Midwife-led birthing centres in four countries: a case study.

BACKGROUND: Midwives are essential providers of primary health care and can play a major role in the provision of health care that can save lives and improve sexual, reproductive, maternal, newborn and adolescent health outcomes. One way for midwives to deliver care is through midwife-led birth centres (MLBCs). Most of the evidence on MLBCs is from high-income countries but the opportunity for impact of MLBCs in low- and middle-income countries (LMICs) could be significant as this is where most maternal and newborn deaths occur. The aim of this study is to explore MLBCs in four low-to-middle income countries, specifically to understand what is needed for a successful MLBC. METHODS: A descriptive case study design was employed in 4 sites in each of four countries: Bangladesh, Pakistan, South Africa and Uganda. We used an Appreciative Inquiry approach, informed by a network of care framework. Key informant interviews were conducted with 77 MLBC clients and 33 health service leaders and senior policymakers. Fifteen focus group discussions were used to collect data from 100 midwives and other MLBC staff. RESULTS: Key enablers to a successful MLBC were: (i) having an effective financing model (ii) providing quality midwifery care that is recognised by the community (iii) having interdisciplinary and interfacility collaboration, coordination and functional referral systems, and (iv) ensuring supportive and enabling leadership and governance at all levels. CONCLUSION: The findings of this study have significant implications for improving maternal and neonatal health outcomes, strengthening healthcare systems, and promoting the role of midwives in LMICs. Understanding factors for success can contribute to inform policies and decision making as well as design tailored maternal and newborn health programmes that can more effectively support midwives and respond to population needs. At an international level, it can contribute to shape guidelines and strengthen the midwifery profession in different settings.

Targeting sterol alpha-14 demethylase of Leishmania donovani to fight against leishmaniasis.

Leishmaniasis is a neglected tropical disease caused by the protozoan parasite Leishmania. It is endemic in more than 89 different countries worldwide. Sterol alpha-14 demethylase (LdSDM), a sterol biosynthetic pathway enzyme in Leishmania donovani, plays an essential role in parasite survival and proliferation. Here, we used a drug repurposing approach to virtually screen the library of the Food and Drug Administration (FDA)-approved drugs against LdSDM to identify the potential lead-drug against leishmaniasis. Zafirlukast and avodart showed the best binding with LdSDM. Zafirlukast was tested for in vitro antileishmanial assay, but no significant effect on L. donovani promastigotes was observed even at higher concentrations. On the other hand, avodart profoundly inhibited parasite growth at relatively lower concentrations. Further, avodart showed a significant decrease in the number of intra-macrophagic amastigotes. Avodart-induced reactive oxygen species (ROS) in the parasites in a dose-dependent manner. ROS induced by avodart led to the induction of apoptosis-like cell death in the parasites as observed through annexin V/PI staining. Here, for the first time, we reported the antileishmanial activity and its possible mechanism of action of FDA-approved drug, avodart, establishing a nice example of the drug-repurposing approach. Our study suggested the possible use of avodart as an effective antileishmanial agent after further detailed validations.

Virtual screening of natural compounds for potential inhibitors of Sterol C-24 methyltransferase of Leishmania donovani to overcome leishmaniasis.

Leishmaniasis is a neglected tropical disease caused by trypanosomatid parasite belonging to the genera Leishmania. Leishmaniasis is transmitted from one human to other through the bite of sandflies. It is endemic in around 98 countries including tropical and subtropical regions of Asia, Africa, Southern America, and the Mediterranean region. Sterol C-24 methyltransferase (LdSMT) of Leishmania donovani (L. donovani) mediates the transfer of CH3-group from S-adenosyl methionine to C-24 position of sterol side chain which makes the ergosterol different from cholesterol. Absence of ortholog in human made it potential druggable target. Here, we performed virtual screening of library of natural compounds against LdSMT to identify the potential inhibitor for it and to fight leishmaniasis. Gigantol, flavan-3-ol, and parthenolide showed the best binding affinity towards LdSMT. Further, based on absorption, distribution, metabolism, and excretion properties and biological activity prediction, gigantol showed the best lead-likeness and drug-likeness properties. Therefore, we further elucidated its antileishmanial properties. We found that gigantol inhibited the growth and proliferation of promastigotes as well as intra-macrophagic amastigotes. Gigantol exerted its antileishmanial action through the induction of reactive oxygen species in dose-dependent manner. Our study, suggested the possible use of gigantol as antileishmanial drug after further validations to overcome leishmaniasis.

