A Systematic Review on the Role of Βeta-Blockers in Reducing Cardiac Arrhythmias in Long QT Syndrome Subtypes 1-3.

Long QT syndrome (LQTS) is one of the most common inherited cardiac channelopathies with a prevalence of 1:2000. The condition can be congenital or acquired with 15 recognized genotypes; the most common subtypes are LQTS 1, 2, and 3 making up to 85%-90% of the cases. LQTS is characterized by delayed ventricular cardiomyocyte repolarization manifesting on the surface electrocardiogram (EKG) by a prolonged corrected QT (QTc) interval. The mainstay of treatment for this condition involves in part or combination medical therapy via ß-blockers as first-line (or other anti-arrhythmic), left cardiac sympathectomy, or implantable cardiac defibrillator placement. Given the high rate of adverse cardiac events (ACE) or sudden cardiac death (SCD) in this population of patients with this disease, this review seeks to highlight the genotype-specific treatment consensus in ß-blocker therapy of the most common subtypes. A database search of PubMed, PMC, and Medline was conducted to ascertain the most recent data in the last five years on the management of LQTS types 1-3 and the role of ß-blockers in reducing ACE in these types. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were adhered to in the study selection, and selected studies focused on humans, written in the English Language, and within the last five years of LQTS subtypes 1, 2, and 3. Eleven relevant studies were selected after considering inclusion criteria, exclusion criteria, and quality appraisal within the last five years, focusing on ß-blocker selection directed based on the subtypes of LQTS. Two meta-analyses, one cohort study, and eight reviews provided significant data that non-selective ß-blockers unequivocally are of benefit in these LQTS types. Summary of findings suggested nadolol followed by propranolol yields the best results in LQTS 1, while nadolol would yield the best effect in LQTS 2 and 3.

Untreated Depression During Pregnancy and Its Effect on Pregnancy Outcomes: A Systematic Review.

Depression is characterized by sad, irritated, or empty moods, as well as somatic and cognitive changes such as loss of concentration, anhedonia, hopelessness, loss of appetite, sleep disturbances, and suicidal ideation, all of which have a negative impact on an individual's ability to function. Depression that occurs during pregnancy is known as antenatal depression. The occurrence of depression during pregnancy and afterward is quite high. Women having a history of depression before pregnancy have a high probability of getting depression during pregnancy again. The purpose of the study is to review the effect of untreated depression during pregnancy on maternal and neonatal outcomes. The primary outcomes of this review were the identification of studies showing the relationship between untreated depression during the pregnancy indicated by depression measures and any associated adverse birth outcomes; specifically, low birth weight, small for gestational age, preterm birth, postpartum depression, and infant neurodevelopmental outcome. We reviewed 20 population-based contemporary cohort studies with a range of populations from 54 to 194,494, all of them representing the population of gestational age located in multiple jurisdictions. It was found that maternal depression during pregnancy has a positive association with preterm birth, small for gestational age, stillbirth, low birth weight, and maternal morbidity including perinatal complications, increased operative delivery, and postpartum depression. To prevent these adverse outcomes, depression should be screened, monitored, and managed appropriately keeping risk-benefit in consideration.

A Systematic Review of Fibromyalgia and Recent Advancements in Treatment: Is Medicinal Cannabis a New Hope?

Fibromyalgia syndrome (FMS) is a pain disorder characterized by chronic widespread pain, fatigue, and sleep disturbance, in the absence of any well-defined underlying organic disease. The exact pathophysiology and the mechanism which links different factors related to the disease is still unknown. Due to unknown precise pathogenesis, the coexistence of other diseases, and overlapping clinical features, FMS diagnosis may be laborious. Various treatment strategies are used, only a few Food and Drug Administration (FDA) approved, still we are facing challenges regarding effective treatment. Recently, medicinal cannabis has proven to be effective in chronic pain conditions such as osteoarthritis, neuropathic pain, and other non-cancer chronic pain. However, further research is needed about how the cannabinoid system works with the pain pathway. Using the fact that medicinal cannabis is effective in the treatment of chronic pain and certain rheumatic diseases, in this review, we aim to analyze the role of the cannabinoid system in fibromyalgia syndrome. We followed Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines in searching PubMed, MEDLINE (through PubMed), PubMed Central, and Google Scholar using keywords "fibromyalgia, chronic pain, cannabis, cannabinoids, pharmacotherapy, alternative therapy" and Medical Subject Heading (MeSH) words. After applying inclusion/exclusion criteria and checking for the quality assessment, 22 articles were retrieved and used for the analysis of the role of cannabis in the treatment of fibromyalgia. The two main compounds of cannabis with analgesic and anti-inflammatory properties are cannabidiol (CBD) and delta-9-tetrahydrocannabinol (THC), and their ratio determines the effect on various symptoms of FMS. We included studies regarding the use of cannabinoids in the treatment of fibromyalgia, investigating the use of nabilone, dronabinol (a synthetic analog of THC), Bedrocan (22.4 mg THC, <1 mg CBD), Bediol (13.4 mg THC, 17.8 mg CBD), and Bedrolite (18.4 mg CBD, <1 mg THC). In the era of the coronavirus disease 2019 (COVID-19) pandemic and opioid crisis, many adverse outcomes are observed in the patients suffering from FMS due to lack of any definitive treatment and promising outcomes from the known treatment options, which led to the need for effective and safer treatment alternatives. Although the studies reviewed in this article suggest that medical cannabis is a safe and effective treatment for fibromyalgia pain, several limitations regarding dosage, length of treatment, adverse effects, long-term follow-up, and dependence needs further investigation.

