Estimating the burden of pediatric HIV in an 'A' category district in India: an epidemiological study.

BACKGROUND: India lacks epidemiological information on the disease burden of pediatric HIV. The National AIDS Control Program (NACP) estimates the numbers of HIV-positive children as a proportion of adult persons living with HIV. A third of HIV-positive children die before their first birthday and a half before they reach their second birthday. The early detection of HIV is crucial for the prevention of morbidities, growth delays, and death among HIV-positive children. METHODS: The study aimed to estimate the disease burden of pediatric HIV among children in 'A' category district of a high HIV prevalence state. An 'A' category district is defined by the presence of > 1% HIV prevalence among the general population, as estimated by HIV Sentinel Surveillance. The study used an innovative three-pronged strategy combining cross-sectional and longitudinal methods. The overall burden of pediatric HIV was calculated as a product of cases detected multiplied by a net inflation factor, for each of three strategies. RESULTS: The existing pool of HIV infection in the district is estimated to be 3266 (95% CI: 2621-4197) HIV positive children < 15 years of age, in a mid-year (2013) projected child population of about 1.4 million, thus giving an HIV prevalence of 0.23% (CI: 0.19-0.30) among children (0-14 years of age). The proportion of children among all people living with HIV in the district works out to 10.4% (CI: 8.6-13.5%). CONCLUSIONS: The study estimate of 0.23% HIV prevalence among children (0-14 years of age) is higher than the NACP estimates (0.02) and is 2.5 higher than the Karnataka state estimate (0.09)22. Similarly, the proportion of children among all persons living with HIV in Belgaum district is 10.4% in this study, as against 6.54% for India. The study methodology is replicable for other settings and other diseases.

mHealth intervention "ImTeCHO" to improve delivery of maternal, neonatal, and child care services-A cluster-randomized trial in tribal areas of Gujarat, India.

BACKGROUND: The coverage of community-based maternal, neonatal, and child health (MNCH) services remains low, especially in hard-to-reach areas. We evaluated the effectiveness of a mobile-phone-and web-based application, Innovative Mobile-phone Technology for Community Health Operations (ImTeCHO), as a job aid to the government's Accredited Social Health Activists (ASHAs) and Primary Health Center (PHC) staff to improve coverage of MNCH services in rural tribal communities of Gujarat, India. METHODS AND FINDINGS: This open cluster-randomized trial was conducted in 22 PHCs in six tribal blocks of Bharuch and Narmada districts in India. The ImTeCHO mobile-phone-and web-based application included various technology-based job aids to facilitate scheduling of home visits, screening for complications, counseling during home visits, and supportive supervision by PHC staff. Primary outcome indicators were a composite index calculated based on coverage of important MNCH services and coverage of at least two home visitations by ASHA within the first week of birth. Primary analysis was intention to treat (ITT). Generalized Estimating Equation (GEE) was used to account for clustering. Eleven PHCs each were randomly allocated to the intervention (280 ASHAs, population: 234,134) and control (281 ASHAs, population: 242,809) arms. The intervention was implemented from February, 2016 to January, 2017. At the end of the implementation, 6,493 mothers were surveyed. Most of the surveyed women were tribal (5,571, 85.8%), and reported having a government-issued certificate for living below poverty line (4,916, 75.7%). The coverage of at least two home visits within first week of birth was 32.4% in the intervention clusters compared to 22.9% in the control clusters (adjusted effect size 10.2 [95% CI: 6.4, 14.0], p < 0.001). Mean number of home visits within first week of birth was 1.11 and 0.80 for intervention and control clusters, respectively (adjusted effect size 0.34 [95% CI: 0.23, 0.45], p < 0.001). The composite coverage index was 43.0% in the intervention clusters compared to 38.5% (adjusted effect size 4.9 [95% CI: 0.2, 9.5], p = 0.03) in the control clusters. There were substantial improvements in coverage home visits by ASHAs during antenatal period (adjusted effect size 15.7 [95% CI: 11.0, 20.4], p < 0.001), postnatal period (adjusted effect size 6.4, [95% CI: 3.2, 9.6], p <0.001), early initiation of breastfeeding (adjusted effect size 7.8 [95% CI: 4.2, 11.4], p < 0.001), and exclusive breastfeeding (adjusted effect size 13.4 [95% CI: 8.9, 17.9], p < 0.001). Number of infant and neonatal deaths was similar in the two arms in the ITT analysis. The limitations of the study include potential risk of inaccuracies in reporting events that occurred during pregnancy by the mothers and the duration of intervention being 12 months, which might be considered short. CONCLUSIONS: In this study, we found that use of ImTeCHO mobile- and web-based application as a job aid by government ASHAs and PHC staff improved coverage and quality of MNCH services in hard-to-reach areas. Supportive supervision, change management, and timely resolution of technology-related issues were critical implementation considerations to ensure adherence to the intervention. TRIAL REGISTRATION: Study was registered at the Clinical Trial Registry of India (www.ctri.nic.in). Trial number: CTRI/2015/06/005847. The trial was registered (prospective) on 3 June, 2015. First enrollment was done on 26 August, 2015.

Incidence, prevalence and associated factors of mother-to-child transmission of HIV, among children exposed to maternal HIV, in Belgaum district, Karnataka, India.

