Mavacamten: A Review of a Novel Therapeutic Approach for Hypertrophic Cardiomyopathy.

Hypertrophic Cardiomyopathy (HCM) is a heart disease that can cause left ventricular hypertrophy, arrhythmias, heart failure, and sudden cardiac death. Currently, pharmacological treatment is limited and ineffective. Mavacamten (CamzyosTM) is a cardiac myosin inhibitor developed as a therapeutic option to reduce myocardial contractility and restoration of myocardial function. The Food and Drug Administration (FDA) approved the use of Mavacamten in 2022 for HCM symptoms. Clinical studies have proven that Mavacamten can reduce Left Ventricular Outflow Tract (LVOT) involvement, cardiac hypercontraction, and hypertrophy. This review provides an overview of HCM, its pathophysiology, current treatments, synthesis of Mavacamten, and the clinical trials of Mavacamten.

Exploring Patient Safety Culture: A Study of Community Pharmacies in Karachi, Pakistan.

Background Community pharmacies are integral to the healthcare system, actively contributing to patient safety through accurate dispensing, education, collaboration, monitoring, and the implementation of safety protocols. Their accessibility and role as medication experts make them key partners in promoting positive health outcomes for individuals and communities. Objective The current study will evaluate the patient safety culture (PSC) among community pharmacies in Karachi, Pakistan. Additionally, this study will measure the association between patient safety culture in community pharmacies and the demographic characteristics of the pharmacy staff. Methods A cross-sectional survey of pharmacy staff was conducted using a survey instrument developed by the US Agency for Healthcare Research and Quality (AHRQ). Demographic variables and assessments of safety culture in pharmacies were studied. The data were analyzed using descriptive statistics. Results Among the 102 participants, positive responses ranged from 30% to 87.5%. The highest positive response was for the dimension "mistakes in communication" (86.3%), followed by "communication across shifts" (82.2%) and "communication openness" (81.7%). The dimensions "overall perceptions of patient safety" and "response to mistakes" had the lowest positive responses (56.0% and 60.9%, respectively). Furthermore, many staff did not regularly record the errors, even if they impacted the practices. Conclusion There was an overall unfavorable perception of patient safety culture among the surveyed pharmacies of Karachi, Pakistan. However, the communication dimensions showed the highest positive response. There is a strong need to improve the overall perception of patient safety among the staff and develop an optimistic response to mistakes.

Effects of muscle specific as compared to movement specific muscle energy technique in mechanical neck pain: A randomized controlled trial.

BACKGROUND: Muscle energy technique (MET) is found to be effective for the management of neck pain and in addition to the muscle specific approach, clinicians may also adopt movement specific approach for METs. However, the literature is deficient in terms of comparison of muscle specific and movement specific METs in the management of mechanical neck pain. OBJECTIVE: To compare the effects of muscle specific and movement specific METs in the management of mechanical neck pain. METHODS: A single blind parallel design randomized controlled trial was conducted on 66 participants with mechanical neck pain ranging from 40-80 mm on visual analogue scale (VAS), aged between 19-44 years with pain and limitation on cervical motion. Once included, the participants were randomly allocated to two groups, namely the muscle specific MET group and the movement specific MET group. Outcome measures included VAS, Neck Disability Index (NDI) and cervical range of motion (ROM). RESULTS: No significant differences (p> 0.05) were observed, neither immediately nor after 5 days, between muscle specific and movement specific MET in terms of VAS, NDI and ROM. However, a significant difference (p< 0.05) was observed in both groups in terms of pre- and post-analysis for all outcome variables. CONCLUSIONS: Both muscle specific and movement specific METs are effective in the management of mechanical neck pain, with no significant differences between the two treatment techniques.

Correlation Of Medial Longitudinal Arch Height With Postural Stability, Sensory Integration, Balance And Fall Risk Among Healthy Young Adults.

