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IntroductionIn resource-limited settings, obstructive sleep apnea (OSA) often goes undiagnosed as polysomnography (PSG) is expensive, time-consuming, and not readily available. Imaging studies of upper airway have been tried as alternatives to PSG to screen for OSA. However, racial differences in upper airway anatomy preclude generalizability of such studies. We sought to test the hypothesis that ultrasonography (USG), an inexpensive, readily available tool to study soft tissue structures of the upper airway, would have predictive value for OSA in South Asian people.MethodsAdult patients with sleep-related complaints suspicious for OSA were taken for overnight PSG. After the PSG, consecutive patients with and without OSA were studied with submental ultrasonography to measure tongue base thickness (TBT) and lateral pharyngeal wall thickness (LPWT).ResultsAmong 50 patients with OSA and 25 controls, mean age was 43.9 ± 11.4 years, and 39 were men. Patients with OSA had higher TBT (6.77 ± 0.63 cm vs 6.34 ± 0.54 cm, P value = 0.004) and higher LPWT (2.47 ± 0.60 cm vs 2.12 ± 0.26 cm, P value = 0.006) compared to patients without OSA. On multivariate analysis, TBT, LPWT, and neck circumference were identified as independent factors associated with OSA. These variables could identify patients with severe OSA with a sensitivity of 72% and a specificity of 76%.ConclusionPatients with OSA have higher tongue base thickness and lateral pharyngeal wall thickness proportionate to the severity of the disease, independent of BMI and neck circumference. These findings suggest that sub-mental ultrasonography may be useful to identify patients with severe OSA in resource-limited settings.

RNA viruses continue to remain a threat for potential pandemics due to their rapid evolution. Potentiating host antiviral pathways to prevent or limit viral infections is a promising strategy. Thus, by testing a library of innate immune agonists targeting pathogen recognition receptors, we observe that Toll-like receptor 3 (TLR3), stimulator of interferon genes (STING), TLR8, and Dectin-1 ligands inhibit arboviruses, Chikungunya virus (CHIKV), West Nile virus, and Zika virus to varying degrees. STING agonists (cAIMP, diABZI, and 2',3'-cGAMP) and Dectin-1 agonist scleroglucan demonstrate the most potent, broad-spectrum antiviral function. Furthermore, STING agonists inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and enterovirus-D68 (EV-D68) infection in cardiomyocytes. Transcriptome analysis reveals that cAIMP treatment rescue cells from CHIKV-induced dysregulation of cell repair, immune, and metabolic pathways. In addition, cAIMP provides protection against CHIKV in a chronic CHIKV-arthritis mouse model. Our study describes innate immune signaling circuits crucial for RNA virus replication and identifies broad-spectrum antivirals effective against multiple families of pandemic potential RNA viruses.

HIV stigma takes a multidimensional toll on a mother's ability to care for herself and subsequently may impact her ability to care for her child, particularly when mother and child are seroconcordant. A cross-sectional analysis was conducted to examine the association between maternal HIV stigma and child CD4 count in rural India. We assessed 108 mother-child dyads and found that a one-unit increase in community stigma fear decreased child CD4 count by 352 cells (95% CI = - 603, - 102), highlighting the need to develop a better understanding of the consequences of HIV-related stigma on the compounded burden of care in households where mother and child both live with HIV.

Loss of lean muscle mass impairs immunity and increases mortality risk among individuals with HIV/AIDS. We evaluated the relative contributions of protein supplementation and nutrition education on body composition among 600 women living with HIV/AIDS in rural Andhra Pradesh, India. We conducted a cluster randomized controlled 2 × 2 factorial trial lasting six months with follow up at twelve and eighteen months. Interventions occurred in the Nellore and Prakasam regions of Andhra Pradesh by trained village women, ASHA (Accredited Social Health Activists), and included: (1) the usual supportive care from ASHA (UC); (2) UC plus nutrition education (NE); (3) UC plus nutritional protein supplementation (NS); (4) combined UC plus NE plus NS. A Bioimpedance Analyzer Model 310e measured body composition. SAS 9.4 analyzed all data. Mixed models using repeated measures evaluated lean mass change from baseline as primary and fat weight and total weight as secondary outcomes. Lean mass change was significantly associated with NS (p = 0.0001), NE (p = 0.0001), and combined NS plus NE (p = 0.0001), with similar associations for secondary outcomes. Stronger associations for total weight were observed with greater ART adherence. Nutritional interventions may improve physiologic response to HIV. Significant increases in lean mass resulted from independent and combined protein supplementation and nutrition education.

