTN using ARBs were included in the study. Patients with a history of stroke, traumatic brain injury, or dementia were excluded. Finally, 65,511 eligible patients were divided into 2 groups: the telmisartan group and the non-telmisartan ARB group. Propensity score matching (1:4) was used to balance the distribution of baseline characteristics and medications. The primary outcome was the diagnosis of dementia. The secondary outcomes included the diagnosis of Alzheimer disease and occurrence of symptomatic ischemic stroke (IS), any IS, and all-cause mortality. The risks between groups were compared using a Cox proportional hazard model. Statistical significance was set at p < 0.05. There were 2,280 and 9,120 patients in the telmisartan and non-telmisartan ARB groups, respectively. Patients in the telmisartan group had a lower risk of dementia diagnosis (telmisartan versus non-telmisartan ARBs: 2.19% versus 3.20%; HR, 0.72; 95% CI, 0.53 to 0.97; p = 0.030). They also had lower risk of dementia diagnosis with IS as a competing risk (subdistribution HR, 0.70; 95% CI, 0.51 to 0.95; p = 0.022) and with all-cause mortality as a competing risk (subdistribution HR, 0.71; 95% CI, 0.53 to 0.97; p = 0.029). In addition, the telmisartan users had a lower risk of any IS (6.84% versus 8.57%; HR, 0.79; 95% CI, 0.67 to 0.94; p = 0.008) during long-term follow-up. Study limitations included potential residual confounding by indication, interpretation of causal effects in an observational study, and bias caused by using diagnostic and medication codes to represent real clinical data. Conclusions The current study suggests that telmisartan use in hypertensive T2DM patients may be associated with a lower risk of dementia and any IS events in an East-Asian population., Chi-Hung Liu and co-workers study associations between antihypertensive medication prescriptions and dementia risk in people with type 2 diabetes., Author summary Why was this study done? The drug of choice for antihypertensive treatment, and its association with dementia in patients with both type 2 diabetes mellitus (T2DM) and hypertension, is a valid question worthy of further investigations. Angiotensin receptor blockers (ARBs) modulate the renin–angiotensin–aldosterone system and potentially associate with cognitive preservation, but internal comparisons of the cognitive protective effects of different ARBs have not previously been performed. Telmisartan is the only ARB that, at a clinical dose, has agonistic effects on peroxisome proliferator-activated receptor γ (PPAR-γ), which maintains insulin sensitivity, reduces insulin resistance, and potentially has a protective impact on dementia. What did the researchers do and find? Using the electronic health records of the National Health Insurance Research Database of Taiwan between 1997 and 2013, we studied whether telmisartan was associated with a lower incidence of dementia compared to other ARBs in patients with T2DM and hypertension. Using telmisartan was associated with a lower risk of dementia diagnosis compared to using non-telmisartan ARBs (2.19% versus 3.20%). What do these findings mean? Telmisartan use in hypertensive T2DM patients may be associated with a lower risk of dementia and any ischemic stroke events in an East-Asian population. Further work will be needed to investigate the observed association, owing to the limitations inherent in this observational study.

Background Given the central role of skeletal muscles in glucose homeostasis, deposition of adipose depots beneath the fascia of muscles (versus subcutaneous adipose tissue [SAT]) may precede insulin resistance and type 2 diabetes (T2D) incidence. This study was aimed to investigate the associations between computed tomography (CT)–derived biomarkers for adipose tissue and T2D incidence in normoglycemic adults. Methods and findings This study was a population-based multiethnic retrospective cohort of 1,744 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with normoglycemia (baseline fasting plasma glucose [FPG] less than 100 mg/dL) from 6 United States of America communities. Participants were followed from April 2010 and January 2012 to December 2017, for a median of 7 years. The intermuscular adipose tissue (IMAT) and SAT areas were measured in baseline chest CT exams and were corrected by height squared (SAT and IMAT indices) using a predefined measurement protocol. T2D incidence, as the main outcome, was based on follow-up FPG, review of hospital records, or self-reported physician diagnoses. Participants’ mean age was 69 ± 9 years at baseline, and 977 (56.0%) were women. Over a median of 7 years, 103 (5.9%) participants were diagnosed with T2D, and 147 (8.4%) participants died. The IMAT index (hazard ratio [HR]: 1.27 [95% confidence interval [CI]: 1.15–1.41] per 1-standard deviation [SD] increment) and the SAT index (HR: 1.43 [95% CI: 1.16–1.77] per 1-SD increment) at baseline were associated with T2D incidence over the follow-up. The associations of the IMAT and SAT indices with T2D incidence were attenuated after adjustment for body mass index (BMI) and waist circumference, with HRs of 1.23 (95% CI: 1.09–1.38) and 1.29 (95% CI: 0.96–1.74) per 1-SD increment, respectively. The limitations of this study include unmeasured residual confounders and one-time measurement of adipose tissue biomarkers. Conclusions In this study, we observed an association between IMAT at baseline and T2D incidence over the follow-up. This study suggests the potential role of intermuscular adipose depots in the pathophysiology of T2D. Trial registration ClinicalTrials.gov NCT00005487, In a cohort study, Shadpour Demehri and colleagues investigate the association between adipose tissue biomarkers and type 2 diabetes incidence in normoglycemic participants in US., Author summary Why was this study done? This study was designed to investigate the associations between computed tomography (CT)–derived biomarkers for adipose tissue at baseline and type 2 diabetes (T2D) incidence in normoglycemic adults. What did the researchers do and find? We assessed 1,744 normoglycemic participants with chest CT exams between 2010 and 2012. The intermuscular adipose tissue (IMAT) and subcutaneous adipose tissue (SAT) areas were measured in these chest CT exams using a predefined measurement protocol. Participants were followed from April 2010 and January 2012 to December 2017, for a median of 7 years, for T2D incidence. T2D incidence was based on follow-up fasting plasma glucose (FPG), review of hospital records, or self-reported physician diagnoses. This study found that a higher CT-derived IMAT at baseline was associated with T2D incidence over the follow-up. What do these findings mean? In normoglycemic participants, the IMAT deposition was associated with T2D incidence. This study suggests the potential role of intermuscular adipose depots in the pathophysiology of T2D. The CT-derived adipose tissue biomarkers are obtainable from CT exams performed for other initial indications and can extend the value of the routinely performed chest CT exams. Such biomarkers may be associated with T2D incidence.

