Virology and safety profile of Molnupiravir at three different doses for treatment of SARS-CoV-2: a systematic review and meta-analysis.

Molnupiravir is incorporated into the viral genome, thereby increasing errors, mismatching, and misdirecting the viral polymerase thereby, halting viral RNA replication of SARS-CoV-2. Following PRISMA guidelines, a thorough literature search was performed on electronic and medical databases from December 2022 till January 2023. Molnupiravir 800 mg showed significance in creating viral RNA error rate at Day 5 (WMD: 4.91; 95% CI; [1.19, 8.63] p = 0.01; I2 = 0%). Similarly, at 400 mg, Molnupiravir creates an RNA error rate (WMD: 2.27; 95% CI; 2.27 [0.50, 4.65] p = 0.02; I2 = 0%). Furthermore, exhibit a significant outcome for mean change in SARS-CoV-2 RNA viral load from baseline in nasopharyngeal sample at 800 mg Molnupiravir on Day 3 (WMD: -0.22; 95% CI; [-0.35, -0.08] p = 0.002; I2 = 0%), Day 5 (WMD: -0.32; 95% CI; [-0.53, -0.11] p = 0.003; I2 = 24%) and overall pooled analysis (WMD: -0.17; 95% CI; [-0.29, 0.33] p = 0.003; I2 = 32%). Moreover, Molnupiravir 400 mg significantly reduced the incidence of death compared to the placebo group (RR: 0.17; 95% CI; [0.07, 0.43] p = 0.0002; I2 = 0%). Molnupiravir effectively treats SARS-CoV-2 patients by eliminating the virus from the host.

Efficacy of tafamidis in transthyretin amyloid cardiomyopathy: a systematic review and meta-analysis.

In May 2019, the U.S. Food and Drug Administration approved tafamidis as the first conservative management of transthyretin amyloid cardiomyopathy (ATTR-CM). Our aim in conducting this systematic review and meta-analysis was to assess the efficacy of tafamidis on patients with ATTR-CM. For that purpose, we thoroughly searched PubMed, ScienceDirect, and Clinical trails.gov by using the appropriate search strategy and following predefined inclusion and exclusion criteria, which retrieved 235 articles initially. Of which two randomized controlled trials (RCTs) and one observational study matched our inclusion criteria. A total of 876 patients are included in this analysis. Based on results, tafamidis significantly reduced cardiovascular (CV) mortality in the ATTR-ACT trial and Ochi et al. (OR 0.58; 95% CI: [0.41-0.83], P=0.003, I 2=87%). A subgroup analysis was conducted for CV mortality due to heart failure (OR 0.89; 95% CI: [0.63-1.25], P=0.50, I 2=93%). The results exhibit that tafamidis reduced all causes of mortality (OR 0.45; 95% CI: [0.32-0.64], P≤0.00001, I 2=22%). Furthermore, mortality remained statistically insignificant in patients with heart transplants (OR 1.18; 95% CI: [0.52-2.70], P=0.70, I 2=0%) and patients with cardiac mechanical assist devices (OR 4.15; 95% CI: [0.48-35.66], P=0.20, I 2=0%). This meta-analysis suggests that tafamidis is a safe and efficient drug to use in patients with ATTR-CM and can possess the potential to be a milestone in enhancing the conservative management of the patients.

A Challenging Diagnosis Of Rare Co-Existent Multiple Myeloma And Prostate Adenocarcinoma: A Systematic Review Of Case Reports.

Objective: To review biochemical parameters, clinical characteristics, demographics, radiological and histopathological findings, treatment modalities and outcomes used to examine patients with coexisting multiple myeloma and prostate adencocarcinoma. METHODS: The systematic review comprised search on PubMed, Google Scholar, Science Direct and the Directory of Open Access Journal databases for case reports published till June 1, 2022. The search was done in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines using appropriate key words. Case reports included were those dealing exclusively with human subjects, were published in the English language and had free, full-text, public access. Quality assessment was done using Joanna Briggs Institute's Critical Appraisal Checklist for Case Reports. Data was extracted and the case reports were evaluated for demographic, diagnostic and treatment parameters. RESULTS: Of the 515 studies initially identified, 5(0.97%) were analysed; all males with mean age 68.6±10.78 years. The most common symptom reported at presentation was low back pain 3(60%), Osteolytic lesions were seen in 4(80%) patients on imaging with elevated prostate surface antigen levels. Anaemia was found in 3(60%) patients and 2(40%) had thrombocytopenia. Conclusion: Multiple myeloma and prostate adenocarcinoma can coexist although it is rare. Awareness regarding the possible coexistence of the two prominent cancer types may further help clinicians during their practice in considering multiple myeloma as a differential diagnosis when encountered with patients having osteolytic bony lesions along with elevated levels of prostate-specific antigen. PROSPERO Registration Number: CRD42022334906.

