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Bacterial vaginosis (BV) is a highly prevalent condition that is associated with adverse health outcomes. It has been proposed that BV’s role as a pathogenic condition is mediated via bacteria-induced inflammation. However, the complex interplay between vaginal microbes and host immune factors has yet to be clearly elucidated. Here, we develop molBV , a 16 S rRNA gene amplicon-based classification pipeline that generates a molecular score and diagnoses BV with the same accuracy as the current gold standard method (i.e., Nugent score). Using 3 confirmatory cohorts we show that molBV is independent of the 16 S rRNA region and generalizable across populations. We use the score in a cohort without clinical BV states, but with measures of HPV infection history and immune markers, to reveal that BV-associated increases in the IL-1β/IP-10 cytokine ratio directly predicts clearance of incident high-risk HPV infection (HR = 1.86, 95% CI: 1.19-2.9). Furthermore, we identify an alternate inflammatory BV signature characterized by elevated TNF-α/MIP-1β ratio that is prospectively associated with progression of incident infections to CIN2 + (OR = 2.81, 95% CI: 1.62-5.42). Thus, BV is a heterogeneous condition that activates different arms of the immune response, which in turn are independent risk factors for HR-HPV clearance and progression. Clinical Trial registration number: The CVT trial has been registered under: NCT00128661. Here, Burk et al. develop an algorithm to diagnose bacterial vaginosis (BV) using the 16S rRNA gene, called molBV , which they use to profile the inflammatory landscape of BV and predict progression of human papillomavirus infection to cervical pre-cancer.

BackgroundMental health problems ranging from depression to more severe acts such as self-harm or suicidal behaviours are a serious problem among adolescents and young adults. Exposure to violence during the life of young people can increase mental health issues for youth. This study examines the relationship between exposure to violence and mental health issues among youth using a nationally representative study in Malawi.MethodsWe analysed data from the nationally representative Violence Against Children Survey from Malawi (2013) to quantify the association between exposures to violence (physical, sexual and emotional) and their relationship with mental distress, self-harm behaviours and suicidal ideation and attempts among youth aged 13–24 years. We evaluated the association of exposures to violence against children with reported mental health conditions among women and men. We used ordinal logistic regression models with appropriate survey weights to assess exposures to violence and the three outcomes of interest.ResultsChildren and youth aged 13–24 years exposed to violence in childhood reported higher levels of adverse mental health effects, including mental distress, self-harm behaviours and suicidal ideation and attempts. The odds of reporting these outcomes increased as the number of violence types increased.ConclusionsUnderstanding the risks based on different combinations of exposures to violence in Malawi can help identify populations at higher risk and optimise violence prevention strategies.

Background Data from India and other low and middle-income countries reveal high rates of parent-reported shaking of infants. Very high rates of developmental disability have been reported in India. The convergence of these observations provides an opportunity to understand the nature and consequences of a potentially harmful child discipline practice. Objective To study whether caregiver shaking of an infant, even shaking insufficient to lead to an acute medical encounter, is associated with subsequent intellectual disability (ID). Methods We conducted a matched case-control study at an academic medical center in Lucknow, India. We compared 75 children with ID of unknown etiology to 75 control children aged 24–72 months, matched by age, gender, maternal age, and maternal education. All children received a neurological evaluation and were IQ and lead tested. We questioned parents about early discipline practices, including shaking. If parents reported shaking, we asked them to demonstrate using a shaken baby simulator. We examined the association between ID and shaking using conditional logistic regression. Results Children’s median age was 43.4 (IQR: 25.1) months; 64% were boys. 24% of all study children were reported shaken before 24 months: 38.% of the case children and 9% of the controls. The adjusted odds of reported shaking of children with ID, before age 24 months, is 8.3 (95% CI: 2.4, 28.2) times higher than controls. Conclusion Shaking children < 2 years of age in northern India is common; a strong association exists between early shaking and unexplained intellectual disability. Possibly contributing to intellectual disability, the role of infant shaking needs to be explored further.