Background Primary prevention of cardiovascular disease (CVD) requires adequate control of hypertension and diabetes. We designed and implemented pharmaceutical and healthy lifestyle interventions for patients with diabetes and/or hypertension in rural primary care, and assessed their effectiveness at reducing severe CVD events. Methods and findings We used a pragmatic, parallel group, 2-arm, controlled, superiority, cluster trial design. We randomised 67 township hospitals in Zhejiang Province, China, to intervention (34) or control (33). A total of 31,326 participants were recruited, with 15,380 in the intervention arm and 15,946 in the control arm. Participants had no known CVD and were either patients with hypertension and a 10-year CVD risk of 20% or higher, or patients with type 2 diabetes regardless of their CVD risk. The intervention included prescription of a standardised package of medicines, individual advice on lifestyle change, and adherence support. Control was usual hypertension and diabetes care. In both arms, as usual in China, most outpatient drug costs were out of pocket. The primary outcome was severe CVD events, including coronary heart disease and stroke, during 36 months of follow-up, as recorded by the CVD surveillance system. The study was implemented between December 2013 and May 2017. A total of 13,385 (87%) and 14,745 (92%) participated in the intervention and control arms, respectively. Their mean age was 64 years, 51% were women, and 90% were farmers. Of all participants, 64% were diagnosed with hypertension with or without diabetes, and 36% were diagnosed with diabetes only. All township hospitals and participants completed the 36-month follow-up. At 36 months, there were 762 and 874 severe CVD events in the intervention and control arms, respectively, yielding a non-significant effect on CVD incidence rate (1.92 and 2.01 per 100 person-years, respectively; crude incidence rate ratio = 0.90 [95% CI: 0.74, 1.08; P = 0.259]). We observed significant, but small, differences in the change from baseline to follow-up for systolic blood pressure (−1.44 mm Hg [95% CI: −2.26, −0.62; P < 0.001]) and diastolic blood pressure (−1.29 mm Hg [95% CI: −1.77, −0.80; P < 0.001]) in the intervention arm compared to the control arm. Self-reported adherence to recommended medicines was significantly higher in the intervention arm compared with the control arm at 36 months. No safety concerns were identified. Main study limitations include all participants being informed about their high CVD risk at baseline, non-blinding of participants, and the relatively short follow-up period available for judging potential changes in rates of CVD events. Conclusions The comprehensive package of pharmaceutical and healthy lifestyle interventions did not reduce severe CVD events over 36 months. Improving health system factors such as universal coverage for the cost of essential medicines is required for successful risk-based CVD prevention programmes. Trial registration ISRCTN registry ISRCTN58988083., Xiaolin Wei and co-workers evaluate a multifactorial intervention for primary prevention of cardiovascular disease in Zhejiang province, China., Author summary Why was this study done? Pharmaceutical interventions have been shown to reduce cardiovascular disease (CVD) events, but the evidence has limited policy implications as medicines in trials have been typically been provided free of charge. Four previous trials examining CVD-risk-based management treatments in high-income countries were focused on healthy lifestyle interventions and did not identify any clear effects on CVD events. Two previous trials in low- and middle-income countries implemented both pharmaceutical and lifestyle interventions, but they were not designed to examine impacts on CVD events. What did the researchers do and find? We conducted a cluster randomised controlled trial in rural China among 31,326 patients with (1) hypertension who had a CVD risk of 20% or higher or (2) diabetes, and followed participants up for 36 months. Interventions included prescription of a standardised package of medicines, individual advice on lifestyle change, and adherence support provided by a team led by family doctors. We compared this to usual existing care. The study found that our comprehensive pharmaceutical and lifestyle interventions did not reduce severe CVD events. We observed significant, but small, differences in the change from baseline to follow-up of systolic blood pressure (−1.44 mm Hg) and diastolic blood pressure (−1.29 mm Hg) in the intervention arm compared to the control arm. Self-reported adherence to recommended medicines was significantly higher in the intervention arm compared with the control arm at 36 months. In the process evaluation, we identified that the unaffordability of the medications, caused by lack of health insurance coverage and the non-availability of cheaper generic medicine, appeared to discourage patients from taking recommended medicines. What do these findings mean? Comprehensive pharmaceutical and lifestyle interventions were feasible and effective in improving medicine uptake and reducing blood pressure, but not in achieving a reduction in severe CVD events, when implemented in a setting where the costs of essential medicines were insufficiently covered. This study highlights the importance of improving universal health coverage as a prerequisite for effective CVD prevention programmes in primary care in similar settings.

