National Institute Of Child Health Research Articles

Acetaminophen for Patent Ductus Arteriosus and Risk of Mortality and Pulmonary Morbidity.

Emerging data indicate that acetaminophen may adversely affect lung health. We examined whether acetaminophen compared with cyclooxygenase (COX) inhibitor alone for patent ductus arteriosus (PDA) is associated with mortality or respiratory morbidity in extremely preterm infants. This is a retrospective cohort study using data from the National Institute of Child Health and Human Development Neonatal Research Network. Infants were born at 22 to 28 weeks' gestation or weighing 401 to 1000 g between 2016 and 2020 and received acetaminophen, ibuprofen, and/or indomethacin for PDA closure. The primary outcome was death or grade 2 to 3 bronchopulmonary dysplasia (BPD) at 36 weeks' postmenstrual age. Secondary outcomes included predischarge mortality and respiratory morbidities. Risk ratios were adjusted for baseline and early postnatal factors. Additional exploratory analyses were adjusted for later postnatal covariates. Of 1921 infants, 627 (32.6%) received acetaminophen and 1294 (67.3%) received COX inhibitor only. Multidrug therapy (42.9% vs 4.7%) and surgical or catheter PDA closure (26.5% vs 19.9%) were more common among acetaminophen-exposed infants. Death or grade 2 to 3 BPD at 36 weeks' postmenstrual age was similar between infants treated with acetaminophen versus COX inhibitor only (57.1% vs 58.3%; adjusted relative risk [aRR] 0.96, 95% confidence interval [CI] 0.87-1.06). Acetaminophen was associated with increased risk of predischarge mortality (13.3% vs 10.0%) when adjusting for perinatal and early postnatal factors (aRR 1.42, 95% CI 1.02-1.93), but not in exploratory analyses that included later postnatal factors (aRR 1.28, 95% CI 0.91-1.82). Treatment with acetaminophen versus COX inhibitor alone for PDA was not associated with the composite outcome of death or BPD in extremely preterm infants. Our results support further evaluation of whether acetaminophen for PDA increases mortality.

Obesity- and diet-induced plasticity in systems that control eating and energy balance.

In April 2023, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), in partnership with the National Institute of Child Health and Human Development, the National Institute on Aging, and the Office of Behavioral and Social Sciences Research, hosted a 2-day online workshop to discuss neural plasticity in energy homeostasis and obesity. The goal was to provide a broad view of current knowledge while identifying research questions and challenges regarding neural systems that control food intake and energy balance. This review includes highlights from the meeting and is intended both to introduce unfamiliar audiences with concepts central to energy homeostasis, feeding, and obesity and to highlight up-and-coming research in these areas that may be of special interest to those with a background in these fields. The overarching theme of this review addresses plasticity within the central and peripheral nervous systems that regulates and influences eating, emphasizing distinctions between healthy and disease states. This is by no means a comprehensive review because this is a broad and rapidly developing area. However, we have pointed out relevant reviews and primary articles throughout, as well as gaps in current understanding and opportunities for developments in the field.

Clinical guideline highlights for the hospitalist: International consensus criteria for pediatric sepsis and septic shock.

International Consensus Criteria for Pediatric Sepsis and Septic Shock RELEASE DATE: January 21, 2024 PRIOR VERSION(S): International Pediatric Sepsis Consensus Conference: Definitions for Sepsis and Organ Dysfunction in Pediatrics (2005) DEVELOPER: Society of Critical Care Medicine FUNDING SOURCE: Society of Critical Care Medicine (grant R01HD105939 from the National Institute of Child Health and Human Development) TARGET POPULATION: Children with sepsis and septic shock.

Recent Developments in Promising Hormonal and Non- Hormonal Male Contraceptives: A Review

New male contraceptive methods would expand male and female contraceptive alternatives and enhance male contraceptive agency. Since 1969, a program for developing contraceptives has been financed by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, which also continues to fund the majority of hormonal male contraceptive development today. Also, the early stages of non-hormonal techniques start to develop. The hormonal male contraceptive methods, include testosterone undecanoate injection plus norethisterone enanthate injection, implants of testosterone plus depo-medroxyprogesterone acetate injection, testosterone enanthate injection, and other testosterone-based methods. The non-hormonal methods, include novel hormone-free substances such as retinoic acid inhibitors, sperm ion channel blockers, and vasal peristalsis blockers. The review provides insights into the efficacy, safety, and potential side effects of each method, and highlights the current state of research and development in the field of male contraception.

