Zuranolone and its role in treating major depressive disorder: a narrative review.

Major Depressive Disorder (MDD) is a mood disorder classified as a persistent depressive mood and loss of interest lasting for more than two weeks and accompanied by a list of symptoms outlined in the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) diagnostic criteria. MDD affects approximately 264 million people worldwide and is the most prevailing form of neuropsychiatric disorder. Owing to the probable hypothesized pathophysiology of MDD being an outcome of abnormalities in the amino acid neurotransmitter system, including glutamate (the primary excitatory neurotransmitter) and γ-aminobutyric acid (GABA), SAGE-217 (Zuranolone) is being evaluated as a possible therapeutic treatment for MDD. Zuranolone is a synthetic, neuroactive steroid (NAS) and positive allosteric modulator (PMA) of GABAA receptors, regulating both synaptic and extra-synaptic release of GABA. It is administered as a once-daily oral dose for 2 weeks due to its low-moderate clearance. A change in total HAM-D score from baseline was the primary end-point of all the trials. A phase II trial conducted to evaluate the efficacy and safety of Zuranolone (30 mg, once-daily dose), described a significant reduction in total HAM-D score at day 14 and reported the drug to be well tolerated with headache, dizziness, nausea, and somnolence as the most common adverse events (AE). Additional phase III trials were also conducted to evaluate similar outcomes, the interim topline results of which have been released. Consequently, this article attempts to briefly analyze the pharmacology of Zuranolone, review the available clinical data and outcomes regarding its use, and evaluate its place as a prospective novel therapy in the effective management of MDD.

Cholera outbreak in Balochistan amidst flash floods: an impending public health crisis.

Despite being the largest province in Pakistan due to inadequate and underdeveloped infrastructure, Balochistan has been the worst-inflicted region with biblical floods. Following these disastrous flash floods, a sudden rise in cholera cases was seen in the affected province. To overcome this public health crisis, the authorities must put in place a system to ensure food safety, an adequate supply of clean drinking water, and the provision of proper sanitation facilities for the locals.

Frequency of COVID-19 vaccine side effects and its associated factors among the vaccinated population of Pakistan: A cross-sectional study.

Background: Coronavirus disease 2019 (COVID-19) vaccine side effects have an important role in the hesitancy of the general population toward vaccine administration. Therefore, this study was conducted to document the COVID-19 vaccine side effects in our population. Materials and Methods: An online survey-based, cross-sectional study was carried out from September 1, 2021, to October 1, 2021, to document the side effects of the COVID-19 vaccine among the general public. The questionnaire included participants' sociodemographic data, type of vaccine, comorbidities, previous COVID-19 infection, and assessment of side effects reported by them. Results: The majority of the participants were <20 years of age (62.2%), females (74.9%), belonged to the educational sector (58.1%), residents of Sindh (65.7%), and were previously unaffected by COVID-19 infection (73.3%). Sinovac (38.7%) followed by Sinopharm (30.4%) and Moderna (18.4%) were administered more frequently. Commonly reported side effects were injection site pain (82%), myalgia (55%), headache (46%), fatigue/malaise (45%), and fever (41%). Vaccine side effects were more likely to be reported with the first dose as compared to the second dose. On regression analysis, factors associated with occurrence of side effects included younger age (odds ratio [OR]: 6.000 [2.065-17.431], p < 0.001), female gender (OR: 2.373 [1.146-4.914], p = 0.020), marital status (OR: 0.217 [0.085-0.556], p < 0.001), graduate level of education (OR: 0.353 [0.153-0.816], p = 0.015), and occupation being either retired, freelancers, or social workers (OR: 0.310 [0.106-0.909]), p = 0.033). Previous infection with COVID-19 (p = 0.458) and comorbidities were found unrelated (p = 0.707) to the occurrence of side effects. Conclusion: The overall prevalence of local side effects was quite higher than the systemic ones. Further large-scale studies on vaccine safety are required to strengthen public confidence in the vaccination drive.

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.

Role and Perspectives of Inflammation and C-Reactive Protein (CRP) in Psychosis: An Economic and Widespread Tool for Assessing the Disease.

