ST segment resolution post MI--a predictor of better outcomes

OBJECTIVE: To compare, the post Myocardial Infarction in-patient outcome of patients with early ST resolution to those without ST resolution on ECG, in a South Asian population.METHODS: This was a prospective study done at the Punjab Institute of Cardiology, Lahore. Consecutive patients of ST elevation myocardial infarction, who were not treated with primary angioplasty but were thrombolysed were recruited at the time of arrival in the emergency department. Streptokinase was administered to all patients as the agent of thrombolysis. ECG was acquired at baseline and at 60 minutes post streptokinase administration. Patients were subsequently divided into two groups (A) Patients with ST segment resolution, after 60 minutes of administration of streptokinase (B). Patients without ST segment resolution, after 60 minutes of administration of streptokinase. This cohort was followed up through the in hospital stay for major complications which were recurrent ischaemic chest pain ,heart failure, arrhythmias and death, during the follow up period (Mean stay 3.01+/- 0.77 days).RESULTS: A total of 148 patients were included in this prospective study. There were 122 males and 26 females. In group A complications developed in 33 (35%) out of 95 patients and 43 (81%) out of 53 patients in group B (p\u3c 0.001). Recurrent chest pain was present in 19 (20%) patients of group A and 31 (59%) patients of group B (p\u3c0.001).Heart failure was the most common complication observed in both groups, 26 (27%) patients in group A and 33 (62%) patients in group B (p\u3c0.001). Arrhythmias were more common in group B, with 17 (32%) patients from group B and 9 (10%) from group A developing this complication (p\u3c0.001).CONCLUSIONS: The extent of ST segment resolution provides useful information about early clinical outcome in post-myocardial infarction patients

DEFECTIVE CALCIUM PUMPS IN NEURONS IN THE AGING BRAIN AND IN PARKINSON’S DISEASE

The plasma membrane Ca2+-ATPase (PMCA) pumps play an important role in the maintenance of precise levels of intracellular Ca2+, quintessential for the optimal functioning and long term survival of neurons. In this paper, we review evidence showing alterations in the PMCAs in aging brain. Additionally, we provide evidence showing defects in these transporters in Parkinson’s disease (PD). PMCA activity and protein levels in brain synaptic plasma membranes (SPMs) decline progressively with increasing age. The PMCAs undergo functional and structural changes when exposed to reactive oxygen species known to be generated in the aging brain and in neurodegenerative disorders such as PD. The major changes in the PMCAs include rapid inactivation, formation of aggregates, internalization from the plasma membrane and fragmentation by proteases. Reduction of PMCA levels as occurs in aging and under conditions of oxidative stress may play an important role in compromised neuronal function in the aging brain and in PD. Therapeutic strategies that protect the PMCAs and stabilize [Ca2+]i homeostasis have the potential of serving as novel interventions in preventing and/or slowing down the degeneration of neurons in various chronic neurodegenerative disorders

Implementation of warning tool to improve maternal newborn health outcomes in a developing country

Objective: To improve health outcomes through the implementation of national early warning sign tool for babies delivered through emergency caesarean section in off-work hours. Methods: This comparative clinical study was conducted at the Aga Khan Hospital for Women and Children, Karachi, from April to August 2014, and comprised women who had an emergency caesarean section. Maternal and perinatal outcomes were compared of patients in Group A and Group B which represented individuals before and after the implementation of the national early warning score respectively. Results: Of the 200 participants, there were 100(50%) in each group. The overall mean age was 26.79±5.10 years. The mean age was 26.3±5 years in Group A, and 27.2±5 years in Group B (p=0.25). The two groups were also comparable in terms of parity (p=0.77) and co-morbidities (p =0.51). There was no stillbirth or maternal death, but decline in complications due to post-partum haemorrhage (p=0.00) was observed due to early recognition and timely management. None of the women required referral to higher facility. Conclusion: National early warning score was found to be a practical early warning tool for obstetric population

The Back Pain and Movement (B-PAM) registry; a study protocol

BACKGROUND:Low back pain (LBP) is a ubiquitous, heterogeneous disorder that affects most people at some point in their lives. The efficient management of LBP remains elusive, with direct and indirect costs attributed to LBP surpassing many other common conditions. An emphasis on a structural basis of LBP often fails to recognize movement, specifically patterns of movement that may provide biomechanical signatures of painful conditions. The primary objective of this registry is to understand the differences in movement patterns among those with LBP and those without pain in a U.S. population sample. METHODS:This ongoing, non-randomized, prospective post-market registry will consist of two groups: patients with LBP, and age and sex-matched controls without LBP. We will seek to recruit 132 subjects in each group. Data collection will take place in two phases: (1) baseline assessment of LBP patients and matched controls; (2) assessment of LBP patients at 6 and 12-months follow up. The primary outcome measure will be differences in movement patterns between those with LBP and those without LBP. Secondary outcomes will include differences in patient reported outcomes including pain, disability and quality of life. DISCUSSION:The findings will help determine if there are meaningful differences in movement patterns between those with and those without LBP. Further, an initial understanding of movement signatures specific to certain subtypes of patients with LBP may be achieved. TRIAL REGISTRATION:The study was registered on the clinicaltrials.gov portal: NCT03001037 . Trial retrospectively registered 12/22/2016

