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Major causes of death in preterm infants in selected hospitals in Ethiopia (SIP): a prospective, cross-sectional, observational study. Muhe Lulu M,McClure Elizabeth M,Nigussie Assaye K,Mekasha Amha,Worku Bogale,Worku Alemayehu,Demtse Asrat,Eshetu Beza,Tigabu Zemene,Gizaw Mahlet A,Workneh Netsanet,Girma Abayneh,Asefa Mesfin,Portales Ramon,Bekele Tiruzer,Bezabih Mesele,Metaferia Gesit,Gashaw Mulatu,Abebe Bewketu,Berta Hailu,Alemu Addisu,Desta Tigist,Hailu Rahell,Gebreyesus Goitom,Aynalem Sara,Abdissa Alemseged L,Pfister Riccardo,Bonger Zelalem Tazu,Gizaw Solomon,Abebe Tamrat,Berhane Melkamu A,Bekuretsion Yonas,Dhaded Sangappa,Patterson Janna,Goldenberg Robert L The Lancet. Global health BACKGROUND:Neonatal deaths now account for 47% of all deaths in children younger than 5 years globally. More than a third of newborn deaths are due to preterm birth complications, which is the leading cause of death. Understanding the causes and factors contributing to neonatal deaths is needed to identify interventions that will reduce mortality. We aimed to establish the major causes of preterm mortality in preterm infants in the first 28 days of life in Ethiopia. METHODS:We did a prospective, cross-sectional, observational study in five hospitals in Ethiopia. Study participants were preterm infants born in the study hospitals at younger than 37 gestational weeks. Infants whose gestational age could not be reliably estimated and those born as a result of induced abortion were excluded from the study. Data were collected on maternal and obstetric history, clinical maternal and neonatal conditions, and laboratory investigations. For neonates who died of those enrolled, consent was requested from parents for post-mortem examinations (both complete diagnostic autopsy and minimally invasive tissue sampling). An independent panel of experts established the primary and contributory causes of preterm mortality with available data. FINDINGS:Between July 1, 2016, to May 31, 2018, 4919 preterm infants were enrolled in the study and 3852 were admitted to neonatal intensive care units. By 28 days of post-natal age, 1109 (29%) of those admitted to the neonatal intensive care unit died. Complete diagnostic autopsy was done in 441 (40%) and minimally invasive tissue sampling in 126 (11%) of the neonatal intensive care unit deaths. The main primary causes of death in the 1109 infants were established as respiratory distress syndrome (502 [45%]); sepsis, pneumonia and meningitis (combined as neonatal infections; 331 [30%]), and asphyxia (151 [14%]). Hypothermia was the most common contributory cause of preterm mortality (770 [69%]). The highest mortality occurred in infants younger than 28 weeks of gestation (89 [86%] of 104), followed by infants aged 28-31 weeks (512 [54%] of 952), 32-34 weeks (349 [18%] of 1975), and 35-36 weeks (159 [8%] of 1888). INTERPRETATION:Three conditions accounted for 89% of all deaths among preterm infants in Ethiopia. Scale-up interventions are needed to prevent or treat these conditions. Further research is required to develop effective and affordable interventions to prevent and treat the major causes of preterm death. FUNDING:Bill & Melinda Gates Foundation. 10.1016/S2214-109X(19)30220-7
Risk of non-fatal cardiovascular diseases in early-onset versus late-onset type 2 diabetes in China: a cross-sectional study. Huo Xiaoxu,Gao Leili,Guo Lixin,Xu Wen,Wang Wenbo,Zhi Xinyue,Li Ling,Ren Yanfeng,Qi Xiuying,Sun Zhong,Li Weidong,Ji Qiuhe,Ran Xingwu,Su Benli,Hao Chuanming,Lu Juming,Guo Xiaohui,Zhuo Hanjing,Zhang Danyi,Pan Changyu,Weng Jianping,Hu Dayi,Yang Xilin,Ji Linong The lancet. Diabetes & endocrinology BACKGROUND:The age of onset of type 2 diabetes is decreasing. Because non-Chinese patients with early-onset type 2 diabetes (defined here as diagnosis at <40 years) have increased risk of vascular complications, we investigated effects of early-onset versus late-onset type 2 diabetes on risk of non-fatal cardiovascular diseases in China. METHODS:We did a cross-sectional survey using data from the China National HbA1c Surveillance System (CNHSS), including 222,773 Chinese patients with type 2 diabetes in 630 hospitals from 106 cities in 30 provinces of China in 2012. We documented demographic information and clinical profiles. Non-fatal cardiovascular disease was defined as non-fatal coronary heart disease or non-fatal stroke. Prevalence of non-fatal cardiovascular diseases was standardised to the Chinese population in 2011. We did logistic regression analysis to obtain odds ratios (ORs) for the risk of cardiovascular disease in patients with early-onset versus late-onset type 2 diabetes. Because the CNHSS did not contain patients on diet or lifestyle treatment alone, and did not capture information on smoking or lipid or antihypertensive treatment, we validated our findings in another dataset from a cross-sectional, multicentre observational study (the 3B study) of outpatients with type 2 diabetes to confirm that exclusion of patients with diet treatment only and non-adjustment for lipid-lowering and antihypertensive drugs did not introduce major biases in the main analysis. FINDINGS:Of 222,773 patients recruited from April 1, 2012, to June 30, 2012, 24,316 (11%) had non-fatal cardiovascular disease. Patients with early-onset diabetes had a higher age-adjusted prevalence of non-fatal cardiovascular disease than did patients with late-onset diabetes (11·1% vs 4·9%; p<0·0001). After adjustment for age and sex, patients with early-onset type 2 diabetes had higher risk of non-fatal cardiovascular disease than did those with late-onset type 2 diabetes (OR 1·91, 95% CI 1·81-2·02). Adjustment for duration of diabetes greatly attenuated the effect size for risk of non-fatal cardiovascular disease (1·13, 1·06-1·20). Results of the validation study showed that exclusion of patients with diet only and non-adjustment for lipid-lowering and antihypertensive drugs resulted in marginal changes in ORs for risk of non-fatal cardiovascular disease in patients with early-onset versus late-onset type 2 diabetes. Early-onset type 2 diabetes remained associated with increased risk of cardiovascular disease, attributable to longer duration of diabetes. INTERPRETATION:Chinese patients with early-onset type 2 diabetes are at increased risk of non-fatal cardiovascular disease, mostly attributable to longer duration of diabetes. FUNDING:Novo Nordisk China (for the China National HbA1c Surveillance System [CNHSS]) and Merck Sharp & Dohme China (for the 3B study). 10.1016/S2213-8587(15)00508-2