A cross-sectional analytical study was conducted on 165 healthy young adults. With pes rectus and pes planus to correlate the medial longitudinal arch height with postural stability, sensory integration of balance and fall risk. Persons with pes cavus, congenital foot anomalies other than pes planus, leg length discrepancies, recent history of trauma, lower limb amputations, history of serious foot injury, ligamentous laxity, or an active inflammatory disorder were excluded. Outcome measurements included normalised truncated navicular height (NTNH), Chippaux Smirak index (CSI), athletic single leg stability (ASLS) index, fall risk (FR) index, postural stability (PS), clinical test of sensory integration of balance (CTSIB), and balance error scoring system (BESS). Spearman correlation and Mann Whitney U test were used for data analysis. CSI and NTNH were noted to have no significant correlation (p<0.05) with PS, FR, CTSIB, ASLS and BESS among healthy young adults. Males were observed to have poorer balance and fall risk as compared to females.

Effect of academic stress, educational environment on academic performance & quality of life of medical & dental students; gauging the understanding of health care professionals on factors affecting stress: A mixed method study.

INTRODUCTION: Throughout their academic careers, medical and dental students face challenges that cause varying levels of stress, affecting their academic performance and quality of life (QoL). Our study aims to ascertain the effect of academic stress and the educational environment on the QoL and academic performance of medical and dental students, encompassing the perspectives of both students and healthcare professionals. METHODS: A mixed-method research was conducted from February to May 2022, comprising students from a medical and dental college in Pakistan. During Phase 1, the students participated in the cross-sectional survey and completed the WHO Quality of Life Scale (WHOQOL-BREF), Academic Stress Scale, and Dundee Ready Educational Environment Measure (DREEM) Inventory questionnaires. Academic performance was evaluated through last year's annual assessment results of the students. During Phase 2 of the study, interviews with healthcare professionals who had experience as the students' counsellors were conducted. RESULTS: The mean age of the sample (n = 440) was 22.24 ±1.4 years. The Cronbach Alpha reliability of the DREEM inventory was 0.877, that of the Academic Stress Scale was 0.939 and the WHOQOL scale was 0.895. More than half of the students (n = 230, 52.3%) reported better QoL and the majority perceived a positive educational environment (n = 323, 73.4%) and higher academic stress (n = 225, 51.1%). Males had significantly more academic stress (p<0.05). Those who perceived a positive educational environment and better QoL had better academic performance (p<0.05). Academic performance was positively and significantly correlated with QoL and academic stress (p = 0.000). In qualitative analysis, 112 codes were generated which converged into 5 themes: challenging educational environment, psychological need and support, individual differences, relationship and family life, and adjustment issues. CONCLUSION: Medical and dental students encounter a myriad of challenges, along with significant academic stress, which detrimentally affects their academic performance, despite perceiving a positive educational environment. Conversely, a better QoL is associated with improved academic performance.

ChatGPT: Transcending Language Limitations in Scientific Research Using Artificial Intelligence.

Health and scientific researchers in non-English speaking countries such as Pakistan, are not proficient in English, which limits their ability to communicate their ideas and findings to the international scientific community. ChatGPT is a large language model that can help non-native English speakers to write high-quality scientific papers much faster by assisting them in conveying their ideas in a clear and understandable manner, as well as avoiding common language errors. In fact, ChatGPT has already been used in publication of research papers, literature reviews, and editorials. However, it is imperative to recognise that ChatGPT is still in its early stages, thus, it is important to recognise its limitations. It is suggested that ChatGPT should be employed to complement writing and reviewing tasks but should not be relied on to generate original content or perform essential analysis, as it cannot replace human expertise, contextual knowledge, experience, and intelligence. Researchers should exercise caution and thoroughly scrutinise the generated text for accuracy and plagiarism before incorporating it into their work. Key Words: Artificial intelligence, ChatGPT, Health research, Scientific research.

Delayed vs early cardioversion in patients with paroxysmal atrial fibrillation: a population-based study (2015-2020).

Aim: There is limited data on clinical outcomes of delayed cardioversion (DCV) compared with early cardioversion (ECV) in paroxysmal atrial fibrillation (AF) patients. Methods: We utilized data from National Inpatient Sample (2015-2020) and propensity-score matched analysis to determine adjusted odds ratio (aOR) of major clinical outcomes, including 17,879 AF cases: 9725 and 8154 underwent ECV and DCV, respectively. Results: Compared with ECV, DCV was associated with higher odds of acute heart failure (AHF; aOR 1.79 [1.67-1.92]; p < 0.01), median length of stay (4 vs 2 days; p < 0.01) and cost of hospitalization ($33,410 vs $21,738; p < 0.01) with no significant difference in inpatient mortality and other cardiovascular and neurological outcomes. Conclusion: Compared with ECV, DCV was associated with more AHF and resource utilization.

