Background: Cardiotoxicity is an important and a common complication of cancer chemotherapeutic drugs. It may not only be associated with significant morbidity and mortality but also often becomes a limiting factor in adequate anti-cancer treatment. Several pharmacological agents are being evaluated for their efficacy in preventing cardiotoxicity of the cancer drugs.

Material and methods: Ninety patients with hematological malignancies undergoing chemotherapy and/or autologous hematopoietic stem cell transplantation (HSCT) were recruited in this study and were randomized to receive a combination of enalapril and cardvedilol (intervention arm) or no intervention (control arm). Comprehensive echocardiography and cardiac magnetic resonance imaging (MRI) were performed at baseline and at 6 months after randomization. The primary efficacy endpoint was the absolute change from baseline in left ventricular ejection fraction (LVEF).

Results: The mean age of the study subjects was 50 ± 13 years. By the end of the 6 months, there was a significant fall in LVEF in controls (3.28% absolute reduction from baseline) but no change was seen in the intervention group. As a result, at 6 months, LVEF was significantly lower in the control group in comparison to the intervention group (an absolute difference of 3.1% by echocardiography and 3.4% by cardiac MRI, p = 0.035 and 0.09, respectively). The beneficial effect was seen almost exclusively in patients receiving chemotherapy alone (absolute difference in LVEF of 6.38% at 6 months, p = 0.025) and not in those undergoing HSCT (absolute difference of 1.01%, p = 0.56). In addition, compared to controls, patients in the intervention group had a lower incidence of the combined event of death or heart failure (6.7% vs. 22%, p = 0.036) and of death, heart failure, or a final LVEF <45% (6.7% vs. 24.4%, p = 0.02).

Conclusions: The present trial showed that a combination of enalapril and carvedilol might prevent cardiotoxicity in patients undergoing chemotherapy for hematological malignancies.

Enalapril and carvedilol for preventing chemotherapy-induced left ventricular systolic dysfunction in patients with malignant hemopathies. The OVERCOME trial (preventiOn of left Ventricular dysfunction with Enalapril and caRvedilol in patients submitted to intensive ChemOtherapy for the treatment of Malignant hEmopathies)

Introduction Patients with schizophrenia have an elevated mortality risk compared to the general population, with cardiovascular-related deaths being the leading cause. The role of clozapine use in the long-term mortality risk is unclear. While clozapine treatment may increase the risk for cardiovascular mortality, it may have protective effects regarding suicidal behavior. Methods We systematically searched EMBASE, MEDLINE, and PsycINFO and reviewed studies that used a long-term follow-up (ie, >52 weeks) and reported on mortality in adults diagnosed with schizophrenia-spectrum disorders who had received clozapine treatment. Results Altogether, 24 studies reported on 1327 deaths from any causes during 217691 patient years in patients treated with clozapine. The unadjusted mortality rate in 22 unique samples during a follow-up of 1.1-12.5 (median = 5.4) years was 6.7 (95% confidence interval [CI] = 5.4-7.9) per 1000 patient years. Long-term, crude mortality rate ratios were not significantly lower in patients ever treated with clozapine during follow-up, but significantly lower in patients continuously treated with clozapine compared to patients with other antipsychotics (mortality rate ratio = 0.56, 95% CI = 0.36-0.85, P-value = .007). Few studies reported on rates of long-term cause-specific mortality (suicide and ischemic heart disease), which showed no significant difference in patients using clozapine compared to patients using other antipsychotics. Statistical heterogeneity was high in all analyses. Discussion Continuous clozapine treatment in schizophrenia patients was associated with a significantly lower long-term all-cause mortality rate compared to other antipsychotic use. These findings, combined with the known efficacy of clozapine, give reason to re-evaluate the hesitancy to prescribe clozapine in regular care settings. Trial registration PROSPERO CRD42017069390.

/pdf/clozapine-and-long-term-mortality-risk-in-patients-with-o0j7y99ss7.pdf

Clozapine and Long-Term Mortality Risk in Patients With Schizophrenia: A Systematic Review and Meta-analysis of Studies Lasting 1.1-12.5 Years.