Global Monkeypox Virus Outbreak 2022: A Bibliometric Analysis.

Monkeypox is a rare zoonotic disease caused by the monkeypox virus, which spreads by direct contact mainly, thus having the propensity to cause future epidemics. The current review aimed to provide an up-to-date literature analysis for evaluating scientific data on monkeypox. A bibliometric analysis was conducted through eight electronic databases. The search period was from May 2022 to December 2023. All the articles were exported to Mendeley (Elsevier, Amsterdam, Netherlands). The literature search resulted in 415 relevant research articles. The growth of publications gradually rose, initiated in January 2022, leading to a rapid upsurge in May 2022. A total of 409 documents reported the number of citations, with two articles documenting the highest number, ranging from 146-150 and 216-220. The European region (EURO) dominated in publishing research articles on monkeypox, with the United States having the highest number of reports (n = 41; 9.87%), followed by the United Kingdom (n = 35; 8.43%) and Italy (n = 15; 3.61%). There were 82 funding agencies that funded 44 research articles, whereas 371 were not funded by any funding agency. Our analysis has presented the outline of the research articles published on monkeypox virus-related literature during the current outbreak. Research articles should be financially and administratively supported. Future research is required to expand research on the monkeypox virus, as there is a growing demand for original articles.

Single-Centre Experience Regarding the Use of Fibular Graft for Reconstruction after Resection of Grade III GCT of Distal Radius.

Background: A giant cell tumour (GCT) is a locally invasive benign tumour of bone in young adults. Treatment includes surgical resection as first-line or denosumab pharmacotherapy in inoperable patients. However, surgical resection of distal radius GCT has produced debatable functional outcomes. Here we study the use of fibular grafts for reconstruction of surgically resected GCT of the distal radius. Methods: A total of 11 patients having Grade III GCT of the distal radius were recruited for a retrospective single-centred study. Five underwent arthrodesis with fibular shaft graft and six received arthroplasty with the proximal fibula. Functional outcomes at 6 weeks, 6 and 12 months were measured by Mayo wrist score (MWS) (>51% = good) and Revised Musculoskeletal tumor society (MSTS) score (>15 = good). Results: At 6 weeks, mean MSTS score and MWS were 23.64 and 58.64% respectively, and the length of the fibular graft was a predictor for both MSTS score (p = 0.014) and MWS (p = 0.006). At 6 months, the mean MSTS and MWS were 26.36 and 76.82%, respectively. At 6 months, the surgical procedure was a predictor in MSTS score (p = 0.02) while MWS was predicted by length of graft (p = 0.02). At 12 months, MSTS score was 28.73, and MWS remained 91.82%. Length of the fibular graft was an insignificant predictor, but a significant risk factor was surgical procedure for MWS (p = 0.04) at 12 months. No variable was found significant for MSTS score. Conclusions: Resection along with reconstruction of Grade III GCT of the radius with fibular graft was found an optimal treatment option. Also, use of the fibular head grafts and shorter length grafts are predictors for better outcomes after surgery. Level of Evidence: Level IV (Therapeutic).

Awake Prone Positioning for Non-Intubated COVID-19 Patients with Acute Respiratory Failure: A Meta-Analysis of Randomised Controlled Trials.

INTRODUCTION: Awake prone positioning (APP) has been widely applied in non-intubated patients with COVID-19-related acute hypoxemic respiratory failure. However, the results from randomised controlled trials (RCTs) are inconsistent. We performed a meta-analysis to assess the efficacy and safety of APP and to identify the subpopulations that may benefit the most from it. METHODS: We searched five electronic databases from inception to August 2022 (PROSPERO registration: CRD42022342426). We included only RCTs comparing APP with supine positioning or standard of care with no prone positioning. Our primary outcomes were the risk of intubation and all-cause mortality. Secondary outcomes included the need for escalating respiratory support, length of ICU and hospital stay, ventilation-free days, and adverse events. RESULTS: We included 11 RCTs and showed that APP reduced the risk of requiring intubation in the overall population (RR 0.84, 95% CI: 0.74-0.95; moderate certainty). Following the subgroup analyses, a greater benefit was observed in two patient cohorts: those receiving a higher level of respiratory support (compared with those receiving conventional oxygen therapy) and those in intensive care unit (ICU) settings (compared to patients in non-ICU settings). APP did not decrease the risk of mortality (RR 0.93, 95% CI: 0.77-1.11; moderate certainty) and did not increase the risk of adverse events. CONCLUSIONS: In patients with COVID-19-related acute hypoxemic respiratory failure, APP likely reduced the risk of requiring intubation, but failed to demonstrate a reduction in overall mortality risk. The benefits of APP are most noticeable in those requiring a higher level of respiratory support in an ICU environment.