Care-seeking for difficulties conceiving in sub-Saharan Africa: findings from population-based surveys in eight geographies.

What is the nature of women's care-seeking for difficulties conceiving in sub-Saharan Africa (SSA), including the correlates of seeking biomedical infertility care at a health facility? Care-seeking for difficulties getting pregnant was low, much of which involved traditional or religious sources of care, with evidence of sociodemographic disparities in receipt of biomedical care. Nearly all research on infertility care-seeking patterns in SSA is limited to clinic-based studies among the minority of people in these settings who obtain facility-based services. In the absence of population-based data on infertility care-seeking, we are unable to determine the demand for services and disparities in the use of more effective biomedical sources of care. We used cross-sectional, population-based data from the Performance Monitoring for Action (PMA) female survey in eight geographies in SSA, including nationally representative data from Burkina Faso, Côte d'Ivoire, Kenya, and Uganda and regionally representative data from two provinces in the Democratic Republic of the Congo (DRC) (Kinshasa and Kongo Central) and two states in Nigeria (Kano and Lagos). We employed a multi-stage cluster random sampling design with probability proportional to size selection of clusters within each geography to produce representative samples of women aged 15-49. Samples ranged from 1144 in Kano, Nigeria, to 9489 in Kenya. PMA collected these data between November 2021 and December 2022. We restricted the sample to women who had ever had sex, with analytic samples ranging from 854 in Kano to 8,059 in Kenya, then conducted descriptive and bivariable analyses to examine characteristics of those who sought care for difficulties getting pregnant. Among those who reported seeking care, we conducted bivariable and multivariable logistic regression analyses to determine factors associated with receipt of biomedical services from a health facility. All analyses were conducted separately by geography. Our study found low levels of care-seeking for difficulties getting pregnant among sexually active women in eight geographies in SSA, ranging from 3.7% (Kenya) to 15.3% (Côte d'Ivoire). Of this, 51.8% (Burkina Faso) to 86.7% (Kinshasa) involved receipt of biomedical services in health facilities. While many factors were consistently associated with infertility care-seeking from any source across geographies, factors associated with receipt of biomedical care specifically were less pronounced. This may be a result of the highly limited sources of infertility services in SSA; thus, even privileged groups may struggle to obtain effective treatment for difficulties getting pregnant. However, we did observe disparities in biomedical care-seeking in our bivariable results in several geographies, with the wealthiest women, those with more education, and those residing in urban areas generally more likely to have sought biomedical care for difficulties getting pregnant. Our data lacked details on the nature of the services received and outcomes, and we do not have information on reasons why women chose the sources they did. Small samples of women who sought care limited our power to detect significant differences in care-seeking by women's characteristics in several geographies. Infertility and access to appropriate treatment are issues of reproductive health and human rights. While our results do not indicate to what extent use of non-biomedical sources of care is driven by preferences, cost, or lack of accessible services, it is clear from our results and existing literature that more needs to be done to ensure access to affordable, quality, cost-effective infertility services in SSA. This study was supported by grants from the Bill & Melinda Gates Foundation (INV009639) and the National Institute of Child Health and Human Development (K01HD107172). The funders were not involved in the study design, analyses, manuscript writing, or the decision to publish. The authors have no conflicts of interest to declare. N/A.

Genomic Differences between Spontaneous versus Indicated Extreme Preterm Birth.

Extremely preterm infants are at high risk of neonatal mortality and morbidity. Extreme preterm birth (PTB) may result from spontaneous preterm labor or preterm premature rupture of membranes or may be indicated due to preeclampsia, eclampsia, hypertension, or other causes. Our objective was to identify single nucleotide polymorphisms (SNPs) and biological pathways associated with spontaneous versus indicated extreme PTB using the neonatal genome. We evaluated 523 spontaneous births and 134 indicated births weighing 401 to 1,000 g at birth from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network's Genomics dataset by genome-wide association study (GWAS) and pathway analysis. The TOLSURF cohort was used to replicate the results. In the NRN GWAS, no statistically significant results were found, although the Manhattan plot showed one almost significant peak (rs60854043 on chromosome 14 at p = 1.03E-07) along with many other modest peaks at p = 1-9E-06, for a total of 15 suggestive associations at this locus. In the NRN pathway analysis, multiple pathways were identified, with the most significant being "GO_mf:go_low_density_lipoprotein_particle_receptor_activity" at p = 1.14E-06. However, these results could not be replicated in the TOLSURF cohort. Genomic differences are seen between infants born by spontaneous versus indicated extreme PTB. Due to the limited sample size, there is a need for larger studies. · Genomic differences are seen between infants born by spontaneous versus indicated very PTB.. · Future studies with large sample sizes evaluating extreme PTB are necessary.. · Spontaneous PTB is more common than indicated extreme PTB..