Global literature examining the association between mental health of women living with HIV (WLWH) and child development is scarce. In this study, we examined the relationship between mothers' mental health and their children's social development outcomes 6 months later. Data for these analyses come from several waves of interviews of 600 WLWH in the South Indian state of Andhra Pradesh, India. These women were enrolled in a 2×2 factorial clinical trial designed to assess the impact of food supplementation and nutrition education, both in addition to ASHA support, on adherence to ART and improved health outcomes for the women and one of their children. They were assessed on food security, stigma, social support, quality of life, depressive symptoms and child development outcomes. Results of longitudinal GEE regression analysis indicate that mother's depressive symptoms were significantly negatively associated with child's social quotient 6 months later. These findings have important implications for targeted health interventions, integrating mental health, both for WLWH and their children in India.

BackgroundObstructive sleep apnoea (OSA) is an important factor in the development and progression of heart failure (HF). The prevalence of OSA is higher in patients with HF than in the general population. We sought to test the hypothesis that OSA severity was predictive of ventricular function and cardiac injury [as assessed by high-sensitivity cardiac troponin I(hs-cTnI)].MethodsA total of 60 patients were recruited after evaluation for sleep disturbances using the Jenkins Sleep Questionnaire (JSQ) and Epworth Sleepiness Scale (ESS). Subsequently, they underwent polysomnography thus confirming the diagnosis of OSA and were equally divided into three groups according to OSA severity grade. Following polysomnography, the next morning patients underwent venous blood sampling and echocardiography.ResultsWe observed a statistically significant association (P = 0.009) between diastolic dysfunction grades and severity grades of OSA. All the three diastolic dysfunction variables E/A ratio, deceleration time and E/e' ratio had a significant association(P

BackgroundMalnutrition is a common clinical concern among children in low-income communities affected by human immunodeficiency virus (HIV). We examined the effect of a community-based nutritional intervention on anthropometric and clinical outcomes of children of women living with HIV in rural India.MethodsWe assigned women living with HIV and their child (oldest 3-8 years) to 1 of 4 programs: (1) community-based HIV care program, (2) program 1 + nutrition education, (3) program 1 + food supplement, and (4) all elements of programs 1-3. Study data were collected at baseline and months 6, 12, and 18. We applied mixed-effects modeling with restricted maximum likelihood estimation to examine changes in weight (all children) and CD4+ T-cell counts (children with HIV only).ResultsOverall, 600 mother-child pairs were enrolled (150/group) with 100% retention at follow-up visits. Approximately 20% of children were living with HIV. Children in program 4 had higher weight gain than those in programs 1, 2, and 3 at all time points (adjusted P < .001). We found a higher increase in CD4+ T cells across all time points among participants in programs 3 and 4 compared with program 1 (adjusted P < .001). Factorial analysis suggested a synergistic effect of combining nutrition education and food supplements for weight gain but not for increase in CD4+ T cells.ConclusionsA combination of nutrition education and food supplements provided to women living with HIV significantly increased weight and CD4+ T cells, and such interventions can be integrated into HIV-care programs in low-income settings.

BackgroundThere is a scarcity of published data on the global prevalence of obstructive sleep apnoea, a disorder associated with major neurocognitive and cardiovascular sequelae. We used publicly available data and contacted key opinion leaders to estimate the global prevalence of obstructive sleep apnoea.MethodsWe searched PubMed and Embase to identify published studies reporting the prevalence of obstructive sleep apnoea based on objective testing methods. A conversion algorithm was created for studies that did not use the American Academy of Sleep Medicine (AASM) 2012 scoring criteria to identify obstructive sleep apnoea, allowing determination of an equivalent apnoea-hypopnoea index (AHI) for publications that used different criteria. The presence of symptoms was not specifically analysed because of scarce information about symptoms in the reference studies and population data. Prevalence estimates for obstructive sleep apnoea across studies using different diagnostic criteria were standardised with a newly developed algorithm. Countries without obstructive sleep apnoea prevalence data were matched to a similar country with available prevalence data; population similarity was based on the population body-mass index, race, and geographical proximity. The primary outcome was prevalence of obstructive sleep apnoea based on AASM 2012 diagnostic criteria in individuals aged 30-69 years (as this age group generally had available data in the published studies and related to information from the UN for all countries).FindingsReliable prevalence data for obstructive sleep apnoea were available for 16 countries, from 17 studies. Using AASM 2012 diagnostic criteria and AHI threshold values of five or more events per h and 15 or more events per h, we estimated that 936 million (95% CI 903-970) adults aged 30-69 years (men and women) have mild to severe obstructive sleep apnoea and 425 million (399-450) adults aged 30-69 years have moderate to severe obstructive sleep apnoea globally. The number of affected individuals was highest in China, followed by the USA, Brazil, and India.InterpretationTo our knowledge, this is the first study to report global prevalence of obstructive sleep apnoea; with almost 1 billion people affected, and with prevalence exceeding 50% in some countries, effective diagnostic and treatment strategies are needed to minimise the negative health impacts and to maximise cost-effectiveness.FundingResMed.