Schizophrenia is a major psychotic disorder affecting nearly 23.6 million people globally and greatly impacting the cognitive and social functioning of individuals. Multiple risk factors, including genetic, environmental, and epigenetic factors have been identified. However, the exact mechanism by which some factors aid in the development of schizophrenia is still uncertain. Acute and/or long-standing inflammation has been implicated as both a cause and effect of schizophrenia. Heightened immune responses have been documented in large cohorts of individuals with schizophrenia. While not completely known, multiple hypotheses, such as disruption of the blood-brain barrier, alterations in the kynurenine/tryptophan pathway, and increased microglial activation, have been presented to correlate inflammation with schizophrenic symptoms. Measurement of C-reactive protein (CRP) is a commonly performed and inexpensive test on patients' serum to determine levels of systemic inflammation in the body. Multiple studies have reported an elevated CRP level in different stages of schizophrenia, indicating its potential to be used as a viable biomarker in the diagnosis and monitoring of schizophrenia along with assessing treatment response to conventional and non-conventional treatment regimens. This review aims to evaluate the role of inflammation, in general, and CRP, in particular, in the pathogenesis of schizophrenia and its potential significance in diagnostic, therapeutic, and preventative approaches towards schizophrenia and psychosis.

The dilemma of treating the infected versus the wounded: Gaza's healthcare system is choked.

Gaza has been facing persistent disturbance since the last 14 years. Even before the pandemic, Gaza faced a dire healthcare consequence with prevalent instability, lack of adequate medical resources, and limited health-related infrastructure. Gaza continued to struggle while responding to the pandemic as the other nearby countries. However, the challenges were compounded with the onset of the conflict that affected Gaza's infrastructure and displaced tens of thousands to make-shift shelters. The testing capacity of Gaza is alarmingly low that makes any outbreak difficult to document. Additionally, all medical centres have been affected by the ongoing conflict. These centres, if not directly impacted, are severely overwhelmed with those injured during the conflict, shifting focus and resources away from coronavirus. Vaccinations in Gaza cover only 1.9% of the population and a great number of unvaccinated people now may act as vectors of transmission in overcrowded shelters. Furthermore, non-availability of clean water to maintain hygienic conditions has heightened the risk of an explosive surge in cases. Hence, beyond the ceasefire, further steps need to be taken to strengthen Gazan response to COVID-19 pandemic.

Treating Postpartum Depression: What Do We Know about Brexanolone?

Postpartum depression (PPD) is defined as the onset of major depressive disorder in mothers, occurring during pregnancy or within 4 weeks post-delivery. With 7% of pregnancy-related death in the United States owing to mental health conditions, including PPD, and a global prevalence of 12%, PPD is a growing public health concern. In 2019, the Food and Drug Administration (FDA) approved brexanolone, an exogenous analog of allopregnanolone, as the first ever drug to be specifically indicated for treating patients with PPD. This approval was preceded by an open-label study and three randomized placebo-controlled trials, each assessing the safety, tolerability, and efficacy of brexanolone, using mean Hamilton Rating Scale for Depression (HAM-D) score reduction as the primary outcome. In each randomized controlled trial, the drug was administered as an intravenous infusion given over 60 h. Enrolled participants were followed up on days 7 and 30 to evaluate the sustained effect. A statistically significant reduction in mean HAM-D score compared to placebo was observed in all three studies, supporting brexanolone's use in treating moderate-to-severe PPD. Therefore, this article attempts to briefly review the pharmacology of brexanolone, evaluate the latest available clinical data and outcomes concerning its use, reevaluate its position as a 'breakthrough' in managing PPD, and review the cost-related barriers to its worldwide standardized use.

Internet and Pornography Use During the COVID-19 Pandemic: Presumed Impact and What Can Be Done.

The COVID-19 pandemic continues to cause an immense psychosocial strain worldwide. Excessive use of the internet during these psychologically trying times, fueled by physical isolation as a result of lockdowns, has translated into dysfunctional behaviors. A growing body of evidence suggests an unprecedented increase in internet use and consumption of online pornography during the pandemic, and possibly even directly caused by it. In this review, the authors report data from relevant sources to show the rise in pornography use during lockdowns in different countries worldwide. In addition to a brief overview of the neurobiology of internet addiction broadly and problematic online pornography use specifically, similarities with substance use disorders are explained. Further, the current status of the debate about defining diagnostic criteria is discussed. Finally, the review sheds light on the potential detrimental outcomes during the future post-pandemic "re-adaptation," while simultaneously offering preventative and management strategies for harm reduction. The authors conclude that foresightedness with utilizing existing tools and therapies and exercising appropriate amounts of caution could go a long way in addressing the challenges that lie ahead in the post-pandemic era.