Safety and Efficacy of Camostat Mesylate for Covid-19: a systematic review and Meta-analysis of Randomized controlled trials.

BACKGROUND: Camostat mesylate, an oral serine protease inhibitor, is a powerful TMPRSS2 inhibitor and has been reported as a possible antiviral treatment against COVID-19. Therefore, we aim to assess the safety and efficacy of camostat mesylate for COVID-19 treatment. METHODS: A systematic review and meta-analysis synthesizing randomized controlled trials from PubMed, Scopus, Embase, Cochrane, Web of Science, clinical trials.gov, and medrxiv until June 2023. The outcomes were pooled using Mean difference (MD) for continuous outcomes and risk ratio (RR) for dichotomous outcomes. The protocol is registered in PROSPERO with ID CRD42023439633. RESULTS: Nine RCTs, including 1,623 patients, were included in this analysis. There was no difference between camostat mesylate and placebo in producing negative PCR test results at 1-7 days (RR: 0.76, 95% CI: [0.54, 1.06] P = 0.1), 8-14 days (RR: 1.02, 95% CI: [0.84, 1.23] P = 0.87), or 15-21 days (RR: 0.99, 95% CI: [0.82, 1.19] P = 0.90); clinical resolution of symptoms at 1-7 days (RR: 0.94 (95% CI: 0.58, 1.53) P = 0.81), 8-14 days (RR: 0.91, 95% CI: [0.74, 1.11] P = 0.33, ), or 15-21 days (RR: 0.77, 95% CI: [0.40, 1.51] P = 0.45); and time to symptom improvement (MD:-0.38 weeks (95% CI: [-1.42, 0.66] P = 0.47, I2 = 85%). CONCLUSION: Camostat mesylate did not improve clinical outcomes in patients with COVID-19, compared to placebo.

Efficacy and Safety of Endoscopic Stricturotomy in Inflammatory Bowel Disease-Related Strictures: A Systematic Review and Meta-Analysis.

BACKGROUND AND AIM: Luminal strictures, common in inflammatory bowel disease (IBD), especially Crohn's disease (CD), are typically treated with endoscopic balloon dilatation (EBD). The newer endoscopic stricturotomy (ESt) approach shows promise, but data is limited. This systematic review and meta-analysis assess the effectiveness and safety of ESt in IBD-related strictures. METHODS: A comprehensive literature search was conducted until November 2023 for studies assessing ESt efficacy and safety in IBD. Primary outcomes were clinical and technical success, with secondary endpoints covering adverse events, subsequent stricture surgery, additional endoscopic treatments (ESt or EBD), medication escalation, disease-related emergency department visits, and hospitalization post-ESt. Technical success was defined as passing the scope through the stricture, and clinical success was defined as symptom improvement. Single-arm meta-analysis (CMA version 3) calculated the event rate per patient with a 95% confidence interval (CI). Heterogeneity was evaluated using I2. RESULTS: Nine studies were included, involving 640 ESt procedures on 287 IBD patients (169 CD, 118 ulcerative colitis). Of these, 53.3% were men, with a mean age of 43.3 ± 14.3 years and a mean stricture length of 1.68 ± 0.84 cm. The technical success rate was 96.4% (95% CI 92.5-98.3, p-value < 0.0001), and the clinical success rate was 62% (95% CI 52.2-70.9, p-value = 0.017, I2 = 34.670). The bleeding rate was 10.5% per patient, and the perforation rate was 3.5%. After an average follow-up of 0.95 ± 1.1 years, 16.4% required surgery for strictures post-ESt, while 44.2% needed additional endoscopic treatment. The medication escalation rate after ESt was 14.7%. The disease-related emergency department visit rate was 14.7%, and the disease-related hospitalization rate post-procedure was 21.3%. CONCLUSION: Our analysis shows that ESt is safe and effective for managing IBD-related strictures, making it a valuable addition to the armamentarium of endoscopists. Formal training efforts should focus on ensuring its widespread adoption.

Intensive Blood Pressure Control After Endovascular Thrombectomy for Acute Ischemic Stroke: a Systematic Review and Meta-Analysis.