Plasma Glycated Albumin in Early Pregnancy and Gestational Diabetes Mellitus: A Prospective and Longitudinal Study.

To investigate associations of plasma glycated albumin (GA) concentrations in early and midpregnancy with gestational diabetes mellitus (GDM) risk. We measured GA concentrations using blood samples collected at 10-14 and 15-26 weeks' gestation (GW) in 107 GDM case subjectsand 214 control subjects from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Fetal Growth Study. We performed generalized linear mixed-effect regression to test the mean GA difference between GDM case subjectsand control subjects and conditional logistic regression to assess prospective associations between GA concentrations and GDM risk. At 15-26 GW, mean GA was lower in GDM case subjectsthan control subjects (mean 11.90% [95% CI 6.42-32.76] vs. 12.46% [8.45-38.35], adjusted P value for difference = 0.004). Consistently, women with higher GA concentrations tended to have a lower GDM risk, although the associations were not statistically significant. This study suggests that GA concentrations in midpregnancy might be lower in women who later develop GDM. Further studies are needed to identify the mechanism.

Clinical spectrum of acute flaccid paralysis among pediatric patients at the National Institute of Child Health, Karachi, Pakistan.

Objective: To evaluate the clinical spectrum and immediate outcomes of acute flaccid paralysis (AFP) in children presenting at National Institute of Child Health, Karachi, Pakistan. Study Design: Cross-sectional study. Setting: Department of Pediatrics, NICH, Karachi, Pakistan. Period: August 2023 to January 2024. Methods: A total of 121 children of either gender, aged 1-15 years, and presenting with AFP were analyzed. AFP was diagnosed by nerve conduction study. Causes of AFP, like Guillian Barre Syndrome (GBS), transverse myelitis, traumatic neuritis were noted. Outcomes were noted in terms of discharged from hospital, left against medical advice, and mortality. Results: In a total of 121 children, 75 (62.0%) were boys. The mean age was 6.00±2.88 years, ranging between 1-12 years. There were 74 (61.2%) children who were fully vaccinated as per age. The most common cause of AFP were GBS, transverse myelitis, and hypokalemic paralysis, noted in 49 (40.5%), 19 (15.7%), and 15 (12.4%) children, respectively. Ninety (74.4%) children were discharged after the treatment, 10 (8.3%) left against medical advice, whereas mortality was noted in 21 (17.4%) children. Children leaving against medical advice were left out from the analysis to compared final outcomes with respect to various study variables. Incomplete vaccination status (p=0.0006), and presentation with sensory loss (p=0.0003) were found to have significant association with mortality. Conclusion: Guillian Barre Syndrome was found to be the most common cause behind acute flaccid paralysis in children. Incomplete vaccination history, and presenting with sensory loss were associated with poor outcomes.

Prevalence of chronic kidney disease in children of school going age visiting outpatient department of A Tertiary Care Hospital in Karachi, Pakistan.

Objective: To determine the prevalence of chronic kidney disease (CKD) among children of school-going age. Study Design: Cross-sectional study. Setting: Department of Pediatric Medicine, National Institute of Child Health, Karachi, Pakistan. Period: July 2023 to December 2023. Methods: A total of 130 children of both genders, aged between 5-15 years, visiting outpatient department of pediatric medicine were analyzed. Demographic and clinical information were noted. Laboratory investigations like urinalysis and serum creatinine were performed. CKD was diagnosed on the basis of “Kidney Disease Outcomes Quality Initiative (KDOQI)” guidelines. Results: In a total of 130 children, 67 (51.5%) children were male. Overall, the mean age was 8.43±2.45 years. Hypertension was diagnosed in 10 (7.7%) children. Anemia was present in 103 (79.2%) patients. The mean hemoglobin, serum creatinine, and blood urea nitrogen were 9.41±1.98 g/dl, 0.48±0.37 mg/dl, and 34.20±33.18 mg/dl, respectively. CKD was diagnosed in 10 (7.7%) children. Among these 10 children diagnosed with CKD, 7 were having CKD stage-1 whereas CKD stage-2 was noted in 3 children. Presence of hypertension (p=0.006), and albuminuria (p<0.001) were associated with CKD. Conclusion: The prevalence of CKD in school going age children was 7.7%. Presence of hypertension, and albuminuria were linked with CKD.

