Antiandrogens for the treatment of COVID-19 patients: A meta-analysis of randomized controlled trials.

Antiandrogens may carry a potential benefit as a therapeutic agent against COVID-19. However, studies have been yielding mixed results, thus hindering any objective recommendations. This necessitates a quantitative synthesis of data to quantify the benefits of antiandrogens. We systematically searched PubMed/MEDLINE, Cochrane Library, clinical trial registers, and reference lists of included studies to identify relevant randomized controlled trials (RCTs). Results from the trials were pooled using a random-effects model and outcomes were reported as risk ratios (RR) and mean differences (MDs) with 95% confidence intervals (CIs). Fourteen RCTs with a total sample size of 2593 patients were included. Antiandrogens yielded a significant mortality benefit (RR 0.37; 95% CI; 0.25-0.55). However, on subgroup analysis, only proxalutamide/enzalutamide and sabizabulin were found to significantly reduce mortality (RR 0.22, 95% CI: 0.16-0.30 and RR 0.42, 95% CI: 0.26-0.68, respectively), while aldosterone receptor antagonists and antigonadotropins did not show any benefit. No significant between-group difference was found in the early or late initiation of therapy. Antiandrogens also reduced hospitalizations and the duration of hospital stay, and improved recovery rates. Proxalutamide and sabizabulin may be effective against COVID-19, however, further large-scale trials are needed to confirm these findings.

Benvitimod for the treatment of psoriasis: A systematic review and meta-analysis of randomized controlled trials.

Benvitimod is a topical drug that has recently been approved for mild to moderate psoriasis and atopic dermatitis. The drug has just completed phase 3 trials for psoriasis, which calls for a systematic update of current evidence on the efficacy and safety of this drug. We searched MEDLINE (PubMed), EMBASE, Science Direct, International Clinical Trials Registry Platform (ICTRP), Cochrane Central Register of Controlled Trials, and Google Scholar for all available randomized controlled trials concerning the topic. We included six randomized controlled trials evaluating the efficacy of benvitimod 1.0% with a total of 1925 patients. Our meta-analysis demonstrated that more patients in the benvitimod group achieved physician global assessment score of 0 or 1 (RR 6.53, 95% CI 4.39-9.71), psoriasis area and severity index (PASI) 75 (RR 4.34, 95% CI 2.96-6.36), PASI 90 (RR 8.83, 95% CI 5.22-14.95) and body surface area reduction (MD -3.85, 95% CI -4.83, -2.88) than placebo at week 12. Patient-reported outcomes were also analyzed, yielding a significant benefit in the benvitimod group for peak pruritus numerical rating scale (PP-NRS) score (MD -1.20, 95% CI -1.98, -0.42), ≥4-point decrease in PP-NRS score (RR 1.58, 95% CI, 1.24-2.03) and dermatology life quality index score (MD -2.54, 95% CI -4.00, -1.07). There was a significantly higher incidence of adverse events in the benvitimod group compared to placebo (RR 1.98, 95% CI 1.73-2.27), while the risk was found to be non-significant for serious adverse events. Benvitimod is an effective treatment of psoriasis as compared to a placebo. However, more large-scale, high-quality trials are needed to comment on the safety of this drug.

A study to evaluate the impact of COVID-19 on Lifestyle of Medical students.