Coronavirus Disease 2019 (COVID-19), caused by a new strain of coronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), was declared a pandemic by WHO on March 11, 2020. Soon after its emergence in late December 2019, it was noticed that diabetic individuals were at an increased risk of COVID-19–associated complications, ICU admissions, and mortality. Maintaining proper blood glucose levels using insulin and/or other oral antidiabetic drugs (such as Metformin) reduced the detrimental effects of COVID-19. Interestingly, in diabetic COVID-19 patients, while insulin administration was associated with adverse outcomes, Metformin treatment was correlated with a significant reduction in disease severity and mortality rates among affected individuals. Metformin was extensively studied for its antioxidant, anti-inflammatory, immunomodulatory, and antiviral capabilities that would explain its ability to confer cardiopulmonary and vascular protection in COVID-19. Here, we describe the various possible molecular mechanisms that contribute to Metformin therapy’s beneficial effects and lay out the scientific basis of repurposing Metformin for use in COVID-19 patients.

Background There is growing recognition of the contribution of the social determinants of health to the burden of many infectious diseases. However, the relationship between socioeconomic status and the incidence and outcome of melioidosis is incompletely defined. Methods All residents of Far North Queensland, tropical Australia with culture-proven melioidosis between January 1998 and December 2020 were eligible for the study. Their demographics, comorbidities and socioeconomic status were correlated with their clinical course. Socioeconomic status was determined using the Socio-Economic Indexes for Areas (SEIFA) Index of Relative Socio-economic Disadvantage score, a measure of socioeconomic disadvantage developed by the Australian Bureau of Statistics. Socioeconomic disadvantage was defined as residence in a region with a SEIFA score in the lowest decile in Australia. Results 321 eligible individuals were diagnosed with melioidosis during the study period, 174 (54.2%) identified as Indigenous Australians; 223/321 (69.5%) were bacteraemic, 85/321 (26.5%) required Intensive Care Unit (ICU) admission and 37/321 (11.5%) died. 156/321 (48.6%) were socioeconomically disadvantaged, compared with 56603/269002 (21.0%) of the local general population (p, Author summary The social determinants of health—the circumstances in which people grow, live, work, and age, and the systems put in place to deal with illness—have a profound effect on how, when, and even if patients access healthcare, and yet they are generally under-appreciated by practicing clinicians whose training emphasises the biomedical model of healthcare. In this region of tropical Australia patients diagnosed with melioidosis were more likely to live in a socioeconomically disadvantaged region. Socioeconomically disadvantaged individuals with melioidosis were also more likely to die from their infection and to die at a younger age. It was notable that socioeconomic disadvantage had a greater independent association with in-hospital death than age, Indigenous status, the presence of bacteraemia or any of the comorbidities that classically predispose individuals to melioidosis. A more holistic approach to the delivery of healthcare—which addresses the social determinants of health—is necessary if we are to reduce the burden of melioidosis and the many other health conditions that disproportionately affect the most disadvantaged members of our society.