BACKGROUND: India lacks data on the incidence of Paediatric HIV. In 2010, the Indian Council of Medical Research commissioned a task force study to estimate the paediatric HIV burden in Belgaum district, Karnataka, India. We estimated the HIV incidence, prevalence and associated risk factors of mother to child transmission of HIV among children exposed to maternal HIV by age 24 months. METHODS: We included Belgaum resident pregnant women who tested HIV positive between January 1st, 2011 and May 31st, 2013 and who provided consent. Their babies were tested for HIV at three time intervals using DNA PCR dry blood spot (DBS) method at 6-10 weeks and 6-9 months, and using Antibody tests at 18-24 months of age. We estimated cumulative incidence using survival analysis that considered censoring of cases and prevalence rates of HIV by age 24 months. Using competing-risk survival regression model, we examined the correlates of transmission of HIV among babies exposed to maternal HIV. RESULTS: Among 487 children of HIV positive mothers recruited in the study, the cumulative incidence rate by 24 months of age was 4.8 per 1000 person months [95% CI: 3.5-6.6]. The HIV prevalence rate among babies exposed to maternal HIV until 24 months was 7.8% [95% CI: 5.7-10.7]. Mother's age above 30 years, and breastfeeding duration of more than six months were factors that significantly increased the HIV transmission; adjusted hazard ratio (AHR) 6.98 [95% CI: 1.73-28.16] and 5.28 [95% CI, 1.75-15.90], respectively. The risk of MTCT was significantly reduced if both mother and baby had received Nevirapine at delivery [AHR 0.25; 95%CI: 0.10-0.61] and if either mother or baby had been given Nevirapine at delivery [AHR 0.12; 95%CI: 0.03-0.49]. CONCLUSION: The study findings suggest that mother's age above 30 years and breastfeeding beyond 26 weeks is associated with higher rates of HIV transmission from mother to child. It confirms the benefits of providing anti-retrovirals (Nevirapine) in reducing mother to child transmission of HIV. Effective strategies to promote safe infant feeding practices, including avoidance of mixed feeding beyond 26 weeks among HIV infected mothers, is critical to reduce incidence of paediatric HIV in India.

Fish intake during pregnancy or infancy and allergic outcomes in children: A systematic review and meta-analysis.

It has been suggested that n-3 long-chain polyunsaturated fatty acids (n-3 LC-PUFAs) have anti-inflammatory properties and may reduce the risk of allergic disease. Fish is a great source of n-3 LC-PUFAs. However, the effect of fish on allergic disease remains controversial. PubMed, EMBASE, and Cochrane Central Register of Controlled Trials were searched for randomized controlled trials (RCTs) and prospective cohort studies regarding the effect of fish intake during pregnancy or infancy on allergic outcomes in children. The outcomes of interest were atopy, eczema, allergic rhinitis, wheeze, asthma, and food allergy. One RCT and 17 publications from 13 prospective cohort studies were included for maternal fish intake during pregnancy, and eight publications from five prospective cohort studies for fish intake in infancy. Pooled analysis suggested that maternal fish intake during pregnancy was not associated with lower risk of any allergic outcome, both in RCT and observational studies. Consumption of fish during the first year of life reduced the risk of eczema (RR 0.61; 95% CI 0.47, 0.80; p = 0.0003; I2  = 68%) and allergic rhinitis (RR 0.54; 95% CI 0.36, 0.81; p = 0.003; I2  = 74%). Current evidence indicates that fish intake in infancy could reduce the risk of eczema and allergic rhinitis in children, whereas maternal fish intake during pregnancy does not affect any atopic outcome. The intake of fish per se in infancy, not specially n-3 LC-PUFAs, may have an allergy protective effect. High-quality and adequately powered RCTs are warranted to confirm this.

Zinc supplementation for the treatment of measles in children.

BACKGROUND: Measles is an important cause of childhood morbidity and mortality globally, despite increasing vaccine coverage. Zinc plays a significant role in the maintenance of normal immunological functions, therefore supplements given to zinc-deficient children will increase the availability of zinc and could reduce measles-related morbidity and mortality. This is an update of a review first published in 2015. OBJECTIVES: To assess the effects of zinc supplementation in reducing morbidity and mortality in children with measles. SEARCH METHODS: We searched CENTRAL (03 February 2017, Issue 2), MEDLINE (1946 to 03 February 2017), Embase (1974 to 03 February 2017), CINAHL (1981 to 03 February 2017), LILACS (1982 to 03 February 2017), Web of Science (1985 to 03 February 2017), and BIOSIS Previews (1985 to 27 June 2014). We also searched ClinicalTrials.gov, the Australian New Zealand Clinical Trials Registry and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) on 03 February 2017 to identify unpublished and ongoing studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs evaluating the effects of zinc in reducing morbidity and mortality in children with measles. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies for inclusion and extracted data on outcomes, details of the interventions, and other study characteristics using a standardised data extraction form. We used risk ratio (RR) and hazard ratio (HR) as measures of effect with 95% confidence intervals (CI). We included only one study, and did not conduct meta-analysis. MAIN RESULTS: We did not identify any new studies for inclusion in this update. One RCT met our inclusion criteria. The study was conducted in India and included 85 children diagnosed with measles and pneumonia. The trial showed no significant difference in mortality between children with measles and pneumonia who received zinc supplements and those who received placebo (RR 0.34, 95% CI 0.01 to 8.14). There was no significant difference in time to absence of fever between children who received zinc supplements and those who did not (HR 1.08, 95% CI 0.67 to 1.74). No treatment-related side effects were reported in either group. We assessed the overall quality of the evidence as very low. AUTHORS' CONCLUSIONS: We could not draw any definitive conclusions from this review about the effects of zinc supplementation on clinical outcomes of children with measles due to the very low quality of the evidence available. There is insufficient evidence to confirm or refute the effect of zinc supplementation in children with measles.