Background The primary healthcare system in Pakistan focuses on providing episodic, disease-based care. Health care for low-middle income communities is largely through a fee-for-service model that ignores preventive and health-promotive services. The growing burden of cardiovascular illnesses requires restructuring of the primary health care system allowing a community-to-clinic model of care to improve patient- and community-level health indicators. Methods We propose a model that integrates a Patient-Centered Medical Home (PCMH) with a Community-Based Health Information System (CBHIS) using hypertension (HTN) as an example. This protocol describes the integration and evaluation of the PCMH-CBHIS infrastructure through a population-based, observational, longitudinal study in a low-middle income, urban community in Pakistan. Participants are being enrolled in CBHIS and will be followed longitudinally over two years for HTN outcomes. A mixed-methods approach is adopted to evaluate the process of integrating PCMH with CBHIS. This involves building partnerships with the community through formal and informal meetings, focus group discussions, and a household health assessment survey (HAS). Community members identified with HTN are linked to PCMH for disease management. A customized electronic medical record system links community-level data with patient-level data to track changes in disease burden. The RE-AIM evaluation framework will be used to monitor community and individual-level metrics to guide implementation assessment, the potential for generalization, and the effectiveness of the PCMH in improving HTN-related health outcomes. Ethical clearance has been obtained from the Ethics Review Committee at Aga Khan University (2022-6723-20985). Discussion This study will evaluate the value of restructuring the primary care health system by ensuring systematic community engagement and measurement of health indicators at the patient- and community-level. While HTN is being used as a prototype to generate evidence for the effectiveness of this model, findings from this initiative will be leveraged towards strengthening the management of other acute and chronic conditions in primary care settings. If effective, the model can be used in Pakistan and other LMICs and resource-limited settings.

Background Electronic Health Records (EHR) has been increasingly used as a tool to monitor population health. However, subject-level errors in the records can yield biased estimates of health indicators. There is an urgent need for methods to estimate the prevalence of health indicators using large and real-time EHR while correcting the potential bias. Methods We demonstrate joint analyses of EHR and a smaller gold-standard health survey. We first adopted Mosteller’s method that pools two estimators, among which one is potentially biased. It only requires knowing the prevalence estimates from two data sources and their standard errors. Then, we adopted the method of Schenker et al., which uses multiple imputations of subject-level health outcomes that are missing for the subjects in EHR. This procedure requires information to link some subjects between two sources and modeling the mechanism of misclassification in EHR as well as modeling inclusion probabilities to both sources. Results In a simulation study, both estimators yielded negligible bias even when EHR was biased. They performed as well as health survey estimator when EHR bias was large and better than health survey estimator when EHR bias was moderate. It may be challenging to model the misclassification mechanism in real data for the subject-level imputation estimator. We illustrated the methods analyzing six health indicators from 2013 to 14 NYC HANES and the 2013 NYC Macroscope, and a study that linked some subjects in both data sources. Conclusions When a small gold-standard health survey exists, it can serve as a safeguard against potential bias in EHR through the joint analysis of the two sources.