Reconstruction of Hemiglossectomy Defects With the Lateral Arm Fasciocutaneous Flap.

INTRODUCTION: Partial tongue reconstruction requires a thin pliable flap to restore volume and mobility. The lateral arm flap is well suited to this as it is a thin fasciocutaneous flap that has consistent vascular anatomy, reliable perfusion, short harvest time and low donor site morbidity. The authors report our experience with use of this flap for reconstruction of hemi-glossectomy defects. METHODS: This is a retrospective cohort of patients who underwent reconstruction of hemi-glossectomy and floor of mouth defects with a lateral arm flap, at Aga Khan University Hospital, Karachi (Pakistan) from November 2016 to January 2020. Flaps were harvested from the nondominant upper extremity. Data were collected for patient demographics, size of defect, size of flap, recipient vessels, postoperative complications and functional outcome. RESULTS: Over a 3-year period, 8 hemi-tongue and extended hemi-tongue, and floor of mouth reconstructions were performed with a lateral arm fasciocutaneous flap. A standard lateral arm flap was harvested in 3 patients and an extended lateral arm flap in 5 patients. Mean flap size was 65.75 cm2 (48-76 cm2). The recipient artery in all cases was the superior thyroid artery. The recipient veins were the common facial vein in 1 patient, the internal jugular in 3 patients, the external jugular in 1 patient and both external and internal jugular in 3 patients. Donor sites were closed primarily. There were no total or partial flap losses. All patients were able to resume an oral diet (unrestricted in 1, soft in 4, pureed in 2 patients). Postoperative speech was intelligible to patients' family in 4 patients and to strangers in 3 patients. One patient succumbed to progressive disease in the early postoperative period. Orocutaneous fistulas developed in 3 patients, all of which healed with nonoperative management. CONCLUSIONS: The lateral arm fasciocutaneous flap is well suited for reconstruction of hemiglossectomy and floor of mouth defect. It has the advantages of straightforward harvest, thin and pliable soft tissue, and low donor site morbidity.

Repurposing of FDA-approved drugs as inhibitors of sterol C-24 methyltransferase of Leishmania donovani to fight against leishmaniasis.

Leishmaniasis is a vector-borne disease caused by around 20 species of Leishmania. The main clinical forms of leishmaniasis are cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL). VL is caused by Leishmania infantum in Central and South America, Mediterranean Basin, Middle East, and by L. donovani in Asia and Africa. Sterol C-24 methyltransferase (LdSMT) of L. donovani is a transferase enzyme of the sterol biosynthesis pathway. This pathway is one of the major targets for drug developments in Leishmania. Due to insufficient evidence about the exact function of SMT inside the cell and the uniqueness of the SMT enzyme in the Leishmania parasites made it a significant target for an effective drug development approach. We performed virtual screening of the Food and Drug Administration (FDA)-approved drug library against LdSMT and found simeprevir, an antiviral drug on top in the binding score. It showed a significant binding affinity with LdSMT. The binding was supported by hydrogen bonds and several other interactions. Simeprevir inhibited L. donovani growth of promastigotes with 50% inhibitory concentration (IC50 ) of 51.49 ± 5.87 µM. Further studies showed that simeprevir induced ROS generation in 44.7% of parasites at 125-µM concentration. Here, we for the first time reported simeprevir as an antileishmanial lead molecule using a drug repurposing approach.

Correlates of Transitions Into Housing Instability Among Veterans Accessing Veterans Health Administration Health Care.