Clozapine, a dibenzodiazepine developed in 1961, is a multireceptorial atypical antipsychotic approved for the treatment of resistant schizophrenia. Since its introduction, it has remained the drug of choice in treatment-resistant schizophrenia, despite a wide range of adverse effects, as it is a very effective drug in everyday clinical practice. However, clozapine is not considered as a top-of-the-line treatment because it may often be difficult for some patients to tolerate as some adverse effects can be particularly bothersome (i.e. sedation, weight gain, sialorrhea etc.) and it has some other potentially dangerous and life-threatening side effects (i.e. myocarditis, seizures, agranulocytosis or granulocytopenia, gastrointestinal hypomotility etc.). As poor treatment adherence in patients with resistant schizophrenia may increase the risk of a psychotic relapse, which may further lead to impaired social and cognitive functioning, psychiatric hospitalizations and increased treatment costs, clozapine adverse effects are a common reason for discontinuing this medication. Therefore, every effort should be made to monitor and minimize these adverse effects in order to improve their early detection and management. The aim of this paper is to briefly summarize and provide an update on major clozapine adverse effects, especially focusing on those that are severe and potentially life threatening, even if most of the latter are relatively uncommon.

https://journals.sagepub.com/doi/pdf/10.1177/2042098618756261

Safety of antipsychotics for the treatment of schizophrenia: a focus on the adverse effects of clozapine:

Importance
Acute myocarditis, defined as a sudden inflammatory injury to the myocardium, affects approximately 4 to 14 people per 100 000 each year globally and is associated with a mortality rate of approximately 1% to 7%.


Observations
The most common causes of myocarditis are viruses, such as influenza and coronavirus; systemic autoimmune disorders, such as systemic lupus erythematosus; drugs, such as immune checkpoint inhibitors; and vaccines, including smallpox and mRNA COVID-19 vaccines. Approximately 82% to 95% of adult patients with acute myocarditis present with chest pain, while 19% to 49% present with dyspnea, and 5% to 7% with syncope. The diagnosis of myocarditis can be suggested by presenting symptoms, elevated biomarkers such as troponins, electrocardiographic changes of ST segments, and echocardiographic wall motion abnormalities or wall thickening. Cardiac magnetic resonance imaging or endomyocardial biopsy are required for definitive diagnosis. Treatment depends on acuity, severity, clinical presentation, and etiology. Approximately 75% of patients admitted with myocarditis have an uncomplicated course, with a mortality rate of approximately 0%. In contrast, acute myocarditis that is complicated by acute heart failure or ventricular arrhythmias is associated with a 12% rate of either in-hospital mortality or need for heart transplant. Approximately 2% to 9% of patients have hemodynamic instability, characterized by inability to maintain adequate end-organ perfusion, and require inotropic agents, or mechanical circulatory devices, such as extracorporeal life support, to facilitate functional recovery. These patients have an approximately 28% rate of mortality or heart transplant at 60 days. Immunosuppression (eg, corticosteroids) is appropriate for patients who have myocarditis characterized by eosinophilic or giant cell myocardial infiltrations or due to systemic autoimmune disorders. However, the specific immune cells that should be targeted to improve outcomes in patients with myocarditis remain unclear.


Conclusions and Relevance
Acute myocarditis affects approximately 4 to 14 per 100 000 people per year. First-line therapy depends on acuity, severity, clinical presentation, and etiology and includes supportive care. While corticosteroids are often used for specific forms of myocarditis (eg, eosinophilic or giant cell infiltrations), this practice is based on anecdotal evidence, and randomized clinical trials of optimal therapeutic interventions for acute myocarditis are needed.

Diagnosis and Treatment of Acute Myocarditis: A Review.

Background:Clozapine is the most effective medication for treatment refractory schizophrenia, but is associated with cardiac adverse drug reactions. Myocarditis and cardiomyopathy are the most seri...

Systematic review and meta-analysis of rates of clozapine-associated myocarditis and cardiomyopathy.

Background
Anthracyclines are commonly used chemotherapeutic medications. In the current analysis we evaluated all-cause mortality and incidence, timing and response to medical therapy of anthracycline cardiotoxicity.

Methods
Left ventricular ejection fraction (LVEF) was serially assessed using gated heart pool scan/echocardiography in patients receiving anthracycline based chemotherapy from January 2009 to December 2014.

Results
A total of 1204 patients were administered anthracyclines during the study period. During a median follow up of 32 (IQR: 15 – 58) months, all-cause mortality was 38% (n = 463) with the incidence of cardiotoxicity 10.2% (n = 123). Only 15.4% (n = 19) patients required heart failure hospitalization with 48% (n = 59) of patients commenced on beta blockade therapy and/or angiotensin converting enzyme inhibitors. The majority of patients (73.2%, n = 90) experienced cardiotoxicity within 1 year of anthracycline initiation. The proportion of patients with complete, partial and no LVEF recovery were 16.3% (n = 20), 29.3% (n = 36) and 54.4% (n = 67) respectively. Mortality was higher in the cardiotoxicity group (49% vs 37%, p < 0.01). History of coronary artery disease, leukaemia, idarubicin use and high cumulative anthracycline dose were predictors of cardiotoxicity.