Frozen shoulder is a painful condition that often requires surgery and affects up to 5% of individuals aged 40–60 years. Little is known about the causes of the condition, but diabetes is a strong risk factor. To begin to understand the biological mechanisms involved, we aimed to identify genetic variants associated with frozen shoulder and to use Mendelian randomization to test the causal role of diabetes. We performed a genome-wide association study (GWAS) of frozen shoulder in the UK Biobank using data from 10,104 cases identified from inpatient, surgical and primary care codes. We used data from FinnGen for replication and meta-analysis. We used one-sample and two-sample Mendelian randomization approaches to test for a causal association of diabetes with frozen shoulder. We identified five genome-wide significant loci. The most significant locus (lead SNP rs28971325; OR = 1.20, [95% CI: 1.16–1.24], p = 5x10-29) contained WNT7B. This variant was also associated with Dupuytren’s disease (OR = 2.31 [2.24, 2.39], p, Author summary Frozen shoulder is a painful condition that often requires surgery and affects up to 5% of individuals aged 40–60 years. Little is known about the causes but it is known to be more common in people with diabetes. In a dataset of 500,000 people, we used a genome-wide association study to find genetic causes and a genetic technique called Mendelian randomisation to test if diabetes causes frozen shoulder. We found five new genetic variants that associate with frozen shoulder, and showed genetic overlap with Dupuytren’s Disease, a similar condition that affects the fingers. We found an association with diabetes and obesity, but that the obesity association disappeared when we accounted for diabetes status, suggesting the condition is glycaemic rather than mechanical. Our Mendelian randomisation study showed evidence that type 1 diabetes has a causal effect on development of frozen shoulder, likely through a pathway involving long-term high blood glucose levels.

Background Coronavirus Disease 2019 (COVID-19) excess deaths refer to increases in mortality over what would normally have been expected in the absence of the COVID-19 pandemic. Several prior studies have calculated excess deaths in the United States but were limited to the national or state level, precluding an examination of area-level variation in excess mortality and excess deaths not assigned to COVID-19. In this study, we take advantage of county-level variation in COVID-19 mortality to estimate excess deaths associated with the pandemic and examine how the extent of excess mortality not assigned to COVID-19 varies across subsets of counties defined by sociodemographic and health characteristics. Methods and findings In this ecological, cross-sectional study, we made use of provisional National Center for Health Statistics (NCHS) data on direct COVID-19 and all-cause mortality occurring in US counties from January 1 to December 31, 2020 and reported before March 12, 2021. We used data with a 10-week time lag between the final day that deaths occurred and the last day that deaths could be reported to improve the completeness of data. Our sample included 2,096 counties with 20 or more COVID-19 deaths. The total number of residents living in these counties was 319.1 million. On average, the counties were 18.7% Hispanic, 12.7% non-Hispanic Black, and 59.6% non-Hispanic White. A total of 15.9% of the population was older than 65 years. We first modeled the relationship between 2020 all-cause mortality and COVID-19 mortality across all counties and then produced fully stratified models to explore differences in this relationship among strata of sociodemographic and health factors. Overall, we found that for every 100 deaths assigned to COVID-19, 120 all-cause deaths occurred (95% CI, 116 to 124), implying that 17% (95% CI, 14% to 19%) of excess deaths were ascribed to causes of death other than COVID-19 itself. Our stratified models revealed that the percentage of excess deaths not assigned to COVID-19 was substantially higher among counties with lower median household incomes and less formal education, counties with poorer health and more diabetes, and counties in the South and West. Counties with more non-Hispanic Black residents, who were already at high risk of COVID-19 death based on direct counts, also reported higher percentages of excess deaths not assigned to COVID-19. Study limitations include the use of provisional data that may be incomplete and the lack of disaggregated data on county-level mortality by age, sex, race/ethnicity, and sociodemographic and health characteristics. Conclusions In this study, we found that direct COVID-19 death counts in the US in 2020 substantially underestimated total excess mortality attributable to COVID-19. Racial and socioeconomic inequities in COVID-19 mortality also increased when excess deaths not assigned to COVID-19 were considered. Our results highlight the importance of considering health equity in the policy response to the pandemic., Andrew Stokes and co-workers report a county-level analysis of excess deaths owing to COVID-19 in the United States., Author summary Why was this study done? The Coronavirus Disease 2019 (COVID-19) pandemic has resulted in excess mortality that would not have occurred in the absence of the pandemic. Excess deaths include deaths assigned to COVID-19 in official statistics as well as deaths that are not assigned to COVID-19 but are attributable directly or indirectly to COVID-19. While prior studies have identified significant racial and socioeconomic inequities in directly assigned COVID-19 deaths, few studies have documented how excess mortality in 2020 has differed across sociodemographic or health factors in the United States. What did the researchers do and find? Leveraging data from 2,096 counties on COVID-19 and all-cause mortality, we assessed what percentage of excess deaths were not assigned to COVID-19 and examined variation in excess deaths by county characteristics. In these counties, we found that for every 100 deaths directly assigned to COVID-19 in official statistics, an additional 20 deaths occurred that were not counted as direct COVID-19 deaths. The proportion of excess deaths not counted as direct COVID-19 deaths was even higher in counties with lower average socioeconomic status, counties with more comorbidities, and counties in the South and West. Counties with more non-Hispanic Black residents, who were already at high risk of COVID-19 death based on direct counts, also reported a higher proportion of excess deaths not assigned to COVID-19. What do these findings mean? Direct COVID-19 death counts significantly underestimate excess mortality in 2020. Monitoring excess mortality will be critical to gain a full picture of socioeconomic and racial inequities in mortality attributable to the COVID-19 pandemic. To prevent inequities in mortality from growing even larger, health equity must be prioritized in the policy response to the COVID-19 pandemic.