Background With the rising epidemic of cardiometabolic diseases (CMDs) in low- and middle-income countries, urban populations face unique challenges such as poor sanitation, environmental pollution, and limited access to healthcare. This study estimates the point prevalence of CMDs and associated risk factors in adults in Karachi, analyses CMD prevalence by sex, and explores the relationship between CMDs and depression. Methods A door-to-door survey was conducted in a densely populated urban community within a 0.5 km radius of a primary health centre. A minimum of 1,480 families were required to estimate the prevalence of CMDs. Depression was screened using PHQ-2 and assessed with PHQ-9. Descriptive analyses summarized family-level sociodemographic data. Sex-specific differences in CMD-related risk factors were analysed using χ 2 and t-tests. Point prevalence and 95% confidence intervals (CIs) for CMDs were calculated. Bivariate analyses compared cardiometabolic risk factors, healthcare utilization, and mental health across CMD categories. Logistic regression assessed associations between CMDs, demographics, risk factors, and depression. Results Of the 1,513 families that participated, 3051 adults were included in the analyses. In this stable community (60% residing for more than five years), there was high Urdu (91%) and English (76%) literacy. There was high cell phone ownership (90%) and internet use (81%). Hypertension was the most prevalent CMD (34%). The likelihood of CMD increased with age, rising 49.39 times (95% CI: 30.21 – 80.74; p : < 0.001) higher in those 60 years and above than those aged 18–29. CMD prevalence was strongly associated with depression, compared to those with no CMDs, there were significantly higher odds of mild (OR: 1.89; 95% CI: 1.28 – 2.78; p : < 0.001) and moderate (OR: 2.21; 95%CI: 1.17 – 4.17; p : < 0.014) depression among participants with CMDs. Median health expenditure was 14.2% (IQR: 11.4—26.7%) of monthly income, with increasing CMD burden linked to higher rates of delay in purchasing medications ( p : < 0.001). Conclusion This study highlights the significant burden of CMDs, multimorbidity, and depression in a low-income urban community in Pakistan. The findings suggest that a cardiometabolic multimorbidity (CMM) epidemic is emerging in urban Pakistan, emphasizing the need for integrated interventions addressing physical, mental, economic, and environmental factors in CMD management.

Introduction Perioperative therapy is standard for patients with borderline-resectable pancreatic ductal adenocarcinoma (BR-PDAC); however, an optimal neoadjuvant regimen is lacking. We assessed the efficacy of FOLFIRINOX chemotherapy followed by gemcitabine-based chemoradiation as preoperative therapy. Methods Patients received 4 cycles of FOLFIRINOX, followed by 6-weekly gemcitabine with concomitant intensity-modulated radiation. The primary endpoint was the R0 resection rate. Secondary outcomes included resection rate, overall-response, overall survival (OS), progression-free survival (PFS), and tolerability. The trial was terminated early due to slow accrual. A Simon’s optimal two-stage phase II trial single arm design was used. The primary hypothesis of treatment efficacy was tested using a multistage group sequential inference procedure. The secondary failure time analysis endpoints were assessed using the Kaplan-Meier procedure and the Cox regression model. Results A total of 22 patients enrolled in the study, 18 (81.8%) completed neoadjuvant treatment. The bias corrected R0 rate was 55.6% (90% CI: 33.3, 68.3; P value = .16) among patients that received at least 1 cycle of FOLFIRINOX and was 80% among patients that underwent surgery. The median OS was 35.1 months. The median PFS among patients that underwent surgery was 34 months. Conclusion An R0 resection rate of 55.6% is favorable. Neoadjuvant FOLFIRINOX followed by concomitant Gemcitabine with radiation was well-tolerated. NCT01897454 Graphical Abstract

Background: The Human Papillomavirus (HPV) vaccine generates high antibody titers against targeted HPV types. This study investigated vaccine-induced anti-HPV18 immunoglobulin (IgG) antibody titers and subsequent HPV18/45 infections. Methods: We performed a nested matched case-control study leveraging a prospective longitudinal cohort of adolescent and young adult women (AYW) vaccinated with the quadrivalent HPV vaccine (4vHPV) attending the Mount Sinai Adolescent Health Center (MSAHC) in Manhattan, NY. The case individuals included AYW who had an incident detection of cervical HPV18 (n = 3) or HPV45 (n = 34) DNA after vaccination and were compared to two vaccinated control individuals (HPV18/45-negative); one random control (RC, n = 37) and one high-risk control (HRC, n = 37) selected from the upper quartile of a sexual risk behavior score. Serological titers against HPV18 were measured by end-point dilution and enzyme-linked immunosorbent assay (ELISA) in serum collected before the incident detection of HPV. Matching was performed based on age at first dose, follow-up time, and sexual risk behavior score. Conditional logistic regression was used to assess the association between case-control status and anti-HPV antibody titers, consistent with the matched-pair design. Results: Antibody titers for HPV18 were most different between AYW who developed an HPV18/45 infection compared to high-risk controls OR = 1.66, 95% CI: 0.96–2.85 (p = 0.1629). Analyses of pooled data from vaccinated recipients including who developed HPV16/31 or HPV18/45 infections demonstrated that the odds of a one-log unit increase in anti-HPV16 or 18 antibody titers, respectively, were 40% higher in the combined control groups (RC + HRC, n = 160) (OR = 1.40, 95% CI: 1.09–1.79, p = 0.0135) and 73% higher in the HRC (n = 80) (OR 1.73, 95% CI: 1.34, 2.52, p = 0.0117) compared to HPV16/18/31/45 cases (n = 80). Conclusions: Overall, these findings suggest that higher IgG antibodies to HPV16/18 after vaccination represent an increased likelihood of protection from homologous and cross-reactive HPV types (HPV16/18/31/45). These results show that differences in antibody titers are associated with breakthrough infection after vaccination, suggesting that further study of long-term antibody titers and infection should be pursued.