BACKGROUND AND PURPOSE: Optimal clinical outcome with successful recanalization from endovascular thrombectomy (EVT) requires optimal blood pressure (BP) management. We aimed to evaluate the efficacy and safety of the intensive BP target (< 140 mm Hg) versus the standard BP target (< 180 mm Hg) after EVT for acute ischemic stroke. METHODS: We conducted a systematic review and meta-analysis synthesizing evidence from randomized controlled trials (RCTs) obtained from PubMed, Embase Cochrane, Scopus, and WOS until September 7th, 2023. We used the fixed-effect model to report dichotomous outcomes using risk ratio (RR) and continuous outcomes using mean difference (MD), with a 95% confidence interval (CI). PROSPERO ID: CRD42023463206. RESULTS: We included four RCTs with 1559 patients. There was no difference between intensive BP and standard BP targets regarding the National Institutes of Health Stroke Scale (NIHSS) change after 24 h [MD: 0.44 with 95% CI (0.0, 0.87), P = 0.05]. However, the intensive BP target was significantly associated with a decreased risk of excellent neurological recovery (mRS ≤ 1) [RR: 0.87 with 95% CI (0.76, 0.99), P = 0.03], functional independence (mRS ≤ 2) [RR: 0.81 with 95% CI (0.73, 0.90), P = 0.0001] and independent ambulation (mRS ≤ 3) [RR: 0.85 with 95% CI (0.79, 0.92), P < 0.0001]. CONCLUSIONS: An intensive BP target after EVT is associated with worse neurological recovery and significantly decreased rates of functional independence and independent ambulation compared to the standard BP target. Therefore, the intensive BP target should be avoided after EVT for acute ischemic stroke.

Evaluation of the General Population's Knowledge Concerning Liver Health: A Cross-Sectional Study.

INTRODUCTION: Liver disease is among the leading causes of global mortality and morbidity. Given their substantial impact on public health, raising awareness about liver diseases is paramount for their prevention and effective management. This study aimed to evaluate the knowledge, awareness, attitudes, and behaviors of Syrians regarding liver health, chronic liver disorders, and their associated serious and irreversible complications. METHODS: We conducted a cross-sectional study encompassing the adult Syrian population between August 25 and September 29, 2023, excluding non-Syrians and individuals below the age of 18 years. A validated questionnaire, adapted from a previous study, was employed, consisting of 31 questions that covered topics related to knowledge and awareness of liver health and diseases (3-point Likert scale), attitudes towards liver screening, diagnosis, and treatment, and awareness of treatment options and vaccination. Statistical analysis including logistic regression was conducted using Statistical Product and Service Solutions (SPSS, version 28; IBM SPSS Statistics for Windows, Armonk, NY), with statistical significance set established at pp-values below 0.05. RESULTS: This study included 941 participants, with an average age of 26.5 years. While two-thirds of respondents demonstrated awareness of hepatitis B and C as viral diseases (663 (70.4%) and 612 (65.4%), respectively), approximately 66 (7%) were unaware of the potential for hepatitis to induce chronic liver inflammation or lead to liver failure. Over half of the participants were knowledgeable about the non-genetic nature of hepatitis B and C, and 579 (61.7%) were informed about the transmission risks associated with these infections. The most common reason cited for not participating in health screening tests was the perception of being in good health (219, 77.4%), and prescription medication was the most frequently sought treatment for hepatitis (543, 83.9%). Bivariate analysis revealed correlations between participant knowledge and sex, socioeconomic status, educational level, and occupation (P < 0.05). Similarly, the study identified significant associations between participant attitudes and age, gender, economic status, job, and educational level (P < 0.05). Moreover, the multivariate analysis demonstrated that gender, occupation, and educational level significantly influenced both participants' knowledge and attitudes. Specifically, males exhibited lower knowledge and less favorable attitudes than females (P = 0.041 and P < 0.001, respectively). CONCLUSION: The Syrian population possessed moderate knowledge of liver health and liver disorders. To bridge this knowledge gap and enhance preventive measures, it is recommended that additional health programs and awareness initiatives be implemented, involving healthcare providers and leveraging their expertise.

Ripple effects of COVID-19 lockdown pertaining to clinical skills among undergraduate medical students of Karachi.

