Analyzing safety and effectiveness of Mavacamten in comparison with placebo for managing hypertrophic cardiomyopathy: a systemic review and meta-analysis.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is a hereditary myocardial disorder, often due to sarcomere gene mutations, characterized by the left ventricular hypertrophy. Current treatments offer symptomatic relief but lack specificity. Mavacamten, an allosteric inhibitor, has shown significant improvements in HCM patients in trials, reducing the requirement for invasive treatments. This meta-analysis assesses Mavacamten's efficacy and safety as a targeted HCM intervention. METHODS: This study examined four randomized controlled trials comparing Mavacamten to placebo in HCM patients. Each trial had a unique primary endpoint, and secondary outcomes included improvements in NYHA-FC, eligibility for septal reduction therapy (SRT) or undergoing it, adverse events (serious and treatment-related), atrial fibrillation, and non-sustained ventricular tachycardia. Statistical analysis involved calculating risk ratios (RRs) and assessing heterogeneity. RESULTS: The four included studies showed minimal risk of bias and involved 503 patients with HCM (273 Mavacamten and 230 placebo). Mavacamten significantly increased the primary endpoint (RR 2.15, 95% CI 1.20-3.86, P = 0.01) and ≥ 1 NYHA-FC class (RR 2.21, 95% CI 1.48-3.3, P = 0.0001). Mavacamten group had lower rates of SRT compared to those receiving placebo (RR, 0.30, 95% CI 0.22-0.40; P < 0.00001). No significant differences existed in rates adverse events between the Mavacamten and placebo groups. CONCLUSIONS: Our study suggests that Mavacamten may have therapeutic benefits for HCM patients, as indicated by its positive impact on certain endpoints. Further research with larger samples, longer follow-up, and comprehensive analysis is needed to understand Mavacamten's safety and efficacy in HCM patients.

Efficacy of an mHealth Behavior Change Intervention for Promoting Physical Activity in the Workplace: Randomized Controlled Trial.

BACKGROUND: Insufficient physical activity (PA) is a well-established risk factor for several noncommunicable diseases such as cardiovascular diseases, cancer, diabetes, depression, and dementia. The World Health Organization (WHO) advises that individuals engage in 150 minutes of moderate PA per week or 75 minutes of intense PA per week. According to the WHO's latest report, 23% of adults fail to meet the minimum recommended level of PA. The percentage was even higher in a recent global study that showed 27% of adults were insufficiently active and reported a 5% increase in the prevalence trend of insufficient PA between 2001 and 2016. The study also showed the rate of insufficient PA among countries varied significantly. For instance, it was estimated that 40% were insufficiently active in the United States, and the percentage was even higher in Saudi Arabia (more than 50%). Governments are actively developing policies and methods to successfully establish a PA-inducing environment that encourages a healthy lifestyle in order to address the global steady decline in PA. OBJECTIVE: The purpose of this study was to determine the effectiveness of mobile health (mHealth) interventions, particularly SMS text messaging interventions, to improve PA and decrease BMI in healthy adults in the workplace. METHODS: In this parallel, 2-arm randomized controlled trial, healthy adults (N=327) were randomized to receive an mHealth intervention (tailored text messages combined with self-monitoring (intervention; n=166) or no intervention (control; n=161). Adults who were fully employed in an academic institution and had limited PA during working hours were recruited for the study. Outcomes, such as PA and BMI, were assessed at baseline and 3 months later. RESULTS: Results showed significant improvement in PA levels (weekly step counts) in the intervention group (ß=1097, 95% CI 922-1272, P<.001). There was also a significant reduction in BMI (ß=0.60, 95% CI 0.50-0.69, P<.001). CONCLUSIONS: Combining tailored text messages and self-monitoring interventions to improve PA and lower BMI was significantly effective and has the potential to leverage current methods to improve wellness among the public.

Smoking cessation and risk of type 2 diabetes.

Risk of type 2 diabetes mellitus (T2DM) is higher in tobacco smokers compared to non-smokers. The risk declines after smoking cessation. However, ex-smokers are also more prone to the metabolic syndrome. The question thus is, whether ex-smokers could temporarily have a higher risk of T2DM than current smokers. The available studies on this topic are not in agreement in their conclusions, as most of them also primarily do not compare ex-smokers to current smokers, but to non-smokers. However, based on the available studies, it rather seems the risk of T2DM is temporarily higher after smoking cessation. The higher risk of T2DM seems to be enhanced by weight gain that typically occurs first years after smoking cessation without intervention. Therefore, smoking cessation in patients who are in an increased risk of T2DM should be accompanied by T2DM preventative measures (lifestyle modification, weight monitoring and recommendation of pharmacotherapy of tobacco addiction to lower the risk of weight gain) and more frequent checks of blood glucose level to ensure early T2DM detection.

Inflammatory markers in type 2 diabetes with vs. without cognitive impairment; a systematic review and meta-analysis.