Measurement of Orbital Dimensions and Its Gender Related Differences in Various Ages of Pakistani Children

Purpose: To measure the orbital dimensions and their gender related differences at various ages in Pakistani children from birth to 12 years of age. Study Design: Cross sectional observational. Place and Duration of Study: Tibri Medical College and Hospital Karachi and National Institute of Child Health, Karachi from June 2022 to February 2023. Methods: Patients who underwent CT Scan head for any reason but with normal orbits were included in the study. The vertical and horizontal measurements were made for anterior, middle and posterior orbit in sagittal and axial views. Results: The mean age of the total sample of 176 children was 6.45±3.40 years. The mean horizontal dimension of the anterior side of the orbit was 28.31 mm for children aged 1-3 years, 30.63 mm for those aged 4-6 years, 32.22 mm for ages 6-9 years, and 32.93 mm for ages 10-12 years. These differences were statistically significant (p<0.05). A significant difference was observed in the mean vertical dimension for the middle and posterior sides across different age groups. There were significant differences in the vertical and horizontal dimensions of the anterior and middle sides of the orbits for children aged 1-3 years (p<0.05). However, for children aged 4-6 years, there were no significant differences between genders in any measured dimension (horizontal, vertical, or depth) (p>0.05). Conclusion: There is a phase of rapid growth from birth to 3 years of age, after which the orbit continues to grow slowly. Gender-related differences were more pronounced during this phase.

Pathways through which intermittent preventive treatment for malaria in pregnancy influences child growth faltering: a mediation analysis.

Intermittent preventive treatment for malaria in pregnancy (IPTp) can improve birth outcomes, but whether it confers benefits to postnatal growth is unclear. We investigated the effect of IPTp on infant growth in Uganda and its pathways of effects using causal mediation analyses. We analyzed data from 633 infants born to mothers enrolled in a randomized trial of monthly IPTp with dihydroartemisinin-piperaquine (DP) vs sulfadoxine-pyrimethamine (SP) (NCT02793622). Weight and length were measured from 0-12 months of age. Using generalized linear models, we estimated effects of DP vs. SP on gravidity-stratified mean length-for-age (LAZ) and weight-for-length Z-scores (WLZ). We investigated mediation by placental malaria, gestational weight change, maternal anemia, maternal inflammation-related proteins, preterm birth, birth length, and birth weight. Mediation models adjusted for infant sex, gravidity, gestational age at enrollment, maternal age, maternal parasitemia at enrollment, education, and wealth. SP increased LAZ by 0.18-0.28 Z from birth through age 4 months compared to DP, while DP increased WLZ by 0.11-0.28 Z from 2-8 months compared to SP among infants of multigravidae. We did not observe these differences among primigravida. Mediators of SP included increased birth weight and length and maternal stem cell factor at delivery. Mediators of DP included placental malaria and birth length, maternal IL-18, CDCP1, and CD6 at delivery. In high malaria transmission settings, different IPTp regimens influenced infant growth among multigravidae through distinct pathways in the period of exclusive breastfeeding, when few other interventions are available. Stanford Center for Innovation and Global Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bill & Melinda Gates Foundation.

Assessment of evidence based care and uniformity of practices through implementation of standardized medical protocols and guidelines in pediatric emergency departments