Research protocol for an epidemiological study on estimating disease burden of pediatric HIV in Belgaum district, India.

BACKGROUND: Pediatric HIV is poised to become a major public health problem in India with the rising trend of HIV infection in pregnant women (Department of AIDS Control, Ministry of Health and Family Welfare, http://www.naco.gov.in). There is lack of information on the epidemiology of pediatric HIV infection in India. Existing surveillance systems tend to underestimate the Pediatric burden. The overall aim of the present study is to estimate the disease burden of pediatric HIV among children in Belgaum district in the state of Karnataka in Southern India. An innovative multipronged epidemiological approach to comb the district is proposed. METHODS: The primary objectives of the study would be attained under three strategies. A prospective cohort design for objective (i) to determine the incidence rate of HIV by early case detection in infants and toddlers (0-18 months) born to HIV infected pregnant women; and cross sectional design for objectives (ii) to determine the prevalence of HIV infection in children (0-14 years) of HIV infected parents and (iii) to determine the prevalence of HIV in sick children (0-14 years) presenting with suspected signs and symptoms using age specific criteria for screening. Burden of pediatric HIV will be calculated as a product of cases detected in each strategy multiplied by a net inflation factor for each strategy. Study participants (i) (ii) (iii): HIV infected pregnant women and their live born children (ii) Any HIV-infected man/woman, of age 18-49 years, having a biological child of age 0-14 years (iii) Sick children of age 0-14 years presenting with suspected signs and symptoms and satisfying age-specific criteria for screening. Setting and conduct: Belgaum district which is a Category 'A' district (with more than 1 % antenatal prevalence in the district over the last 3 years before the study). Age-appropriate testing is used to detect HIV infection. DISCUSSION: There is a need to strengthen existing pediatric HIV estimation methods in India and other developing countries. We hope that the novel methodology emanating from this study would be applicable for estimating the burden of HIV in other settings and it would be adaptable for estimating the burden of other infectious/chronic diseases. Findings from this study will give future direction to the national program for prevention and control of HIV in India and other developing countries.

Male circumcision for HIV prevention in India: emerging viewpoints and practices of health care providers.

A compelling case for promoting male circumcision (MC) as an intervention for reducing the risk of heterosexually acquired HIV infection was made by dissemination of the results of three studies in Africa. The WHO/UNAIDS recommendation for MC for countries like India, where the epidemic in concentrated in high-risk groups, advocates MC for specific population groups such as men at higher risk for HIV acquisition. A multicentre qualitative study was conducted in four geographically distinct districts (Belgaum, Kolkata, Meerut and Mumbai) in India during June 2009 to June 2011. Two categories of health care providers: Registered Healthcare Providers (RHCPs) and traditional circumcisers were interviewed by trained research staff who had received master's level education using interview guides with probes and open-ended questions. Respondents were selected using purposive sampling. A comparative analysis of the perspectives of the RHCP vs. traditional circumcisers is presented. Representatives of both categories of providers expressed the need for Indian data on MC. Providers feared that promoting circumcision might jeopardize/undermine the progress already made in the field of condom promotion. Reservation was expressed regarding its adoption by Hindus. Behavioural disinhibition was perceived as an important limitation. A contrast in the practice of circumcision was apparent between the traditional and the trained providers. MC should be mentioned as a part of comprehensive HIV prevention services in India that includes HIV counselling and testing, condom distribution and diagnosis and treatment of sexually transmitted infections. It should become an issue of informed personal choice rather than ethnic identity.

Chlorhexidine skin or cord care for prevention of mortality and infections in neonates.