Glucocorticoids are key regulators of glucose homeostasis and pancreatic islet function, but the gene regulatory programs driving responses to glucocorticoid signaling in islets and the contribution of these programs to diabetes risk are unknown. In this study we used ATAC-seq and RNA-seq to map chromatin accessibility and gene expression from eleven primary human islet samples cultured in vitro with the glucocorticoid dexamethasone at multiple doses and durations. We identified thousands of accessible chromatin sites and genes with significant changes in activity in response to glucocorticoids. Chromatin sites up-regulated in glucocorticoid signaling were prominently enriched for glucocorticoid receptor binding sites and up-regulated genes were enriched for ion transport and lipid metabolism, whereas down-regulated chromatin sites and genes were enriched for inflammatory, stress response and proliferative processes. Genetic variants associated with glucose levels and T2D risk were enriched in glucocorticoid-responsive chromatin sites, including fine-mapped variants at 51 known signals. Among fine-mapped variants in glucocorticoid-responsive chromatin, a likely casual variant at the 2p21 locus had glucocorticoid-dependent allelic effects on beta cell enhancer activity and affected SIX2 and SIX3 expression. Our results provide a comprehensive map of islet regulatory programs in response to glucocorticoids through which we uncover a role for islet glucocorticoid signaling in mediating genetic risk of T2D., Author summary Glucocorticoids regulate inflammation and metabolism and are widely used in the treatment of immune disorders, although prolonged exposure to glucocorticoids can lead to the development of diabetes. In this study we determined the response of primary pancreatic islets, which are central to the development of diabetes, to the glucocorticoid dexamethasone at multiple doses and durations. We observed widespread changes in pancreatic islets after glucocorticoid treatment at glucocorticoid receptor binding sites, as well as at key genes involved in islet function and processes related to steroid and lipid metabolism, ion channel activity, inflammation, and growth. Genetic variants affecting type 2 diabetes and glucose levels were located in sites affected by glucocorticoids at many genomic regions, and highlighted genes regulated by these sites through which glucocorticoid signaling may contribute directly to the development of diabetes. Together these results provide key insight into how glucocorticoid treatment affects pancreatic islet function and risk of diabetes.

Background Increased risk of miscarriage has been reported for women with specific chronic health conditions. A broader investigation of chronic diseases and miscarriage risk may uncover patterns across categories of illness. The objective of this study was to study the risk of miscarriage according to various preexisting chronic diseases. Methods and findings We conducted a registry-based study. Registered pregnancies (n = 593,009) in Norway between 2010 and 2016 were identified through 3 national health registries (birth register, general practitioner data, and patient registries). Six broad categories of illness were identified, comprising 25 chronic diseases defined by diagnostic codes used in general practitioner and patient registries. We required that the diseases were diagnosed before the pregnancy of interest. Miscarriage risk according to underlying chronic diseases was estimated as odds ratios (ORs) using generalized estimating equations adjusting for woman’s age. The mean age of women at the start of pregnancy was 29.7 years (SD 5.6 years). We observed an increased risk of miscarriage among women with cardiometabolic diseases (OR 1.25, 95% CI 1.20 to 1.31; p-value, In this registry data study, Maria Magnus and colleagues study associations between miscarriage risk and chronic conditions., Author summary Why was this study done? Scattered findings indicate that women with different chronic disease have an increased risk of miscarriage. To our knowledge, none of the existing studies have evaluated a broader range of chronic diseases to further evaluate the role of common as opposed to independent biological mechanisms. What did the researchers do and find? With linked data from Norwegian national registries (including 593,009 pregnancies), we examined the risk of miscarriage according to 25 different chronic diseases diagnosed prior to pregnancy. Although risk of miscarriage was largely unaffected by maternal chronic diseases, risk of miscarriage was associated with conditions related to cardiometabolic health. Other conditions associated with risk of miscarriage included hypoparathyroidism, Cushing syndrome, Crohn’s disease, and endometriosis. What do these findings mean? This finding is consistent with emerging evidence linking cardiovascular risk factors to pregnancy complications. Further investigation is necessary to better understand the underlying mechanisms resulting in an increased risk of miscarriage across a range of chronic diseases.

In a response to a Formal Comment critiquing their model for classifying individualized glucose patterns into glucotypes, these authors stand by their results and conclusions, which can be reproduced using their publicly available data, and maintain that improved algorithms for analyzing CGM data will continue to emerge and enrich the field.