OBJECTIVE: To determine the outcomes of coronavirus disease-2019 lockdown pertaining to clinical skills among undergraduate medical students. METHODS: The cross-sectional questionnaire-based study was conducted after approval from the Jinnah Sindh Medical University, Karachi, at 6 public and private medical education institutions in Karachi from July 3 to August 3, 2021, and comprised undergraduate students from the 3rd, 4th and final academic years. Data was collected using a pre-designed questionnaire. Data was analysed using SPSS 20. RESULTS: Of the 383 subjects, 260(67.9%) were females and 123(32.1%) were males. The overall age range was 20-25 years. There were 145(37.9%) students from the 3rd year, 154(40.2%) from 4th and 84(21.9%) from the final year. Among them, 251(84.2%) accepted having decreased efficiency in clinical skills because they were not being able to train in person, 157(41%) claimed that certain topics related to clinical study were given in exams even though they were not taught, and 164(72.6%) faced difficulty in exams related to clinical skills. CONCLUSIONS: Coronavirus disease-2019 caused disruption in routine life, and medical education was not an exception. E-learning modality was found to be insufficient, and patient exposure elevates confidence, eliminates hesitation, and improves clinical skills.

Opalski syndrome, a rare variant of wallenberg syndrome, the first case reported from Pakistan: A case report.

Background: Wallenberg syndrome, also known as a lateral medullary syndrome, is a rare neurological condition caused by an infarction in the brainstem's lateral medulla. There are subtypes of Wallenberg syndrome with distinctive and atypical symptoms, such as Opalski syndrome. Case presentation: A 41-year-old hypertensive male arrived at the emergency department with abrupt onset of right-sided bodily weakness, vertigo, facial numbness, dysphagia, hoarseness of voice, and double vision. The neurological examination indicated right hemiparesis, right facial numbness, crossed sensory deficit, right limb ataxia, right uvulopalatal deviation, and vertical double vision. An MRI showed a lateral medullary infarct leading to the suspicion of the atypical lateral medullary syndrome. The patient was treated with physiotherapy and daily oral medications including aspirin, clopidogrel, atorvastatin, and Cap Risek. On follow-up 14 days later, the patient's condition had significantly improved. Conclusion: This case study demonstrates the significance of recognizing atypical variants of Wallenberg syndrome, such as Opalski syndrome, in order to provide a correct diagnosis and the most effective treatment. Our patient's condition improved as a result of the therapy measures used, however, people with Opalski syndrome may have a poor prognosis and require continuous monitoring.

Precision Medicine and Cardiac Channelopathies: Human iPSCs Take the Lead.

Sudden cardiac death (SCD) is one of the leading causes of death worldwide, usually involving young people. SCD remains a critical public health problem accounting for 185,000-450,000 deaths annually, representing around 7%-18% of all deaths globally. As per evidence, ∼2%-54% of sudden unexpected deaths in people under the age of 35 years fail to show evidence of structural cardiac abnormalities at autopsy, making ion channelopathies the probable causes in such cases. The most generally recognized cardiac ion channelopathies with genetic testing are long QT syndrome (LQTS), Brugada syndrome (BrS), short QT syndrome (SQTS), and catecholaminergic polymorphic ventricular tachycardia (CPVT). The substantial progress in understanding the genetics of ion channelopathies in the last 2 decades has obliged the early diagnosis and prevention of SCD to a certain extent. In this review, we analyze the critical challenges and recent advancements in the identification, risk stratification, and clinical management of potentially fatal cardiac ion channel disorders. We also emphasize the application of precision medicine (PM) and artificial intelligence (AI) for comprehending the underlying genetic mechanisms, especially the role of human induced pluripotent stem cell (iPSC) based platforms to unravel the primary refractory clinical problems associated with channelopathies.

A Gradient Lithiophilic Structure for Stable Lithium Metal Anodes with Ultrahigh Rate and Ultradeep Capacity.