Infection prevention and control compliance in Tanzanian outpatient facilities: a cross-sectional study with implications for the control of COVID-19. The Lancet. Global health BACKGROUND:As coronavirus disease 2019 (COVID-19) spreads, weak health systems must not become a vehicle for transmission through poor infection prevention and control practices. We assessed the compliance of health workers with infection prevention and control practices relevant to COVID-19 in outpatient settings in Tanzania, before the pandemic. METHODS:This study was based on a secondary analysis of cross-sectional data collected as part of a randomised controlled trial in private for-profit dispensaries and health centres and in faith-based dispensaries, health centres, and hospitals, in 18 regions. We observed provider-patient interactions in outpatient consultation rooms, laboratories, and dressing rooms, and categorised infection prevention and control practices into four domains: hand hygiene, glove use, disinfection of reusable equipment, and waste management. We calculated compliance as the proportion of indications (infection risks) in which a health worker performed a correct action, and examined associations between compliance and health worker and facility characteristics using multilevel mixed-effects logistic regression models. FINDINGS:Between Feb 7 and April 5, 2018, we visited 228 health facilities, and observed at least one infection prevention and control indication in 220 facilities (118 [54%] dispensaries, 66 [30%] health centres, and 36 [16%] hospitals). 18 710 indications were observed across 734 health workers (49 [7%] medical doctors, 214 [29%] assistant medical officers or clinical officers, 106 [14%] nurses or midwives, 126 [17%] clinical assistants, and 238 [32%] laboratory technicians or assistants). Compliance was 6·9% for hand hygiene (n=8655 indications), 74·8% for glove use (n=4915), 4·8% for disinfection of reusable equipment (n=841), and 43·3% for waste management (n=4299). Facility location was not associated with compliance in any of the infection prevention and control domains. Facility level and ownership were also not significantly associated with compliance, except for waste management. For hand hygiene, nurses and midwives (odds ratio 5·80 [95% CI 3·91-8·61]) and nursing and medical assistants (2·65 [1·67-4·20]) significantly outperformed the reference category of assistant medical officers or clinical officers. For glove use, nurses and midwives (10·06 [6·68-15·13]) and nursing and medical assistants (5·93 [4·05-8·71]) also significantly outperformed the reference category. Laboratory technicians performed significantly better in glove use (11·95 [8·98-15·89]), but significantly worse in hand hygiene (0·27 [0·17-0·43]) and waste management (0·25 [0·14-0·44] than the reference category. Health worker age was negatively associated with correct glove use and female health workers were more likely to comply with hand hygiene. INTERPRETATION:Health worker infection prevention and control compliance, particularly for hand hygiene and disinfection, was inadequate in these outpatient settings. Improvements in provision of supplies and health worker behaviours are urgently needed in the face of the current pandemic. FUNDING:UK Medical Research Council, Economic and Social Research Council, Department for International Development, Global Challenges Research Fund, Wellcome Trust. 10.1016/S2214-109X(20)30222-9
Temporal change in population-level prevalence of detectable HIV viraemia and its association with HIV incidence in key populations in India: a serial cross-sectional study. The lancet. HIV BACKGROUND:Population-level prevalence of detectable HIV viraemia (PDV) has been proposed as a metric for monitoring the population-level effectiveness of HIV treatment as prevention. We aimed to characterise temporal changes in PDV in people who inject drugs (PWID) and men who have sex with men (MSM) in India and evaluate community-level and individual-level associations with cross-sectional HIV incidence. METHODS:We did a serial cross-sectional study in which baseline (from Oct 1, 2012, to Dec 19, 2013) and follow-up (from Aug 1, 2016, to May 28, 2017) respondent-driven sampling (RDS) surveys were done in MSM (ten community sites) and PWID (12 community sites) across 21 cities in India. Eligible participants were those aged 18 years or older who provided informed consent and possessed a valid RDS referral coupon. Annualised HIV incidence was estimated with validated multiple-assay algorithms. PDV was calculated as the percentage of people with detectable HIV RNA (>150 copies per mL) in a community site. Community-level associations were determined by linear regression. Multivariable, multilevel Poisson regression was used to assess associations with recent HIV infection. FINDINGS:We recruited 21 990 individuals in the baseline survey and 21 726 individuals in the follow-up survey. The median community-level HIV incidence estimate increased from 0·9% (range 0·0-2·2) at baseline to 1·5% (0·5-3·0) at follow-up in MSM and from 1·6% (0·5-12·4) to 3·6% (0·0-18·4) in PWID. At the community-level, every 1 percentage point increase in baseline PDV and temporal change in PDV between surveys was associated with higher annualised HIV incidence at follow-up: for baseline PDV β=0·41 (95% CI 0·18-0·63) and for change in PDV β=0·52 (0·38-0·66). After accounting for individual-level risk factors, every 10 percentage point increase in baseline PDV and temporal change in PDV was associated with higher individual-level risk of recent HIV infection at follow-up: adjusted risk ratio 1·85 (95% CI 1·44-2·37) for baseline PDV and 1·81 (1·43-2·29) for change in PDV. INTERPRETATION:PDV was temporally associated with community-level and individual-level HIV incidence. These data support scale-up of treatment as prevention programmes to reduce HIV incidence and the programmatic use of PDV to monitor community HIV risk potential. FUNDING:US National Institutes of Health, Elton John AIDS Foundation. 10.1016/S2352-3018(21)00098-9