Impact of combined component separation technique and shoelace repair on big medline abdominal wall defect.

BACKGROUND: Closure of large anterior abdominal wall defects, regardless of their etiology, is challenging. There is no standardized information describing definitive management. Therefore, we conducted this study to illustrate our experience on large midline abdominal wall defect repair using an effective modified reconstructive technique. METHODS: This retrospective study was conducted at Al Naqib Hospital in Aden/Yemen between 2012 and 2019. Twenty-six patients with large midline abdominal wall defects of various etiologies underwent surgical repair using a combination of shoelace repair and the component separation technique. The procedure involved bilateral longitudinal division of the anterior rectus sheet and creation of a posterior layer by approximation of the medial edges of the divided rectus sheet (shoelace abdominoplasty) and anterior external oblique muscle aponeurosis separation (component separation technique) to approximate the lateral edges of the divided rectus sheet and move the rectus muscles toward the midline for constructing the anterior abdominal wall layer. The posterior and anterior layers and bilateral separated sheets were covered with a polypropylene mesh in all patients, except in those who underwent emergency damage control surgery. RESULTS: Four, one, and two patients developed seroma, skin necrosis and chronic pain, and post-surgical wound infection, respectively. No recurrent herniation was recorded during the median follow-up of 5 years. CONCLUSION: This technique is effective in restoring the integrity of the abdominal wall in large midline abdominal wall defects and has an acceptable aesthetic appearance. In our study, minimal complications were reported, and no cases of recurrent hernias were diagnosed during follow-up.

Third wave COVID-19 delta variant breakthrough infection in a Hispanic-dominant suburb of Miami, Florida: ethical dilemma and vaccination hesitancy.

Background and Aims: The peak of the third wave of COVID-19 infection was in the summer (August-September) of 2021, dominated by the Delta variant. Florida was the epicenter of the third wave with more than 151,449 cases in the first week of August with a positivity rate of 20%. The purpose of this study is to identify the percentage of COVID-19 infection in vaccinated patients in a minority population in south Florida and to elucidate the relationship, if any, between demographics and breakthrough infections, the rate of vaccine hesitancy, as well as the willingness to receive the monoclonal antibody REGEN-COV for the treatment of COVID-19. Methods: This cross-sectional study was performed at the Emergency Department, Larkin Community Hospital Palm Spring Campus, located in Hialeah, the fourth largest city in Florida. Hialeah is dominated (94.7%) by Hispanics and Latinos. This city represents a cross-sectional sample of US cities in general and Florida in specific. We enrolled 127 COVID-19 PCR-positive patients. Results: The infection in vaccinated patients (breakthrough) was found to be about one in three (34%). Despite the high infection rate and mounting death toll, about 73% of our unvaccinated patients answered no to the question 'knowing the consequences of being infected with COVID-19 and the fact that you are positive, would you have chosen to be vaccinated earlier?' However, about 27% of these patients agreed to receive the vaccine and 20.5% received the monoclonal antibody REGEN-COV. Conclusions: Our study revealed that vaccine hesitancy in South Florida continues to be a major challenge, especially with the emergence of mutations including Delta plus and Omicron.

Detection of vaccine-derived poliovirus type 2 amid the burden of infectious diseases in the UK: A cause for alarm.

The re-emergence of polio in the UK reminds us that the global threat of polio remains. Viruses know no bounds or borders. COVID-19, Monkeypox, and polio are evidence of this. Poliomyelitis was once the leading cause of death and paralysis in the UK and globally. With the introduction of vaccines during the 1950s-1960s, polio was eradicated from most developed countries, including the UK. The last case of wild polio was in 1984, and the UK was polio-free in 2003. The recent detection of vaccine-derived poliovirus type 2 in London sewage samples is alarming. Routine inoculations were adversely affected due to COVID-19, and UK's wastewater monitoring program was suspended due to economic restrictions. The UK faces several challenges with the burden of COVID-19, Monkeypox, and the return of polio could further burden the already pandemic-stricken healthcare system. To prevent further epidemics in the UK, wastewater sampling remains crucial in evaluating, searching, and eradicating the spread of poliovirus. Further epidemiological surveillance in adjacent areas to the Beckton plant is crucial to filling any gaps in understanding the outbreak's extent and guiding the initiation of appropriate and timely public health measures. The importance of vaccination in unvaccinated or incompletely vaccinated individuals cannot be overstated, especially in areas where vaccination rates are low. The risk of polio remains globally until its complete eradication from endemic countries. Until elimination, a global effort should be made to minimize the risk and the consequent spread of poliovirus by maintaining strong population immunity levels through high vaccination coverage.