ObjectiveThis study aims to assess compliance with medical protocols and outcomes, as well as determine the consistency in clinical practice across different Pediatric Emergency Departments (PED) in public sector hospitals of a low-middle income country. MethodsA retrospective analysis was conducted on patients presenting to PEDs of five public sector hospitals, namely Civil Hospital Karachi (CHK), National Institute of Child Health (NICH), Abbasi Shaheed Hospital (ASH), Sheikh Zayed Hospital Larkana (LRK), and Ghulam Muhammad Mahar College Hospital Sukkur (SKR). The analysis covered a three-month period from February 1, 2023, to April 30, 2023. Patients diagnosed with Asthma, Sepsis, and Septic Shock during the study duration were included. Outcomes for each disease were evaluated based on compliance with standardized protocols. ResultsA total of 13,240 patients were diagnosed with the three diseases during the study period. Of these, 74% (n = 9751) had Sepsis, 12% (n = 1591) had Asthma, and 14% (n = 1898) had Septic Shock. The overall compliance rate for the three diseases was 77% (n = 10,240). Adherence to standard protocols was 98% (n = 1561) for Asthma, 85% (n = 8240) for Sepsis, and 23% (n = 439) for Septic Shock across the five emergency departments. Of the patients who were managed according to standard protocol, 31% (n = 3135) were discharged, 30% (n- 3094) were admitted, 11% (n = 1151) were referred, 15% (n = 1501) left against medical advice and 13% (n = 1359) did not survive. On the other hand, in patients where there was noncompliance to standard protocols, 27% (n = 805) did not survive, 27% (n = 807) were discharged, 24% (n = 710) were admitted, 8% (n = 260) were referred and 14% (n = 418) left against medical advice. ConclusionThe majority of PED demonstrated good compliance with standardized practices. However, this study identified areas that require attention and further training, especially early management of septic shock where compliances seem alarmingly low. Our data analysis indicates that adherence to guidelines has resulted in uniformity in clinical practice and the provision of early evidence-based quality care. Nevertheless, there is still room for improvement in ensuring consistent adherence to medical protocols in pediatric emergency settings and thus improving patient outcomes.

Effect of prematurely elevated late follicular progesterone on pregnancy outcomes following ovarian stimulation-intrauterine insemination for unexplained infertility: secondary analysis of the AMIGOS trial.

What is the relationship between late follicular phase progesterone levels and clinic pregnancy and live birth rates in couples with unexplained infertility undergoing ovarian stimulation with IUI (OS-IUI)? Late follicular progesterone levels between 1.0 and <1.5 ng/ml were associated with higher live birth and clinical pregnancy rates while the outcomes in groups with higher progesterone levels did not differ appreciably from the <1.0 ng/ml reference group. Elevated late follicular progesterone levels have been associated with lower live birth rates after fresh embryo transfer following controlled ovarian stimulation and egg retrieval, but less is known about whether an association exists with outcomes in OS-IUI cycles. Existing studies are few and have been limited to ovarian stimulation with gonadotrophins, but the use of oral agents, such as clomiphene citrate and letrozole, is common with these treatments and has not been well studied. The study was a prospective cohort analysis of the Assessment of Multiple Intrauterine Gestations from Ovarian Stimulation (AMIGOS) randomized controlled trial. Frozen serum was available for evaluation from 2121 cycles in 828 AMIGOS participants. The primary pregnancy outcome was live birth per cycle, and the secondary pregnancy outcome was clinical pregnancy rate per cycle. Couples with unexplained infertility in the AMIGOS trial, for whom female serum from day of trigger with hCG was available in at least one cycle of treatment, were included. Stored frozen serum samples from day of hCG trigger during treatment with OS-IUI were evaluated for serum progesterone level. Progesterone level <1.0 ng/ml was the reference group for comparison with progesterone categorized in increments of 0.5 ng/ml up to ≥3.0 ng/ml. Unadjusted and adjusted risk ratios (RR) and 95% CI were estimated using cluster-weighted generalized estimating equations to estimate modified Poisson regression models with robust standard errors. Compared to the reference group with 110/1363 live births (8.07%), live birth rates were significantly increased in cycles with progesterone 1.0 to <1.5 ng/ml (49/401 live births, 12.22%) in both the unadjusted (RR 1.56, 95% CI 1.14, 2.13) and treatment-adjusted models (RR 1.51, 95% CI 1.10, 2.06). Clinical pregnancy rates were also higher in this group (55/401 clinical pregnancies, 13.72%) compared to reference group with 130/1363 (9.54%) (unadjusted RR 1.46, 95% CI 1.10, 1.94 and adjusted RR 1.42, 95% CI 1.07, 1.89). In cycles with progesterone 1.5 ng/ml and above, there was no evidence of a difference in clinical pregnancy or live birth rates relative to the reference group. This pattern remained when stratified by ovarian stimulation treatment group but was only statistically significant in letrozole cycles. The AMIGOS trial was not designed to answer this clinical question, and with small numbers in some progesterone categories our analyses were underpowered to detect differences between some groups. Inclusion of cycles with progesterone values above 3.0 ng/ml may have included those wherein ovulation had already occurred at the time the IUI was performed. These cycles would be expected to experience a lower success rate but pregnancy may have occurred with intercourse in the same cycle. Compared to previous literature focusing primarily on OS-IUI cycles using gonadotrophins, these data include patients using oral agents and therefore may be generalizable to the wider population of infertility patients undergoing IUI treatments. Because live births were significantly higher when progesterone ranged from 1.0 to <1.5 ng/ml, further study is needed to clarify whether this progesterone range may truly represent a prognostic indicator in OS-IUI cycles. Oklahoma Shared Clinical and Translational Resources (U54GM104938) National Institute of General Medical Sciences (NIGMS). AMIGOS was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development: U10 HD077680, U10 HD39005, U10 HD38992, U10 HD27049, U10 HD38998, U10 HD055942, HD055944, U10 HD055936, and U10HD055925. Research made possible by the funding by American Recovery and Reinvestment Act. Dr Burks has disclosed that she is a member of the Board of Directors of the Pacific Coast Reproductive Society. Dr Hansen has disclosed that he is the recipient of NIH grants unrelated to the present work, and contracts with Ferring International Pharmascience Center US and with May Health unrelated to the present work, as well as consulting fees with May Health also unrelated to the present work. Dr Diamond has disclosed that he is a stockholder and a member of the Board of Directors of Advanced Reproductive Care, Inc., and that he has a patent pending for the administration of progesterone to trigger ovulation. Dr Anderson, Dr Gavrizi, and Dr Peck do not have conflicts of interest to disclose. N/A.