BACKGROUND: Affordable, feasible and efficacious interventions to reduce neonatal infections and improve neonatal survival are needed. Chlorhexidine, a broad spectrum topical antiseptic agent, is active against aerobic and anaerobic organisms and reduces neonatal bacterial colonisation and may reduce infection. OBJECTIVES: To evaluate the efficacy of neonatal skin or cord care with chlorhexidine versus routine care or no treatment for prevention of infections in late preterm or term newborn infants in hospital and community settings. SEARCH METHODS: We searched CENTRAL, latest issue of The Cochrane Library, MEDLINE (1966 to November 2013), EMBASE (1980 to November 2013), and CINAHL (1982 to November 2013). Ongoing trials were detected by searching the following databases: www.clinicaltrials.gov and www.controlled-trials.com. SELECTION CRITERIA: Cluster and individual patient randomised controlled trials of chlorhexidine use (for skin care, or cord care, or both) in term or late preterm neonates in hospital and community settings were eligible for inclusion. Three authors independently screened and selected studies for inclusion. DATA COLLECTION AND ANALYSIS: Two review authors independently extracted data, and assessed study risk of bias. The quality of evidence for each outcome was assessed using GRADE. We calculated pooled risk ratios (RRs) and risk differences (RDs) with 95% confidence intervals (CIs), and presented results using GRADE 'Summary of findings' tables. MAIN RESULTS: We included 12 trials in this review. There were seven hospital-based and five community-based studies. In four studies maternal vaginal wash with chlorhexidine was done in addition to neonatal skin and cord care. Newborn skin or cord cleansing with chlorhexidine compared to usual care in hospitalsLow-quality evidence from one trial showed that chlorhexidine cord cleansing compared to dry cord care may lead to no difference in neonatal mortality (RR 0.11, 95% CI 0.01 to 2.04). Moderate-quality evidence from two trials showed that chlorhexidine cord cleansing compared to dry cord care probably reduces the risk of omphalitis/infections (RR 0.48, 95% CI 0.28 to 0.84).Low-quality evidence from two trials showed that chlorhexidine skin cleansing compared to dry cord care may lead to no difference in omphalitis/infections (RR 0.88, 95% CI 0.56 to 1.39). None of the studies in this comparison reported effects of the treatments on neonatal mortality. Newborn skin or cord cleansing with chlorhexidine compared to usual care in the communityHigh-quality evidence from three trials showed that chlorhexidine cord cleansing compared to dry cord care reduces neonatal mortality (RR 0.81, 95% CI 0.71 to 0.92) and omphalitis/infections (RR 0.48, 95% CI 0.40 to 0.57).High-quality evidence from one trial showed no difference between chlorhexidine skin cleansing and usual skin care on neonatal mortality (RR 1.03, 95% CI 0.87 to 1.23). None of the studies in this comparison reported effects of the treatments on omphalitis/infections. Maternal vaginal chlorhexidine in addition to total body cleansing compared to no intervention (sterile saline solution) in hospitalsModerate-quality evidence from one trial showed no difference between maternal vaginal chlorhexidine in addition to total body cleansing and no intervention on neonatal mortality (RR 0.98, 95% CI 0.67 to 1.42). High-quality evidence from two trials showed no difference between maternal vaginal chlorhexidine in addition to total body cleansing and no intervention on the risk of infections (RR 0.93, 95% CI 0.82 to 1.16).Findings from one trial showed that maternal vaginal cleansing in addition to total body cleansing results in increased risk of hypothermia (RR 1.33, 95% CI 1.19 to 1.49). Maternal vaginal chlorhexidine in addition to total body cleansing compared to no intervention (sterile saline solution) in the communityLow-quality evidence from one trial showed no difference between maternal vaginal chlorhexidine in addition to total body cleansing and no intervention on neonatal mortality (RR 0.20, 95% CI 0.01 to 4.03). Moderate-quality evidence from one trial showed that maternal vaginal chlorhexidine in addition to total body cleansing compared to no intervention probably reduces the risk of neonatal infections (RR 0.69, 95% CI 0.49 to 0.95). These studies did not report effect on omphalitis. AUTHORS' CONCLUSIONS: There is some uncertainty as to the effect of chlorhexidine applied to the umbilical cords of newborns in hospital settings on neonatal mortality. The quality of evidence for the effects on infection are moderate for cord application and low for application to skin. There is high-quality evidence that chlorhexidine skin or cord care in the community setting results in a 50% reduction in the incidence of omphalitis and a 12% reduction in neonatal mortality. Maternal vaginal chlorhexidine compared to usual care probably leads to no difference in neonatal mortality in hospital settings. Maternal vaginal chlorhexidine compared to usual care results in no difference in the risk of infections in hospital settings. The uncertainty over the effect of maternal vaginal chlorhexidine on mortality outcomes reflects small sample sizes and low event rates in the community settings.

Zinc supplementation for the treatment of measles in children.

BACKGROUND: Measles is still an important cause of childhood morbidity and mortality globally, despite increasing vaccine coverage. Zinc plays a significant role in the maintenance of normal immunological functions, therefore supplements given to zinc-deficient children will increase the availability of zinc and could reduce measles-related morbidity and mortality. OBJECTIVES: To assess the effects of zinc supplementation in reducing morbidity and mortality in children with measles. SEARCH METHODS: We searched CENTRAL (2014, Issue 5), MEDLINE (1946 to June week 3, 2014), EMBASE (1974 to June 2014), CINAHL (1981 to June 2014), LILACS (1982 to June 2014), Web of Science (1985 to June 2014) and BIOSIS Previews (1985 to June 2014). We also searched ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP) to identify unpublished and ongoing studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs evaluating the effects of zinc in reducing morbidity and mortality in children with measles. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies for inclusion and extracted data on outcomes, details of the interventions and other study characteristics using a standardised data extraction form. We used the risk ratio (RR) and hazard ratio as measures of effect with 95% confidence intervals (CI). We included only one study and we did not conduct any meta-analysis. MAIN RESULTS: One RCT met our inclusion criteria. The study was conducted in India and included 85 children diagnosed with measles and pneumonia. The trial showed that there was no significant difference in mortality between the two groups (risk ratio (RR) 0.34, 95% confidence interval (CI) 0.01 to 8.14). Also, there was no significant difference in time to absence of fever between the two groups (hazard ratio (HR) 1.08, 95% CI 0.67 to 1.74). No treatment-related side effects were reported in either group. The overall quality of the evidence can be described as very low. AUTHORS' CONCLUSIONS: We cannot draw any definite conclusions from this review about the effects of zinc supplementation on clinical outcomes of children with measles due to the very low quality of the evidence available. There is insufficient evidence to confirm or refute the effect of zinc supplementation in measles.

Uterine artery embolization for symptomatic uterine fibroids.