Pneumothorax as a Complication of Bevacizumab-Containing Chemotherapy: A Systematic Review of Case Reports.

Bevacizumab is a monoclonal anti-vascular endothelial growth factor (VEGF) antibody that binds to and makes all of the VEGF isoforms inactive, and thus prevents angiogenesis, development, and the spread of the tumor. The most reported side effects after administering bevacizumab include bleeding, high blood pressure, heart failure, proteinuria, thrombosis, and gastrointestinal perforation. Pneumothorax has rarely been reported as a complication of bevacizumab, but with an unclear mechanism. This article aims to explore the occurrence of pneumothorax as a side effect after using bevacizumab through a systematic review of current case reports published on the topic. A literature search was conducted using PubMed, Google Scholar, ScienceDirect, and Directory of Open Access through the utilization of appropriate keywords, and case reports were selected based on predefined inclusion and exclusion criteria. Our results encompass five case reports that were further evaluated for demographic, clinical, and treatment parameters. This systematic review concludes that pneumothorax can occur after bevacizumab-containing chemotherapy although this side effect is relatively rare. Awareness regarding this possible side effect can assist clinicians during their practice in considering pneumothorax as a possible differential diagnosis when encountering patients presenting with pulmonary symptoms after starting bevacizumab-containing chemotherapy; hence, timely diagnosis and treatment can save a life.

Emergence of Omicron BA.1 and BA.2 variants and concern over vaccine breakthrough infection.

The COVID-19 pandemic since 2020 created havoc across the globe. This led to the establishment of effective vaccines to mitigate the virus. Several vaccines are developed to create immunity amongst the population. However, due to emerging variants of SARS-CoV-2, despite a double dose of vaccines, people have still infected that termed vaccine breakthrough infection. This paper aims to highlight the recent re-surging massive outbreak of COVID-19 in China despite mass vaccination and, discuss the issue of vaccine breakthrough infection, possible causes, and recommendations to enhance immunity and curb the transmission.

Tuberculosis amidst COVID-19 in Pakistan: a massive threat of overlapping crises for the fragile healthcare systems.

Mycobacterium tuberculosis is the cause of tuberculosis (TB), a granulomatous illness that mostly affects the lungs. Pakistan is one of the eight nations that accounts for two-thirds of all new cases of developing TB. TB has long been an endemic disease in Pakistan. According to the World Health Organization (WHO) estimates, the nation has over 500 000 incident TB infections per year, with a rising number of drug-resistant cases. Recently, the coexistence of COVID-19 and TB in Pakistan has provided doctors with a problem. Fever or chills, cough, shortness of breath or difficulty breathing are all signs of COVID-19. After SARS-CoV-2 infection, cough might persist for weeks or months and it is frequently accompanied by persistent tiredness, cognitive impairment, dyspnoea or pain - a group of long-term consequences known as post-COVID syndrome or protracted COVID. Coughing with mucus or blood, and coughing that continues over 2 months are indications of TB. The same clinical presentation features make it difficult for healthcare personnel to effectively evaluate the illness and prevent the spread of these fatal diseases. Pakistan lacks the necessary healthcare resources to tackle two contagious diseases at the same time. To counteract the sudden increase in TB cases, appropriate management and effective policies must be implemented. Thus, in order to prevent the spread of these infectious diseases, it is critical to recognise and address the problems that the healthcare sector faces, as well as to create an atmosphere in which the healthcare sector can function at its full potential.

Histiocytic Sarcoma Secondary to Gastrointestinal Stromal Tumors: A Literature Review.

Histiocytic sarcoma (HS) is a rare tumor that may result from the transdifferentiation of preexisting hematolymphoid neoplasms in a subset of patients. There are instances of correlation or concurrence between HS and a number of cancers, particularly B-cell-associated hematopoietic tumors. Only three cases of HS occurring subsequent to or concurrently with gastrointestinal stromal tumors (GIST) have been recorded. Our main objective was to give an overview of demographics, clinical signs and symptoms, histopathological findings, and immunohistochemical and molecular analysis when HS develops secondary to or concurrently with GIST. A search of PubMed, Google Scholar, and ScienceDirect was undertaken using Medical Subject Headings (MeSH) keywords. According to the findings of our review, there were two males (66.6%) and one female (33.3%). The average age of patients at presentation was 59.6 years. On the immunohistochemistry, three patients were positive for cluster of differentiation (CD) 68 (100%), two patients were positive for CD 163 (67%), one patient was positive for leukocyte common antigen (LCA) (33%), and only one patient was positive for CD 4, CD 10, CD 31, CD 45, human leukocyte antigen (HLA)-DR, lysozyme, and vimentin (33%). On molecular investigation, the gastric mass of only one patient (33.33%) contained a KIT mutation on exon 11. Emperipolesis was observed in one patient (33.33%) on histological examination. Our study provides an important overview of the available literature and gives insight into important diagnostic markers of HS when it occurs secondary to or concurrently with GIST.

