ABSTRACT
An increase in the incidence of melanoma has been observed in recent decades, which poses a significant challenge due to its poor prognosis in the advanced and metastatic stages. Previously, chemotherapy and high doses of interleukin-2 were available treatments for melanoma; however, they offered limited survival benefits and were associated with severe toxicities. The treatment of metastatic melanoma has been transformed by new developments in immunotherapy. Immune checkpoint inhibitors (ICIs), monoclonal antibodies that target cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4), programmed cell death protein 1 (PD-1) and its ligand, PDL-1, have emerged as promising therapeutic options. Commonly used ICIs, such as ipilimumab, nivolumab and pembrolizumab, have been found to be associated with an improved median overall survival, recurrence-free survival and response rates compared to traditional chemotherapies. Combination therapies involving different types of ICIs, such as anti-PD1 with anti-CTLA-4, have further enhanced the overall survival and response rates by targeting various phases of T-cell activation. Additionally, the development of novel biomarkers has facilitated the assessment of responses to ICI therapy, with tissue and serum-based prognostic and predictive biomarkers now available. The increased response observed with ICIs also provides potential for immune-related adverse effects on various organ systems. Further research is required to evaluate the efficacy and safety of various combinations of ICIs, while ongoing clinical trials explore the potential of newer ICIs. Concerns regarding the development of resistance to ICIs also warrant attention. The present review summarizes and discusses the advent of ICIs with a marked significant breakthrough in the treatment of metastatic melanoma, providing improved outcomes compared to traditional therapies.
ABSTRACT
Upadacitinib, an oral Janus kinase (JAK) inhibitor, is used to manage rheumatoid arthritis. The objective was to generate statistical evidence from the existing data for upadacitinib efficacy and safety in various treatment regimens with different dosages in active rheumatoid arthritis patients. We searched PubMed, Cochrane, and ClinicalTrials.gov using PRISMA guidelines, providing data on the efficacy and safety of upadacitinib versus placebo in rheumatoid arthritis. 20% improvement in the American College of Rheumatology (ACR20) score response at 12 weeks was the primary outcome measure. Safety in adverse events, infections, or hepatic dysfunction was considered. The Mantel-Haenszel formula with random effect was used for the pooled odds ratio (OR) at a 95% confidence interval (CI) for dichotomous data. Meta-analysis was performed using RevMan version 5.4. Statistical heterogeneity was reported using I2 statistics; I2 > 75% was considered significant heterogeneity. A P value of less than 0.05 was considered significant. Data from 3233 patients were included in the analysis. The use of upadacitinib was associated with increased rates of achieving an ACR20 response compared with placebo (pooled OR 3.71; 95% CI 3.26-4.23; p-value <0.00001). Compared to a placebo, a 12 mg twice daily dose had the greatest effect, followed by a 15 mg once daily dose. Compared to the placebo, the incidence of any adverse event (pooled OR 1.66; 95% CI 1.36-2.02; p-value 0.0001) and infection (pooled OR 1.46; 95% CI 1.23-1.74; p-value 0.001) was found to be significantly higher in upadacitinib. Other adverse events, such as hepatic disorders and herpes zoster infections, were not statistically significant (p-value> 0.05). Maximum adverse events were seen at 12 mg twice daily. Upadacitinib, 15 mg once daily in combination with Methotrexate, was the most efficacious treatment regimen and was not associated with a significant risk for treatment-related adverse events in rheumatoid arthritis patients.
ABSTRACT
Introduction: SARS-CoV-2 infection is associated with myocardial inflammation, new onset cardiomyopathy, and arrhythmias. Here, we describe the utilization of POCUS and management of concurrent new onset atrial tachycardia and heart failure with reduced ejection fraction (HfrEF) in a patient with SARS-CoV-2 infection. Presentation: An 80-year-old female with multiple medical problems presented with sudden onset of shortness of breath and cough. She tested positive for SARS-CoV-2. Initially, she was hypoxic on room air and her heart rhythm was sinus tachycardia. CT angiogram of the chest showed consolidation, pleural effusion, and absence of pulmonary embolism. Because of persistent tachycardia, repeat EKGs and POCUS were performed. Subsequent EKGs showed intermittent atrial tachycardia and sinus tachycardia. Initially, home beta blockers were continued on admission, and additional dosages were considered for rate control, but Cardiac POCUS revealed HfrEF and was subsequently confirmed by comprehensive cardiac echocardiogram, consistent with SARS-CoV-2 infection-related cardiomyopathy. Beta blockers were discontinued, and treatment with amiodarone and furosemide showed improvement in symptoms. The patient was discharged with oral amiodarone and supplemental oxygen. Additionally, once the patient's hemodynamics improved, oral carvedilol was also started as part of GDMT for HfrEF. Follow-up echocardiogram 4 months later showed recovery of systolic EF to 60%. Conclusion: It is essential to consider new onset HFrEF in the evaluation and management of new onset tachyarrhythmias since IV fluids and AV nodal blocking agents can be harmful in decompensated HFrEF. With the advent of POCUS, HFrEF can be quickly identified, and therapy can be tailored to that diagnosis.
ABSTRACT
CONTEXT: The Indian government is dispensing newer direct-acting antiviral (DAA) drugs, which may have impact on hepatitis C virus (HCV) patients' quality of life (QoL). AIMS: To evaluate different DAA regimens and impact on QoL in terms of quality-adjusted life year (QALY) in HCV patients and to measure cost-effectiveness. METHODS: This prospective, observational study was carried out on patients who were diagnosed with HCV. Recruited patients were followed up until 12-24 weeks. Patients were recruited following the selection criteria. Along with demographic and drug details, the regimens used were analyzed and evaluated for cost minimization, cost-effectiveness, and cost-utility analysis. For health quality check, the Chronic Liver Disease questionnaire (CLDQ) was used which was also used for QALY assessment. Data were entered into MS Excel 2016. Difference in between the regimens for total cost was done using unpaired t-test and ANOVA test using SPSS 25.0. Overall cost-effectiveness, cost minimization, cost utility and cost of illness analysis was also calculated. P < 0.05 was considered statistically significant. RESULTS: A total of 31 patients were enrolled. A total of five drugs, namely, sofosbuvir, daclatasvir, ribavirin, velpatasvir, and ledipasvir were widely used. Sofosbuvir was most common (46.25%)component of drug combination in our study. A total of five types of regimen were used according to the genotype of patients. With 44,260.13 ± 15,884.92 INR of the total drug cost, 70.97% of patients spent around 30,000-40,000 INR for the whole pharmacotherapy. The total indirect cost was 2768.39 ± 3916.13 INR with the total direct cost of 48,660.90 ± 15,356.39 INR. The total cost including direct as well as indirect cost spent during 6-month therapy by 61.29% of patients was 40,000-50,000 INR. Based on the CLDQ score, QoL was 64.1 ± 25. Regimen 2 (sofosbuvir + velpatasavir) stood out with the lowest cost. Regimen 5 (ribavirin [200 mg] + sofosbuvir [400 mg] + velpatasvir [100 mg]) was found to be the most cost-effective. Considering 1 life year with good health after treatment, QALY was 0.31. CONCLUSIONS: Ribavirin (200 mg) + sofosbuvir (400 mg) + velpatasvir (100 mg) was found to be the cost-effective and cost-saving regimen among DAAs.