BackgroundWomen living with HIV (WLH) in rural communities face challenges to obtaining treatment and accurate disease-related information. Nutritional deficits exacerbate disease progression.SettingWLH were recruited from primary health centers in rural India.MethodA quasi-experimental trial of a comprehensive Accredited Social Health Activist (Asha)-supported intervention compared 4 distinct Asha-based programs [(1) standard education (SE) alone; (2) nutrition education (+NE); (3) nutrition supplements (+NS); or (4) nutrition education and nutrition supplements (+NENS)] on key disease and nutrition-related outcomes [CD4 count, body mass index (BMI), serum albumin, and hemoglobin]. Assessments occurred at baseline, and months 6 (immediately after intervention), 12, and 18. Multilevel modeling examined effects of program (group) over time.FindingsAmong 600 WLH enrolled (n = 150 per arm), mean age, CD4 count, and BMI (kg/m) were 34.31, 447.42, and 20.09, respectively, at baseline. At 18-month follow-up, program 4 (+NENS) experienced greatest improvements in CD4 counts compared with program 1 (+SE) [adjusted difference = 223.81, 95% confidence interval (CI): 170.29 to 277.32]. For BMI, programs 3 (+NS; adjusted difference = 2.33, 95% CI: 1.39 to 3.26) and 4 (+NENS; adjusted difference = 2.14, 95% CI: 1.17 to 3.12) exhibited greater gains compared with program 1 (+SE). Programs 3 and 4 were not significantly different from each other (adjusted difference = -0.18, 95% CI: -1.12 to 0.76). Hemoglobin and serum albumin also improved over time; program 4 (+NENS) exhibited the greatest gains.ConclusionsA low-cost Asha-supported behavioral and nutritional intervention improved outcomes for WLH. Gains were sustained at 18-month follow-up. Similar approaches may help improve HIV and other infectious disease-related outcomes in vulnerable populations.

Cervical cancer is a leading cause of death among women in low- and middle-income countries, and women living with HIV are at high risk for cervical cancer. The objective of this study was to estimate the prevalence and correlates of cervical cancer and pre-cancer lesions and to examine cervical cancer knowledge among women living with HIV receiving antiretroviral therapy in rural Andhra Pradesh, India. We conducted cytology-based screening and administered a standardized questionnaire among 598 HIV-infected women. We found 5 (0.8%), 39 (6.5%), 29 (4.9%), and 4 (0.7%) had atypical squamous cells of undetermined significance (ASCUS), low-grade squamous intraepithelial lesion (LSIL), high-grade squamous intraepithelial lesion (HSIL), and squamous cervical carcinoma (SCC), respectively. In multivariable logistic regression analysis, ASCUS/LSIL was independently associated with age >16 years old at first sexual encounter and smokeless tobacco use. We found no factors associated with HSIL/SCC. In total, 101 women (16.9%) had heard of cervical cancer and 28 (27.7%) of them correctly identified HIV infection as a risk factor. In light of the high prevalence of pre-cancer lesions and low level of cervical cancer knowledge in our study population, focused interventions are needed to improve cervical cancer literacy and prevention among rural women living with HIV.