BACKGROUND: Uterine fibroids cause heavy prolonged bleeding, pain, pressure symptoms and subfertility. The traditional method of treatment has been surgery as medical therapies have not proven effective. Uterine artery embolization has been reported to be an effective and safe alternative to treat fibroids in women not desiring future fertility. There is a significant body of evidence that is based on case controlled studies and case reports. This is an update of the review previously published in 2012. OBJECTIVES: To review the benefits and risks of uterine artery embolization (UAE) versus other medical or surgical interventions for symptomatic uterine fibroids. SEARCH METHODS: We searched sources including the Cochrane Menstrual Disorders and Subfertility Group Specialised Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE and trial registries. The search was last conducted in April 2014. We contacted authors of eligible randomised controlled trials to request unpublished data. SELECTION CRITERIA: Randomised controlled trials (RCTs) of UAE versus any medical or surgical therapy for symptomatic uterine fibroids. The primary outcomes of the review were patient satisfaction and live birth rate (among women seeking live birth). DATA COLLECTION AND ANALYSIS: Two of the authors (AS and JKG) independently selected studies, assessed quality and extracted data. Evidence quality was assessed using GRADE methods. MAIN RESULTS: Seven RCTs with 793 women were included in this review. Three trials compared UAE with abdominal hysterectomy, two trials compared UAE with myomectomy, and two trials compared UAE with either type of surgery (53 hysterectomies and 62 myomectomies).With regard to patient satisfaction rates, our findings were consistent with satisfaction rates being up to 41% lower or up to 48% higher with UAE compared to surgery within 24 months of having the procedure (odds ratio (OR) 0.94; 95% confidence interval (CI) 0.59 to 1.48, 6 trials, 640 women, I(2) = 5%, moderate quality evidence). Findings were also inconclusive at five years of follow-up (OR 0.90; 95% CI 0.45 to 1.80, 2 trials, 295 women, I(2) = 0%, moderate quality evidence). There was some indication that UAE may be associated with less favourable fertility outcomes than myomectomy, but it was very low quality evidence from a subgroup of a single study and should be regarded with extreme caution (live birth: OR 0.26; 95% CI 0.08 to 0.84; pregnancy: OR 0.29; 95% CI 0.10 to 0.85, 1 study, 66 women).Similarly, for several safety outcomes our findings showed evidence of a substantially higher risk of adverse events in either arm or of no difference between the groups. This applied to intra-procedural complications (OR 0.91; 95% CI 0.42 to 1.97, 4 trials, 452 women, I(2) = 40%, low quality evidence), major complications within one year (OR 0.65; 95% CI 0.33 to 1.26, 5 trials, 611 women, I(2) = 4%, moderate quality evidence) and major complications within five years (OR 0.56; CI 0.27 to 1.18, 2 trials, 268 women). However, the rate of minor complications within one year was higher in the UAE group (OR 1.99; CI 1.41 to 2.81, 6 trials, 735 women, I(2) = 0%, moderate quality evidence) and two trials found a higher minor complication rate in the UAE group at up to five years (OR 2.93; CI 1.73 to 4.93, 2 trials, 268 women).UAE was associated with a higher rate of further surgical interventions (re-interventions within 2 years: OR 3.72; 95% CI 2.28 to 6.04, 6 trials, 732 women, I(2) = 45%, moderate quality evidence; within 5 years: OR 5.79; 95% CI 2.65 to 12.65, 2 trials, 289 women, I(2) = 65%). If we assumed that 7% of women will require further surgery within two years of hysterectomy or myomectomy, between 15% and 32% will require further surgery within two years of UAE.The evidence suggested that women in the UAE group were less likely to require a blood transfusion than women receiving surgery (OR 0.07; 95% CI 0.01 to 0.52, 2 trials, 277 women, I(2) = 0%). UAE was also associated with a shorter procedural time (two studies), shorter length of hospital stay (seven studies) and faster resumption of usual activities (six studies) in all studies that measured these outcomes; however, most of these data could not be pooled due to heterogeneity between the studies.The quality of the evidence varied, and was very low for live birth, moderate for satisfaction ratings, and moderate for most safety outcomes. The main limitations in the evidence were serious imprecision due to wide confidence intervals, failure to clearly report methods, and lack of blinding for subjective outcomes. AUTHORS' CONCLUSIONS: When we compared patient satisfaction rates at up to two years following UAE versus surgery (myomectomy or hysterectomy) our findings are that there is no evidence of a difference between the interventions. Findings at five year follow-up were similarly inconclusive. There was very low quality evidence to suggest that myomectomy may be associated with better fertility outcomes than UAE, but this information was only available from a selected subgroup in one small trial.We found no clear evidence of a difference between UAE and surgery in the risk of major complications, but UAE was associated with a higher rate of minor complications and an increased likelihood of requiring surgical intervention within two to five years of the initial procedure. If we assume that 7% of women will require further surgery within two years of hysterectomy or myomectomy, between 15% and 32% will require further surgery within two years of UAE. This increase in the surgical re-intervention rate may balance out any initial cost advantage of UAE. Thus although UAE is a safe, minimally invasive alternative to surgery, patient selection and counselling are paramount due to the much higher risk of requiring further surgical intervention.

Compensation in Neonatal Clinical Trials: A Perspective.

Well conducted clinical trials are the mainstay for generating evidence on preferred treatments. In order to adequately protect the interests of the trial participants, the Central Licensing Authority of India has formulated guidelines to determine the quantum of compensation in cases of regulatory clinical trial related injury or death. However, these guidelines do not address the nuances of trials recruiting children aged under 16 years, within which, neonates are the most vulnerable population. Thus, there is a need for addressing this lacuna in the current guidelines. This article examines the challenges in determining the quantum of compensation in neonatal clinical trials using the current formula, which is a corollary to the challenges faced by the authors in procuring clinical trial insurance for the Probiotic supplementation for Prevention of Neonatal Sepsis (ProSPoNS) trial. Further, it suggests a template for a differential formula using birthweight of infants, which is one of the many important factors impacting neonatal mortality.