Sex-Based Differences in Clinical Outcomes of Acute Coronary Syndrome Among Patients With Mediastinal Radiation Exposure: Insights From The National Inpatient Sample (2009-2020).

There is a paucity of data about the sex differences in acute coronary syndrome (ACS) outcomes in patients with prior mediastinal radiation. The National Inpatient Sample database from years 2009 to 2020 were queried for ACS hospitalizations of patients with prior mediastinal radiation. The primary outcome was MACCE (major cardiovascular events), and secondary outcomes included other clinical outcomes. A total of 23,385 hospitalizations for ACS with prior mediastinal radiation exposure ([15,904 (68.01%) females, and 7481 (31.99%) males]) were included in analysis. Males were slightly younger than females (median, age (70 [62-78] vs 72 [64-80]). Female patients with ACS had a higher burden of hypertension (80.82% vs 73.55%), diabetes mellitus (33% vs 28.35%), hyperlipidemia (66.09% vs 62.2%), obesity (17.02% vs 8.6%) however, males had a higher burden of peripheral vascular disease (18.29% vs 12.51%), congestive heart failure (41.8% vs 39.35%) and smoking (70.33% vs 46.92%). After propensity matching, primary outcome MACCE was higher in males (20.85% vs 13.29%, aOR: 1.80 95% CI (1.65-1.96), P < 0.0001) along with cardiogenic shock (8.74% vs 2.42%, aOR: 1.77 95% CI (1.55-2.02), P < 0.0001) and mechanical circulatory support use (aOR: 1.48 95% CI [1.29 -1.71], P < 0.0001). We observed no differences in the length of hospital stay, however total hospitalization cost was higher in males. This nationwide analysis showed significant disparities in outcomes among male and female ACS patients with prior mediastinal radiation history, with increasing trend in hospitalization for ACS among males and females but decreasing mortality among females.

Effect of Ramadan Fasting on Body Weight and Body Mass Index (BMI) in Public Sector Undergraduate Medical Students of Peshawar.

Objective: To determine the effects of fasting on weight and eventually on Body Mass Index (BMI) in medical students of a Public Sector Medical College. Methods: It was a prospective analytical study conducted in a Public Sector Medical College in Peshawar City from 28th March to 20th May 2022 (1443 Hijri). Convenience Sampling was used and 115 students (58 male and 57 female) of 1st Year MBBS to Final Year MBBS were enrolled. Four readings of weight were taken, one before, two during, and one after Ramadan. A well-structured self-administered questionnaire was used to inquire about basic demographic characteristics, sleep patterns during Ramadan and normal routine, and family history of obesity. The collected data were analyzed through SPSS software and a repeated measures ANOVA test was used for drawing statistical conclusions. Results: A slight increase in the mean weight was observed during the second week of Ramadan while a loss of 0.4 kg occurred during the fourth week of Ramadan, F (1, 81) = 1777.55; p < 0.0001. The same pattern was observed for BMI, F (1, 81) = 2705.18; p < 0.0001. However, the weight and the BMI were regained in two to three weeks following Ramadan. Conclusion: Ramadan offers a non-hazardous way of weight loss. Further studies across different geographical locations with larger sample sizes should be conducted to identify and quantify the association between weight and fasting and also to identify potential confounders.

Trends and in-hospital cardiac complications in patients with atrial fibrillation undergoing allogeneic stem cell transplant: A National Inpatient Sample analysis (2002-2019).