Quality of life (QOL) is associated with better outcomes in HIV/AIDS populations. We explored predictors of improved QOL over time in 600 Women Living with HIV/AIDS (WLH/A) in India [mean age = 34.31, SD = 6.97], enrolled in a nurse-led-Asha (Accredited Social Health Activist) intervention. Trained local interviewers ascertained self-report data at baseline and six-month follow-up (post-intervention). Latent Class Analysis (LCA) identified constellations of responses on psychosocial indicators (depression, social support, internalized stigma and stigma fears); their relationship with QOL over time was examined. We identified three classes: Class 1) Highest Social Resources/Lowest Depression; Class 2) Some Social Resources/Highest Depression; and Class 3) Lowest Social Resources/Higher Depression. At baseline, Class 3 reported the lowest QOL (M = 0.25, SD = 0.26); Class 1 reported the highest (M = 0.37, SD = 0.33). Class 2's QOL did not differ from Class 3's QOL, likely due to the potent effects of high depression. At six-month follow-up, all groups reported improved QOL; class membership no longer predicted variability (contrast between Class 2 and 1 = -0.05, 95% CI = -0.14, 0.04; contrast between Class 3 and 1 = 0.01, 95% CI = -0.03, 0.05; contrast between Class 3 and 2 = 0.07, 95% CI = -0.02, 0.16). Psychosocial indicators are important predictors of QOL; an Asha-supported approach may have broad applicability to improve QOL in WLH/A in India.

Internalized HIV stigma can affect health outcomes, but the mechanism underlying this relationship is poorly understood. We investigated the potential pathways for the association between internalized stigma and opportunistic infections (OIs) among women living with HIV in rural India. We conducted a cross-sectional study involving in-person interviews with 600 participants. We modeled two outcome variables, total number of OIs and fungal dermatoses, which was the most frequently reported OI. Causal mediation analysis was performed to estimate the total effect, direct effect, and indirect effect through mediators while controlling for confounders. Food insecurity was a strong mediator of the association between internalized stigma and the number of OIs (70% of the total effect) and fungal dermatoses (83% of the total effect), while the indirect effect of stigma through adherence was minimal for both outcomes. Household food insecurity may be an important mediator of the impact of HIV-related stigma on opportunistic infections.

HIV stigma continues to be a barrier to physical and mental health among people living with HIV globally, especially in vulnerable populations. We examined how stigma is associated with health outcomes and quality of life among rural women living with HIV in South India (N = 600). Interviewer-administered measures assessed multiple dimensions of stigma, as well as loneliness, social support, ART adherence, time since diagnosis, and quality of life. Internalized stigma and a lack of social support were associated with a lower quality of life, while the association between internalized stigma and adherence was mediated by the use of stigma-avoidant coping strategies, suggesting that keeping one's diagnosis a secret may make it more difficult to take one's medications. These findings suggest that these women constitute a vulnerable population who need additional services to optimize their health and who might benefit from peer support interventions and stigma-reduction programs for family and community members.

ObjectiveTo assess the impact of nurse-led Asha (Accredited Social Health Activist)-support behavioral and nutritional intervention among women living with HIV/AIDS (WLH/A) in rural India.DesignCluster randomized controlled trial.MethodsSixteen Primary Health Centers serving WLH/A in Andhra Pradesh were grouped into four regional clusters that were randomly allocated into one of four arms. All four groups included Asha-support and consisted of: Asha-support only (control group); nutrition education; nutrition supplementation; and the combination of supplementation and education. Differences between baseline and 6-month follow-up for key physiological outcomes (BMI, CD4 cell count) were analyzed using factorial mixed models that accounted for geographic clustering.ResultsAt 6 months, all groups improved CD4 cell count: Asha only [mean difference score (D) = 343.97, standard deviation (SD) = 106.94], nutrition education (D = 356.15, SD = 0.69), nutrition supplement (D = 469.66, SD = 116.0), and nutrition supplement and education (D = 530.82, SD = 128.56). In multivariable models, Asha-support and nutrition, and Asha-support and nutrition supplement interventions demonstrated independent significant improvements in CD4 cell count; the interaction term was significant [estimate = 529.9; 95% confidence interval (CI) 512.0, 547.8; P = 0.006]. BMI also increased for all groups: Asha only (D = 0.95, SD = 0.82), Asha and nutrition education (D = 1.28, SD = 0.53), Asha and nutrition supplement (D = 2.38, SD = 0.60), nutrition supplement, and nutrition supplement and education (D = 2.72, SD = 0.84). Nutrition supplementation and nutrition education demonstrated independent effects on BMI; the interaction term was not significant (estimate = 0.27; 95% CI = 2.5, 2.7; P = 0.80).ConclusionInterventions supported by community workers were efficacious at improving physiological outcomes and may be beneficial at meeting critical healthcare needs of vulnerable WLH/A in India.