Small airways disease in mild and moderate chronic obstructive pulmonary disease: a cross-sectional study. Koo Hyun-Kyoung,Vasilescu Dragoş M,Booth Steven,Hsieh Aileen,Katsamenis Orestis L,Fishbane Nick,Elliott W Mark,Kirby Miranda,Lackie Peter,Sinclair Ian,Warner Jane A,Cooper Joel D,Coxson Harvey O,Paré Peter D,Hogg James C,Hackett Tillie-Louise The Lancet. Respiratory medicine BACKGROUND:The concept that small conducting airways less than 2 mm in diameter become the major site of airflow obstruction in chronic obstructive pulmonary disease (COPD) is well established in the scientific literature, and the last generation of small conducting airways, terminal bronchioles, are known to be destroyed in patients with very severe COPD. We aimed to determine whether destruction of the terminal and transitional bronchioles (the first generation of respiratory airways) occurs before, or in parallel with, emphysematous tissue destruction. METHODS:In this cross-sectional analysis, we applied a novel multiresolution CT imaging protocol to tissue samples obtained using a systematic uniform sampling method to obtain representative unbiased samples of the whole lung or lobe of smokers with normal lung function (controls) and patients with mild COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 1), moderate COPD (GOLD 2), or very severe COPD (GOLD 4). Patients with GOLD 1 or GOLD 2 COPD and smokers with normal lung function had undergone lobectomy and pneumonectomy, and patients with GOLD 4 COPD had undergone lung transplantation. Lung tissue samples were used for stereological assessment of the number and morphology of terminal and transitional bronchioles, airspace size (mean linear intercept), and alveolar surface area. FINDINGS:Of the 34 patients included in this study, ten were controls (smokers with normal lung function), ten patients had GOLD 1 COPD, eight had GOLD 2 COPD, and six had GOLD 4 COPD with centrilobular emphysema. The 34 lung specimens provided 262 lung samples. Compared with control smokers, the number of terminal bronchioles decreased by 40% in patients with GOLD 1 COPD (p=0·014) and 43% in patients with GOLD 2 COPD (p=0·036), the number of transitional bronchioles decreased by 56% in patients with GOLD 1 COPD (p=0·0001) and 59% in patients with GOLD 2 COPD (p=0·0001), and alveolar surface area decreased by 33% in patients with GOLD 1 COPD (p=0·019) and 45% in patients with GOLD 2 COPD (p=0·0021). These pathological changes were found to correlate with lung function decline. We also showed significant loss of terminal and transitional bronchioles in lung samples from patients with GOLD 1 or GOLD 2 COPD that had a normal alveolar surface area. Remaining small airways were found to have thickened walls and narrowed lumens, which become more obstructed with increasing COPD GOLD stage. INTERPRETATION:These data show that small airways disease is a pathological feature in mild and moderate COPD. Importantly, this study emphasises that early intervention for disease modification might be required by patients with mild or moderate COPD. FUNDING:Canadian Institutes of Health Research. 10.1016/S2213-2600(18)30196-6
Culture-confirmed neonatal bloodstream infections and meningitis in South Africa, 2014-19: a cross-sectional study. The Lancet. Global health BACKGROUND:Few population-level estimates of invasive neonatal infections have been reported from sub-Saharan Africa. We estimated the national incidence risk, aetiology, and pathogen antimicrobial susceptibility for culture-confirmed neonatal bloodstream infections and meningitis in South Africa. METHODS:We conducted a cross-sectional study of neonates (<28 days of life) admitted to neonatal or paediatric wards of 256 public sector health facilities in South Africa during 2014-19. Diagnostic pathology records from Jan 1, 2014, to Dec 31, 2019, were extracted from a national pathology data warehouse. A case was defined as a neonate with at least one positive blood or cerebrospinal fluid culture during a 14-day period. Incidence risk was calculated using annual numbers of registered livebirths. Among the causative pathogens identified, we calculated the proportion of cases attributed to each of them, as well as the rates of antibiotic susceptibility of Gram-positive and Gram-negative bacteria. FINDINGS:Among 43 438 records of positive cultures, there were 37 631 incident cases of neonatal infection with at least one pathogen isolated. The overall incidence risk of culture-confirmed infections was 6·0 per 1000 livebirths (95% CI 6·0-6·1). The incidence risk of late-onset sepsis (days 3-27 of life) was 4·9 per 1000 livebirths (4·9-5·0) and that of early-onset sepsis (days 0-2 of life) was 1·1 per 1000 livebirths (1·1-1·1); risk ratio 4·4 (95% CI 4·3-4·5). The cause of infection differed by syndrome, timing of infection onset, facility, and province, although Klebsiella pneumoniae (26%), Acinetobacter baumannii (13%), and Staphylococcus aureus (12%) were the dominant pathogens overall. Gram-negative bacteria had declining susceptibility to most antibiotics over the study period. INTERPRETATION:We found a high incidence risk of late-onset sepsis with provincial variations, predominance of K pneumoniae, and declining antibiotic susceptibility among Gram-negative bacteria. This national surveillance in an upper-middle-income country provides a baseline burden of neonatal infections against which the impact of future clinical and public health interventions can be measured. FUNDING:Bill & Melinda Gates Foundation. 10.1016/S2214-109X(22)00246-7
