Scaling Up Safer Birth Bundle Through Quality Improvement in Nepal (SUSTAIN) - A stepped wedge cluster randomized controlled trial in public hospitals

Background: Each year, 2.2 million intrapartum-related deaths (intrapartum stillbirths and first day neonatal deaths) occur worldwide with 99% of them taking place in low- and middle-income countries. Despite the accelerated increase in the proportion of deliveries taking place in health facilities in these settings, the stillborn and neonatal mortality rates have not reduced proportionately. Poor quality of care in health facilities is attributed to two-thirds of these deaths. Improving quality of care during the intrapartum period needs investments in evidence-based interventions. We aim to evaluate the quality improvement packageScaling Up Safer Bundle Through Quality Improvement in Nepal (SUSTAIN)on intrapartum care and intrapartum-related mortality in public hospitals of Nepal. Methods: We will conduct a stepped wedge cluster randomized controlled trial in eight public hospitals with each having least 3000 deliveries a year. Each hospital will represent a cluster with an intervention transition period of 2months in each. With a level of significance of 95%, the statistical power of 90% and an intra-cluster correlation of 0.00015, a study period of 19months should detect at least a 15% change in intrapartum-related mortality. Quality improvement training, mentoring, systematic feedback, and a continuous improvement cycle will be instituted based on bottleneck analyses in each hospital. All concerned health workers will be trained on standard basic neonatal resuscitation and essential newborn care. Portable fetal heart monitors (Moyo (R)) and neonatal heart rate monitors (Neobeat (R)) will be introduced in the hospitals to identify fetal distress during labor and to improve neonatal resuscitation. Independent research teams will collect data in each hospital on intervention inputs, processes, and outcomes by reviewing records and carrying out observations and interviews. The dose-response effect will be evaluated through process evaluations. Discussion: With the global momentum to improve quality of intrapartum care, better understanding of QI package within a health facility context is important. The proposed package is based on experiences from a similar previous scale-up trial carried out in Nepal. The proposed evaluation will provide evidence on QI package and technology for implementation and scale up in similar settings

Host-Directed Drug Therapies for Neglected Tropical Diseases Caused by Protozoan Parasites

The neglected tropical diseases (NTDs) caused by protozoan parasites are responsible for significant morbidity and mortality worldwide. Current treatments using anti-parasitic drugs are toxic and prolonged with poor patient compliance. In addition, emergence of drug-resistant parasites is increasing worldwide. Hence, there is a need for safer and better therapeutics for these infections. Host-directed therapy using drugs that target host pathways required for pathogen survival or its clearance is a promising approach for treating infections. This review will give a summary of the current status and advances of host-targeted therapies for treating NTDs caused by protozoa

EN-BIRTH Data Collector Training - Handbook and Manual

The EN-BIRTH study aims to validate selected newborn and maternal indicators for routine facility-based tracking of coverage and quality of care for use at district, national and global levels. The item contains the EN-BIRTH_Trainer's Manual (14 June 2017) and EN-BIRTH_Training Handbook (23 May 2017)

EN-BIRTH Data Collector Training - Supporting Annexes

The EN-BIRTH study aims to validate selected newborn and maternal indicators for routine facility-based tracking of coverage and quality of care for use at district, national and global levels. The item contains consent forms and participant information, in addition to standard operating procedures (SOP) for adverse clinical events, and managing distress in interviews. The full complement of annex files used during the training can be requested via this site if required

EN-BIRTH Data Collection Tools

The EN-BIRTH study aims to validate selected newborn and maternal indicators for routine facility-based tracking of coverage and quality of care for use at district, national and global levels. The item contains the following data collection tools: Register data extraction, Observation checklist (labour and delivery ward), Observation checklist (kangaroo mother care), Patient record verification tools for antenatal corticosteroid administration, Patient record verification tools for antibiotic administration, and the Maternal recall survey

EN-BIRTH Data Collector Training – Training Module material

The EN-BIRTH study aims to validate selected newborn and maternal indicators for routine facility-based tracking of coverage and quality of care for use at district, national and global levels. The item contains PowerPoint slides used for the nine modules of the Data Collector's Training Programme delivered during May and June 2017. Module 1 (introduction) provides an overview of the training syllabus; Module 2 (Registration) helps tracking officers to understand their roles and responsibilities in the project and how to best execute them; Module 3 (Observation: Labour & Delivery) is intended to help Labour & Delivery observers to conduct themselves, and their work, in accordance with project guidelines and training handbook; Module 4 (Observation: Resuscitation - Nepal) covers the function of CCTV cameras and the value of collecting extra observation data from filmed clinical events; Module 5 (Observation: KMC) outlines expectations and practices to be applied by KMC (kangaroo mother care) observers; Module 6 (Data Extraction & Verification) outlines how data collectors should extract and verify register data and record information in the app extraction form in the L&D ward and KMC ward; Module 7 (Maternal Pre-discharge Recall Survey) outlines how to conduct high-quality interviews and administer the maternal pre-discharge recall survey; Module 8 (Supervision) equips supervisors with the skills to be good team managers, ensure team effectiveness and happiness, respond to incidents in the health facility, and monitor data quality; and finally Module 9 (Training Summary) provides a recap of key information taught over the week

Dissecting mechanisms of resistance to targeted drug combination therapy in human colorectal cancer.