Zika virus endemic challenges during COVID-19 pandemic in Africa.

Zika virus remains endemic and opportunistic of high transmission in the tropical region of Africa, and the repeated cases of the Zika virus in Africa made it public health emergency in 2016. Amidst the COVID-19 pandemic, the catastrophic cases of unknown and unreported deaths overwhelming the region of Africa could not give health attention to respond to other endemic diseases. Here, we present the possible complication and challenges associated with the Zika virus in Africa and COVID-19 predominance, shifting the attention from the Zika virus surveillance. This paper determines to enlighten the reader about the situation, the efforts to curb the transmission of both the Zika virus and the COVID-19 pandemic. Therefore, the report recommends sustainable solutions that can lessen the threat to public health.

Association of Diabetes With Lower Back Pain: A Narrative Review.

Diabetes mellitus with its increasing prevalence is one of the four major non-communicable diseases. It is characterized by hyperglycemia, which may progress to chronic complications such as peripheral vascular disease and neuropathy. This paper highlights the pathophysiology associated with diabetes, which is restricted to not only hyperglycemia but also other comorbidities including chronic lower back pain. Diabetes is a metabolic disorder associated with hypercholesteremia, hypertriglyceridemia, and hypertension. This chain of events leads to free plasma fatty acids and a pro-inflammatory state, therefore promoting calcification of blood vessels, which may block the blood supply to vertebral discs and thereby increase vulnerability in the patients with ongoing inflammatory disease such as osteoarthritis and also causing costochondritis. Functional limitation due to increased load on the weight-bearing joints is a common mechanical complication of diabetes. Obesity in diabetes is more prevalent due to a disturbed metabolism, which is aggravated with a persistent inflammatory state. Moreover, the aim of this review is to encourage further conduction of clinical studies to explore the definite cause and potential therapy for chronic lower back pain in diabetes, thereby investigating the association of lipid metabolism and skeletal muscle atrophy leading to chronic back pain, the role of diabetic medications, and vulnerability in the female gender. Diminished physical activity and depression in diabetic patients disrupt the hypothalamic-pituitary-adrenal axis (HPA), which further contributes to lower back pain. Further clinical investigation and research in this regard will establish substantial data for the linkage between depression in diabetes and back pain. However, despite all the advancements of medical literature, the exact cause of lower back pain in diabetes is arguable. Pain impedes the health status and life quality; therefore, it is essential to maintain the quality of health in patients with diabetes by treating not only hyperglycemia but also other multifactorial causes leading to lower back pain.

Postpartum Depression: Prevalence and Associated Risk Factors Among Women in Sindh, Pakistan.

Introduction Postpartum depression (PPD) is defined as the onset of depressive symptoms within six weeks of childbirth. PPD is more common in resource-constrained countries as compared to developed countries. The study aimed to evaluate the factors associated with PPD among women in Sindh, Pakistan. Methods A multi-centre, cross-sectional study was conducted at three major tertiary care setups in Sindh, Pakistan. All women presenting to the outpatient department within six weeks of giving live birth were eligible to participate. All women who had stillbirths, abortions, or were treated for a past psychiatric illness or neurological disease were excluded from the study. The Edinburgh postpartum depression scale (EPDS) was used as a screening tool. All socio-demographic factors were documented in a predefined pro forma. The data was analyzed using Statistical Package for Social Sciences (SPSS, Version 26, IBM, Chicago, IL). Results According to the Edinburgh postpartum depression scale (EPDS), the incidence of postpartum depression in the current study population was 19.3%. Of these, 12 (3.3%) women had persistently thought about self-harming. Over 100 women did not receive any formal education, constituting the majority of the study population. Formula milk feeding of the newborn was significantly associated with an increased frequency of postpartum depression (p= 0.0001). Conclusion The current study highlights the significant burden of postpartum depression in Pakistan. However, the present study failed to find any significant risk factors associated with postpartum depression. Only formula milk feeding was significantly associated with a higher frequency of PPD among study patients.