Using three-dimensional current collectors (3DCC) as frameworks for lithium metal anodes (LMAs) is a promising approach to inhibit dendrite growth. However, the intrinsically accumulated current density on the top surface and limited Li-ion transfer in the interior of 3DCC still lead to the formation of lithium dendrites, which can pose safety risks. In this study, it reports that gradient lithiophilic structures can induce uniform lithium deposition within the interior of the 3DCC, greatly suppressing dendrite formation, as confirmed by COMSOL simulations and experimental results. With this concept, a gradient-structured zinc oxide-loaded copper foam (GSZO-CF) is synthesized via an easy solution-combustion method at low cost. The resulting Li@GSZO-CF symmetric cells demonstrate stable cycling performance for over 800 cycles, with an ultra-deep capacity of 10 mAh cm-2 even under an ultra-high current density of 50 mA cm-2 , the top results reported in the literature. Moreover, when combined with a LiFePO4 (LFP) cathode under a low negative/positive (N/P) capacity ratio of 2.9, the Li@GSZO-CF||LFP full cells exhibit stable performance for 200 cycles, with a discharge capacity of 130 mAh g-1 and retention of 85.5% at a charging/discharging rate of 1C. These findings suggest a promising strategy for the development of new-generation LMAs.

Assessing Syrian women's knowledge of breast cancer risk factors, warning signs, and barriers to preventive measures: A cross-sectional study.

BACKGROUND: This study aims to investigate the knowledge of Syrian women about breast cancer risk factors, warning signals, and barriers. Breast cancer is the most common cancer worldwide and the leading cause of cancer death among women. It develops when cells in the breast tissue grow uncontrollably, forming a tumor that can spread to other parts of the body. MATERIALS AND METHODS: This survey was conducted online from September 3 to September 27, 2022, and focused on Syrian women over the age of 18. It was divided into two sections, one focusing on sociodemographic characteristics and the other on breast cancer risk factors, warning signals, and barriers. RESULTS: This study found that the majority of the 1305 participants had inadequate knowledge of breast cancer risk factors, warning signs, and barriers. Those with higher levels of education, such as Ph.D. students, had the highest overall scores. The sample was mostly made up of housewives, married women, and women with moderate monthly incomes. CONCLUSION: This research found that Syrian women have inadequate knowledge about breast cancer, including risk factors, warning signs, and barriers. To reduce mortality rates, increase survival rates, and improve early diagnosis, local health organizations should provide awareness courses to emphasize the importance of annual breast exams.

High-altitude cerebral edema manifesting as T2/FLAIR hyperintensity and microbleeds in the white matter on MRI brain.

High-altitude cerebral edema is a rare type of acute mountain illness characterized by consciousness disruption and truncal ataxia. Here we discuss a 40-year-old nondiabetic, nonsmoker male who went on a tour to Nanga Parbat. On returning home, the patient developed symptoms of headache, nausea, and vomiting. His symptoms worsened with time and he developed lower limb weakness and shortness of breath. Later, he underwent a computerized tomography chest scan. On the basis of CT scan findings, the doctors decided that the patient was suffering from COVID-19 Pneumonia despite having negative COVID-19 PCR tests multiple times. Later, the patient presented to our hospital with similar complaints. MRI of the brain revealed T2/fluid-attenuated inversion recovery hyperintense and T1 hypointense signals in the bilateral semioval centrum, posterior periventricular white matter, and corpus callosum genu, body, and splenium. These abnormal signals were discovered to be more evident in the corpus callosum's splenium. Moreover, susceptibility-weighted imaging revealed micro hemorrhages in the corpus callosum. This verified the diagnosis that the patient is suffering from high-altitude cerebral edema. Within 5 days, his symptoms resolved and he was discharged with full recovery.

Attitude of Syrian students toward GAD patients: An online cross-sectional study.

Generalized Anxiety Disorder (GAD) is a prevalent condition and a significant cause of mental disability and poor quality of life. People with GAD have chronic worrying, restlessness, and discrimination from the general public; Little is known about the stigmatizing attitudes toward people with GAD among Syrian students. The questionnaires contained demographic data about age, gender, social status, personal stigma toward GAD scale, perceived stigma toward GAD scale, social distance with those with GAD, the participants' usual source of their knowledge about GAD, helpful interventions, and supporting information. A total of 1,370 replies were collected, but only 1,358 were used for analysis as 12 participants declined to complete the survey. About 44.1% of participants agreed that people with GAD could snap out of the problem, most of them being females (32.4% of the total population). Compared to medical students, more non-medical students (7.1% of the total population) believed that anxiety is a sign of personal weakness. This study demonstrated that Syrian college students showed a high level of stigmatizing and socially distancing attitudes toward people with GAD, particularly female and non-medical students.