BACKGROUND: Cardiovascular comorbidities increase the risk of transplant-associated complications. However, the impact of atrial fibrillation (AF) as an independent risk factor remains limited. METHODS: The National Inpatient Sample (NIS) database was queried using the International Classification of Diseases codes to identify patients admitted for allogeneic stem cell transplant (ASCT). The patients were then subclassified into with and without AF. Subsequently, a multivariate logistic regression model was constructed to account for patient demographics, comorbidities, and hospital characteristics to evaluate the impact of AF on the primary outcome of interest: all-cause mortality, and secondary outcomes of interest that included common hospitalization complications. RESULTS: The data for 77 157 cases of ASCT were collected between 2002 and 2019. Among these 5086 (6.6%) cases had concurrent AF. Multivariate logistic regression revealed patients undergoing ASCT with AF had almost a three times higher risk of all-cause mortality (odds ratio = 2.99 [95% confidence interval: 2.73-3.28]; p < .01). AF patients also had a higher risk for cardiac arrest, cardiogenic shock, acute kidney injury, and need for hemodialysis (all p < .01). CONCLUSION: AF causes a higher risk of death and cardiovascular complications among patients undergoing ASCT. This signifies the importance of pretransplant consultation and optimization for cardiovascular comorbidities to improve hospitalization outcomes.

Development of myocarditis and pericarditis after COVID-19 vaccination in children and adolescents: A systematic review.

Myocarditis and pericarditis have been reported after COVID-19 vaccine administration in children and adolescents, raising the concern about their possible association with these vaccines. The objective was to explore the incidence, clinical presentation, and association of myocarditis and pericarditis with COVID-19 vaccines in children and adolescents. We conducted a systematic literature search on three databases, that is, Cochrane, MEDLINE/PubMed, and EMBASE from inception till March 2022. A total of three case reports, four case series, and six observational studies were included in the review. For case reports and case series, the mean age of the patients was 17.4 years, with 96.9% being male. Chest pain (n = 31, 93.9%), fever (n = 18, 54.5%), myalgias (n = 15, 45.4%) and headache (n = 9, 27.2%) were the most common presentations. Out of 33 patients, 32 (96.9%) of patients received Pfizer-BioNTech whereas only one (3.03%) received Moderna (mRNA 1273). Clinical investigations revealed ST elevation (n = 32, 97%), and elevated CRP (n = 9, 27.2%) and cardiac troponin (n = 29, 87.8%). The pooled incidence of myocarditis and pericarditis from observational studies was (0.00063%) and (0.000074%) %, respectively. Myocarditis and pericarditis in children and adolescents after the COVID-19 vaccines were more prevalent among males and more commonly observed after the second dose of Pfizer. Though the overall incidence was low, however, the clinicians should consider myocarditis and pericarditis as probable diagnosis when encountering young patients, with a history of vaccine administration, presenting with suggestive findings.

Extramedullary chronic lymphocytic leukemia disguised as urinary tract infection.

Extramedullary and nonlymphoid organ involvement in chronic lymphocytic leukemia (CLL) is exceedingly rare, with only a few cases of bladder infiltration reported to date. Here, we present a case of a 71-year-old man with advanced-stage CLL who presented with gross hematuria initially thought to be secondary to a urinary tract infection. However, a cystoscopy with biopsy confirmed the diagnosis of extramedullary CLL with bladder involvement. The patient was started on venetoclax with improvement in symptoms and no recurrence of hematuria.

Pheochromocytoma with fever and iron deficiency anemia.

Pheochromocytoma is a rare neuroendocrine tumor of the adrenal gland. With its heterogeneous clinical presentation, its diagnosis is frequently elusive. This case focuses on an unusual presentation of pheochromocytoma without the typical picture of hypertension, palpitations, and headaches. A few similar reports suggest a role of interleukin-6 production by the tumor in this presentation, indicating that not all symptoms and signs of the disease are due to catecholamine secretion.

Effects of glucosamine and chondroitin sulfate supplementation in addition to resistance exercise training and manual therapy in patients with knee osteoarthritis: A randomized controlled trial.