Background: Stressful situations are often linked with poor health and lifestyle behaviors (e.g., unhealthy diet, limited physical activity, poor sleep quality etc.). Subsequent to the nationwide lockdown in Pakistan due to COVID-19 pandemic, medical students experienced substantial lifestyle changes along with academic stresses. The goal of this study was to measure the impact that the COVID-19 lockdown had on lifestyle like sleep, physical activity and nutrition, substance abuse, dealing with finances, spirituality and family life, with respect to a sample of Pakistani medical students. Methods: This cross- sectional online study involving 1100 medical students (68.7% females) from five medical colleges in Pakistan, used self-administered questionnaire to evaluate the impact of pandemic related restrictions on lifestyle of medical students in Pakistan from August- September 2020. Parameters such as physical activity, sleep, nutrition, smoking and substance abuse, family life, finances, internet use and spirituality were studied. Results: Fifty-nine percent of medical students reported a significant effect of lockdown on their physical activity. Only 5.8% people clearly followed or adhered to a routine during the pandemic. About 54.6% students have found that physical activity and exercise significantly reduced their anxiety. More than half of respondents reported increase in screen time, weight gain and poor sleep with 3.1% of students stating an increased use of sleeping pills to fall asleep Another 18.3% students had an increased worry regarding COVID19 based on the information they received on internet. No significant increase in substance uses and alcohol use or family conflicts among students post pandemic was noted. Conclusion: Our findings underscore that COVID-19 pandemic has led to undesired changes in health and lifestyle habits of medical students, which may, to some extent, be responsible for higher negative impact. Hence it is important for medical colleges to start awareness campaigns to tackle challenges for medical students physical and emotional well-being.

Molnupiravir for the treatment of COVID-19 outpatients: An updated meta-analysis.

BACKGROUND: The majority of available data on molnupiravir come from an unvaccinated COVID-19 population. Therefore, we conducted this meta-analysis to integrate evidence from recent randomized controlled trials (RCTs) as well as observational studies stratified by vaccination status to determine the clinical efficacy and safety of molnupiravir in COVID-19 outpatients. METHODS: We searched PubMed, Embase, the Cochrane Library, medRxiv, and ClinicalTrials.gov from inception to November 2023. We conducted our meta-analysis using RevMan 5.4 with risk ratio (RR) as the effect measure. RESULTS: We included 8 RCTs and 5 observational studies in our meta-analysis. Molnupiravir reduced the risk of all-cause mortality (RR 0.28; 95% CI: 0.20-0.79, I2 = 0%) but did not decrease the hospitalization rate (RR 0.67; 95% CI: 0.45-1.00, I2 = 53%) in the overall population; in the immunized population, no benefits were observed. Molnupiravir lowered the rate of no recovery (RR 0.78; 95% CI: 0.76-0.81, I2 = 0%) and increased virological clearance at day 5 (RR 2.68; 95% CI: 1.94-4.22, I2 = 85%). There was no increase in the incidence of adverse events. CONCLUSIONS: Molnupiravir does not decrease mortality and hospitalization rates in immunized patients with COVID-19. However, it does shorten the disease course and increases the recovery rate. The use of molnupiravir will need to be considered on a case-by-case basis in the context of the prevailing social circumstances, the resource setting, drug costs, and the healthcare burden.

Perception of Neurosurgery as a Career Choice Among Early Career Doctors in Pakistan: A Nationwide Cross-Sectional Survey.

BACKGROUND: A low neurosurgeon-to-patient ratio persists in many developing nations including Pakistan. We aimed to investigate the perceptions of medical students regarding neurosurgery as a first step toward recognizing this problem and potentially suggesting ways to solve it. METHODS: A questionnaire was designed comprising 3 sections: 1) demographics, 2) possible challenges and perceptions regarding neurosurgery as a profession, and 3) general perceptions about neurosurgery. Statistical analysis was conducted, and a P value < 0.05 was considered significant. RESULTS: Of 387 responses received, 44.4% of male respondents and 50.6% of female respondents revealed intent to consider opting for neurosurgery as a profession. Regression analysis revealed inadequate dexterity (P = 0.001) and inability to carry out private practice (P = 0.002) were responsible for increased likelihood of opting out of neurosurgery by medical students. CONCLUSIONS: This study identified the perceptions that may influence the decision to pursue neurosurgical training among physicians early in their careers. Interventions including availability of day care facilities for children and introduction of curricula to promote neurosurgical knowledge in clinical training are expected to encourage the decision to pursue neurosurgery among medical students in Pakistan.

Gender Differences in Perception of Neurosurgery as a Career Choice in Pakistan: A Nationwide Cross-Sectional Survey.