This study evaluates a video-feedback program's effectiveness in promoting responsive and sensitive parenting for families in care in a community health center located in the South Bronx, New York City. Change in measures of parent responsiveness/sensitivity (Global Rating Scale), depression (Patient Health Questionnaire 9), anxiety (Generalized Anxiety Disorder 7), and parenting stress (Parenting Stress Index-Short Form) were analyzed for mother-infant dyads (N=34) completing a six-session videofeedback program between 2014 and 2016. Participants were primarily mothers of color (30% African American; 63% Hispanic) with young infants (mean age 8 months). At program completion, mothers demonstrated a significant improvement of 19% in maternal responsiveness and fewer depressive and anxious symptoms. Cost-effectiveness studies are needed to compare parenting interventions by setting (community health center, home, or mental health facility) for acceptability and effectiveness to determine best practice models for communities challenged by poverty, trauma, and health disparities.

Background Childhood overweight/obesity has been associated with an elevated risk of insulin resistance and cardiometabolic disorders. Waist-to-height ratio (WHtR) may be a simple screening tool to quickly identify children at elevated risk for cardiometabolic disorders. The primary objective of the present study was to create sex-specific tertile cut points of WHtR and assess its association with Insulin resistance and elevated liver enzyme concentrations in children, factors using cross-sectional data from the randomized, controlled Family Weight Management Study. Methods Baseline data from 360 children (7–12 years, mean Body Mass Index (BMI) ≥ 85 th percentile for age and sex) were used to calculate WHtR tertiles by sex, male: ≤ 0.55 (T1), > 0.55- ≤ 0.59 (T2), > 0.59 (T3); female: ≤ 0.56 (T1), > 0.56- ≤ 0.6 (T2), > 0.6 (T3). The Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) was used to categorize participants as insulin-resistant (HOMA-IR ≥ 2.6) and insulin-sensitive (HOMA-IR < 2.6). Liver enzymes aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were categorized as normal vs. elevated (AST of < 36.0 µkat/L or ≥ 36.0 µkat/L; ALT of < 30.0 µkat/L or ≥ 30.0 µkat/L; ALT > 26 µkat/L males, > 22 µkat/L females). We examined differences in baseline cardiometabolic risk factors by WHtR tertiles and sex-specific multivariable logistic regression models to predict HOMA-IR and elevation of liver enzymes. Results Study participants had a mean WHtR of 0.59 ([SD: 0.06]). Irrespective of sex, children in WHtR T3 had higher BMIz scores, blood pressure, triglycerides, 2-h glucose, fasting 2-h insulin, and lower high-density lipoprotein cholesterol (HDL-C) concentrations than those in T2 and T1. After adjusting for covariates, the odds of elevated HOMA-IR (> 2.6) were over five-fold higher among males in T3 versus T1 [OR, 95%CI: 5.83, 2.34–14.52] and T2 [OR, 95%CI: 4.81, 1.94–11.92] and females in T3 [OR, 95%CI: 5.06, 2.10–12.20] versus T1. The odds of elevated ALT values (≥ 30) were 2.9 [95%CI: 1.01–8.41] fold higher among females in T3 compared to T1. Conclusion In public health settings, WHtR may be a practical screening tool in pediatric populations to identify children at risk of metabolic syndrome.