BACKGROUND: Prior research has explored the patterns and dynamics of homelessness; such an understanding is necessary to improve policy and programmatic responses and prevent new episodes of housing instability. OBJECTIVES: The objectives of this study are to identify correlates of veterans' transitions into housing instability and inform initiatives aimed to address their needs, with a focus on how to prevent new episodes of housing instability. METHODS: The cohort for this study includes 4,633,069 veterans who responded to the Veterans Health Administration's universal screen for housing instability at least twice between October 1, 2012, and September 30, 2016; 1.2% reported recent housing instability and 98.8% reported ongoing housing stability. The χ or Fisher exact tests, as appropriate, compared veterans' characteristics by housing status. A multivariate logistic regression identified independent risk factors associated with recent housing instability, controlling for sociodemographic, military service, diagnostic, and health services use variables. RESULTS: Sociodemographic and health services use variables increased veterans' odds of transitioning into housing instability. The diagnoses with the greatest effect sizes were drug use disorder (adjusted odds ratio=1.50, 95% confidence interval: 1.45-1.55) and opioid use disorder, which was associated with a >2-fold increase in the odds of experiencing recent housing instability (adjusted odds ratio=2.22, 95% confidence interval: 2.04-2.41). CONCLUSIONS: The present study provides evidence to inform existing and future interventions to prevent new episodes of housing instability. Veterans with opioid use disorder were at greatest risk of becoming unstably housed; increasing access to medication-assisted treatment in homeless-focused services is needed.

Furosemide Response Predicts Acute Kidney Injury After Cardiac Surgery in Infants and Neonates.

OBJECTIVE: Cardiac surgery-induced acute kidney injury occurs frequently in neonates and infants and is associated with postoperative morbidity/mortality; early identification of cardiac surgery-induced acute kidney injury may be crucial to mitigate postoperative morbidity. We sought to determine if hourly or 6-hour cumulative urine output after furosemide in the first 24 hours after cardiopulmonary bypass could predict development of cardiac surgery-induced acute kidney injury and other deleterious outcomes. DESIGN: Retrospective chart review. SETTING: Pediatric cardiac ICU. PATIENTS: All infants younger than 90 days old admitted to the cardiac ICU from October 2012 to December 2015 who received at least one dose of furosemide in the first 24 hours after cardiopulmonary bypass surgery. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Ninety-nine patients met inclusion and exclusion criteria. In total, 45.5% developed cardiac surgery-induced acute kidney injury. Median time between cardiopulmonary bypass and furosemide was 7.7 hours (interquartile range, 4.4-9.5). Six-hour cumulative urine output was 33% lower (p = 0.031) in patients with cardiac surgery-induced acute kidney injury. Area under the curve for prediction of cardiac surgery-induced acute kidney injury was 0.69 (p = 0.002). Other models demonstrated urine output response to furosemide had significant area under the curves for prediction of peak fluid over load greater than 15% (0.68; p = 0.047), prolonged peritoneal dialysis (area under the curve, 0.79; p = 0.007), prolonged mechanical ventilation (area under the curve, 0.79; p < 0.001), prolonged hospitalization (area under the curve, 0.62; p = 0.069) and mortality (area under the curve, 0.72; p = 0.05). CONCLUSIONS: Urine output response to furosemide within 24 hours of cardiopulmonary bypass predicts cardiac surgery-induced acute kidney injury development and other important morbidity in children younger than 90 days old; prospective validation is warranted.

Exploring perceptions of common practices immediately following burn injuries in rural communities of Bangladesh.

BACKGROUND: Burns can be the most devastating injuries in the world, they constitute a global public health problem and cause widespread public health concern. Every year in Bangladesh more than 365,000 people are injured by electrical, thermal and other causes of burn injuries. Among them 27,000 need hospital admission and over 5600 people die. Immediate treatment and medication has been found to be significant in the success of recovering from a burn. However, common practices used in the treatment of burn injuries in the community is not well documented in Bangladesh. This study was designed to explore the perception of local communities in Bangladesh the common practices used and health-seeking behaviors sought immediately after a burn injury has occurred. METHODS: A qualitative study was conducted using Focus Group Discussions (FGD) as the data collection method. Six unions of three districts in rural Bangladesh were randomly selected and FGDs were conducted in these districts with six burn survivors and their relatives and neighbours. Data were analyzed manually, codes were identified and the grouped into themes. RESULTS: The participants stated that burn injuries are common during the winter in Bangladesh. Inhabitants in the rural areas said that it was common practice, and correct, to apply the following to the injured area immediately after a burn: egg albumin, salty water, toothpaste, kerosene, coconut oil, cow dung or soil. Some also believed that applying water is harmful to a burn injury. Most participants did not know about any referral system for burn patients. They expressed their dissatisfaction about the lack of available health service facilities at the recommended health care centers at both the district level and above. CONCLUSIONS: In rural Bangladesh, the current first-aid practices for burn injuries are incorrect; there is a widely held belief that using water on burns is harmful.