Psychoactive Substance Use among Second-Year and Third-Year Medical Students of a Medical College: A Descriptive Cross-sectional Study.

INTRODUCTION: Psychoactive substance use among medical students is common. This may not only pose a threat to their health and academic performance but may have medico-legal and ethical ramifications. The aim of this study was to find out the prevalence of six psychoactive substances (alcohol, tobacco, cannabis, cocaine, benzodiazepines, opioids) among second year and third year medical students. METHODS: A descriptive cross-sectional study was done in a medical college. Whole sampling was done and ethical approval was taken from the Institutional Review Committee (Reference Number: 54-074/075). The study was conducted from May 2018 to June 2018. A semi-structured self-administered questionnaire modified and adapted from World Health Organization's guidelines for student substance use survey was used to collect data from second year and third year medical students. Statistical Package for Social Sciences version 16.0 was used for analysis. Point estimate at 95% Confidence Interval was calculated along with frequency and proportion for binary data. RESULTS: Out of 226 total respondents, 95 (42.0%) (35.55- 48.45 at 95% Confidence Interval) reported current use of one or more psychoactive substances. Most frequently used substance was alcohol with current use prevalence of 87 (38.5%), followed by smoking 39 (17.3%) and cannabis 27 (11.9%). Cocaine, benzodiazepines and opioids were the least consumed substances with current use prevalence of 2 (0.9%) each. CONCLUSIONS: Almost half of the students were currently using one or more psychoactive substances which is concerning, and therefore strategies must be adopted to alleviate such use.

Depression, Anxiety, and Stress among First-year Medical Students in a Tertiary Care Hospital: A Descriptive Cross-sectional Study.

INTRODUCTION: Medical students are prone to develop stress, anxiety and depression owing to vastness of curriculum, hectic lifestyle, economic burden, and competitiveness of medical field. The study aims to find out the prevalence of depression, anxiety, and stress among first-year medical students. METHODS: A descriptive cross-sectional study was conducted among 91 first-year students of Bachelor of Medicine and Bachelor of Surgery enrolled in a tertiary care hospital using depression, anxiety, and stress-42 scale along with a questionnaire regarding sociodemographic and stressors for their problems. Whole sampling was done and the study was conducted between June and July 2018 after taking ethical approval from the Research and Institutional Review Committee (Reference Number: 57-074/075). RESULTS: The highest prevalence among undergraduate medical students was found to be anxiety 54 (59.3%), followed by stress 41 (45.1%) and depression 40 (44%). CONCLUSIONS: Almost half of the first-year medical students reported some level of depression, anxiety, or stress. It is important to implement programs in the early years of the medical school from the administrative level to help and identify students suffering from depression, anxiety, and stress.

Statins' Effect on Cognitive Outcome After Traumatic Brain Injury: A Systematic Review.

Traumatic brain injury (TBI), also known as the "Silent Epidemic," is a growing devastating global health problem estimated to affect millions of individuals yearly worldwide with little public recognition, leading to many individuals living with a TBI-related disability. TBI has been associated with up to five times increase in the risk of dementia among multiple neurologic complications compared with the general population. Several therapies, including statins, have been tried and showed promising benefits for TBI patients. In this systematic review, we evaluated the recent literature that tested the role of statins on neurological and cognitive outcomes such as Alzheimer's Disease and non-Alzheimer's dementia in survivors of TBI with various severities. We conducted a systematic search on PubMed, PubMed Central, MEDLINE, and Google Scholar. MeSH terms and keywords were used to search for full-text randomized clinical trials (RCTs), cross-sectional, case-control, cohort studies, systematic reviews, and animal studies published in English. Inclusion and exclusion criteria were applied, and the articles were subjected to quality appraisal by two reviewers. Our data search retrieved 4948 nonduplicate records. A total of 18 studies were included - nine human studies, and nine animal laboratory trials - after meeting inclusion, eligibility, and quality assessment criteria. Simvastatin was the most tested statin, and the oral route of administration was the most used. Eight human studies showed a significant neuroprotective effect and improvement in the cognitive outcomes, including dementia. Four randomized clinical trials with 296 patients showed that statins play a neuroprotective role and improve cognitive outcomes through different mechanisms, especially their anti-inflammatory effect; they were shown to lower tumor necrosis factor (TNF)-α and C-reactive protein (CRP) levels. Also, they decreased axonal injury and cortical thickness changes. In addition, four cohort studies compared a total of 867.953 patients. One study showed a decrease in mortality in statin-treated patients (p=0.05). Another study showed a reduction in the incidence of Alzheimer's disease and related dementias (RR, 0.77; 95% CI, 0.73-0.81), while one study showed a decreased risk of dementia after concussions by 6.13% (p=0.001). On the other hand, one cohort study showed no significant difference with the use of statins. In eight animal trials, statins showed a significant neuroprotective effect, improved cognitive outcomes, and neurological functions. Different molecular and cellular mechanisms were suggested, including anti-inflammatory effects, promoting angiogenesis, neurogenesis, increasing cerebral blood flow, neurite outgrowth, promoting the proliferation and differentiation of neural stem cells, and reducing axonal injury. On the contrary, one study showed no benefit and actual adverse effect on the cognitive outcome. Most of the studies showed promising neuroprotective effects of statins in TBI patients. Cognitive outcomes, especially dementia, were improved. However, the optimal therapeutic protocol is still unknown. Thus, statins are candidates for more advanced studies to test their efficacy in preventing cognitive decline in patients with TBI.