Etiology and outcomes of pleural effusion in children admitted in national institute of child health.

Etiology and outcomes of pleural effusion in children admitted in national institute of child health.

Apical Suspension Repair for Vaginal Vault Prolapse: A Randomized Clinical Trial.

The optimal surgical repair of vaginal vault prolapse after hysterectomy remains undetermined. To compare the efficacy and safety of 3 surgical approaches for vaginal vault prolapse after hysterectomy. This was a multisite, 3-arm, superiority and noninferiority randomized clinical trial. Outcomes were assessed biannually up to 60 months, until the last participant reached 36 months of follow-up. Settings included 9 clinical sites in the US National Institute of Child Health and Human Development (NICHD) Pelvic Floor Disorders Network. Between February 2016 and April 2019, women with symptomatic vaginal vault prolapse after hysterectomy who desired surgical correction were randomized. Data were analyzed from November 2022 to January 2023. Mesh-augmented (either abdominally [sacrocolpopexy] or through a vaginal incision [transvaginal mesh]) vs transvaginal native tissue repair. The primary outcome was time until composite treatment failure (including retreatment for prolapse, prolapse beyond the hymen, or prolapse symptoms) evaluated with survival models. Secondary outcomes included patient-reported symptom-specific results, objective measures, and adverse events. Of 376 randomized participants (mean [SD] age, 66.1 [8.7] years), 360 (96%) had surgery, and 296 (82%) completed follow-up. Adjusted 36-month failure incidence was 28% (95% CI, 20%-37%) for sacrocolpopexy, 29% (95% CI, 21%-38%) for transvaginal mesh, and 43% (95% CI, 35%-53%) for native tissue repair. Sacrocolpopexy was found to be superior to native tissue repair (adjusted hazard ratio [aHR], 0.57; 99% CI, 0.33-0.98; P = .01). Transvaginal mesh was not statistically superior to native tissue after adjustment for multiple comparisons (aHR, 0.60; 99% CI, 0.34-1.03; P = .02) but was noninferior to sacrocolpopexy (aHR, 1.05; 97% CI, 0-1.65; P = .01). All 3 surgeries resulted in sustained benefits in subjective outcomes. Mesh exposure rates were low (4 of 120 [3%] for sacrocolpopexy and 6 of 115 [5%] for transvaginal mesh) as were the rates of dyspareunia. Among participants undergoing apical repair for vaginal vault prolapse, sacrocolpopexy and transvaginal mesh resulted in similar composite failure rates at study completion; both had lower failure rates than native tissue repair, although only sacrocolpopexy met a statistically significant difference. Low rates of mesh complications and adverse events corroborated the overall safety of each approach. ClinicalTrials.gov Identifier: NCT02676973.