Exploration of social factors associated to maternal deaths due to haemorrhage and convulsions: Analysis of 28 social autopsies in rural Bangladesh.

BACKGROUND: Social autopsy is an innovative approach to explore social barriers and factors associated to a death in the community. The process also sensitize the community people to avert future deaths. Social autopsy has been introduced in maternal deaths in Bangladesh first time in 2010. This study is to identify the social factors in the rural community associated to maternal deaths. It also looks at how the community responses in social autopsy intervention to prevent future maternal deaths. METHODS: The study was conducted in the Thakurgaon district of Bangladesh in 2010. We have purposively selected 28 social autopsy cases of which maternal deaths occurred due to either haemorrhage or due to convulsions. The autopsy was conducted by the Government health and family planning first line field supervisors in rural community. Family members and neighbours of the deceased participated in each autopsy and provided their comments and responses. RESULTS: A number of social factors including delivery conducted by the untrained birth attendant or family members, delays in understanding about maternal complications, delays in decision making to transfer the mother, lack of proper knowledge, education and traditional myth influences the maternal deaths. The community identified their own problems, shared within them and decide upon rectify themselves for future death prevention. CONCLUSIONS: Social autopsy is a useful tools to identify social community within the community by discussing the factors that took place during a maternal death. The process supports villagers to think and change their behavioural patterns and commit towards preventing such deaths in the future.

Perceptions of health care providers and patients on quality of care in maternal and neonatal health in fourteen Bangladesh government healthcare facilities: a mixed-method study.

BACKGROUND: Bangladesh has achieved remarkable progress in healthcare with a steady decline in maternal and under-5 child mortality rates in efforts to achieve Millennium Development Goals 4 and 5. However, the mortality rates are still very high compared with high-income countries. The quality of healthcare needs improve to reduce mortality rates further. It is essential to investigate the current quality of healthcare before implementing any interventions. The study was conducted to explore the perception of healthcare providers about the quality of maternal and neonatal health (MNH) care. The study also investigated patient satisfaction with the MNH care received from district and sub-district hospitals. METHODOLOGY: Both qualitative and quantitative methods were used in the study. Two district and 12 sub-district hospitals in Thakurgaon and Jamalpur in Bangladesh were the study settings. Fourteen group discussions and 56 in-depth interviews were conducted among the healthcare providers. Client exit interviews were conducted with 112 patients and their attendants from maternity, labor, and neonatal wards before being discharged from the hospitals. Eight physicians and four anthropologists collected data between November and December 2011 using pretested guidelines. RESULTS: The hospital staff identified several key factors that affected the quality of patient care: shortage of staff and logistics; lack of laboratory support; under use of patient-management protocols; a lack of training; and insufficient supervision. Doctors were unable to provide optimal care because of the high volume of patients. The exit interviews revealed that 85 % of respondents were satisfied with the hospital services received. Seven out of 14 respondents were satisfied with the cleanliness of the hospital facilities. More than half of the respondents were satisfied with the drugs they received. In half of the facilities, patients did not get an opportunity to ask the healthcare providers questions about their health conditions and treatments. CONCLUSION: The quality of healthcare is poor in district and sub-district hospitals in Bangladesh because of the lack of healthcare personnel and logistic support. An integrated quality improvement approach is needed to improve MNH care service in district and sub-district hospitals in Bangladesh.

Willingness to administer mouth-to-mouth ventilation in a first response program in rural Bangladesh.