People with type 2 diabetes mellitus (T2DM) are at increased risk of mild cognitive impairment and dementia. Systemic inflammation has been proposed as a common risk factor. This study aimed to summarize the clinical data pertaining to peripheral blood inflammatory markers. We identified original peer-reviewed articles reporting blood inflammatory marker concentrations in groups of people with a T2DM diagnosis who have cognitive impairment (CI; including mild cognitive impairment, Alzheimer's disease, vascular cognitive impairment) vs. normal cognition (NC). Between-group standardized mean differences (SMD) were summarized in random effects meta-analyses. From 2108 records, data were combined quantitatively from 40 studies. Concentrations of interleukin-6 (IL-6; NCI/NNC = 934/3154, SMD 0.74 95% confidence interval [0.07, 1.42], Z5 = 2.15, p = 0.03; I2 = 98.08%), C-reactive protein (CRP; NCI/NNC = 1610/4363, SMD 0.80 [0.50, 1.11], Z14 = 5.25, p < 0.01; I2 = 94.59%), soluble vascular cell adhesion molecule-1 (sVCAM-1; NCI/NNC = 104/1063, SMD 1.64 95% confidence interval [0.21, 3.07], Z2 = 2.25, p = 0.02; I2 = 95.19%), and advanced glycation end products (AGEs; NCI/NNC = 227/317, SMD 0.84 95% confidence interval [0.41, 1.27], Z2 = 3.82, p < 0.01; I2 = 81.07%) were higher among CI groups compared to NC. Brain derived neurotropic factor (BDNF) concentrations were significantly lower in CI compared to NC (NCI/NNC = 848/2063, SMD -0.67 95% confidence interval [-0.99, -0.35], Z3 = -4.09, p < 0.01; I2 = 89.20%). Cognitive impairment among people with T2DM was associated with systemic inflammation and lower BDNF concentrations. These inflammatory characteristics support an increased inflammatory-vascular interaction associated with cognitive impairment in T2DM. PROSPERO (CRD42020188625).

Impact of redo sternotomy on proximal aortic repair: Does previous aortic repair affect outcomes?

PURPOSE: Proximal aortic repair (AoR) in the setting of previous sternotomy may be associated with greater risk than primary repair. Our objective was to determine whether redo sternotomy increases the risk of adverse outcomes following proximal aortic surgery. METHODS: We reviewed all proximal AoRs from 1991 to 2014. Outcomes were compared between first-time AoR (non-redo = 1305) and redo AoRs, which were further classified into 3 categories: (1) previous acute type A aortic dissection (AAD) repair (redo-AAD = 146, 8.3%); (2) previous proximal aneurysm repair (redo-aneurysm = 165, 9.4%); and (3) previous cardiac (non-aortic) sternotomy (redo-cardiac = 145, 8.2%). Data were analyzed by contingency tables and multiple regression. RESULTS: In total, 456 of 1761 (25.9%) proximal AoRs had redo sternotomy. Aortic redos (redo-AAD and redo-cardiac) had significantly more connective tissue disorders (P < .001). On presentation, AAD was least common in aortic redos followed by cardiac redos (redo-cardiac) versus non-redos (5% vs 28% vs 31%, P < .001). At reoperation, 190 underwent ascending + hemiarch (21% redo-AAD, 50% redo-aneurysm, 53% redo-cardiac), 140 total arch (64% redo-AAD, 15% redo-aneurysm, 15% redo-cardiac), 110 elephant trunk (52% redo-AAD, 12% redo-aneurysm, 11% redo-cardiac), 159 AVR (36% redo-AAD, 42% redo-aneurysm, 25% redo-cardiac), and 100 aortic root (34% redo-AAD, 22% redo-aneurysm, 10% redo-cardiac). Except for pulmonary, redo sternotomy did not increase risk of postoperative complications. Thirty-day mortality after redo sternotomy was 14%-the greatest among cardiac redos. Over a median follow-up of 13 years, non-redos had significantly greater long-term survival (P < .001). Coronary artery disease was a significant predictor of mortality (P < .001). After adjustment for coronary artery disease, cardiac redos had the greatest long-term mortality risk (hazard ratio, 1.43, P < .005). Previous AoR did not significantly add risk above redo sternotomy alone (P = .734). CONCLUSIONS: Redo sternotomy is associated with increased risk for short- and long-term mortality after proximal aortic repair. Despite need for extensive repair, previous proximal aortic (for aneurysm or AAD) repair did not add further risk above that attributable to redo sternotomy.

Perceptions and Practices towards Medication Non-Adherence among Hypertensive Patients: An Observational Study.