OBJECTIVE: To determine the added benefits of short-term glucosamine and chondroitin sulfate supplementation in combination with manual therapy and resistance exercise training in the management of knee osteoarthritis. METHODS: A parallel-design, double-blind randomised controlled trial was conducted from January to September 2020 at the Foundation University Institute of Rehabilitation Sciences and Fauji Foundation Hospital, Rawalpindi, Pakistan, and comprised of knee osteoarthritis patients of either gender having radiological evidence of grade III or less on Kellgren classification. The subjects were randomly allocated to active comparator group A and experimental group B. Both the groups received manual therapy and resistance exercise training, while group B additionally received glucosamine and chondroitin sulfate supplementation for 4 weeks. Study outcomes included pain, function, quality of life, range of motion, strength, fall risk, skeletal muscle mass, visceral fat area, body fat, intracellular water ratio, and segmental lean and fat mass. Data was analysed using SPSS 21. RESULTS: Of the 24 subjects, there were 12(50%) in each of the two groups. Each groups had 9(75%) males and 3(25%) females. In terms knee osteoarthritis grade, there was no significant difference between the groups (p=1.00). No significant differences were observed in any of the outcome measures neither at 2 weeks, nor at 4 weeks post-intervention between the groups (p>0.05) except for percentage change in segmental lean mass of the right leg at 2nd week and of the left leg at 4th week (p<0.05). CONCLUSIONS: Manual therapy and resistance exercise training are effective in the management of knee osteoarthritis, however, glucosamine and chondroitin sulfate supplementation for 4 weeks showed no additional benefits. Clinical Trial Number: NCT04654871. https://www.clinicaltrials.gov/ct2/show/NCT04654871.

Prevalence of urinary incontinence among young female adults.

A cross sectional survey was conducted in 2018-2019 to determine the prevalence of urinary incontinence among university going nulligravid young female adults in Rawalpindi/Islamabad, Pakistan. A total of 608 participants were included in the study via convenience sampling. Data was collected regarding demographic and personal information, in addition to Medical, Epidemiologic, and Social Aspects of Aging (MESA) Urinary Incontinence Questionnaire (UIQ). Independent t-test and One-way ANOVA were used for inter-group comparisons. Pearson and Spearman correlation was used to determine the relationship between variables. The overall prevalence of urinary incontinence was observed to be 193(31.7%) and of stress, urge and mixed incontinence was found to be 64(10.5%), 56(9.2%) and 73(12%) respectively. A significant difference (p<0.05) was observed in terms of MESA-UIQ stress incontinence and urge incontinence scores based on tobacco use, menstrual disorders, eating disorders and marital status.

Combined deep learning and molecular docking simulations approach identifies potentially effective FDA approved drugs for repurposing against SARS-CoV-2.

The ongoing pandemic of Coronavirus Disease 2019 (COVID-19) has posed a serious threat to global public health. Drug repurposing is a time-efficient approach to finding effective drugs against SARS-CoV-2 in this emergency. Here, we present a robust experimental design combining deep learning with molecular docking experiments to identify the most promising candidates from the list of FDA-approved drugs that can be repurposed to treat COVID-19. We have employed a deep learning-based Drug Target Interaction (DTI) model, called DeepDTA, with few improvements to predict drug-protein binding affinities, represented as KIBA scores, for 2440 FDA-approved and 8168 investigational drugs against 24 SARS-CoV-2 viral proteins. FDA-approved drugs with the highest KIBA scores were selected for molecular docking simulations. We ran around 50,000 docking simulations for 168 selected drugs against 285 total predicted and/or experimentally proven active sites of all 24 SARS-CoV-2 viral proteins. A list of 49 most promising FDA-approved drugs with the best consensus KIBA scores and binding affinity values against selected SARS-CoV-2 viral proteins was generated. Most importantly, 16 drugs including anidulafungin, velpatasvir, glecaprevir, rifapentine, flavin adenine dinucleotide (FAD), terlipressin, and selinexor demonstrated the highest predicted inhibitory potential against key SARS-CoV-2 viral proteins. We further measured the inhibitory activity of 5 compounds (rifapentine, velpatasvir, glecaprevir, anidulafungin, and FAD disodium) on SARS-CoV-2 PLpro using Ubiquitin-Rhodamine 110 Gly fluorescent intensity assay. The highest inhibition of PLpro activity was seen with rifapentine (IC50: 15.18 µM) and FAD disodium (IC50: 12.39 µM), the drugs with high predicted KIBA scores and binding affinities.