BACKGROUND: A low neurosurgeon-to-patient ratio persists to be a problem in many developing nations including Pakistan. Concurrent gender disparities further exacerbate the challenges posed by the already limited workforce. An understanding of the perceptions of neurosurgery among female early career doctors is crucial in the evolution of the field in terms of both, workforce strength and inclusivity. METHODS: A cross-sectional study was conducted across public and private medical schools of Pakistan. A close-ended self-administered questionnaire was employed to assess subject-reported challenges and perceptions regarding neurosurgery. Statistical analysis was performed using SPSS version 28, and p< 0.05 was considered significant. The influence of these perceptions on the choice of neurosurgery as a career was determined by binary logistic regression analysis. RESULTS: Of the 387 responses received from over 45 institutions across the country, 55.6% were females and 44.4% were male respondents. Compared to men, women were more likely to opt out of neurosurgery due to fear of problems with parenting (p<0.001), absence of daycare facilities (p<0.001), lack of female role models (p=0.001), fear of gender discrimination (p<0.001), and the mental (p=0.04) and physical distress (p=0.008) associated with neurosurgery. Binary logistic regression revealed that these concerns were responsible for an increased likelihood of opting out of neurosurgery among female medical students and intern doctors. CONCLUSIONS: Significant differences exist in how male and female medical students perceive neurosurgery as a career choice. Interventions including availability of day care facilities for children, creation of inclusive workplace environment, and promotion of mentorship programs catering to women can help bridge this gap and contribute to evolution of the field of neurosurgery in the developing world.

International Neurosurgery: The Role for Collaboration.

The global death toll from lack of access to basic surgical care is three times as much as for tuberculosis, HIV and malaria combined. Patients dying of curable neurosurgical conditions solely because of inadequacy or absence of neurosurgical infrastructure is an issue deserving immediate attention and action. Global neurosurgery is an important step forward in this regard, under which different models of collaboration between HICs and LMICs aim to increase both the number of neurosurgeons as well the quality of neurosurgical care available in these countries through arranging surgical camps, providing neurosurgical training and education, and restructuring the health system in these countries in order to create an environment conducive to the provision of the highest form of neurosurgical care. Despite the many challenges faced by LMICs in furthering neurosurgery programs such as poor resource allocation, brain drain, turbulent socioeconomic conditions, limited training facilities, and population explosion, data now being reported from LMICs the world over, exemplifies the immense positive impact that collaborations have had over the last few decades in improving neurosurgical capacity and infrastructure. So far, conventional methods of collaboration (i.e. neurosurgical missions to LMICs and training of neurosurgeons in HICs) have been effective in progressively bringing about the desired change in LMICs. However, these methods have been limited by a finite funding, pushing the global neurosurgical community to look for alternatives such as online curricula, task shifting and sharing, and long distance mentor-mentee relationships. In this review, we aim to provide an update on the current state of neurosurgical collaborations and identify the barriers in the way of collaborations and what alternative models of collaboration might be used to overcome them..

Association of Parsonage-Turner syndrome with COVID-19 infection and vaccination: a systematic review.

OBJECTIVES: The exact etiology of Parsonage-Turner syndrome is unknown, but it is known to be preceded by infection, vaccination, or surgical intervention. In this review, we describe associations of Parsonage-Turner syndrome with COVID-19 infection and vaccination. METHODS: A systematic literature search was conducted using PubMed/MEDLINE, ScienceDirect, and Google Scholar. Microsoft Excel was used for data extraction and statistical analysis. The quality of case reports and case series was assessed using the Joanna Briggs Institute Critical Appraisal Tool. RESULTS: We selected 44 case reports and 10 case series, including 68 patients (32 post-vaccination and 36 with post-COVID-19 infection Parsonage-Turner syndrome). Middle-aged males were predominantly affected in both groups. The most frequently administered vaccine was Comirnaty (Pfizer) (53%). The mean latency was 11.7 days in the post-vaccination group and 20.3 days in the post-infection group. The most affected nerves in both groups were the axillary, suprascapular, and musculocutaneous nerves; and 78.1% and 38.9% of patients showed partial amelioration of their symptoms in the post-vaccination and post-infection groups, respectively. CONCLUSION: Post-vaccination Parsonage-Turner syndrome presents earlier than post-infection disease. Pain and sensorimotor deficits of the upper limb are common in both situations. Complete or partial recovery occurs in most cases.