Genomic alterations in cancer cells result in vulnerabilities that clinicians can exploit using molecularly targeted drugs, guided by knowledge of the tumour genotype. However, the selective activity of these drugs exerts an evolutionary pressure on cancers that can result in the outgrowth of resistant clones. Use of rational drug combinations can overcome resistance to targeted drugs, but resistance may eventually develop to combinatorial therapies. We selected MAPK- and PI3K-pathway inhibition in colorectal cancer as a model system to dissect out mechanisms of resistance. We focused on these signalling pathways because they are frequently activated in colorectal tumours, have well-characterised mutations and are clinically relevant. By treating a panel of 47 human colorectal cancer cell lines with a combination of MEK- and PI3K-inhibitors, we observe a synergistic inhibition of growth in almost all cell lines. Cells with KRAS mutations are less sensitive to PI3K inhibition, but are particularly sensitive to the combined treatment. Colorectal cancer cell lines with inherent or acquired resistance to monotherapy do not show a synergistic response to the combination treatment. Cells that acquire resistance to an MEK-PI3K inhibitor combination treatment still respond to an ERK-PI3K inhibitor regimen, but subsequently also acquire resistance to this combination treatment. Importantly, the mechanisms of resistance to MEK and PI3K inhibitors observed, MEK1/2 mutation or loss of PTEN, are similar to those detected in the clinic. ERK inhibitors may have clinical utility in overcoming resistance to MEK inhibitor regimes; however, we find a recurrent active site mutation of ERK2 that drives resistance to ERK inhibitors in mono- or combined regimens, suggesting that resistance will remain a hurdle. Importantly, we find that the addition of low concentrations of the BCL2-family inhibitor navitoclax to the MEK-PI3K inhibitor regimen improves the synergistic interaction and blocks the acquisition of resistance

A study of utilization of abortion service in the tertiary hospital of Western Region of Nepal

Introduction: Unsafe abortion is one of the major public health problems in developing countries including Nepal. After the integration of comprehensive abortion care in safe motherhood service, there has been an improvement in maternal and women health in Nepal. Furthermore, improvements are required in raising awareness and accessibility to safe abortion services to all the women in throughout the country. Methods: This is a retrospective study carried out in Western Regional Hospital after reviewing the data from the hospital records. Demographic details, parity, types of abortion for spontaneous abortion, and methods of induced abortion were noted and analyzed. Results: Maximum number of women belonged to 20-24 years of age and is Brahmin/Chhetri. Multigravida is more than primi and they underwent induced abortion by medical termination of pregnancy. Similarly, incomplete abortion was in the highest number among the spontaneous abortion. Conclusion: Easy availability of safe abortion services and awareness among the people regarding it would certainly improve the maternal health and quality of life. Keywords: Maternal health, Comprehensive abortion care, Safe abortion. DOI: http://dx.doi.org/10.3126/jkahs.v2i1.2441

The role of vascular endothelium and exosomes in human protozoan parasitic diseases

The vascular endothelium is a vital component in maintaining the structure and function of blood vessels. The endothelial cells (ECs) mediate vital regulatory functions such as the proliferation of cells, permeability of various tissue membranes, and exchange of gases, thrombolysis, blood flow, and homeostasis. The vascular endothelium also regulates inflammation and immune cell trafficking, and ECs serve as a replicative niche for many bacterial, viral, and protozoan infectious diseases. Endothelial dysfunction can lead to vasodilation and pro-inflammation, which are the hallmarks of many severe diseases. Exosomes are nanoscale membrane-bound vesicles that emerge from cells and serve as important extracellular components, which facilitate communication between cells and maintain homeostasis during normal and pathophysiological states. Exosomes are also involved in gene transfer, inflammation and antigen presentation, and mediation of the immune response during pathogenic states. Protozoa are a diverse group of unicellular organisms that cause many infectious diseases in humans. In this regard, it is becoming increasingly evident that many protozoan parasites (such as Plasmodium, Trypanosoma, Leishmania, and Toxoplasma) utilize exosomes for the transfer of their virulence factors and effector molecules into the host cells, which manipulate the host gene expression, immune responses, and other biological activities to establish and modulate infection. In this review, we discuss the role of the vascular endothelium and exosomes in and their contribution to pathogenesis in malaria, African sleeping sickness, Chagas disease, and leishmaniasis and toxoplasmosis with an emphasis on their actions on the innate and adaptive immune mechanisms of resistance