Colorectal cancer screening with fecal immunochemical testing: a community-based, cross-sectional study in average-risk individuals in Nigeria. The Lancet. Global health BACKGROUND:The estimated incidence of colorectal cancer is rising in Nigeria, where most patients present with advanced disease. Earlier detection of colorectal cancer is a goal of the Nigerian National Cancer Control Plan, but the utility of fecal-based screening is unclear. This study aimed to assess the fecal immunochemical test as a colorectal cancer screening modality in average-risk individualS in Nigeria. METHODS:A population-based, cross-sectional study of qualitative fecal immunochemical test-based colorectal cancer screening was done in asymptomatic, average-risk participants aged 45-75 years in three states in Nigeria (Osun, Kwara, and Lagos). Participants were invited to enrol using age-stratified and sex-stratified convenience sampling following community outreach. Exclusion criteria included a personal history of colorectal cancer or rectal bleeding in the previous 6 months, a first-degree relative with a known diagnosis of colorectal cancer, or a comorbidity that would preclude conscious sedation or general anesthesia. Participants with positive fecal immunochemical test results underwent colonoscopy, and the positive predictive value of fecal immunochemical testing for colorectal cancer and advanced adenomas (≥10 mm, tubulovillous or villous or high-grade dysplasia) was calculated. Data on demographics and acceptability of fecal immunochemical testing and colonoscopy were collected. FINDINGS:Between January and April 2021, 2330 participants were enrolled in the study and received a fecal immunochemical test, which was returned by 2109 participants. 1677 participants tested negative and 432 tested positive. Of these 432 participants, 285 underwent a colonoscopy (235 showed no polyps or cancer, 47 had polyps identified, and three had colorectal cancer identified). Of the 47 participants who had polyps identified, 20 had advanced adenomas diagnosed. The median age was 57 years (IQR 50-63), 958 (41%) were male and 1372 (59%) were female, and 68% had at least a secondary-level education. Participants were evenly spread across wealth quintiles. The positivity rate of the fecal immunochemical test was 21% overall (432 of 2109; 95% CI 20-21%), 11% (51 of 455; 95% CI 10-12) in Lagos, 20% (215 of 1052; 95% CI 20-21) in Osun, and 28% (166 of 597; 95% CI 27-29) in Kwara. Among the patients with a positive fecal immunochemical test who completed colonoscopy, the positive predictive value for invasive colorectal cancer was 1·1% (95% CI 0·3-3·3), and 7·0% (4·5-10·8) for advanced adenoma. The acceptability of fecal immunochemical screening among participants was very high. INTERPRETATION:Colorectal cancer screening with qualitative fecal immunochemical tests in Nigeria is feasible and acceptable to average-risk asymptomatic participants. However, the low positive predictive value for advanced neoplasia and high endoscopy burden investigating false positives suggests it might not be an appropriate screening tool in this setting. FUNDING:Thompson Family Foundation, Prevent Cancer Foundation, National Institutes of Health/National Cancer Institute Program Cancer Center. 10.1016/S2214-109X(22)00121-8
Associations between androgens and sexual function in premenopausal women: a cross-sectional study. Zheng Jia,Islam Rakibul M,Skiba Marina A,Bell Robin J,Davis Susan R The lancet. Diabetes & endocrinology BACKGROUND:Although clinicians often measure the serum concentration of androgens in premenopausal women presenting with sexual dysfunction, with some women given testosterone or dehydroepiandrosterone as treatment if their concentrations are low, whether androgens are determinants of sexual function in women of reproductive age is uncertain. We aimed to clarify the associations between androgens and sexual function in a community-based sample of non-health-care-seeking women. METHODS:This is a substudy of the Grollo-Ruzzene cross-sectional study, which recruited women aged 18-39 years from eastern states in Australia (QLD, NSW, VIC). After providing consent, women completed an online survey that included the Profile of Female Secual Function (PFSF) questionnaire, and those who were who were not pregnant, breastfeeding, or using systemic steroids were asked to provide a blood sample. At sampling, women were asked the dates of their last menstrual bleed. Serum androgens was measured by liquid chromatography and tandem mass spectrometry and sex hormone binding globulin (SHBG) by immunoassay. Associations between androgens and domains of sexual function, assessed by the PFSF, were examined in participants with regular menstrual cycles. After univariable linear regression (model 1), age, BMI, stage of menstrual cycle, and smoking status were added to the model (model 2), and then parity, partner status, and psychotropic medication use (model 3). FINDINGS:Of 6986 women who completed the online survey (surveys completed between Nov 11, 2016, and July 21, 2017), 3698 were eligible and 761 (20·6%) provided blood samples by Sept 30, 2017. Of those who provided a blood sample, 588 (77·3%) had regular menstrual cycles and were included in the analysis. Adjusting for age, BMI, cycle stage, smoking, parity, partner status, and psychoactive medication, sexual desire was positively associated with serum dehydroepiandrosterone (β-coefficient 3·39, 95% CI 0·65 to 6·03) and androstenedione (4·81, 0·16 to 9·12), and negatively with SHBG (-5.74, -9.54 to -1·90), each model explaining less than 4% of the variation in desire. Testosterone (6·00, 1·29 to 10·94) and androstenedione (6·05, 0·70 to 11·51) were significantly associated with orgasm, with the final models explaining less than 1% of the variation in orgasm. Significant associations were found between androstenedione (7·32, 0·93 to 13·08) and dehydroepiandrosterone (4·44, 0·86 to 7·95) and pleasure, and between testosterone and sexual self-image 5·87 (1·27 to 10·61), with inclusion of parity, partners status, and psychotropic drug use increasing the proportion of variation explained by each model to approximately 10%. There were no statistically significant associations between 11-oxygenated steroids and any PFSF domain, or between arousal or responsiveness and any hormone. No associations were seen between 11-oxygenated steroids and any sexual domain, or between arousal or responsiveness and any hormone. INTERPRETATION:Associations between androgens and sexual function in premenopausal women are small, and their measurement offers no diagnostic use in this context. Further research to determine whether 11-ketoandrostenedione or 11-ketotestosterone are of clinical significance is warranted. FUNDING:The Grollo-Ruzzene Foundation. 10.1016/S2213-8587(20)30239-4