The purpose of this longitudinal follow-up study was to investigate the risk of ischemic stroke nationwide in patients with seropositive rheumatoid arthritis (RA) and controls who were matched in age and sex. Patient data were collected from the National Health Insurance Service (NHIS) Health Screening (HEALS) cohort. Using the International Classification of Diseases code M05 (seropositive RA), with a prescription of any disease-modifying anti-rheumatic drug (DMARD), RA was identified. A total of 2,765 patients and 13,825 control subjects were included in our study. The 12-year incidence of ischemic stroke in each group was calculated using the Kaplan–Meier method. The risk ratio of ischemic stroke was estimated using Cox proportional hazards regression. Sixty-four patients (2.31%) in the seropositive RA group and 512 (3.70%) in the control group experienced ischemic stroke (P < 0.001) during the follow-up period. The hazard ratio of ischemic stroke in the seropositive RA group was 1.32 (95% confidence interval (CI), 1.02–1.73) after adjusting for age and sex. The adjusted hazard ratio of ischemic stroke in the seropositive RA group was 1.40 (95% CI, 1.07–1.82) after adjusting for demographics and comorbid medical disorders. According to the subgroup analysis, the hazard ratios of ischemic stroke risks in the female and hypertensive subgroups were 1.44 (95% CI, 1.05–1.97) and 1.66 (95% CI, 1.16–2.38), respectively. In the non-diabetes and non-dyslipidemia subgroups, the corresponding hazard ratios of ischemic stroke were 1.47 (95% CI, 1.11–1.95) and 1.43 (95% CI, 1.07–1.91). Seropositive RA patients have an increased risk of ischemic stroke. In female, hypertension, non-diabetes, and non-dyslipidemia RA subgroups, even without the traditional risk factors for stroke (except for hypertension), increased the risk, which could be potentially attributed to RA.

COVID-19 is a respiratory disease caused by SARS-CoV-2, which has significantly impacted economic and public healthcare systems worldwide. SARS-CoV-2 is highly lethal in older adults (>65 years old) and in cases with underlying medical conditions, including chronic respiratory diseases, immunosuppression, and cardio-metabolic diseases, including severe obesity, diabetes, and hypertension. The course of the COVID-19 pandemic in Mexico has led to many fatal cases in younger patients attributable to cardio-metabolic conditions. Thus, in the present study, we aimed to perform an early spatial epidemiological analysis for the COVID-19 outbreak in Mexico. Firstly, to evaluate how mortality risk from COVID-19 among tested individuals (MRt) is geographically distributed and secondly, to analyze the association of spatial predictors of MRt across different states in Mexico, controlling for the severity of the disease. Among health-related variables, diabetes and obesity were positively associated with COVID-19 fatality. When analyzing Mexico as a whole, we identified that both the percentages of external and internal migration had positive associations with early COVID-19 mortality risk with external migration having the second-highest positive association. As an indirect measure of urbanicity, population density, and overcrowding in households, the physicians-to-population ratio has the highest positive association with MRt. In contrast, the percentage of individuals in the age group between 10 to 39 years had a negative association with MRt. Geographically, Quintana Roo, Baja California, Chihuahua, and Tabasco (until April 2020) had higher MRt and standardized mortality ratios, suggesting that risks in these states were above what was nationally expected. Additionally, the strength of the association between some spatial predictors and the COVID-19 fatality risk varied by zone.

Diabetic neuropathy is the most common complication affecting more than 50% of patients with longstanding diabetes. Till date, there are no reports to explain the scientific basis of alternative medicine as an adjunct therapy for treating diabetic neuropathy. Hence, we studied the effect of honey and insulin treatment on hyperglycemia, dyslipidemia, oxidant and anti-oxidant status and nerve conduction in experimental diabetic neuropathy Wistar rats. In this experimental study, forty healthy male Wistar albino rats of 10–12 weeks age, weighing between 150 to 200g were obtained from our institute central animal house. After acclimatization, the rats were divided into control (n = 8) and experimental (n = 32) groups randomly. In the experimental group, type 2 diabetic neuropathy was induced with high fat and high sugar diet for 8 weeks followed by streptozotocin at a dose of 35 mg/kg body weight. Three days after streptozotocin injection, blood glucose levels of rats were measured from fasting samples to confirm diabetes. After the development of diabetes, rats were given standard rodent chow and allowed four more weeks to remain diabetic and to develop neuropathy. Every second week, nerve conduction study was done to confirm neuropathy. All the diabetic rats of experimental group developed neuropathy after 4 weeks of developing diabetes, which was confirmed by significant reduction in conduction velocity of sensory and motor nerve when compared to non-diabetic control group. After the development of neuropathy, these rats were randomly divided into diabetic neuropathy with no treatment group (n = 8) and three treatment groups (n = 8, each). The rats of treatment group were administered with either honey or insulin or honey+insulin for six weeks. After six-weeks of intervention, there was significant decrease in blood glucose and lipids in honey, insulin and honey+insulin treated neuropathy rats, when compared with no treatment group. Malondialdehyde was reduced and total anti-oxidant status improved in all the three treatment groups. There was no significant increase in conduction velocity of sciatic tibial motor nerve in treatment groups when compared with no treatment group. However, the sensory nerve conduction velocity improved significantly in honey+insulin treated neuropathy rats. In conclusion, six-week honey treatment helped in reducing dyslipidemia and oxidative stress. Honey given along with insulin for six-weeks improved sensory nerve conduction velocity in experimental diabetic neuropathy Wistar rats.