Etiology and risk factors of stroke in young adults: A multicentric study.

Objective: The main objective of this research was to assess the risk factors and causes of ischemic stroke in the young population (age less than 50 years). Methods: This was a prospective multicenter study conducted at Pakistan Atomic Energy Commission General Hospital, Islamabad, and Mayo hospital Lahore from June 2019 to June 2020. In this research, patients with ischemic stroke, aged 15-50 years were included. Prior to noting demographics, each patient gave ethical approval via filling out consent forms. After that, all demographical details including residence, education, gender and age, and socioeconomic status were noted. Risk factors were evaluated on the questionnaire proforma. Outcomes were measured using the modified Rankin scale (MRS) score. Additionally, data were analyzed by using SPSS V26. A P-value of <0.05 was set as statistically significant. Results: Out of 80 patients, 53 (66.25%) were male, while 27 (33.75%) were female. Six (7.5%) patients were between the ages of 15 and 25 years, 18 (22.5%) patients were between 26 and 35 years, 48 (60%) patients were between the ages of 36 and 45, and eight (10%) patients were between the ages of 46 and 50. According to this research, hypertension was found to be the most frequently occurring risk factor in 28 participants (35%), Diabetes mellitus in 23 patients (28.75%), dyslipidemia in 20 patients (22.5%), and smoking in 18 patients (22.5%). The etiology remained undetermined in 30 patients (37.5%). Most of the patients (87.5%) reported positive functional outcomes (MRS score 0-2). However, 3 (3.75%) patients died during the study period. Conclusion: This research showed that common risk factors of ischemic stroke in the local young population included hypertension, diabetes mellitus, and smoking, whereas the etiology of stroke remained unidentified in the majority of patients.

An infant with patau syndrome associated with congenital heart defects.

Introduction: and background: Patau syndrome or trisomy 13 is a clinically severe condition; 85 percent of patients die before reaching the age of one year, and the majority of children die before reaching the age of six months. Case presentation: This report discusses a case of a male infant, two days old diagnosed with Patau syndrome. After birth, his APGAR score was satisfactory. The initial clinical examination revealed cleft palate, cleft lip, and congenital clubfoot. A pansystolic murmur was heard at the left sternal border. The patient was managed according and was referred to a surgeon for pulmonary binding, PDA ligation, VSD closure, and repair of ASA with disbanding of the pulmonary artery. Clinical discussion: Studies have reported that patients with Patau syndrome present with cleft lip and palate, congenital heart defects, omphalocele, and holoprosencephaly. we also discovered dysmorphic characteristics such as the cleft palate and cleft lip, as well as serious congenital cardiac abnormalities. In addition, up to 80% of patients have been documented to have cardiac abnormalities, with patent ductus arteriosus, atrial septal defect, and ventricular septal defect. Conclusion: Patau syndrome is the third most common trisomy found in infants. The clinical manifestation of Patau syndrome includes cleft palate, cleft lip, limb impairments, and congenital heart problems. Despite the fact that early diagnosis and management prognosis is poor for patients suffering from Patau syndrome. Genetic counseling may be beneficial not just for increasing awareness of the diagnosis and its implications.

Household COVID-19 secondary attack rate and associated determinants in Pakistan; A retrospective cohort study.

