Search

Background: Receptor-interacting protein kinase 1 (RIPK1), a serine/threonine protein kinase, is mainly activated by pro-inflammatory cytokines and pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and its activation could result in apoptosis, necroptosis, or inflammation. This study was conducted to evaluate the safety and efficacy of a potent and selective inhibitor of RIPK1, SIR1-365, in hospitalized patients with severe coronavirus disease 2019 (COVID-19). Methods: This multicenter, randomized, double-blind, phase 1b study screened patients from December 18, 2020 until November 27, 2021. Adults hospitalized with severe COVID-19 (diagnosed ≤2 weeks before screening) were randomized 1:1 to receive oral placebo or SIR1-365 100 mg three times daily for ≤14 consecutive days, with standard-of-care. The primary objective was to evaluate SIR1-365 safety and tolerability. Secondary objectives included an assessment of SIR1-365 efficacy. Descriptive statistics were used to summarize safety. The study was not powered for efficacy testing. Relevant inferential statistical tests were used to aid interpretation of differences in clinical efficacy. Results: Forty-five patients were randomized, 42 were treated. Eighteen patients experienced treatment-emergent adverse events (TEAEs) and 7 patients were ≥ grade 3. Fewer SIR1-365-treated vs. placebo-treated patients experienced TEAEs (30.4% vs. 57.9%) and serious TEAEs (13.0% vs. 26.3%) within 28 days of the first dose. There were no serious treatment-related TEAEs or deaths. Compare to placebo, SIR1-365 significantly increased arterial oxygenation from baseline to day 7 (least-squares mean change [standard error]: 109.4 [26.4] vs. -24.2 [23.6]; P=0.0095), significantly reduced hospitalization duration after treatment (mean±standard deviation: [4.7±3.7] days vs. [8.6±5.6] days; P=0.0145) and respiratory failure incidence (8.3% vs. 38.1%; two-sided P=0.0291) during the study, and numerically shortened the time to clinical improvement in World Health Organization ordinal scale (median: 5.0 days vs. 9.0 days, P=0.0766). Conclusions: SIR1-365 was well tolerated and demonstrated a trend toward quicker recovery than placebo in hospitalized patients with severe COVID-19.Trial Registration ClinicalTrials.gov number: NCT04622332

Floods are the most common natural disasters in the world. Currently Pakistan is in an acute emergency situation due to the recent flood that occurred as a result of the monsoon rains in July–August 2022. Unfortunately, the country was already under an economic crisis and was just recovering from the COVID pandemic when this devastating calamity struck. Almost one-third of the country’s land was affected, with millions of houses damaged and property lost. As the victims are displaced and local health units are flooded, their medical needs are being met through medical flood relief camps arranged by public and private sector welfare organizations. Due to a lack of disaster preparedness and policies, most of the healthcare workers are untrained to manage medical flood relief camps and are hence learning from experience rather than following any standardized policy guidelines. We did not find any guidelines for organization and management of a flood relief camp in previous literature. As natural disasters continue to cause mass destruction every few years, there is a need to devise policies and procedures for disaster preparedness and hazard reduction. This paper is thus an effort to provide the best possible delivery of acute health services in a developing country during and after a flood in the transit phase, while the government and other non-governmental organizations (NGOs) help communities rebuild their health system.

Waning of neutralizing titres along with decline of protection efficacy after the second dose of COVID-19 vaccines was observed, including China-made inactivated vaccines. Efficacy of a heterologous boosting using one dose of a recombinant SARS-CoV-2 fusion protein vaccine (V-01) in inactivated vaccine-primed population was studied, aimed to restore the immunity. A randomized, double-blind and placebo-controlled phase III trial was conducted in healthy people aged 18 years or older in Pakistan and Malaysia. Each eligible participant received one dose of the V-01 vaccine developed by Livzon Mabpharm Inc. or placebo within the 3-6 months after the two-dose primary regimen, and was monitored for safety and efficacy. The primary endpoint was protection against confirmed symptomatic SARS-CoV-2 infection. A total of 10,218 participants were randomly assigned to receive a vaccine or placebo. Virus-neutralizing antibodies were assessed in 419 participants. A dramatic increase (11.3-fold; 128.3–1452.8) of neutralizing titres was measured in the V-01 group at 14 days after the booster. Over two months of surveillance, vaccine efficacy was 47.8% (95%CI: 22.6–64.7) according to the intention-to-treat principle. The most common adverse events were transient, mild-to-moderate pain at the injection site, fever, headache, and fatigue. Serious adverse events occurred almost equally in V-01 (0.12%) and placebo (0.16%) groups. The heterologous boosting with the V-01 vaccine was safe and efficacious, which could elicit robust humoral immunity under the epidemic of the Omicron variant.Trial registration: ClinicalTrials.gov identifier: NCT05096832.

Background: The Healthcare workers (HCWs) are at the forefront of care-giving and hence understanding of the knowledge, attitudes and practices among HCWs is necessary to identify potential risk factors of COVID-19 dissemination. Objective: The objective of the study was to investigate the knowledge, attitude and practice (KAP) regarding novel coronavirus disease 2019 (COVID-19) among healthcare workers in Karachi Pakistan. Material and Methods: This was a cross-sectional study using a self-reported questionnaire which enrolled all the HCWs (doctors, nurses, pharmacists and technicians) in hospitals of Karachi from March to May 2020.Binary logistic regression analysis was performed to estimate the odds ratio with 95% confidence interval for KAP of HCWs regarding COVID-19. P-values less than 0.05 were considered statistically significant. Results: The total of 547 participants included in study. HCWs gross category and clinical setting were found to be statistically associated with overall KAP (P