Frequency of C-peptide and antibody levels (anti GAD, Islet cell antibodies, insulin auto antibodies) in children of Pakistan with Type-1 diabetes

Background and Objective: The autoimmune mechanism in T1DM causes gradual loss of pancreatic β-cell, which progresses to hyperglycemia and ultimate reliance on consistent insulin therapy. T1DM has been the commonest type of diabetes in children and this study will help in refining indulgent towards the problem and its pathophysiology in our people. The objective was to find out the prevalence of C-peptide and antibody levels (anti GAD, ICA, IAA and IA2) in children and adolescents of Pakistan with T1DM. Methods: We conducted this cross-sectional study at Department of Pediatric Endocrinology, National Institute of Child Health, Karachi between August 2019 to February 2020 and included 98 children who had T1DM for more than one month. Subjects whose GFR was &lt;30ml/min were omitted from the study. Among those registered subjects, C-peptide, human islet cell antibody (ICA), insulin auto antibodies (IAA) and anti-glutamic acid decarboxylase were assessed. Demographical and laboratorial facts were noted on a pre-constructed proforma. Results: There were 77(78.3%) cases who had level of C-peptide &lt;0.8 and anti-GAD was found in 47(48%) subjects. 35(35.7%) cases found positive for IA2 .and 7(7.1%) patients had insulin auto antibodies positive while ICA was negative in total 98(100%) subjects. Conclusion: Children with T1 DM possessed increased levels of anti-GAD antibodies, insulin autoantibodies and anti (IA2) but islet cells antibodies were negligible in our population when checked at a point of time. C-peptide may be normal in some, but its level declines with long duration of diabetes in children. doi: https://doi.org/10.12669/pjms.40.6.7794 How to cite this: Riaz M, Akram M, Ibrahim MN, Khoso ZA. Frequency of C-peptide and antibody levels (anti GAD, Islet cell antibodies, insulin auto antibodies) in children of Pakistan with Type-1 diabetes. Pak J Med Sci. 2024;40(6):1083-1086. doi: https://doi.org/10.12669/pjms.40.6.7794 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Development of new hormonal male contraception for the couple.

Current options for male contraception are limited to condoms, the withdrawal method, or a vasectomy. Studies indicate that men have expressed growing interest in bearing responsibility for family planning. To review prior studies investigating the role of an androgen-only or androgen with progestin regimen for hormonal male contraception and to provide an update of a promising new hormonal agent, a transdermal gel. Thus far, there have been six studies conducted in couples evaluating the contraceptive efficacy of an androgen-only or androgen co-administered with a progestin regimen for hormonal male contraception. The only ongoing study is by the National Institute of Child Health and Human Development, in collaboration with the Population Council. They have developed a novel transdermal gel containing testosterone and segesterone acetate (Nestorone), a progestin. An ongoing phase II study enrolling more than 460 couples has shown great potential with respect to the product's efficacy, safety, reversibility, and acceptability. As this agent advances in development, a rapid at-home test for sperm concentration will provide couples with immediate feedback regarding their potential for pregnancy. There is promise for the first-of-its-kind hormonal male contraceptive, a transdermal gel, to achieve market approval for distribution in the United States and elsewhere. Its safety, efficacy, reversibility, and user-control are all appealing qualities that make it readily adoptable for clinical practice.

Identification of bacterial determinants of tuberculosis infection and treatment outcomes: a phenogenomic analysis of clinical strains

Bacterial diversity could contribute to the diversity of tuberculosis infection and treatment outcomes observed clinically, but the biological basis of this association is poorly understood. The aim of this study was to identify associations between phenogenomic variation in Mycobacterium tuberculosis and tuberculosis clinical features. We developed a high-throughput platform to define phenotype-genotype relationships in M tuberculosis clinical isolates, which we tested on a set of 158 drug-sensitive M tuberculosis strains sampled from a large tuberculosis clinical study in Ho Chi Minh City, Viet Nam. We tagged the strains with unique genetic barcodes in multiplicate, allowing us to pool the strains for in-vitro competitive fitness assays across 16 host-relevant antibiotic and metabolic conditions. Relative fitness was quantified by deep sequencing, enumerating output barcode read counts relative to input normalised values. We performed a genome-wide association study to identify phylogenetically linked and monogenic mutations associated with the in-vitro fitness phenotypes. These genetic determinants were further associated with relevant clinical outcomes (cavitary disease and treatment failure) by calculating odds ratios (ORs) with binomial logistic regressions. We also assessed the population-level transmission of strains associated with cavitary disease and treatment failure using terminal branch length analysis of the phylogenetic data. M tuberculosis clinical strains had diverse growth characteristics in host-like metabolic and drug conditions. These fitness phenotypes were highly heritable, and we identified monogenic and phylogenetically linked variants associated with the fitness phenotypes. These data enabled us to define two genetic features that were associated with clinical outcomes. First, mutations in Rv1339, a phosphodiesterase, which were associated with slow growth in glycerol, were further associated with treatment failure (OR 5·34, 95% CI 1·21-23·58, p=0·027). Second, we identified a phenotypically distinct slow-growing subclade of lineage 1 strains (L1.1.1.1) that was associated with cavitary disease (OR 2·49, 1·11-5·59, p=0·027) and treatment failure (OR 4·76, 1·53-14·78, p=0·0069), and which had shorter terminal branch lengths on the phylogenetic tree, suggesting increased transmission. Slow growth under various antibiotic and metabolic conditions served as in-vitro intermediate phenotypes underlying the association between M tuberculosis monogenic and phylogenetically linked mutations and outcomes such as cavitary disease, treatment failure, and transmission potential. These data suggest that Mtuberculosis growth regulation is an adaptive advantage for bacterial success in human populations, at least in some circumstances. These data further suggest markers for the underlying bacterial processes that contribute to these clinical outcomes. National Health and Medical Research Council/A∗STAR, National Institutes of Allergy and Infectious Diseases, National Institute of Child Health and Human Development, and the Wellcome Trust Fellowship in Public Health and Tropical Medicine.

