Cardiac Repolarization Abnormalities and Potential Evidence for Loss of Cardiac Sodium Currents on ECGs of Patients with Chagas' Heart Disease

Some individuals with Chagas disease develop right precordial lead ST segment elevation in response to an ajmaline challenge test, and the prevalence of right bundle branch block (RBBB) is also high in Chagas disease. Because these same electrocardiographic abnormalities occur in the Brugada syndrome, which involves genetically defective cardiac sodium channels, acquired damage to cardiac sodium channels may also occur in Chagas disease. We studied several conventional and advanced resting 12-lead/derived Frank-lead ECG parameters in 34 patients with Chagas -related heart disease (mean age 39 14 years) and in 34 age-/gender-matched healthy controls. All ECG recordings were of 5-10 min duration, obtained in the supine position using high fidelity hardware/software (CardioSoft, Houston, TX). Even after excluding those Chagas patients who had resting BBBs, tachycardia and/or pathologic arrhythmia (n=8), significant differences remained in multiple conventional and advanced ECG parameters between the Chagas and control groups (n=26/group), especially in their respective QT interval variability indices, maximal spatial QRS-T angles and low frequency HRV powers (p=0.0006, p=0.0015 and p=0.0314 respectively). In relation to the issue of potential damage to cardiac sodium channels, the Chagas patients had: 1) greater than or equal to twice the incidence of resting ST segment elevation in leads V1-V3 (n=10/26 vs. n=5/26) and of both leftward (n=5/26 versus n=0/26) and rightward (n=7/26 versus n=3/26) QRS axis deviation than controls; 2) significantly increased filtered (40-250 Hz) QRS interval durations (92.1 8.5 versus 85.3 plus or minus 9.0 ms, p=0.022) versus controls; and 3) significantly decreased QT and especially JT interval durations versus controls (QT interval: 387.5 plus or minus 26.4 versus 408.9 plus or minus 34.6 ms, p=0.013; JT interval: 290.5 plus or minus 26.3 versus 314.8 plus or minus 31.3 ms; p=0.0029). Heart rates and Bazett-corrected QTc/JTc intervals were not significantly different between groups. Patients with Chagas heart disease have increased cardiac repolarization abnormalities, especially by advanced ECG. Moreover, as a group, they have decreased uncorrected JT and QT interval durations and increased filtered QRS interval durations (versus age/gender-matched controls), all suggesting a potential loss of cardiac sodium channel function that might be mediated, in part, by cardiac autonomic damage. Overall findings support Brugada et al's recent hypothesis that the pathway leading to sudden death may often be similar in Chagas' disease and Brugada syndrome i.e., damage to the sodium channel (infectious/immunologic/autonomic in Chagas' genetic in Brugada) with consequent loss of sodium currents may facilitate a phase II-reentry based arrhythmic substrate for ventricular fibrillation in both conditions. In general, JT interval-related results have been underreported in the Chagas literature

lba14_prthe hoboe 2 multicenter randomized phase iii trial in premenopausal patients with hormone receptor positive early breast cancer comparing triptorelin plus either tamoxifen or letrozole or letrozole zoledronic acid

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Cross-sectional study to develop and describe psychometric characteristics of a patient-reported instrument (PROFFIT) for measuring financial toxicity of cancer within a public healthcare system

Objectives To measure and explain financial toxicity (FT) of cancer in Italy, where a public healthcare system exists and patients with cancer are not expected (or only marginally) to pay out-of-pocket for healthcare. Setting Ten clinical oncological centres, distributed across Italian macroregions (North, Centre, South and Islands), including hospitals, university hospitals and national research institutes. Participants From 8 October 2019 to 11 December 2019, 184 patients, aged 18 or more, who were receiving or had received within the previous 3 months active anticancer treatment were enrolled, 108 (59%) females and 76 (41%) males. Intervention A 30-item prefinal questionnaire, previously developed within the qualitative tasks of the project, was administered, either electronically (n=115) or by paper sheet (n=69). Primary and secondary outcome measures According to the protocol and the International Society for Pharmacoeconomics and Outcomes Research methodology, the final questionnaire was developed by mean of explanatory factor analysis and tested for reliability, internal consistency (Cronbach's α test and item-total correlation) and stability of measurements over time (test-retest reliability by intraclass correlation coefficient and weighted Cohen's kappa coefficient). Results After exploratory factor analysis, a score measuring FT (FT score) was identified, made by seven items dealing with outcomes of FT. The Cronbach's alpha coefficient for the FT score was 0.87 and the item-total correlation coefficients ranged from 0.53 to 0.74. Further, nine single items representing possible determinants of FT were also retained in the final instrument. Test-retest analysis revealed a good internal validity of the FT score and of the 16 items retained in the final questionnaire. Conclusions The Patient-Reported Outcome for Fighting FInancial Toxicity (PROFFIT) instrument consists of 16 items and is the first reported instrument to assess FT of cancer developed in a country with a fully public healthcare system. Trial registration number NCT03473379