Background A year after the COVID-19 pandemic started, there are still few scientific reports on COVID-19 in Africa. This study explores the clinical profiles and factors associated with COVID-19 in Cameroon. Materials and methods In this prospective cohort study, we followed patients admitted for suspicion of COVID-19 at Djoungolo Hospital between 01st April and 31st July 2020. Patients were categorised by age groups and disease severity: mild (symptomatic without clinical signs of pneumonia), moderate (with clinical signs of pneumonia without respiratory distress) and severe cases (clinical signs of pneumonia and respiratory distress not requiring invasive ventilation). Demographic information and clinical features were summarised. Multivariable analysis was performed to predict risk. Findings A total of 313 patients were admitted during the study period; 259 were confirmed cases of COVID-19 by Polymerase Chain Reaction (PCR). Among the confirmed cases, the male group aged 40 to 49 years (13.9%) was predominant. Disease severity ranged from mild (26.2%; n = 68) to moderate (59%; n = 153) to severe (14.7%; n = 38); the case fatality rate was 1% (n = 4). Dysgusia (46%; n = 119) and hyposmia/anosmia (37.8%; n = 98) were common features of COVID-19. Nearly one-third of patients had comorbidities (29%; n = 53), of which hypertension was the most common (18.9%; n = 49). Participation in mass gatherings (Odds Ratio (OR) = 2.37; P = 0.03) and dysgusia (OR = 2.09, P = 0.02) were predictive of diagnosis of COVID-19. Age groups 60 to 69 (OR = 7.41; P = 0.0001), 50 to 59 (OR = 4.09; P = 0.03), 40 to 49 (OR = 4.54; P = 0.01), male gender (OR = 2.53; P = 0.04), diabetes (OR = 4.05; P = 0.01), HIV infection (OR = 5.57; P = 0.03), lung disease (OR = 6.29; P = 0.01), dyspnoea (OR = 3.70; P = 0.008) and fatigue (OR = 3.35; P = 0.02) significantly predicted COVID-19 severity. Conclusions Most COVID-19 cases in this study were benign with low fatality. Age (40–70), male gender, HIV infection, lung disease, dyspnoea and fatigue are associated with severe COVID-19. Such findings may guide public health decision-making.

Objectives In this study we aimed to 1) describe healthy ageing trajectory patterns, 2) examine the association between multimorbidity and patterns of healthy ageing trajectories, and 3) evaluate how different groups of diseases might affect the projection of healthy ageing trajectories over time. Setting and participants Our study was based on 130880 individuals from the Ageing Trajectories of Health: Longitudinal Opportunities and Synergies (ATHLOS) harmonised dataset, as well as 9171 individuals from Waves 2–7 of the English Longitudinal Study of Ageing (ELSA). Methods Using a healthy ageing index score, which comprised 41 items, covering various domains of health and ageing, as outcome, we employed the growth mixture model approach to identify the latent classes of individuals with different healthy ageing trajectories. A multinomial logistic regression was conducted to assess if and how multimorbidity status and multimorbidity patterns were associated with changes in healthy ageing, controlled for sociodemographic and lifestyle risk factors. Results Three similar patterns of healthy ageing trajectories were identified in the ATHLOS and ELSA datasets: 1) a ‘high stable’ group (76% in ATHLOS, 61% in ELSA), 2) a ‘low stable’ group (22% in ATHLOS, 36% in ELSA) and 3) a ‘rapid decline’ group (2% in ATHLOS, 3% in ELSA). Those with multimorbidity were 1.7 times (OR = 1.7, 95% CI: 1.4–2.1) more likely to be in the ‘rapid decline’ group and 11.7 times (OR = 11.7 95% CI: 10.9–12.6) more likely to be in the ‘low stable’ group, compared with people without multimorbidity. The cardiorespiratory/arthritis/cataracts group was associated with both the ‘rapid decline’ and the ‘low stable’ groups (OR = 2.1, 95% CI: 1.2–3.8 and OR = 9.8, 95% CI: 7.5–12.7 respectively). Conclusion Healthy ageing is heterogeneous. While multimorbidity was associated with higher odds of having poorer healthy ageing trajectories, the extent to which healthy ageing trajectories were projected to decline depended on the specific patterns of multimorbidity.