Efficacy and Safety of Intranasal Esketamine in Treatment-Resistant Depression in Adults: A Systematic Review.

Intranasal form of esketamine, the S-enantiomer of racemic ketamine, was approved by the US FDA in 2019 for treatment-resistant depression (TRD) in adults. Since intranasal esketamine is a newly approved drug with a novel mechanism of action, much still remains unknown in regard to its use in TRD. The objective of this study is to systematically review the latest existing evidence on intranasal esketamine, and provide a better insight into its safety and efficacy in TRD in adults. PubMed, MEDLINE (through PubMed), and Google Scholar were systematically searched from 2016 to 2021, using automation tools. After removal of duplicates and screening on the basis of title/abstract, eligibility criteria were applied and quality appraisal was done independently by two reviewers. A total of 10 studies were selected for the final review which included five clinical trials (three short-term trials, one withdrawal design relapse prevention study, and one long-term study), three post hoc studies, one case/non-case study, and one review article. Out of three short-term clinical trials, only one demonstrated a statistically significant difference between treatment with esketamine plus oral antidepressant (OAD) vs placebo plus OAD. The result of the relapse prevention study showed significantly delayed relapse of depressive symptoms in esketamine plus OAD arm when compared to placebo plus OAD arm. Similarly, the result of the long-term clinical trial showed that the improvement in depressive symptoms was found to be sustained in those using esketamine. The most common adverse effects of esketamine included nausea, dizziness, dissociation, headache, vertigo, somnolence, and dysgeusia (altered sense of taste); most were mild-moderate in severity. One case/non-case study reported rare adverse effects including panic attacks, mania, ataxia, akathisia, self-harm ideation, increased loquacity (talkativeness), and autoscopy. Intranasal esketamine has shown efficacy in reducing depressive symptoms in clinical trials, but the clinical meaningfulness of the treatment effect in the real-world population still needs to be explored. Although the safety profile of esketamine appears to be favorable in most clinical trials, some serious side effects are being reported to the FDA Adverse Event Reporting System, and therefore requires further investigation. More robust clinical trials, especially long-term randomized controlled trials are needed which can help provide a better assessment on the efficacy and safety of intranasal esketamine in the treatment of TRD.

Clinical Mortality Review of COVID-19 Patients at Sukraraj Tropical and Infectious Disease Hospital, Nepal; A Retrospective Study.

Coronavirus Disease 2019 (COVID-19) has challenged the health system worldwide, including the low and middle income countries like Nepal. In view of the rising number of infections and prediction of multiple waves of this disease, mortalities due to COVID-19 need to be critically analyzed so that every possible effort could be made to prevent COVID-19 related mortalities in future. Main aim of this research was to study about the mortalities due to COVID-19 at a tertiary level hospital, in Nepal. This was a retrospective, observational study that included all inpatients from Sukraraj Tropical and Infectious Disease Hospital, who were reverse transcriptase polymerase chain reaction positive for SARS-COV-2 and died during hospital stay from January 2020 till January 2021. Medical records of the patients were evaluated. Out of 860 total admissions in a year, there were 50 mortalities in the study center. Out of 50 mortalities, majority were males (76%) with male to female ratio of 3.17:1. Most were above 65 years of age (72%) and had two or more comorbidities (64%). The most common comorbidities among the patients who had died during hospital stay were hypertension (58%) followed by diabetes mellitus (50%) and chronic obstructive airway disease (24%). The median duration from the symptom onset to death was 18 days, ranged from the minimum of 2 days till maximum of 39 days. D-dimer was found to be >1 mg/L in 58% cases and ferritin was >500 ng/ml in 42% patients at presentation. A total of 42% patients had thrombocytopenia, 80% patients had lymphocytopenia and 60% had Neutrophil to Lymphocyte ratio >11.75 with the mean NLR of 18.38. Of total mortalities, 16% patients also showed microbiological evidence of secondary infection; Male gender, age more than 65 years, multiple comorbidities with lymphocytopenia, elevated Neutrophil lymphocyte ratio and elevated inflammatory markers were risk factors found in majority of mortalities in our study. These findings could be utilized for early triage and risk assessment in COVID-19 patients so that aggressive treatment strategies could be employed at the earliest to reduce mortalities due to COVID-19 in future.