BACKGROUND: Timely mouth-to-mouth ventilation is critical to resuscitate drowning victims. While drowning is frequent, there are no lay persons trained in cardio-pulmonary resuscitation (CPR) in rural Bangladesh. As part of a feasibility study to create a first response system in a conservative Islamic village environment, a pilot was undertaken to examine willingness to provide mouth-to-mouth ventilation for drowning resuscitation. METHODS: A questionnaire was administered to 721 participants at the beginning of a village-based CPR training course. Trainees were asked regarding willingness to administer mouth-to-mouth ventilation on a variety of hypothetical victims. Responses were tabulated according to the age, sex and relationship of the trainee to the postulated victim. RESULTS: Willingness to deliver mouth-to-mouth ventilation was influenced by sex of a potential recipient and relationship to the trainee. Adolescent participants were significantly more willing to perform mouth-to-mouth ventilation on someone of the same sex. Willingness increased for both sexes when the postulated victim was an immediate family member. Willingness was lower with extended family members and lowest with strangers. Adult trainees were more likely to perform mouth-to-mouth ventilation than adolescent trainees in any scenario. CONCLUSION: Adults express more willingness to resuscitate a broader range of drowning victims than adolescents. However in rural Bangladesh, adolescents are more likely to be in close proximity to a drowning in progress. Further efforts are needed to increase willingness of adolescents to provide resuscitation to drowning victims. However, despite potential cultural limitations, trained responders appear to be willing to give mouth-to-mouth ventilation to various recipients. Final determination will require evidence on response outcomes which is being collected.

The prevalence of naturally acquired swimming ability among children in Bangladesh: a cross sectional survey.

BACKGROUND: Most rural homes in Bangladesh have ponds nearby to serve as household water sources. As a result children of all ages are exposed to water bodies on a daily basis. Children learn to swim early in childhood from peers and relatives in a natural process that involves play and structured learning. In a large, national injury survey in Bangladesh, the ability to swim was associated with reduced risk of drowning. This study determines the prevalence of swimming ability in children in Bangladesh as a step in assessing whether this is a potential component of a national drowning prevention program. METHODS: A descriptive study design using a subset of a national sample survey determined the prevalence of naturally acquired swimming ability (NASA) reported by children of rural and urban communities in Bangladesh. A total of 2,598 households (1,999 rural and 599 urban) housing 4,336 children (2,263 male and 2,073 female) aged 5-17 years were chosen from 4 randomly selected districts using multistage random sampling. NASA was defined as the ability to cross 25 meters of water deeper than the child's height using any body movement for self-propulsion. RESULTS: Reported NASA was greater in males (55.6%) than females (47.9%) and among rural children (57.8%) than urban children (25.5%) for children 5-17 years. The proportion reporting NASA increased with increasing age. At age 5, 5.8% of males and 6.3% of females reported NASA, rising to 84.3% of males and 70.7% of females by age 17. By age 17, 83.1% of rural children and 57.5% of urban children reported NASA. CONCLUSION: Most children in Bangladesh report being able to swim 25 meters and learning it by middle childhood. Reported NASA is higher for males than females and for rural children than urban children. High rates of swimming appear to be achievable in the absence of pools and a swim-teaching industry. This may facilitate development of a low cost, national drowning prevention program with swimming an integral part.

A framework for addressing implementation gap in global drowning prevention interventions: experiences from Bangladesh.

Drowning is the commonest cause of injury-related deaths among under-five children worldwide, and 95% of deaths occur in low- and middle-income countries (LMICs) where there are implementation gaps in the drowning prevention interventions. This article reviews common interventions for drowning prevention, introduces a framework for effective implementation of such interventions, and describes the Saving of Lives from Drowning (SoLiD) Project in Bangladesh, which is based on this framework. A review of the systematic reviews on drowning interventions was conducted, and original research articles were pulled and summarized into broad prevention categories. The implementation framework builds upon two existing frameworks and categorizes the implementing process for drowning prevention interventions into four phases: planning, engaging, executing, and evaluating. Eleven key characteristics are mapped in these phases. The framework was applied to drowning prevention projects that have been undertaken in some LMICs to illustrate major challenges to implementation. The implementation process for the SoLiD Project in Bangladesh is used as an example to illustrate the practical utilization of the framework. Drowning interventions, such as pool fencing and covering of water hazards, are effective in high-income countries; however, most of these interventions have not been tested in LMICs. The critical components of the four phases of implementing drowning prevention interventions may include: (i) planning-global funding, political will, scale, sustainability, and capacity building; (ii) engaging-coordination, involvement of appropriate individuals; (iii) executing-focused action, multisectoral actions, quality of execution; and (iv) evaluating-rigorous monitoring and evaluation. Some of the challenges to implementing drowning prevention interventions in LMICs include insufficient funds, lack of technical capacity, and limited coordination among stakeholders and implementers. The SoLiD Project in Bangladesh incorporates some of these lessons and key features of the proposed framework. The framework presented in this paper was a useful tool for implementing drowning prevention interventions in Bangladesh and may be useful for adaptation in drowning and injury prevention programmes of other LMIC settings.