Background The present study broadly evaluates the adherence to pharmacotherapy, perceptions, and practices among ambulatory hypertensive patients attending a cardiac institution in Karachi, Pakistan. Methods A cross-sectional, single-center study was conducted at the National Institute of Cardiovascular Diseases Karachi, Pakistan. The study continued from 4 July 2019 to 3 September 2019. A total of 200 patients with a primary diagnosis of hypertension (HTN) were recruited for the study. The data was collected through a questionnaire based on a nine-item modified adherence predictor scale to assess medication adherence. Along with the demographic details patients smoking status, history of comorbidities and past complications were noted. Results It was found that the mean age of the study population was 56.45±12.36 years. A total of 62.5% of patients were taking medication daily while 15.5% were consuming medications intermittently and only 6.5% patients were not adherent at all. Around 35% patients preferred follow-up visits once in a month. Besides this, 35.5% patients never monitored their blood pressure while more than half of the studied population believed that their BP has mostly been controlled and skipped the prescribed medication. Conclusion The study indicated that the perception and awareness among the hypertensive patients regarding their medical condition are suboptimal. Concerted strategies like health education program and campaigns must be launched in order to help the sufferers.

Pyrolysis, kinetics analysis, thermodynamics parameters and reaction mechanism of Typha latifolia to evaluate its bioenergy potential.

This work was focused on understanding the pyrolysis of Typha latifolia. Kinetics, thermodynamics parameters and pyrolysis reaction mechanism were studied using thermogravimetric data. Based on activation energies and conversion points, two regions of pyrolysis were established. Region-I occurred between the conversion rate 0.1-0.4 with peak temperatures 538K, 555K, 556K at the heating rates of 10Kmin-1, 30Kmin-1, and 50Kmin-1, respectively. Similarly, the Region-II occurred between 0.4 and 0.8 with peak temperatures of 606K, 621K, 623K at same heating rates. The best model was diffusion mechanism in Region-I. In Region-II, the reaction order was shown to be 2nd and 3rd. The values of activation energy calculated using FWO and KAS methods (134-204kJmol-1) remained same in both regions reflecting that the best reaction mechanism was predicted. Kinetics and thermodynamic parameters including E, ΔH, ΔS, ΔG shown that T. latifolia biomass is a remarkable feedstock for bioenergy.

Role of Endoplasmic Reticulum Stress, Autophagy, and Inflammation in Cardiovascular Disease.

Cardiovascular diseases are a class of heart or blood vessels diseases, which are now considered to be the leading cause of death globally. A number of recent studies have reported key roles for inflammation in the progression of diseased vessels and systematic heart failure. In particular, endoplasmic reticulum (ER) stress, which is mechanistically implicated in inflammation and autophagy, has now been associated with pathophysiological states in the cardiovascular system. Autophagy has also been identified as an important process in the progression of multiple cardiovascular diseases such as in atherosclerosis plaque progression and ischemia and/or reperfusion. In light of the above, it has been proposed that a link between inflammation, autophagy, and ER stress may exist that contribute to diseases of the heart and its supporting vessels. This review highlights current knowledge on the cross talk between these three biological processes, and the potential of targeting this pathway as a therapeutic approach for cardiovascular disorders and its related diseases.

Low omega-6 vs. low omega-6 plus high omega-3 dietary intervention for chronic daily headache: protocol for a randomized clinical trial.

BACKGROUND: Targeted analgesic dietary interventions are a promising strategy for alleviating pain and improving quality of life in patients with persistent pain syndromes, such as chronic daily headache (CDH). High intakes of the omega-6 (n-6) polyunsaturated fatty acids (PUFAs), linoleic acid (LA) and arachidonic acid (AA) may promote physical pain by increasing the abundance, and subsequent metabolism, of LA and AA in immune and nervous system tissues. Here we describe methodology for an ongoing randomized clinical trial comparing the metabolic and clinical effects of a low n-6, average n-3 PUFA diet, to the effects of a low n-6 plus high n-3 PUFA diet, in patients with CDH. Our primary aim is to determine if: A) both diets reduce n-6 PUFAs in plasma and erythrocyte lipid pools, compared to baseline; and B) the low n-6 plus high n-3 diet produces a greater decline in n-6 PUFAs, compared to the low n-6 diet alone. Secondary clinical outcomes include headache-specific quality-of-life, and headache frequency and intensity. METHODS: Adults meeting the International Classification of Headache Disorders criteria for CDH are included. After a 6-week baseline phase, participants are randomized to a low n-6 diet, or a low n-6 plus high n-3 diet, for 12 weeks. Foods meeting nutrient intake targets are provided for 2 meals and 2 snacks per day. A research dietitian provides intensive dietary counseling at 2-week intervals. Web-based intervention materials complement dietitian advice. Blood and clinical outcome data are collected every 4 weeks. RESULTS: Subject recruitment and retention has been excellent; 35 of 40 randomized participants completed the 12-week intervention. Preliminary blinded analysis of composite data from the first 20 participants found significant reductions in erythrocyte n-6 LA, AA and %n-6 in HUFA, and increases in n-3 EPA, DHA and the omega-3 index, indicating adherence. TRIAL REGISTRATION: ClinicalTrials.gov (NCT01157208).