Comparative efficacy and safety of tenecteplase and alteplase in acute ischemic stroke: A pairwise and network meta-analysis of randomized controlled trials.

BACKGROUND: Studies on tenecteplase have been yielding mixed results for several important outcomes at different doses, thus hampering objective guideline recommendations in acute ischemic stroke management. This meta-analysis stratifies doses in order to refine our interpretation of outcomes and quantify the benefits and harms of tenecteplase at different doses. METHODS: PubMed/MEDLINE, the Cochrane Library, and reference lists of the included articles were systematically searched. Several efficacy and safety outcomes were pooled and reported as risk ratios (RRs) with 95% confidence intervals (CIs). Network meta-analysis was used to find the optimal dose of tenecteplase. Meta-regression was run to investigate the impact of baseline NIHSS scores on functional outcomes and mortality. RESULTS: Ten randomized controlled trials with a total of 4140 patients were included. 2166 (52.32%) patients were enrolled in the tenecteplase group and 1974 (47.68%) in the alteplase group. Tenecteplase at 0.25 mg/kg dose demonstrated significant improvement in excellent functional outcome at 3 months (RR 1.14, 95% CI 1.04-1.26), and early neurological improvement (RR 1.53, 95% CI 1.03-2.26). There was no statistically significant difference between tenecteplase and alteplase in terms of good functional outcome, intracerebral hemorrhage (ICH), symptomatic intracerebral hemorrhage (sICH), and 90-day mortality at any dose. Meta-regression demonstrated superior tenecteplase efficacy with increasing stroke severity, however, the results were statistically nonsignificant. CONCLUSIONS: Tenecteplase at 0.25 mg/kg dose is more efficacious and at least as safe as alteplase for stroke thrombolysis. Newer analyses need to focus on direct comparison of tenecteplase doses and whether tenecteplase is efficacious at longer needle times.

Aseptic meningitis in Kikuchi-Fujimoto Disease - Rare manifestation of a rare disease.

Kikuchi-Fujimoto Disease (KFD) is a rare disease marked by necrotizing lymphadenitis, often presenting as unilateral cervical lymphadenopathy, along with various extranodal manifestations such as fever, skin rash, hepatosplenomegaly, and arthritis, etc. KFD is thought to be secondary to either a viral infection or an autoimmune process, however, evidence in favor of both models is scarce and non-definitive. We report a case of a young female who presented with persistent high-grade fever, bilateral cervical and axillary lymphadenopathy, and leukopenia. Excisional biopsy of affected lymph nodes revealed well-circumscribed foci of necrosis with karyorrhectic debris and scattered fibrin deposits characteristic of KFD. The patient was promptly initiated on non-steroidal anti-inflammatory drugs (NSAIDs), however, despite an early improvement in symptoms, the patient soon developed aseptic meningitis, a rare neurological complication of KFD. Intravenous followed by oral corticosteroid therapy reported a good prognosis, with no observable residual neurological deficits. Knowledge of the disease and its complications significantly helped in the avoidance of unnecessary investigations and a delay in treatment.

Solitary and multiple thyroid nodules as predictors of malignancy: a systematic review and meta-analysis.