Conclusions
Cardiotoxicity after anthracycline use predictably occurs within first year of therapy and is dose related, with variable degrees of recovery. While the need for hospitalisation for heart failure was uncommon, medical therapy appears underutilised, suggesting there may be a role for improved surveillance and early initiation of treatment.

Incidence, time of occurrence and response to heart failure therapy in patients with anthracycline cardiotoxicity

Methacrylate Powder Dressing in Traumatic, Pressure sore, Venous ulcers and Burn Wounds Healing

The human brain is not only one of the most important organs in the human body, but it is also one of the most convoluted and is still not fully understood.As the process of aging continues, the brain goes through a number of changes as a whole, including both physical and histological shifts Study Design: Research utilizing a cross-sectional prospective study design Study Duration: January 2021 and continuing through November 2021. Place of Study: Allama Iqbal memorial teaching hospital khawaja Muhammad safdar medical college Sialkot Methodology: The participants in the study were given a standardized questionnaire to complete, in addition to a variety of checklists, in order to complete their assessments. The data was transferred over to SPSS version 23 for additional analysis. In order to investigate the nature of the connection that exists between age and gender, in addition to the height and diameter of the third ventricle, we turned to Pearson's product-moment correlation coefficient. Result: The analysis of variance (ANOVA), which calculates the mean difference between age groups, was performed. The p-value needs to be lower than 0.05 in order for the experiment to be considered statistically significant. The mean height of the third ventricle in males was 13.57 millimeters and the mean height in females was 13.52 millimeters. The mean diameter of the third ventricle in males was 2.98 millimeters and the mean diameter in females was 2.56 millimeters. When the size of the third ventricle in males was compared to that of the third ventricle in females, it was discovered that the size of the third ventricle in males is greater than that of the third ventricle in females. Keywords: CT Scan, ventricles dimensions, hydrocephalus, schizophrenia, psychotic disorders

CT Scan Study of Third Ventricles Dimensions in Normal Population

Background and objective: Low back pain is common in the elderly due to adaptive changes to stress and osteoporosis of the lumbar spine. Skeletal geometry varies in different population groups. Objective of this study was to record reference values of morphometric data of lumbar spine in normal adult male and female subjects of Punjab. Study design: Cross-sectional population study Material and methods: Anterior and central height and concavity index for each vertebra were measured and calculated from radiographs. Anterior and posterior height and anteroposterior diameter were measured for each disc and wedge index was calculated. Results: All parameters were significantly larger in the males as compared to the females. Significant difference was found in the anterior height of the intervertebral discs at L1-2 to L4-5 while it was insignificant at L5-S1. Posterior height of discs was significantly larger in the male group at L1-2 to L3-4. Wedge index (WI) for discs was relatively larger in the female group. Conclusion: The study has provided some reference values of measurements of lumbar spine in adult male and female population of Punjab which may be valuable for better assessments of morphological changes by the clinician and for further research in this area. Keywords: Lumbar vertebrae, intervertebral disc, morphometry, concavity index, wedge index, lumbar spine

Lumbar Vertebral Body and Disc Morphometry in Punjab

Objective: To compare the efficacy of Tazarotene 0.1% cream versus Clindamycin 1% gel in treating acne vulgaris. 
Study Design: Quasi-experimental study. 
Place and Duration of the Study: Dermatology Department, Pak Emirates Military Hospital, Rawalpindi Pakistan, from Jan to Jul 2018. 
Methodology: One hundred and fifty-four patients of both genders who had moderate acne vulgaris for more than four weeks were divided into two Groups. In both Groups, patients applied one-fourth fingertip unit of Tazarotene 0.1% cream in the evening once daily and Clindamycin 1% gel over the affected area in the morning once daily for 12 weeks. The Global Acne Grading System Score (GAGS score) was used for severity and efficacy assessment. 
Results: The majority of the patients belonged to 13-25 years of age, i.e., 61(79.2%) and 54(70.1%) in Group-A (Tazarotene 0.1% cream) and Group-B (Clindamycin 1% gel), respectively. The efficacy of topical Tazarotene cream (0.1%) was better than topical Clindamycin 1% gel, and the difference was statistically significant with a p-value less than 0.01. GAGS score <10 was observed in 54.5% and 33.8% of patients in Group-A and Group-B, respectively. 
Conclusion: Topical Tazarotene cream (0.1%) was more effective than topical Clindamycin 1% gel in treating acne vulgaris.

https://www.pafmj.org/index.php/PAFMJ/article/download/6764/4354

Comparison of the Efficacy of Tazarotene 0.1% Cream Versus Clindamycin 1% Gel in the Treatment of Acne Vulgaris

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