Non-Medical Determinants of Access and Quality of Maternal Health Services in India-Protocol for a Scoping Review.

Introduction: The Maternal Mortality Rate (MMR) is one of the most important health indicators of a country. In India, MMR has decline from 130 to 113 per 100,000 live births between 2014 and 2018, however, there are wide disparities in utilization of maternal health services (MHS) among different states and across different socioeconomic groups within the states. Although the government is providing MHS through various health programs in India, there are several non medical factors leading to the underutilization of MHS services. Objective: To map and summarise the non-medical determinants of access and quality of MHS in India. Methods: We are conducting a scoping review of the published literature from 2000 till date in databases such as PubMed, Cochrane, Science Direct and CINAHL by including eligible qualitative as well as quantitative studies conducted in India. Data extraction and analysis will be conducted through a narrative integrative synthesis approach to summarize the non-medical determinants of access and quality of MHS in India and understand their mechanisms of influence.At the third SPINE20 summit 2022 which took place in Bali, Indonesia, in August 2022, 17 associations endorsed its recommendations. Results: We will summarise the non-medical determinants that influence the access and quality of MHS. Conclusion: This scoping review would help to understand and summarise the existing non-medical determinants of access and quality of MHS, highlight the research gaps and suggest potential modalities for improvement of access and quality of MHS.

Effect of IV ferric carboxy maltose for moderate/severe anemia: a systematic review and meta-analysis.

Introduction: Anemia remains a prevalent global health issue with varying severity. Intravenous iron supplementation, particularly with ferric carboxymaltose (FCM), has appeared as a possible therapeutic intervention for individuals with moderate to severe anemia. The study aimed to assess the efficacy and safety of ferric carboxymaltose (FCM) in reducing anemia. Methods: We searched electronic databases, registries, websites, e-libraries, reference lists of reviews, citations, etc. We included randomized control trials (RCTs), non-RCTs, and single-arm studies, while observational studies, case series, and case studies were excluded. Two reviewers independently screened the studies and extracted the data. We included studies of moderate-to-severely anemic Indians and excluded Indians with other comorbidities. We assessed the risk of bias and the overall quality of evidence (QoE) using GRADE GDT. Result: We identified 255 studies and included 14 studies (11 RCT, one non-RCT, and two single-arm studies) with 1,972 participants for qualitative analysis and 10 studies in the meta-analysis. All the included studies detailed the use of FCM for anemia. The primary outcomes assessed in the included studies were anemia, hemoglobin, and adverse events. The outcomes assessed ranged from 2 weeks to 12 weeks. The risk of bias varied across different studies with different outcomes. FCM is consistent with a fewer number of adverse events as compared to other interventions and provides "moderate" to "very low" QoE. Conclusion: A slow single infusion of 1 gram of FCM is well-tolerated, safe, and effective in treating iron deficiency anemia (IDA) and surpasses other interventions (Iron Sucrose Complex (ISC), Iron sucrose, and ferrous ascorbate) in elevating hemoglobin levels and replenishing iron stores. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=459363, CRD42023459363.

Role of central endpoint adjudication and challenges in trials on neonatal sepsis-a case of ProSPoNS trial.

Despite progress in reducing the infant mortality in India, the neonatal mortality decline has been slower, necessitating concerted efforts to achieve Sustainable Development Goal-3. A promising strategy aiming to prevent neonatal sepsis in high-risk, vulnerable, low birth weight neonates through an innovative intervention includes probiotic supplementation. This article communicates the decision by the ProSPoNS trial investigators to establish a Central Endpoint Adjudication Committee (CEAC) as an addendum to the protocol published in Trials in 2021 for the purpose of clarifying the primary outcome. In the published protocol, the study hypothesis and primary objective are based on "sepsis," the primary outcome has been specified as sepsis/PSBI, whereas the sample size estimation was performed based on the "physician diagnosed sepsis." To align all the three above, the investigators meeting, held on 17th-18th August 2023, at MGIMS Sevagram, Wardha, deliberated and unanimously agreed that "physician diagnosed sepsis" is the primary study outcome which includes sepsis/PSBI. The CEAC, chaired by an external subject expert and members including trial statistician, a microbiologist, and all site principal investigators will employ four criteria to determine "physician diagnosed sepsis": (1) blood culture status, (2) sepsis screen status, (3) PSBI/non-PSBI signs and symptoms, and (4) the clinical course for each sickness event. Importantly, this clarification maintains consistency with the approved study protocol (Protocol No. 5/7/915/2012 version 3.1 dated 14 Feb 2020), emphasizing the commitment to methodological transparency and adherence to predefined standards. The decision to utilize the guidance of a CEAC is recommended as the gold standard in multicentric complex clinical trials to achieve consistency and accuracy in assessment of outcomes.Trial registrationClinical Trial Registry of India (CTRI) CTRI/2019/05/019197. Registered on 16 May 2019.

Community acquisition of ß-lactamase producing Enterobacteriaceae in neonatal gut.