Effect of bovine lactoferrin on seroconversion following polio vaccine administration in children: Protocol for a double-blinded randomised controlled trial

Introduction: The oral polio vaccine (OPV) has substantial results in eliminating wild poliovirus and the vaccine of choice in polio eradication. However, the mucosal immunity induced by the OPV is still uncertain. Literature has shown that bovine lactoferrin (BLF) is a safe and useful protein found in cow\u27s milk with extraordinary antimicrobial, antiviral, antiinflammatory and immune-modulatory functions that help children\u27s gut to fight against micro-organisms like poliovirus. However, limited data exist regarding the effect of BLF on polio vaccine immune response. The primary objective is to evaluate the effect of BLF in enhancing mucosal and humoral immunity in children following the administration of oral and inactivated polio vaccines.Methods and analysis: This is a two-arm double-blinded randomised controlled trial comparing 462 neonates (231 in both groups) receiving either BLF or placebo with breast milk. The intervention is administered from day 1 till 6 weeks of age to a full-term healthy singleton newborn born at the Aga Khan University Hospitals, Karachi, Pakistan. The primary outcome is the seroconversion, 1 month after the receipt of two doses of OPV (at 10 weeks). For descriptive statistical analysis, Stata will be used, the frequency with percentages will be reported to describe baseline characteristics of the participants. A χ2 test will be used to compare categorical variables and a simple t test to compare continuous variables. The proportion of seroconversion and shedding will be compared using χ2 test or Fisher\u27s exact test.Ethics and dissemination: The Ethics approval has been granted by the Ethics Review Committee (ERC) of Aga Khan University for the proposed trial (ID: 2019-1955-5013). Furthermore, the National Bioethics Committee (NBC) of Pakistan has also approved the study for human subject research (ID: 4-87/NBC-443/19/669). Study findings will be disseminated through presentations at scientific conferences and educational practice workshops and will be published in an international peer-reviewed scientific journal

Fear of COVID-19 among pregnant women in Pakistan: A cross-sectional study

Background: The emergence of COVID-19 and its pandemic nature has exacerbated fears worldwide. Pregnant women are considered a vulnerable group during the COVID-19 pandemic because the physiological changes make them more susceptible to infections. Pregnant women are found expressing much of the fear related to their course of pregnancy, the in-utero transmission of the disease, and questions related to infection control in healthcare settings. Hence, the purpose of this paper was to explore the fears faced by pregnant women related to COVID.Methods: It was a cross-sectional survey among 201 pregnant women attending antenatal clinics of Aga Khan University Hospital. The survey tool contains demographic variables and a 7-item scale of “Fear in COVID” which is pre tested in the Iranian population. The survey form was made on google drive and sent to pregnant females on WhatsApp.Results: 201 pregnant women mostly belonging to middle and low socioeconomic class were enrolled. The majority (80%) of women were less than 30 years of age. Only 26 (12.9%) were primigravids, remaining were multigravidas of a different order of pregnancy. 60% of our study population showed high fear scores (27-35) from coronavirus whereas another 30% had moderate fear. No association of study variables was found with fear scores.Conclusions: We found a high level of fear of COVID-19 among the pregnant population with a higher level of anxiety and stress related symptoms. The amount of fear and stress is independent of the trimester or order of pregnancy

A phase three open label randomized controlled trial to compare the efficacy of oral hypoglycemic agents (OHA) with insulin in the treatment of gestational diabetes mellitus (GDM)

Background: The incidence of GDM is 1 – 14 % (5 – 8 % reported in most areas). It is globally on the rise in parallel with type 2 diabetes. The short and long term adverse maternal, fetal and neonatal outcomes in pregnancy with Diabetes are well known. Insulin therapy has been regarded as the gold standard medical intervention in pregnancy. It has limitations especially in poorly resourced, illiterate and non-compliant population. Studies have shown that some oral hypoglycemic agents (OHA) ( FDA category B:Glibenclamide and Metformin) are safe in pregnancy. Studies comparing these with insulin have found them to be as effective as insulin with comparable outcomes in pregnancy. Objectives: Primary objective:To compare efficacy of Oral Hypoglycemic Agents and Insulin in the treatment of GDM (percentage of subjects achieving target blood sugars at delivery). Secondary objective :To compare cost and acceptability to treatment in both groups. Methods: This is a collaborative study between the Department of Obstetrics and Gynaecology and the Section of Endocrinology, Department of Medicine. Results and conclusions: This clinical trial is in progress and is recruiting patients. Results will be communicated later o

In silico elucidation of potential drug targets against oxygenase domain of Human eNOS Dysfunction