Personalized lung care: Bronchopulmonary dysplasia risk prediction tool tailored for neonates born in resource-limited settings.

Predicting bronchopulmonary dysplasia (BPD) to assess the risk-benefit of therapy is necessary considering the side effects of medications. We developed and validated an instrument for predicting BPD and compared it with an instrument currently used for neonates born in a Brazilian hospital. This was a retrospective cohort study of patients born between 2016 and 2020 with a gestational age (GA) between 23 and 30 weeks. Predictive equations were elaborated using methods of component variable selection collected on the 14th day of life; 70% of the sample was randomly selected for the construction of risk prediction equations and the remaining 30% for their validation, application, and comparison with the National Institute of Child Health and Human Development (NICHD) instrument. The sensitivity, specificity, and predictive values of the equations were calculated. The equation that used variables with p < 5% in Fisher's exact test presented the best results: specificity of 98% and positive predictive value of 93% and could be used for BPD prediction of all small-for-gestational-age (SGA) infants. The NICHD calculator applied to our population had a specificity of 93% and a positive predictive value of 75% and could not be applied to extremely SGA infants. Our tool can predict the risk of BPD on the 14th day of life, has higher specificity and positive predictive value to our population than the NICHD instrument, and can be suitable for SGA infants. The results must be confirmed by applying it to other populations to validate our tool.

Spectrum of respiratory distress and outcome in neonates admitted in National Institute of Child Health, Karachi, Pakistan.

Objective: To find out the spectrum of respiratory distress and outcome in neonates admitted to Neonatal Intensive care unit (NICU) of National Institute of Child Health (NICH), Karachi, Pakistan. Study Design: Cross-sectional study. Setting: NICU of NICH, Karachi, Pakistan. Period: June 2022 to May 2023. Methods: We analyzed 148 neonates of either gender presenting with respiratory distress. At the time of enrollment, demographic and clinical information was noted in all neonates along with detailed maternal history. Relevant laboratory and radiological studies were performed. Final outcomes were recorded in terms of discharged, expired or referred. Results: In a total of 148 neonates, 96 (64.9%) were boys. The mean age was 4.04±5.65 days. Tachypnea, nasal flaring, intercostal recession, subcostal recession, grunting, and cyanosis 148 (100%), 146 (98.6%), 138 (93.2%), 133 (89.9%), 97 (65.5%), and 83 (56.1%) were the most frequent clinical presentations among neonates with respiratory distress. The most frequent causes behind respiratory distress were noted to be respiratory distress syndrome, sepsis, and meconium staining of labour in 31 (20.9%), 25 (16.9%), and 24 (16.2%) neonates. Mortality was observed in 21 (14.2%) neonates. Significant association of neonates presenting with congenital pneumonia (p=0.048), or congenital anomalies (p&lt;0.001) were found to with poor outcomes. Mechanical ventilation was found to have significant relationship with poor outcomes (p&lt;0.001). Conclusion: Tachypnea, Nasal flaring, intercostal and subcostal recessions, grunting, and cyanosis were the primary clinical presentations among the neonates with respiratory distress. Congenital pneumonia, and congenital anomalies emerged as key predictors of poor outcomes.