BACKGROUND: Commensal flora constitutes a reservoir of antibiotic resistance. The increasing variety of ß-lactamases and the emergence of Carbapenem resistant Enterobacteriaceae (CRE) in community, raise concerns regarding efficacy of ß-lactams. It is important to know the exact load of antibiotic resistance in the absence of any antibiotic selection pressure including via food and water.In the present study gut colonization in neonates with no direct antibiotic pressure was used as a model to evaluate ß-lactam resistance in the community. RESULTS: In this prospective study, 75 healthy, vaginally delivered, antibiotic naive, breast fed neonates were studied for gut colonization by Extended spectrum ß-lactamases (ESBL), AmpC ß-lactamases hyperproducing Enterobacteriaceae and CRE on day 0, 21 and 60. Total 267 Enterobacteriaceae were isolated and E.coli was the predominant flora. ESBL, AmpC and coproduction was seen in 20.6%, 19.9% and 11.2% isolates respectively. ESBL carriage increased threefold from day 1 to 60 showing predominance of CTX-M group 15 (82.5%), ampC genes were heterogeneous. Colonization with CRE was rare, only one baby harboured Enterobacter sp positive for kpc-2. The reservoirs for these genes are likely to be mother and the environment. CONCLUSIONS: Data strongly suggests that in absence of any antibiotic pressure there is tremendous load of antibiotic resistance to ß-lactam drugs. Wide spread presence of ESBL and AmpC can drive rapid emergence and dissemination of CRE. This is the first report from India which depicts the smaller picture of true antibiotic pressure present in the Indian community.

Acceptability of PrEP among MSM and transgender communities-Qualitative findings from two metropolitan cities in India.

BACKGROUND: Global evidence suggests that Pre-Exposure Prophylaxis (PrEP) plays a pivotal role in reducing new HIV-infections among key populations (KP). However, the acceptability of PrEP differs across different geographical and cultural settings and among different KP typologies. Men who have sex with men (MSM) and transgender (TG) communities in India have around 15-17 times higher prevalence of human immunodeficiency virus (HIV) than the general population. The low rates of consistent condom use and poor coverage of HIV testing and treatment among the MSM and transgender communities highlight the need for alternative HIV prevention options. METHODS: We used data from 20 in-depth interviews and 24 focused group discussions involving 143 MSM and 97 transgender individuals from the two metropolitan cities (Bengaluru and Delhi) in India to qualitatively explore their acceptability of PrEP as a HIV prevention tool. We coded data in NVivo and conducted extensive thematic content analysis. RESULTS: Awareness and use of PrEP were minimal among the MSM and transgender communities in both cities. However, on being provided with information on PrEP, both MSM and transgender communities expressed willingness to use PrEP as an additional HIV-prevention tool, to complement inability to consistently use condoms. PrEP was also perceived as a tool that could enhance the uptake of HIV-testing and counseling services. PrEP awareness, availability, accessibility and affordability were identified as determining factors that could influence its acceptability. Challenges such as stigma and discrimination, interrupted supply of drugs and non-community-friendly drug dispensing sites were identified barriers to continuing PrEP. CONCLUSIONS: Using qualitative data from two Indian settings, this study provides community perspectives and recommendations to stakeholders and policymakers for introduction of PrEP into programs as a prevention tool among MSM and transgender communities in India.

Prevention of recurrence of bacterial vaginosis using lactobacilli-containing vaginal tablets among women with HIV: a randomized, placebo-controlled, double-blinded phase IV trial.

OBJECTIVES: The effectiveness of lactobacilli-containing vaginal tablets (VT) in bacterial vaginosis (BV) recurrence prevention among women infected with HIV treated with standard oral metronidazole in Pune, India was studied. METHODS: Women infected with HIV with confirmed BV diagnosis (Nugent score ≥7 and Amsel criteria >3) were enrolled in a 12-month, double-blind, randomized, placebo-controlled, phase IV study between 2018 and 2021. After a standard course of oral metronidazole for 7 days (400 mg three times a day), women were randomly assigned to either lactobacilli-containing or placebo VT arms to receive VTs for 4 months. BV recurrence was assessed after the initial cure from BV. RESULTS: Of the 464 women infected with HIV, 80 women with confirmed BV were enrolled. The retention was affected due to the COVID-19 pandemic (6-month retention rates 78%). The cure was seen in 85% and 93.5% of participants from the treatment and placebo arms, respectively, after four VT cycles. BV recurrence was seen in 41.4% and 44.8% in the treatment and placebo arm, respectively, with no significant difference in the two groups. CONCLUSION: The lactobacilli-containing VT was acceptable and safe; however, the addition of VT over standard oral metronidazole did not show any additional benefit in the prevention of BV recurrence in women infected with HIV, indicating the need for long-term randomized trials among them. Registered at Clinical Trials Registry- India, (CTRI) Number: CTRI/2018/04/013298.

Study protocol for economic evaluation of probiotic intervention for prevention of neonatal sepsis in 0-2-month old low-birth weight infants in India: the ProSPoNS trial.

INTRODUCTION: The ProSPoNS trial is a multicentre, double-blind, placebo-controlled trial to evaluate the role of probiotics in prevention of neonatal sepsis. The present protocol describes the data and methodology for the cost utility of the probiotic intervention alongside the controlled trial. METHODS AND ANALYSIS: A societal perspective will be adopted in the economic evaluation. Direct medical and non-medical costs associated with neonatal sepsis and its treatment would be ascertained in both the intervention and the control arm. Intervention costs will be facilitated through primary data collection and programme budgetary records. Treatment cost for neonatal sepsis and associated conditions will be accessed from Indian national costing database estimating healthcare system costs. A cost-utility design will be employed with outcome as incremental cost per disability-adjusted life year averted. Considering a time-horizon of 6 months, trial estimates will be extrapolated to model the cost and consequences among high-risk neonatal population in India. A discount rate of 3% will be used. Impact of uncertainties present in analysis will be addressed through both deterministic and probabilistic sensitivity analysis. ETHICS AND DISSEMINATION: Has been obtained from EC of the six participating sites (MGIMS Wardha, KEM Pune, JIPMER Puducherry, AIPH, Bhubaneswar, LHMC New Delhi, SMC Meerut) as well as from the ERC of LSTM, UK. A peer-reviewed article will be published after completion of the study. Findings will be disseminated to the community of the study sites, with academic bodies and policymakers. REGISTRATION: The protocol has been approved by the regulatory authority (Central Drugs Standards Control Organisation; CDSCO) in India (CT-NOC No. CT/NOC/17/2019 dated 1 March 2019). The ProSPoNS trial is registered at the Clinical Trial Registry of India (CTRI). Registered on 16 May 2019. TRIAL REGISTRATION NUMBER: CTRI/2019/05/019197; Clinical Trial Registry.