Long-Term Video Electroencephalographic Monitoring in <30-Week Gestational Age Infants With High-Grade Intraventricular Hemorrhage.

BACKGROUND: Despite recognizing high seizure risk, the current consensus guidelines on evaluating seizures in preterm neonates are based on limited data. We chose to investigate the seizure risk in high-risk preterm (<30 weeks gestation) asymptomatic (without a clinical concern for seizures) infants with high-grade intraventricular hemorrhage who underwent long-term video electroencephalographic monitoring. METHODS: We performed a comprehensive retrospective review on all infants of <30-week gestational age admitted to the University of Alabama at Birmingham Regional Neonatal Intensive Care Unit from June 2018 to October 2022. We selected those patients who underwent electroencephalographic monitoring without a prior clinical concern for seizures. We recorded gender, gestational age, APGAR scores (one and five minutes), intraventricular hemorrhage (grade, age at diagnosis), and electroencephalographic monitoring (timing and duration) data. RESULTS: Among 37 premature infants, six had seizures detected on electroencephalographic monitoring. All six infants had subclinical seizures. Only two of six patients had a clinical correlation (although not identified by the providers) with some of their seizures. Patients with seizures were significantly younger in chronological age (median age 6.5 days vs 9 days, P value 0.009) at the time of the electroencephalographic monitoring initiation and were more likely to have subsequent monitoring studies (P value 0.0418). CONCLUSIONS: Long-term video electroencephalographic monitoring performed after the diagnosis of high-grade intraventricular hemorrhage captured seizures in ∼16% of asymptomatic premature neonates of <30 weeks' gestation. Patients identified to have seizures were significantly younger (chronological age) at the time of the electroencephalographic monitoring initiation and were more likely to be remonitored.

Feasibility and acceptability of sexually transmitted infection screening during antenatal care of women in Dhaka, Bangladesh.

BACKGROUND: Sexually transmitted infections (STIs) are a major public health concern worldwide. Untreated STIs may have serious sequelae, particularly in pregnant women. The objective of this study was to assess the feasibility and acceptability of screening and treating common STIs in women during pregnancy in Bangladesh. METHODS: Women were enrolled from four maternity clinics/hospitals serving the lower-middle class population in Dhaka, Bangladesh. The participants were interviewed, and vaginal swab samples were collected by clinical staff. Specimens were tested for Neisseria gonorrhoeae, Chlamydia trachomatis, Trichomonas vaginalis and high-risk Human Papilloma Viruses (HPVs) using GeneXpert (Cepheid, Sunnyvale, California). Women were informed of their test results and were provided treatment for curable infections. A test of cure was performed. RESULTS: Out of 1157 pregnant women approached, 1000 (86.4%) participated. Ninety-one percent women learned of their test results on the same day of testing. Out of the 996 valid results, 7 (0.7%) tested positive for Chlamydia trachomatis and 1 (0.1%) for Trichomonas vaginalis. There were no gonorrhoea cases. Out of the 971 women with valid results for high-risk HPVs, 46 (4.7%) tested positive. CONCLUSIONS: Screening women for STIs during antenatal care was highly feasible and well-accepted in Bangladesh. While the prevalence of common curable STIs was very low, hrHPV infection prevalence was moderately high. Our findings support period monitoring of STIs and continued prevention efforts for cervical cancer in Bangladesh.

Children's perceptions about falls and their prevention: a qualitative study from a rural setting in Bangladesh.