Tailoring care for frail and lonely older people with HIV in Canada: a cross-sectional study. The lancet. HIV BACKGROUND:40-60% of people with HIV report experiencing loneliness, and 5-29% of PWH are frail (depending on the definition used). The risk of death in individuals who are frail and lonely, or frail and socially isolated has recently been estimated to be 1·8 times that in individuals who are not frail, lonely, or socially isolated. The aim of the present study was to determine the prevalence of loneliness, and other vulnerabilities related to ageing, in frail older adults with HIV. METHODS:We assessed frailty with the Clinical Frailty Scale (CFS) in a cross-sectional, convenience sample of people with HIV aged 50 years or older in Southern Alberta, Canada. All Southern Alberta Clinic patients aged 50 years or older who attended a virtual or in-person clinic visit between March and October, 2020, and who underwent frailty screening were included in the present analyses. Individuals scoring 4 or higher on the CFS then completed a structured questionnaire to provide information on additional co-factors, including loneliness (Three-item Loneliness Scale), falls, impaired gait and balance, polypharmacy, unintentional weight loss, food insecurity, and subjective cognitive concerns. Age, sex, nadir CD4 cell count, duration of known HIV infection, ethnicity, and risk category were evaluated for associations with frailty. We used t tests to compare means and Pearson χ tests to compare proportions. Patients gave written informed consent for use of data. The use of data was approved by the University of Calgary Conjoint Heath Research Ethics Board. FINDINGS:We assessed frailty in 292 older people with HIV. The mean age was 59 years (range 50-86 years) and 45 (16%) were women. On the basis of a score of 4 or greater on the CFS, 40 (14%) participants were identified as frail. Frail individuals tended to be older than those who were not frail (mean age 61·9 years, SD 8·5 versus 58·4 years, SD 6·3; t test difference 3·5, 95% CI 1·3-5·7; p=0·0011). However, there was no association between frailty status and sex, nadir CD4 cell count, duration of known HIV infection, or self-reported ethnicity. Frail individuals were more likely to report injection drug use as a component of their risk for acquisition than were non-frail individuals. Of the frail participants, 15 (42%) reported loneliness, 15 (42%) had fallen in the past year, and 18 (50%) reported impaired gait or balance. One-fifth (8) reported unintentional weight loss and 12 (33%) experienced food insecurity. Nearly 40% (14) reported subjective memory concerns. INTERPRETATION:In this sample of ageing people with HIV, frailty and loneliness were prevalent. Given the increased risk of death when frailty and loneliness are both present, upstream and targeted interventions are urgently needed. These might include measures to address loneliness, risk of falls, weight loss, food insecurity, and memory concerns. FUNDING:Canadian Foundation for Healthcare Improvement, Advancing Frailty Care in the Community. 10.1016/S2352-3018(22)00068-6
Influence of methodological and patient factors on serum NMDAR IgG antibody detection in psychotic disorders: a meta-analysis of cross-sectional and case-control studies. The lancet. Psychiatry BACKGROUND:Antibodies targeting the N-methyl-D-aspartate receptor (NMDAR) have been detected in patients with psychosis. However, studies measuring the IgG subclass in serum have provided variable estimates of prevalence, and it is unclear whether these antibodies are more common in patients than controls. Because these inconsistencies could be due to methodological approaches and patient characteristics, we aimed to investigate the effect of these factors on heterogeneity. METHODS:We searched Web of Science and Ovid (MEDLINE and PsycINFO) for cross-sectional and case-control studies published between Jan 1, 2000, and May 5, 2019, that reported NMDAR IgG antibody seropositivity in patients with psychosis. Pooled proportions and odds ratios (ORs) were derived using random-effects models. We estimated between-study variance (τ) and the proportion of observed variance due to heterogeneity (I). We then used univariable random-effects meta-regression analysis to investigate the effect of study factors on heterogeneity of proportions and ORs. Our protocol was registered on PROSPERO (CRD42018099874). FINDINGS:Of 1276 articles in the initial search, 28 studies were eligible for inclusion, including 14 cross-sectional studies and 14 case-control studies. In cross-sectional studies, NMDAR IgG antibodies were detected in 0·73% (95% CI 0·09-1·38; I 56%; p=0·026) of patients with psychosis, and in case-control studies, patients with psychosis were not significantly more likely to be seropositive than healthy individuals (OR 1·57, 95% CI 0·78-3·16; I 15%; p=0·20). Meta-regression analyses indicated that heterogeneity was significantly associated with assay type across both study designs, illness stage in cross-sectional studies, and study quality in case-control studies. Compared with studies using a fixed cell-based assay, cross-sectional and case-control studies using the live method yielded higher pooled prevalence estimates (0·36% [95% CI -0·23 to 0·95] vs 2·97% [0·70 to 5·25]) and higher ORs (0·65 [0·33 to 1·29] vs 4·43 [1·73 to 11·36]). In cross-sectional studies, the prevalence was higher in exclusively first-episode samples than in multi-episode or mixed samples (2·18% [0·25 to 4·12] vs 0·16% [-0·31 to 0·63]), and in case-control studies, higher ORs were reported in low-quality studies than in high-quality studies (3·80 [1·47 to 9·83] vs 0·72 [0·36 to 1·42]). INTERPRETATION:Higher estimates of NMDAR IgG antibody prevalence have been obtained with the live cell-based assay, and studies using this method find that seropositivity is more common in patients with psychosis than in controls. The effects of illness stage and study quality on heterogeneity were not consistent across study designs, and we provide clear recommendations for clinicians and researchers regarding interpreting these findings. FUNDING:None. 10.1016/S2215-0366(20)30432-6