Prev Chronic Dis

IntroductionObesity is highly prevalent among American Indians, and effective prevention efforts require caregiver involvement. We examined American Indian (AI) parents' assessment of and level of concern about their kindergarten child's weight status.MethodsWe collected baseline data (fall of 2005 and fall of 2006) on children and their parents or caregivers for a school-based obesity prevention trial (Bright Start) on an AI reservation in South Dakota. The current study uses 413 parent-child pairs. Age- and sex-adjusted body mass index percentiles were categorized as very underweight (<5th percentile), slightly underweight (5th to <15th percentile), normal weight (15th to <85th percentile), overweight (85th to <95th percentile), and obese ( 6595th percentile). Parents or caregivers reported their assessment of and concerns about their child's weight status as well as sociodemographic characteristics. We used mixed-model multivariable analysis to examine associations between sociodemographic characteristics and the probability of parents underclassifying or overclassifying their child's weight status; analyses were adjusted for school as a random effect.ResultsChildren were evenly divided by sex and had a mean age of 5.8 years. Twenty-nine percent of children and 86% of parents were overweight or obese. Approximately 33% (n = 138) of parents underclassified and 7% (n = 29) of parents overclassified their child's weight status. Higher parental weight status and higher concern about their child's weight status increased the probability of underclassification (P for trend = .02 for both).ConclusionIn this sample of at-risk children, one-third of parents underclassified their child's weight status. Childhood obesity prevention programs need to increase awareness and recognition of childhood obesity and address parental weight issues.2012649

Confirmatory validation analysis of the PROFFIT questionnaire to assess financial toxicity in cancer patients.

BACKGROUND The Patient Reported Outcome for Fighting FInancial Toxicity (PROFFIT) questionnaire was developed to measure financial toxicity (FT) and identify its determinants. The aim of the present study was to confirm its validity in a prospective cohort of patients receiving anticancer treatment. PATIENTS AND METHODS From March 2021 to July 2022, 221 patients were enrolled at 10 Italian centres. Selected items of the EORTC-QLQ-C30 questionnaire represented the anchors, specifically, question 28 (Q-28) on financial difficulties, and questions 29-30 measuring global health status/quality of life (HR-QOL). The study had 80% power to detect a 0.20 correlation coefficient (r) between anchors and PROFFIT-score (items 1-7, range 0-100, 100 indicating maximum FT) with bilateral alpha 0.05 and 80% power. Confirmatory factor analysis was conducted. FT determinants (items 8-16) were described. RESULTS Median age of patients was 65 years, 116 (52.5%) were females, 96 (43.4%) had low education level. Confirmatory factor analysis confirmed goodness of fit of the PROFFIT-score. Significant partial correlation of PROFFIT-score was found with Q-28 (r = 0.51) and HR-QOL (r = -0.23). Mean (SD) PROFFIT-score at baseline was 36.5 (24.9); it was statistically significantly higher for patients living in South Italy, those with lower education level, those who were freelancer/unemployed at diagnosis and those who reported significant economic impact from the COVID-19 pandemic. Mean (SD) scores of determinants ranged from 17.6 (27.1) for item 14 (support from medical staff) to 49.0 (36.3) for item 10 (expenses for medicines or supplements). PROFFIT-score significantly increased with worsening response to determinants. CONCLUSIONS External validation of PROFFIT-score in an independent sample of patients was successful. The instrument is now being used in clinical studies

A phase 2, open label, multicenter, single arm study of tocilizumab on the efficacy and tolerability of tocilizumab in the treatment of patients with COVID-19 pneumonia (TOCIVID-19 trial): Statistical analysis plan

Background: Tocilizumab, an IL-6 receptor antagonist, was suggested as a possible treatment of severe or critical COVID-19 pneumonia in a small Chinese study. The TOCIVID-19 trial evaluates efficacy and tolerability of tocilizumab in the treatment of patients with severe or critical COVID-19 pneumonia. Methods: TOCIVID-19 is an academic multicenter, single-arm, open-label, phase 2 study. All the patients are being offered a single shot of 8 mg/kg of Tocilizumab (up to a maximum of 800 mg), with an eventual second administration at the discretion of the Investigator. A companion prospective cohort, added to corroborate internal validity, includes either patients not eligible for phase 2 or subjects eligible for phase 2 but exceeding the planned sample size. 14- and 30-days lethality rates are the two co-primary endpoints in the intention-to-treat (ITT) population. Secondary objectives are to evaluate mortality and clinical improvement in the modified-ITT population of subjects who received the drug. Details of the methodological and statistical approaches are reported here reflecting the amendments impelled by the continuously increasing knowledge on COVID-19 progression and challenges in data collection. Conclusion: This paper provides details of planned statistical analyses for TOCIVID19 trial to reduce the risk of reporting bias and increase validity of the study findings. TOCIVID-19 trial is registered in the EudraCT database with number 2020-001110-38 and in clinicaltrials.gov with ID NCT04317092