BACKGROUND: Childhood falls is a major public health problem in Bangladesh. In-depth understanding of the situation by the target groups and their families is necessary for successful development, implementation and evaluation of any intervention. The study aimed at knowing the views of Bangladeshi rural children about childhood falls and their suggestions for prevention. METHODS: Children of 10-17 were selected purposely from 4 villages of Sherpur Sadar upazila (sub-district), Sherpur district of Bangladesh. Six focus group discussions and ten in-depth interviews were conducted during July-August 2010 for this study. Gender and education of the participants were considered. Major themes were identified, coded and categorized from content analysis. RESULTS: Participants stated that young children (<5 years of age) and boys appeared to be the main victims of falls and majority of these injuries occurred in and around the households. Boys commonly fall from the tree around their premises and high places. Girls usually fall when they remain busy in household chores and playing with friends around their premises. Participants also mentioned that children mostly sustained injury when they are unsupervised. Supervision, public awareness and putting barriers (e.g. door barrier, putting pillow and use net around the bed etc.) were suggested as the preventive measures. CONCLUSION: Findings of this study could be considered as part of knowledge-base in designing interventions to address childhood falls.

Risk Factors for Extubation Failure After Pediatric Cardiac Surgery and Impact on Outcomes: A Multicenter Analysis.

IMPORTANCE: Extubation failure (EF) after pediatric cardiac surgery is associated with increased morbidity and mortality. OBJECTIVES: We sought to describe the risk factors associated with early (< 48 hr) and late (48 hr ≤ 168 hr) EF after pediatric cardiac surgery and the clinical implications of these two types of EF. DESIGN SETTING AND PARTICIPANTS: Retrospective cohort study using prospectively collected clinical data for the Pediatric Cardiac Critical Care Consortium (PC4) Registry. Pediatric patients undergoing Society of Thoracic Surgeons benchmark operation or heart transplant between 2013 and 2018 available in the PC4 Registry were included. MAIN OUTCOMES AND MEASURES: We analyzed demographics and risk factors associated with EFs (primary outcome) including by type of surgery. We identified potentially modifiable risk factors. Clinical outcomes of mortality and length of stay (LOS) were reported. RESULTS: Overall 18,278 extubations were analyzed. Unplanned extubations were excluded from the analysis. The rate of early EF was 5.2% (948) and late EF was 2.5% (461). Cardiopulmonary bypass time, ventilator duration, airway anomaly, genetic abnormalities, pleural effusion, and diaphragm paralysis contributed to both early and late EF. Extubation during day remote from shift change and nasotracheal route of initial intubation was associated with decreased risk of early EF. Extubation in the operating room was associated with an increased risk of early EF but with decreased risk of late EF. Across all operations except arterial switch, EF portrayed an increased burden of LOS and mortality. CONCLUSION AND RELEVANCE: Both early and late EF are associated with significant increase in LOS and mortality. Study provides potential benchmarking data by type of surgery. Modifiable risk factors such as route of intubation, time of extubation as well as treatment of potential contributors such as diaphragm paralysis or pleural effusion can serve as focus areas for reducing EFs.

Exploration of potential inhibitors for autophagy-related protein 8 as antileishmanial agents.

Leishmaniasis is considered a tropical neglected disease, which is caused by an intramacrophagic parasite, Leishmania. It is endemic in 89 different countries. Autophagy-related protein 8 (Ldatg8) is responsible for the transformation of parasites from promastigote to amastigote differentiation. Ldatg8 is one of the key drug targets of Leishmania donovani (L. donovani) responsible for the defense of parasites during stress conditions. Virtual screening of natural ligand library had been performed against Ldatg8 to identify novel and potent inhibitors. Molecular docking and molecular dynamics simulation studies showed that urolithin A stably blocked Ldatg8. Urolithins are combinations of coumarin and isocoumarin. Further, we evaluated the antileishmanial effects of urolithin A by antileishmanial assays. Urolithin A inhibited the growth and proliferation of L. donovani promastigotes with an IC50  value of 90.3 ± 6.014 µM. It also inhibited the intramacrophagic parasite significantly with an IC50  value of 78.67 ± 4.62 µM. It showed limited cytotoxicity to the human THP-1 differentiated macrophages with a CC50  value of 190.80 ± 16.89 µM. Further, we assayed reactive oxygen species (ROS) generation and annexin V/PI staining upon urolithin A treatment of parasites to have an insight into the mechanism of its action. It induced ROS significantly in a dose-dependent manner, which caused apoptosis partially in parasites. The potential inhibitors for Ldatg8, identified in this study, would provide the platform for the development of an effective and affordable antileishmanial drug.