BACKGROUND: COVID-19 household transmissibility remains unclear in Pakistan. To understand the dynamics of Severe Acute Respiratory Syndrome Coronavirus disease epidemiology, this study estimated Secondary Attack Rate (SAR) among household and close contacts of index cases in Pakistan using a statistical transmission model. METHODOLOGY: A retrospective cohort study was conducted using an inclusive contact tracing dataset from the provinces of Punjab and Khyber-Pakhtunkhwa to estimate SAR. We considered the probability of an infected person transmitting the infection to close contacts regardless of residential addresses. This means that close contacts were identified irrespective of their relationship with the index case. We assessed demographic determinants of COVID-19 infectivity and transmissibility. For this purpose based on evolving evidence, and as CDC recommends fully vaccinated people get tested 5-7 days after close contact with a person with suspected or confirmed COVID-19. Therefore we followed the same procedure in the close contacts for secondary infection. FINDINGS: During the study period from 15th May 2020 to 15th Jan 2021, a total of 339 (33.9%) index cases were studied from 1000 cases initially notified. Among close contact groups (n = 739), households were identified with an assumed mean incubation period of 8.2+4.3 days and a maximum incubation period of 15 days. SAR estimated here is among the household contacts. 117 secondary cases from 739 household contacts, with SAR 11.1% (95% CI 9.0-13.6). All together (240) SAR achieved was 32.48% (95% CI; 29.12-37.87) for symptomatic and confirmed cases. The potential risk factors for SAR identified here included; old age group (>45 years of age), male (gender), household members >5, and residency in urban areas and for index cases high age group. Overall local reproductive number (R) based on the observed household contact frequencies for index/primary cases was 0.9 (95% CI 0.47-1.21) in Khyber Pakhtunkhwa and 1.3 (95% CI 0.73-1.56) in Punjab. CONCLUSIONS: SAR estimated here was high especially in the second phase of the COVID-19 pandemic in Pakistan. The results highlight the need to adopt rigorous preventive measures to cut the chain of viral transmission and prevent another wave of COVID-19.

An infant with omenn syndrome: A case report.

BACKGROUND: Omenn syndrome is a rare, autosomal recessive disorder. It is a disorder that stems from severe combined immunodeficiency in an affected individual. The disease is also of rare occurrence in children in Pakistan because this is the age where this disease usually presents, after having developed in the child. This case report will explore all the reasons that lead to the occurrence of this syndrome while also reflecting on the management profile of the child. CASE PRESENTATION: This case report deals with the discussion of one such child who was diagnosed with Omenn Syndrome after being diagnosed with several other diseases, which were being mistaken for being the actual problem and disease, but the reality was that the child was suffering from Omenn syndrome. DISCUSSION: The child is only 3 months old and his symptoms pose a great risk to his overall health status while also making him predisposed to develop several complications and nutritional deficiencies as a result, all of which keep on adding to the burden of diseases that the child faced. In Omenn syndrome, there is an increased susceptibility to develop infections of the skin, lungs, joints, as well as sepsis. Usually, the death of the patient ensues due to pneumonia and septicemia or septic shock. CONCLUSION: Omenn syndrome is a rare disease caused by missense mutations in the recombinase activating genes. It can be treated by bone marrow transplantation or lymphocytic stimulation depending on the severity of the presenting underlying immunodeficiency.

Parvovirus b19-Induced Acute Hepatitis With Hepatosplenomegaly and Polyarthropathy.

Parvovirus B19 infection can present with myriads of clinical diseases and syndromes; hepatitis and polyarthropathy are a few of these examples. Parvovirus frequently affects children but this condition has also been reported in adults.  The present case report discusses a case of a 43-year-old female who presented to the outpatient department (OPD) with complaints of high-grade fever and pain in multiple joints of her body for three days. On examination, stiffness and swelling of the hand, knees, wrist, and ankles were noted. Laboratory investigations showed highly elevated aspartate transaminase (AST), alanine transaminase (ALT), and bilirubin. Electrocardiogram (ECG) and echocardiogram (ECHO) findings were unremarkable. PCR testing showed the presence of parvovirus. Parvovirus B19 infection led to the development of acute hepatitis, which appeared as yellowing of skin (jaundice) and led to hepatosplenomegaly. Parvovirus-induced polyarthropathy was also observed in the patient. The patient was managed with a parenteral course of ceftriaxone, paracetamol, and a normal saline infusion. Anti-viral drugs were also prescribed to the patient including ribavirin and pegylated interferon. This case study will explore how the patient was diagnosed and managed with conventional therapy and anti-viral to relieve parvovirus-induced hepatitis with hepatosplenomegaly and polyarthritis. Acute hepatitis can be caused by viruses and other noninfectious causes, all of which must be cleared out to avoid chronic disease development. When patients present with joint pain and skin rashes, a thorough workup for viral indicators, medication histories, autoimmune and metabolic illnesses, and parvovirus b19 infection is required.

Corrigendum: Attitude of Syrian students toward GAD patients: An online cross-sectional study.

[This corrects the article DOI: 10.3389/fpubh.2022.955321.].