Uterine artery embolization for symptomatic uterine fibroids.

BACKGROUND: Uterine fibroids cause heavy prolonged bleeding, pain, pressure symptoms and subfertility. The traditional method of treatment has been surgery as medical therapies have not proven effective. Uterine artery embolization (UAE) has been reported to be an effective and safe alternative to treat fibroids in women not desiring future fertility. There is a significant body of evidence based on case controlled studies and case reports. This is an update of the review previously published in 2006. OBJECTIVES: To review the benefits and risks of uterine artery embolization (UAE) versus other medical or surgical interventions for symptomatic uterine fibroids. SEARCH METHODS: We searched the Cochrane Menstrual Disorders & Subfertility Group Trials register (searched November 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library, 4th Quarter 2011), MEDLINE (1950 to November 2011) and EMBASE (January 1980 to November 2011). We also contacted authors of eligible RCTs for unpublished data. SELECTION CRITERIA: Randomised controlled trials (RCTs) of UAE versus any medical or surgical therapy for symptomatic uterine fibroids. DATA COLLECTION AND ANALYSIS: Two of the authors (AS and JKG) assessed the trials and extracted the data independently. MAIN RESULTS: Five RCTs were included in this review. Three trials compared UAE with abdominal hysterectomy in 291 women. A fourth trial included 157 women and compared UAE with surgery (43 hysterectomies and 8 myomectomies). The fifth trial included 121 women and compared UAE with myomectomy in women wishing to preserve fertility.There was moderately good evidence that there is no significant difference between UAE and surgery in patient satisfaction rates at two years (OR 0.69, 0.40 to 1.21, 516 women, 5 trials) nor at five years (OR 0.90, 95% CI 0.45 to 1.80, 295 women, 2 trials). There was very low level evidence suggesting that myomectomy may be associated with better fertility outcomes than UAE, but this analysis was restricted to the limited cohort of women (n=66) who tried to conceive in the single study of UAE versus myomectomy (live birth: OR 0.33, 95% CI 0.11 to 1.00; pregnancy: OR 0.29, 95% CI 0.10 to 0.85). There was no significant difference between the two interventions in the rate of major complications. Compared to surgery, UAE significantly reduced the length of the procedure, length of hospital stay and time to resumption of routine activities and also decreased the likelihood of needing a blood transfusion. However, UAE was associated with higher rates of minor short term and long term complications, more unscheduled readmissions after discharge and an increased surgical reintervention rate. This increase in the surgical reintervention rate may balance out the initial cost advantage of UAE (reinterventions within 2 years: OR 5.64, 95% CI 2.92 to 10.90, 486 women, 4 trials; within 5 years: OR 5.79, 95% CI 2.65 to 12.65. 289 women, 2 trials). There was no significant difference in ovarian failure rates at long term follow-up. AUTHORS' CONCLUSIONS: UAE appears to have an overall patient satisfaction rate similar to hysterectomy and myomectomy and offers an advantage with regards to a shorter hospital stay and a quicker return to routine activities. However, UAE is associated with a higher rate of minor complications and an increased likelihood of requiring surgical intervention within two to five years of the initial procedure. There is very low level evidence suggesting that myomectomy may be associated with better fertility outcomes than UAE, but more research is needed.

Rapid control of foetal supraventricular tachycardia with digoxin and flecainide combination treatment.

OBJECTIVES: To evaluate the efficacy of flecainide and digoxin combination in foetal supraventricular tachycardia. SETTING: This study was carried out in a tertiary referral centre. METHODS: We conducted a retrospective review of 29 patients diagnosed with supraventricular foetal tachycardia between 2001 and 2009. Mode of presentation, foetal cardiac function, maternal anti-arrhythmic serum levels, drug tolerance, and maternal electrocardiogram recordings were assessed. The postnatal outcome of each infant was also evaluated for tachycardia recurrence. RESULTS: In all, 27 foetuses were treated with digoxin and flecainide combination, and two foetuses were delivered without any treatment. Of the 27 foetuses treated, six [corrected] had atrial flutter and the remaining 21 [corrected] had atrioventricular re-entry tachycardia. There were eight foetuses with hydrops (27%), of whom three had atrial flutter and five had atrioventricular re-entry tachycardia; 26 foetuses (96%) responded to flecainide and digoxin combination, with restoration of sinus rhythm in 22 (81.4%) and rate control in the other four. In one severely hydropic foetus, there was no response to treatment. In all, 26 treated infants were delivered alive, but one pregnancy was terminated for non-cardiac causes when the foetus was in sinus rhythm. There was no intrauterine death due to tachycardia. Although there were minor side effects to anti-arrhythmic medications, none of the pregnant women developed proarrhythmia. CONCLUSION: Flecainide and digoxin combination treatment offers a safe and effective treatment for foetal supraventricular tachycardia with fast restoration of sinus rhythm.