Compliance to playpen usages to enhance parental supervision of under-five children in rural community of Bangladesh.

INTRODUCTION: In Bangladesh, injury is one of the leading causes of death and morbidity in children. All children under 5 years of age are at high risk for drowning though the risks are highest when children first learn to walk and crawl while they do not understand the danger of water. The Centre for Injury Prevention and Research, Bangladesh (CIPRB) in collaboration with Johns Hopkins International Injury Research Unit (JH-IIRU) has been implementing two drowning prevention interventions, providing playpens and community day care centres (anchal), or both in three rural sub-districts of Bangladesh under Saving of Lives from Drowning (SoLiD) project in Bangladesh. In CIPRB intervention areas, wooden playpens were distributed among the children nine months to three years at household (HH) level. OBJECTIVE: The aim of this study was to explore and understand the acceptability and perceptions of parents towards playpen and its relevance for drowning and injury related mortality and morbidity prevention. METHODS: Anchal mothers ('anchal maa' in Bangla) distributed 30,553 playpens and collected compliance information at the HH level using a structured questionnaire. 1600 trained anchal maas collected data via face to face interviews from May 2014 to November 2015. Playpen compliance visits were conducted periodically on the second and seventh days and every two months after delivering the playpen. Data were entered using standard data entry formats and analyzed using SPSS software version 23. RESULTS: Parents reported that playpen is a safe place and protects children from drowning and other injuries. During compliance data collection, anchal maa founds that 71.8% of all children were using playpen and 93.7% (of 71.8%) children were playing inside the playpen while mothers were busy with their household chores like cooking, washing dishes and clothes, taking care of their poultry and domestic animals etc. 95.7% parents reported playpen is being used for keeping the child safe. On an average, the children were placed two to six times per day in a playpen. 99.1% of the children who reported using a playpen did not get any injuries (falls, cuts and bruises) while using the playpen. Satisfaction level with the playpen intervention among mothers was 90.5%. Some respondents suggested improving the playpen utilization by providing toys, adding wheels for ease of mobility, and increasing the height. CONCLUSION: The playpens were found to be well accepted and utilized for the children, especially when mothers were busy with their household chores.

Molecular docking analysis of rutin reveals possible inhibition of SARS-CoV-2 vital proteins.

BACKGROUND AND AIM: COVID-19 emerged by the end of 2019 in Wuhan, China. It spreaded and became a public health emergency all over the world by mid of April 2020. Flavonoids are specialized metabolites that have antimicrobial properties including anti-viral activity. Rutin, a medicinally important flavonoid belongs to one of the best natural antioxidant classes. It has antiprotozoal, antibacterial, and antiviral properties. Keeping the antimicrobial potential of rutin in mind, we studied its role in the inhibition of essential proteins of SARS-CoV-2 including main protease (Mpro), RNA-dependent RNA polymerase (RdRp), papain-like protease (PLpro), and spike (S)-protein through different in silico approaches. EXPERIMENTAL PROCEDURE: Molecular docking, inhibition constant, hydrogen bond calculations, and ADMET-properties prediction were performed using different softwares. RESULTS AND CONCLUSION: Molecular docking study showed significant binding of rutin with Mpro, RdRp, PLpro, and S-proteins of SARS-CoV-2. Out of these four proteins, Mpro exhibited the strongest binding affinity with the least binding energy (-8.9 kcal/mol) and stabilized through hydrogen bonds with bond lengths ranging from 1.18 Å to 3.17 Å as well as hydrophobic interactions. The predicted ADMET and bioactivity showed its optimal solubility, non-toxic, and non-carcinogenic properties. The values of the predicted inhibitory constant of the rutin with SARS-CoV-2 vital proteins ranged between 5.66 µM and 6.54 µM which suggested its promising drug candidature. This study suggested rutin alone or in combination as a dietary supplement may be used to fight against COVID-19 after detailed in vitro and in vivo studies.