BACKGROUND: The debate on whether or not there is a difference in the incidence of thyroid cancer between the patients with Solitary thyroid Nodule (STN) and Multinodular Goiter (MNG) has been constantly present for the last few decades. With newer studies yielding mixed results, it was imperative to systematically compile all available literature on the topic. METHODS: PubMed/MEDLINE, Cochrane Central, ScienceDirect, GoogleScholar, International Clinical Trials registry, and reference lists of the included articles were systematically searched for article retrieval. No filter was applied in terms of time, study design, language or country of publication. Rigorous screening as per PRISMA guidelines was undertaken by 2 independent reviewers in order to identify the articles that were most relevant to the topic. RESULTS: Twenty-two studies spanning from 1992 to 2018 were included in this analysis and encompassed 50,321 patients, 44.2% of which belonged to the STN subgroup and 55.37% to the MNG subgroup. MNG was found to be associated with a significantly lower risk of thyroid cancer (OR = 0.76; 95% CI 0.61-0.96) when compared with STN. Papillary carcinoma was the most frequently occurring carcinoma across both groups, followed by follicular and medullary carcinomas. A subgroup analysis was performed to assess the efficacy of the two most commonly employed diagnostic tools i.e. surgery and fine needle aspiration cytology (FNAC), however it yielded nonsignificant results, indicating a comparable usefulness of the two. Another subgroup analysis run on the basis of the presumed iodine status of the participants also yielded nonsignificant results. CONCLUSION: There is a higher incidence of thyroid cancer among patients of STN, however, given the low quality of existing evidence on the topic, it is crucial to conduct larger studies that can establish association with a greater precision.

Vitamin D supplementation for the prevention of total cancer incidence and mortality: An updated systematic review and meta-analysis.

Introduction: Previous randomized controlled trials (RCTs) and meta-analyses of RCTs evaluating vitamin D supplementation for the prevention of cancer incidence and mortality have found inconsistent results and no meta-analysis has assessed the quality of the evidence available. We, therefore, aimed to perform an updated meta-analysis by including recent large-scale RCTs and assessing the quality of the pooled evidence. Methods: We searched several databases and trial registers from inception to April 2022. We used a random-effects model to estimate pooled risk ratios (RRs) and 95% confidence intervals (CIs). We used the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) considerations to evaluate the certainty of evidence. Results: We included 13 RCTs in our study. Vitamin D supplementation had no effect on the risk of total cancer incidence (RR 0.99, 95% CI: 0.94-1.04; I 2 = 0%), total cancer mortality (RR 0.93, 95% CI: 0.84-1.03; I 2 = 24%) and total mortality (RR 0.92, 95% CI: 0.82-1.04; I 2 = 36%). The overall quality of evidence was high for all outcomes. Discussion: Vitamin D supplementation is ineffective in reducing total cancer incidence and mortality in largely vitamin D-replete older adult populations. Future research should be based on populations with a higher prevalence of vitamin D deficiency and should involve more extended follow-up periods. Study protocol: PROSPERO database, CRD42021285401.

The association of posterior reversible encephalopathy syndrome with COVID-19: A systematic review.

The rise in Coronavirus disease 2019 (COVID-19) cases is revealing its unique neurological manifestations. In light of the emerging evidence, a possible association with Posterior Reversible Encephalopathy Syndrome (PRES) is being consistently reported. We conducted a systematic literature search on four databases namely Pubmed/MEDLINE, Cochrane, Google Scholar, and Science Direct. After rigorous screening as per Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a total of 34 articles describing 56 cases were selected as a part of this review. The mean age of the patients was 56.6 ± 15.3 years. The most common clinical presentation of PRES was altered mental status (58.9%) followed by seizures (46.4%) and visual disturbances (23.2%) while hypertension and diabetes mellitus were the most commonly reported comorbidities. 91.1% of the cases reported Magnetic Resonance Imaging (MRI) or Computed Tomography (CT) findings suggestive of PRES in the brain. Symptomatic management was employed in most of the cases to control seizures and blood pressure, and 44 patients (78.5%) fully or partially recovered. The most likely underlying mechanism involves COVID-19 mediated cytokine storm syndrome that leads to endothelial damage and increased permeability of the cerebral vessels, thus causing the characteristic edema of PRES. High neuronal and glial cell expression of Angiotensin Converting Enzyme-2 (ACE-2) receptors also suggests the possibility of direct viral damage. Since timely diagnosis and treatment reports a good prognosis, it is vital for physicians and neurologists to be well-versed with this association.