Abstract Objectives The aim of this trial is to investigate the safety and clinical efficacy of passive immunization therapy through Hyperimmune anti-COVID-19 Intravenous Immunoglobulin (C-IVIG: 5% liquid formulation), on severe and critically ill patients with COVID-19. Trial design This is a phase I/II single centre, randomised controlled, single-blinded, superiority trial, through parallel-group design with sequential assignment. Participants will be randomised either to receive both C-IVIG and standard care or only standard care (4:1). Participants The study is mono-centric with the participants including COVID19 infected individuals (positive SARS-CoV-2 PCR on nasopharyngeal and/or oropharyngeal swabs) admitted in institute affiliated with Dow University Hospital, Dow University of Health Sciences, Karachi, Pakistan. Consenting patients above 18 years that are classified by the treating physician as severely ill i.e. showing symptoms of COVID-19 pneumonia; dyspnea, respiratory rate ≥30/min, blood oxygen saturation ≤93%, PaO2/FiO2 50% on CXR; or critically ill i.e. respiratory failure, septic shock, and multiple organ dysfunction or failure. Patients with reported IgA deficiency, autoimmune disorder, thromboembolic disorder, and allergic reaction to immunoglobulin treatment were excluded from study. Similarly, pregnant females, patients requiring two or more inotropic agents to maintain blood pressure and patients with acute or chronic kidney injury/failure, were also excluded from the study. Intervention and comparator The study consists of four interventions and one comparator arm. All participants receive standard hospital care which includes airway support, anti-viral medication, antibiotics, fluid resuscitation, hemodynamic support, steroids, painkillers, and anti-pyretics. Randomised test patients will receive single dose of C-IVIG in following four dosage groups: Group 1: 0.15g/Kg with standard hospital care Group 2: 0.2g/Kg with standard hospital care Group 3: 0.25g/Kg with standard hospital care Group 4: 0.3g/Kg with standard hospital care Group 5 (comparator) will receive standard hospital care only Main outcomes The primary outcomes are assessment and follow-up of participants to observe 28-day mortality and, • the level and duration of assisted ventilation during hospital stay, • number of days to step down (shifting from ICU to isolation ward), • number of days to hospital discharge, • adverse events (Kidney failure, hypersensitivity with cutaneous or hemodynamic manifestations, aseptic meningitis, hemolytic anemia, leuko-neutropenia, transfusion related acute lung injury (TRALI)) during hospital stay, • change in C-Reactive Protein (CRP) levels, • change in neutrophil lymphocyte ratio to monitor inflammation. Randomisation Consenting participants who fulfill the criteria are allocated to either intervention or comparator arm with a ratio of 4:1, using sequentially numbered opaque sealed envelope simple randomization method. The participant allocated for intervention will be sequentially assigned dosage group 1-4 in ascending order. Participants will not be recruited in the next dosage group before a set number of participants in one group (10) are achieved. Blinding (masking) Single blinded study, with participants blinded to allocation. Numbers to be randomised (sample size) Total 50 patients are randomised. The intervention arms consist of 40 participants divided in four groups of 10 participants while the comparator group consists of 10 patients. Trial Status Current version of the protocol is “Version 2” dated 29th September, 2020. Participants are being recruited. Recruitment started on June, 2020 and is estimated to primarily end on January, 2021. Trial registration This trial was registered at ClinicalTrials.gov, NCT04521309 on 20 August 2020 and is retrospectively registered. Full protocol The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1).

Kidney transplantation has indisputably revamped renal medicine and restored hope among patients coming across fatal end-stage renal disease. However, sensitization of human leukocyte antigen (HLA) triggers extensive immunological fences to successful kidney transplantation and henceforth, transplant candidates are frequently demoted to the ever-growing waiting list owing to preformed donor specific antibodies (DSAs). Over the past few years, the advent of desensitization protocols has significantly overpowered the immunological barriers and enhanced the outcomes of kidney transplant recipients with DSAs against HLA. Those desensitization protocols include combination of plasmapheresis, high-dose intravenous immunoglobulin (IVIG), low-dose IVIG, rituximab, and/or bortezomib. These immunomodulatory treatments either eliminate DSAs or prevent their production. Lately, our transplant center developed and used a desensitization protocol (Two sessions of plasmapheresis on day 1 and 2 → injection rituximab on day 2 after plasmapheresis →no plasmapheresis on day 3 → eight sessions of plasmapheresis after day 3 and IVIG 100 mg/Kg/dose after each session of plasmapheresis → repeat HLA antibody detection test to confirm if DSAs are present against HLA with median fluorescence intensity (MFI)values

The study determines the effect of fear of being infected on anxiety and influence of anxiety on the disturbance of their mental well-being and to analyze the indirect effect of anxiety between fear of being infected and mental well-being. Cross-Sectional study carried out in the months of November –December 2020, by conducting a survey from health care workers (Doctors, Nurses and Trainees) covering hospitals from the region of Hyderabad, Jamshoro and Karachi. Analysis of the data done using two-step method of Structural Equation Model (SEM) approach. The findings of the study supported the positive and negative relationship fear of being infected to anxiety and anxiety to mental wellbeing respectively. In addition, the indirect relationship of anxiety also supported. Numerous unanswered queries pertinent to COVID-19 pandemic, and dubious situation leads towards huge size of disturbance in the lives of health care workers across the globe, therefore literature entails the necessity for researchers to study various factors that could have influence on mental well-being of an individual . The majority of relevant literature focused on mental well-being is from China, Europe, USA and other developed countries, however, fewer studies focused on South Asian region in general, and Pakistan in particular. So, present study fills the gap to unearth the factors of well-being for Pakistani health care workers. Pakistan have so far lost the lives of 58 healthcare providers to COVID-19 in the country and still counting while 240 healthcare providers are hospitalized. So there is intense need to study effect of mental well-being on health care workers as there is a need to save the survivors.