Nitric Oxide (NO) signaling pathway plays a vital role in various physiological and pathophysiological processes including vasodilation, neurogenesis, inflammation, translation and protein regulation. NO signaling pathway is associated with various diseases such as cardiovascular diseases, vision impairment, hypertension and Alzheimer’s disease. Human Endothelial Nitric Oxide Synthase (eNOS) bound with calcium regulatory protein (calmodulin (CaM)) to produce NO which initiates cGMP pathway. The current study employs to screen the novel compounds against human eNOS independent of calcium regulatory protein (CaM). The current effort emphasized that the deficiency of CaM leads to dysfunction of cGMP signaling pathway. In this work, a hybrid approach of high-throughput virtual screening and comparative molecular docking studies followed by molecular dynamic simulation analyses were applied. The screening of top ranked two novel compounds against eNOS were reported that showed effective binding affinity, retrieved through the DrugBank and ZINC database libraries. Comparative molecular docking analyses revealed that Val-104, Phe-105, Gln-247, Arg-250, Ala-266, Trp-330, Tyr-331, Pro-334, Ala-335, Val-336, Tyr-357, Met-358, Thr-360, Glu-361, Ile-362, Arg-365, Asn-366, Asp-369, Arg-372, Trp-447 and Tyr-475 are potent residues for interactional studies. High-throughput virtual screening approach coupled with molecular dynamic simulation and drug likeness rules depicted that ZINC59677432 and DB00456 are potent compounds to target eNOS. In conclusion, the proposed compounds are potent against eNOS based on extensive in silico analyses. Overall, the findings of this study may be helpful to design therapeutic targets against eNOS

In silico elucidation of potential drug targets against oxygenase domain of Human eNOS Dysfunction.

Nitric Oxide (NO) signaling pathway plays a vital role in various physiological and pathophysiological processes including vasodilation, neurogenesis, inflammation, translation and protein regulation. NO signaling pathway is associated with various diseases such as cardiovascular diseases, vision impairment, hypertension and Alzheimer's disease. Human Endothelial Nitric Oxide Synthase (eNOS) bound with calcium regulatory protein (calmodulin (CaM)) to produce NO which initiates cGMP pathway. The current study employs to screen the novel compounds against human eNOS independent of calcium regulatory protein (CaM). The current effort emphasized that the deficiency of CaM leads to dysfunction of cGMP signaling pathway. In this work, a hybrid approach of high-throughput virtual screening and comparative molecular docking studies followed by molecular dynamic simulation analyses were applied. The screening of top ranked two novel compounds against eNOS were reported that showed effective binding affinity, retrieved through the DrugBank and ZINC database libraries. Comparative molecular docking analyses revealed that Val-104, Phe-105, Gln-247, Arg-250, Ala-266, Trp-330, Tyr-331, Pro-334, Ala-335, Val-336, Tyr-357, Met-358, Thr-360, Glu-361, Ile-362, Arg-365, Asn-366, Asp-369, Arg-372, Trp-447 and Tyr-475 are potent residues for interactional studies. High-throughput virtual screening approach coupled with molecular dynamic simulation and drug likeness rules depicted that ZINC59677432 and DB00456 are potent compounds to target eNOS. In conclusion, the proposed compounds are potent against eNOS based on extensive in silico analyses. Overall, the findings of this study may be helpful to design therapeutic targets against eNOS

Randomized trial of early detection and treatment of postpartum hemorrhage

Background: Delays in the detection or treatment of postpartum hemorrhage can result in complications or death. A blood-collection drape can help provide objective, accurate, and early diagnosis of postpartum hemorrhage, and delayed or inconsistent use of effective interventions may be able to be addressed by a treatment bundle. Methods: We conducted an international, cluster-randomized trial to assess a multicomponent clinical intervention for postpartum hemorrhage in patients having vaginal delivery. The intervention included a calibrated blood-collection drape for early detection of postpartum hemorrhage and a bundle of first-response treatments (uterine massage, oxytocic drugs, tranexamic acid, intravenous fluids, examination, and escalation), supported by an implementation strategy (intervention group). Hospitals in the control group provided usual care. The primary outcome was a composite of severe postpartum hemorrhage (blood loss, ≥1000 ml), laparotomy for bleeding, or maternal death from bleeding. Key secondary implementation outcomes were the detection of postpartum hemorrhage and adherence to the treatment bundle. Results: A total of 80 secondary-level hospitals across Kenya, Nigeria, South Africa, and Tanzania, in which 210,132 patients underwent vaginal delivery, were randomly assigned to the intervention group or the usual-care group. Among hospitals and patients with data, a primary-outcome event occurred in 1.6% of the patients in the intervention group, as compared with 4.3% of those in the usual-care group (risk ratio, 0.40; 95% confidence interval [CI], 0.32 to 0.50; PConclusions: Early detection of postpartum hemorrhage and use of bundled treatment led to a lower risk of the primary outcome, a composite of severe postpartum hemorrhage, laparotomy for bleeding, or death from bleeding, than usual care among patients having vaginal delivery. (Funded by the Bill and Melinda Gates Foundation; E-MOTIVE ClinicalTrials.gov number, NCT04341662.