Risk factors for lower bone mineral density in older adults with type 1 diabetes: a cross-sectional study. The lancet. Diabetes & endocrinology BACKGROUND:Type 1 diabetes is associated with lower bone mineral density (BMD) and increased fracture risk, but little is known regarding the effects of diabetes-related factors on BMD. We assessed whether these factors are associated with lower hip BMD among older adults with type 1 diabetes. METHODS:This cross-sectional study was embedded in a long-term observational study, the Epidemiology of Diabetes Interventions and Complications study (EDIC), a cohort of participants with type 1 diabetes, who were originally enrolled in the Diabetes Control and Complications Trial (DCCT), and were followed-up for more than 30 years at 27 sites in the USA and Canada. All active EDIC participants were eligible except if they were pregnant, weighed above the dual-energy x-ray absorptiometry (DXA) scanner limit, had an implanted neurostimulator, or were not willing to participate. The primary study outcome was total hip BMD. Hip, spine, and radius BMD and trabecular bone score (TBS) were measured with DXA at an annual EDIC visit (2017-19). Time-weighted mean HbA, kidney disease, and peripheral neuropathy were measured annually during EDIC, and retinopathy was measured every 4 years. Skin intrinsic fluorescence, a measure of advanced glycation end products (AGEs), and cardiac autonomic neuropathy were assessed once (2009-10) during EDIC. FINDINGS:1147 of the 1441 participants who were enrolled in the DCCT trial remained active EDIC participants at the start of this cross-sectional study. Between Sept 20, 2017, and Sept 19, 2019, 1094 of 1147 participants were screened for the EDIC Skeletal Health study. 1058 participants completed at least one of a set of DXA scans and were included in the analysis. 47·8% were women and 52·2% were men, 96·6% were White and 3·4% were of other race or ethnicity. The mean age of participants was 59·2 years (SD 6·7). Higher mean HbA, higher skin intrinsic fluorescence, and kidney disease (but not retinopathy or neuropathy) were independently associated with a lower total hip BMD. Total hip BMD differed by -10·7 mg/cm (95% CI -19·6 to -1·7) for each 1% increase in mean HbA, -20·5 mg/cm (-29·9 to -11·0) for each 5 unit higher skin intrinsic fluorescence, and -51·7 mg/cm (-80·6 to -22·7) in the presence of kidney disease. Similar associations were found for femoral neck and ultra-distal radius BMD, but not for lumbar spine BMD or TBS. INTERPRETATION:Poorer glycaemic control, AGE accumulation, and kidney disease are independent risk factors for lower hip BMD in older adults with type 1 diabetes. Maintenance of glycaemic control and prevention of kidney disease might reduce bone loss and ultimately fractures in this population. Osteoporosis screening might be particularly important in people with these risk factors. Further research to identify AGE blockers could benefit skeletal health. FUNDING:National Institute of Diabetes and Digestive and Kidney Disease. 10.1016/S2213-8587(22)00103-6
Association of disrupted circadian rhythmicity with mood disorders, subjective wellbeing, and cognitive function: a cross-sectional study of 91 105 participants from the UK Biobank. The lancet. Psychiatry BACKGROUND:Disruption of sleep and circadian rhythmicity is a core feature of mood disorders and might be associated with increased susceptibility to such disorders. Previous studies in this area have used subjective reports of activity and sleep patterns, but the availability of accelerometer-based data from UK Biobank participants permits the derivation and analysis of new, objectively ascertained circadian rhythmicity parameters. We examined associations between objectively assessed circadian rhythmicity and mental health and wellbeing phenotypes, including lifetime history of mood disorder. METHODS:UK residents aged 37-73 years were recruited into the UK Biobank general population cohort from 2006 to 2010. We used data from a subset of participants whose activity levels were recorded by wearing a wrist-worn accelerometer for 7 days. From these data, we derived a circadian relative amplitude variable, which is a measure of the extent to which circadian rhythmicity of rest-activity cycles is disrupted. In the same sample, we examined cross-sectional associations between low relative amplitude and mood disorder, wellbeing, and cognitive variables using a series of regression models. Our final model adjusted for age and season at the time that accelerometry started, sex, ethnic origin, Townsend deprivation score, smoking status, alcohol intake, educational attainment, overall mean acceleration recorded by accelerometry, body-mass index, and a binary measure of childhood trauma. FINDINGS:We included 91 105 participants with accelerometery data collected between 2013 and 2015 in our analyses. A one-quintile reduction in relative amplitude was associated with increased risk of lifetime major depressive disorder (odds ratio [OR] 1·06, 95% CI 1·04-1·08) and lifetime bipolar disorder (1·11, 1·03-1·20), as well as with greater mood instability (1·02, 1·01-1·04), higher neuroticism scores (incident rate ratio 1·01, 1·01-1·02), more subjective loneliness (OR 1·09, 1·07-1·11), lower happiness (0·91, 0·90-0·93), lower health satisfaction (0·90, 0·89-0·91), and slower reaction times (linear regression coefficient 1·75, 1·05-2·45). These associations were independent of demographic, lifestyle, education, and overall activity confounders. INTERPRETATION:Circadian disruption is reliably associated with various adverse mental health and wellbeing outcomes, including major depressive disorder and bipolar disorder. Lower relative amplitude might be linked to increased susceptibility to mood disorders. FUNDING:Lister Institute of Preventive Medicine. 10.1016/S2215-0366(18)30139-1