Background The association between prolong metformin usage and B12 deficiency has been documented. However, the prevalence estimates of metformin-induced vitamin B12 deficiency showed substantial disparity among studies due to varied study definitions of vitamin B12 deficiency. Metformin blocks the calcium dependent absorption of the vitamin B12-Intrinsic Factor complex at the terminal ileum. Lack of intrinsic factor due to the presence of auto-antibodies to parietal cells (IFA) could lead to vitamin B12 deficiency and subsequently cause peripheral neuropathy. We investigated the prevalence of vitamin B12 deficiency using more sensitive, combined markers of vitamin B12 status (4cB12) and the immuno-biochemical mediators of vitamin B12 deficiency. Methods In this observational study, 200 consecutive consenting metformin-treated T2DM patients, aged 35 and above, attending the diabetic clinic at KATH were recruited. Vitamin B12 deficiency was classified based on the Fedosov age-normalized wellness quotient. Anthropometric measurement was taken as well as blood samples for immunological and biochemical mediators. Peripheral neuropathy was assessed using the Michigan Neuropathy Screening Instrument (MNSI). Statistical analysis was performed using the R Language for Statistical Computing. Results Using the combined indicator (4cB12), the prevalence of metformin induced vitamin B12 deficiency was 40.5% whilst the prevalence of MNSI-Q and MNSI-PE diabetic neuropathy was 32.5% and 6.5% respectively. Participants with vitamin B12 deficiency had significantly higher levels of IFA, GPA, TNF-α, TC, LDL and albumin compared to those with normal vitamin B12 levels (p < 0.05). Correlation analysis revealed a statistically significant negative association between 4cB12 and the immunological markers [IFA (rs = -0.301, p12 was negatively associated with TC (rs = -0.203, p = 0.004) and LDL (rs = -0.222, p = 0.002) but positively correlated with HDL (rs = 0.196, p = 0.005). Conclusion Vitamin B12 deficiency and diabetic neuropathy are very high among metformin-treated T2DM patients and it is associated with increased GPA, IFA, TNF-α and cardiometabolic risk factors (higher LDL and TC and lower HDL). Upon verification of these findings in a prospective case-control study, it may be beneficial to include periodic measurement of Vitamin B12 using the more sensitive combined indicators (4cB 12) in the management of patients with T2DM treated with metformin in Ghana.

Background Diabetes is a global public health problem and associated with metabolic, cellular, and blood disturbances. Hematological changes have been reported in diabetes and play a major role in diabetes-associated complications. However, reports are contradicting and data on hematological parameters of type 2 diabetic patients in the study area are scarce. Therefore, the aim of this study was to assess the hematological parameters of type 2 diabetic adult patients at Debre Berhan Referral Hospital, Northeast Ethiopia from May 01 to June 30, 2020. Methods A comparative cross-sectional study was conducted on 268 (134 type 2 diabetic patients and 134 controls) study participants selected by systematic random sampling technique. Socio-demographic, behavioral, and clinical data were collected using a structured questionnaire and checklist. Ethical approval was obtained from Jimma University. All phase of quality assurance was maintained. Hematological parameters and blood glucose levels were determined using UniCel DxH 800 (Beckman Coulter, USA) and Biosystems A25 (Costa Brava, Spain) analyzers, respectively. Independent t-test, Mann–Whitney U-test, correlation, and logistic regression were used during data analysis. P-value Results The current study found that total white blood cell count, absolute counts of neutrophil, lymphocyte, eosinophil, and basophil, red blood cell distribution width, platelet count, and mean platelet volume were significantly higher in type 2 diabetic patients as compared to the control group (P Conclusion This study showed a statistically significant variation in some hematological parameters of type 2 diabetic patients compared to control group. Anemia among type 2 diabetic patients was found to be a mild public health problem. Therefore, routine screening of hematological parameters should be considered for proper management of type 2 diabetic patients. Close attention should also be given to the duration of diabetes and dietary practice.

Introduction Taxes on sugar-sweetened beverages (SSBs) have gained support as a policy response to adverse health effects associated with SSB consumption. On July 1, 2017, Oakland, California, implemented a one-cent/ounce tax on SSBs with ≥25 calories/12 fluid ounces. This study estimated the long-term impact of the tax on taxed and untaxed beverage prices. Methods Data on 5,830 taxed and 5,146 untaxed beverage prices were obtained from 99 stores in Oakland and 111 stores in Sacramento (comparison site), California, in late May-June 2017 and June 2019. Linear regression difference-in-differences models were computed with store and product fixed effects, with robust standard errors clustered on store, weighted based on volume sold by beverage sweetener status, type, and size. Results Taxed beverage prices increased by 0.73 cents/ounce (95% CI = 0.47,1.00) on average in supermarkets and grocery stores in Oakland relative to Sacramento and 0.74 cents/ounce (95% CI = 0.39,1.09) in pharmacies, but did not change in convenience stores (-0.09 cents/ounce, 95% CI = -0.56,0.39). Untaxed beverage prices overall increased by 0.40 cents/ounce (95% CI = 0.05,0.75) in pharmacies but did not change in other store types. Prices of taxed individual-size soda specifically increased in all store types, by 0.91–2.39 cents/ounce (p Conclusions Two years following SSB tax implementation, there was partial tax pass-through with differences by store type and by beverage type and size within store type.