Prevalence, risk factors, and management of dementia and mild cognitive impairment in adults aged 60 years or older in China: a cross-sectional study. Jia Longfei,Du Yifeng,Chu Lan,Zhang Zhanjun,Li Fangyu,Lyu Diyang,Li Yan,Li Yan,Zhu Min,Jiao Haishan,Song Yang,Shi Yuqing,Zhang Heng,Gong Min,Wei Cuibai,Tang Yi,Fang Boyan,Guo Dongmei,Wang Fen,Zhou Aihong,Chu Changbiao,Zuo Xiumei,Yu Yueyi,Yuan Quan,Wang Wei,Li Fang,Shi Shengliang,Yang Heyun,Zhou Chunkui,Liao Zhengluan,Lv Yan,Li Yang,Kan Minchen,Zhao Huiying,Wang Shan,Yang Shanshan,Li Hao,Liu Zhongling,Wang Qi,Qin Wei,Jia Jianping, The Lancet. Public health BACKGROUND:China has a large population of older people, but has not yet undertaken a comprehensive study on the prevalence, risk factors, and management of both dementia and mild cognitive impairment (MCI). METHODS:For this national cross-sectional study, 46 011 adults aged 60 years or older were recruited between March 10, 2015, and Dec 26, 2018, using a multistage, stratified, cluster-sampling method, which considered geographical region, degree of urbanisation, economic development status, and sex and age distribution. 96 sites were randomly selected in 12 provinces and municipalities representative of all socioeconomic and geographical regions in China. Participants were interviewed to obtain data on sociodemographic characteristics, lifestyle, medical history, current medications, and family history, and then completed a neuropsychological testing battery administered by a psychological evaluator. The prevalence of dementia (Alzheimer's disease, vascular dementia, and other dementias) and MCI were calculated and the risk factors for different groups were examined using multivariable-adjusted analyses. FINDINGS:Overall age-adjusted and sex-adjusted prevalence was estimated to be 6·0% (95% CI 5·8-6·3) for dementia, 3·9% (3·8-4·1) for Alzheimer's disease, 1·6% (1·5-1·7) for vascular dementia, and 0·5% (0·5-0·6) for other dementias. We estimated that 15·07 million (95% CI 14·53-15·62) people aged 60 years or older in China have dementia: 9·83 million (9·39-10·29) with Alzheimer's disease, 3·92 million (3·64-4·22) with vascular dementia, and 1·32 million (1·16-1·50) with other dementias. Overall MCI prevalence was estimated to be 15·5% (15·2-15·9), representing 38·77 million (37·95-39·62) people in China. Dementia and MCI shared similar risk factors including old age (dementia: odds ratios ranging from 2·69 [95% CI 2·43-2·98] to 6·60 [5·24-8·32]; MCI: from 1·89 [1·77-2·00] to 4·70 [3·77-5·87]); female sex (dementia: 1·43 [1·31-1·56]; MCI: 1·51 [1·43-1·59]); parental history of dementia (dementia: 7·20 [5·68-9·12]; MCI: 1·91 [1·48-2·46]); rural residence (dementia: 1·16 [1·06-1·27]; MCI: 1·45 [1·38-1·54]); fewer years of education (dementia: from 1·17 [1·06-1·29] to 1·55 [1·38-1·73]; MCI: from 1·48 [1·39-1·58] to 3·48 [3·25-3·73]); being widowed, divorced, or living alone (dementia: from 2·59 [2·30-2·90] to 2·66 [2·29-3·10]; MCI: from 1·58 [1·44-1·73] to 1·74 [1·56-1·95]); smoking (dementia: 1·85 [1·67-2·04]; MCI: 1·27 [1·19-1·36]), hypertension (dementia: 1·86 [1·70-2·03]; MCI: 1·62 [1·54-1·71] for MCI), hyperlipidaemia (dementia: 1·87 [1·71-2·05]; MCI: 1·29 [1·21-1·37]), diabetes (dementia: 2·14 [1·96-2·34]; MCI: 1·44 [1·35-1·53]), heart disease (dementia: 1·98 [1·73-2·26]; MCI: 1·17 [1·06-1·30]), and cerebrovascular disease (dementia: 5·44 [4·95-5·97]; MCI: 1·49 [1·36-1·62]). Nine of these risk factors are modifiable. INTERPRETATION:Dementia and MCI are highly prevalent in China and share similar risk factors. A prevention strategy should be developed to target the identified risk factors in the MCI population to thwart or slow down disease progression. It is also crucial to optimise the management of dementia and MCI as an important part of China's public health system. FUNDING:Key Project of the National Natural Science Foundation of China, National Key Scientific Instrument and Equipment Development Project, Mission Program of Beijing Municipal Administration of Hospitals, Beijing Scholars Program, Beijing Brain Initiative from Beijing Municipal Science & Technology Commission, Project for Outstanding Doctor with Combined Ability of Western and Chinese Medicine, and Beijing Municipal Commission of Health and Family Planning. 10.1016/S2468-2667(20)30185-7
Association between physical exercise and mental health in 1·2 million individuals in the USA between 2011 and 2015: a cross-sectional study. Chekroud Sammi R,Gueorguieva Ralitza,Zheutlin Amanda B,Paulus Martin,Krumholz Harlan M,Krystal John H,Chekroud Adam M The lancet. Psychiatry BACKGROUND:Exercise is known to be associated with reduced risk of all-cause mortality, cardiovascular disease, stroke, and diabetes, but its association with mental health remains unclear. We aimed to examine the association between exercise and mental health burden in a large sample, and to better understand the influence of exercise type, frequency, duration, and intensity. METHODS:In this cross-sectional study, we analysed data from 1 237 194 people aged 18 years or older in the USA from the 2011, 2013, and 2015 Centers for Disease Control and Prevention Behavioral Risk Factors Surveillance System survey. We compared the number of days of bad self-reported mental health between individuals who exercised and those who did not, using an exact non-parametric matching procedure to balance the two groups in terms of age, race, gender, marital status, income, education level, body-mass index category, self-reported physical health, and previous diagnosis of depression. We examined the effects of exercise type, duration, frequency, and intensity using regression methods adjusted for potential confounders, and did multiple sensitivity analyses. FINDINGS:Individuals who exercised had 1·49 (43·2%) fewer days of poor mental health in the past month than individuals who did not exercise but were otherwise matched for several physical and sociodemographic characteristics (W=7·42 × 10, p<2·2 × 10). All exercise types were associated with a lower mental health burden (minimum reduction of 11·8% and maximum reduction of 22·3%) than not exercising (p<2·2 × 10 for all exercise types). The largest associations were seen for popular team sports (22·3% lower), cycling (21·6% lower), and aerobic and gym activities (20·1% lower), as well as durations of 45 min and frequencies of three to five times per week. INTERPRETATION:In a large US sample, physical exercise was significantly and meaningfully associated with self-reported mental health burden in the past month. More exercise was not always better. Differences as a function of exercise were large relative to other demographic variables such as education and income. Specific types, durations, and frequencies of exercise might be more effective clinical targets than others for reducing mental health burden, and merit interventional study. FUNDING:Cloud computing resources were provided by Microsoft. 10.1016/S2215-0366(18)30227-X
The Gut Microbiota in Prediabetes and Diabetes: A Population-Based Cross-Sectional Study. Wu Hao,Tremaroli Valentina,Schmidt Caroline,Lundqvist Annika,Olsson Lisa M,Krämer Manuela,Gummesson Anders,Perkins Rosie,Bergström Göran,Bäckhed Fredrik Cell metabolism The link between the gut microbiota and type 2 diabetes (T2D) warrants further investigation because of known confounding effects from antidiabetic treatment. Here, we profiled the gut microbiota in a discovery (n = 1,011) and validation (n = 484) cohort comprising Swedish subjects naive for diabetes treatment and grouped by glycemic status. We observed that overall gut microbiota composition was altered in groups with impaired glucose tolerance, combined glucose intolerance and T2D, but not in those with impaired fasting glucose. In addition, the abundance of several butyrate producers and functional potential for butyrate production were decreased both in prediabetes and T2D groups. Multivariate analyses and machine learning microbiome models indicated that insulin resistance was strongly associated with microbial variations. Therefore, our study indicates that the gut microbiota represents an important modifiable factor to consider when developing precision medicine approaches for the prevention and/or delay of T2D. 10.1016/j.cmet.2020.06.011
Prevalence of depressive disorders and treatment in China: a cross-sectional epidemiological study. The lancet. Psychiatry BACKGROUND:In China, depressive disorders have been estimated to be the second leading cause of years lived with disability. However, nationally representative epidemiological data for depressive disorders, in particular use of mental health services by adults with these disorders, are unavailable in China. The present study, part of the China Mental Health Survey, 2012-15, aims to describe the socioeconomic characteristics and the use of mental health services in people with depressive disorders in China. METHODS:The China Mental Health Survey was a cross-sectional epidemiological survey of mental disorders in a multistage clustered-area probability sample of adults of Chinese nationality (≥18 years) from 157 nationwide representative population-based disease surveillance points in 31 provinces across China. Trained investigators interviewed the participants with the Composite International Diagnostic Interview 3.0 to ascertain the presence of lifetime and 12-month depressive disorders according to DSM-IV criteria, including major depressive disorder, dysthymic disorder, and depressive disorder not otherwise specified. Participants with 12-month depressive disorders were asked whether they received any treatment for their emotional problems during the past 12 months and, if so, the specific types of treatment providers. The Sheehan Disability Scale (SDS) was used to assess impairments associated with 12-month depressive symptoms. Data-quality control procedures included logic check by computers, sequential recording check, and phone-call check by the quality controllers, and reinterview check by the psychiatrists. Data were weighted according to the age-sex-residence distribution data from China's 2010 census population survey to adjust for differential probabilities of selection and differential response, as well as to post-stratify the sample to match the population distribution. FINDINGS:28 140 respondents (12 537 [44·6%] men and 15 603 [55·4%] women) completed the survey between July 22, 2013, and March 5, 2015. Ethnicity data (Han or non-Han) were collected for only a subsample. Prevalence of any depressive disorders was higher in women than men (lifetime prevalence odds ratio [OR] 1·44 [95% CI 1·20-1·72] and 12-month prevalence OR 1·41 [1·12-1·78]), in unemployed people than employed people (lifetime OR 2·38 [95% CI 1·68-3·38] and 12-month OR 2·80 [95% CI 1·88-4·18]), and in people who were separated, widowed, or divorced compared with those who were married or cohabiting (lifetime OR 1·87 [95% CI 1·39-2·51] and 12-month OR 1·85 [95% CI 1·40-2·46]). Overall, 574 (weighted % 75·9%) of 744 people with 12-month depressive disorders had role impairment of any SDS domain: 439 (83·6%) of 534 respondents with major depressive disorder, 207 (79·8%) of 254 respondents with dysthymic disorder, and 122 (59·9%) of 189 respondents with depressive disorder not otherwise specified. Only an estimated 84 (weighted % 9·5%) of 1007 participants with 12-month depressive disorders were treated in any treatment sector: 38 (3·6%) in speciality mental health, 20 (1·5%) in general medical, two (0·3%) in human services, and 21 (2·7%) in complementary and alternative medicine. Only 12 (0·5%) of 1007 participants with depressive disorders were treated adequately. INTERPRETATION:Depressive disorders in China were more prevalent in women than men, unemployed people than employed, and those who were separated, widowed, or divorced than people who were married or cohabiting. Most people with depressive disorders reported social impairment. Treatment rates were very low, and few people received adequate treatment. National programmes are needed to remove barriers to availability, accessibility, and acceptability of care for depression in China. FUNDING:National Health Commission and Ministry of Science and Technology of People's Republic of China. TRANSLATION:For the Chinese translation of the abstract see Supplementary Materials section. 10.1016/S2215-0366(21)00251-0