Cardioprotective Potential of Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Cancer Treated With Anthracyclines: An Observational Study.

Anthracyclines are pivotal in cancer treatment, yet their clinical utility is hindered by the risk of cardiotoxicity. Preclinical studies highlight the effectiveness of sodium-glucose cotransporter-2 inhibitors (SGLT2i) in mitigating anthracycline-induced cardiotoxicity. Nonetheless, the translation of these findings to clinical practice remains uncertain. This study aims to evaluate the safety and potential of SGLT2i for preventing cardiotoxicity in patients with cancer, without preexisting heart failure (HF), receiving anthracyclines therapy. Using the TriNetX Global Research Network, patients with cancer, without previous HF diagnosis, receiving anthracycline therapy were identified and classified into 2 groups based on SGLT2i usage. A 1:1 propensity score matching was used to control for baseline characteristics between the 2 groups. Patients were followed for 2 years. The primary end point was new-onset HF, and the secondary end points were HF exacerbation, new-onset arrhythmia, myocardial infarction, all-cause mortality, and all-cause hospitalization. Safety outcomes included acute renal failure and creatinine levels. A total of 79,074 patients were identified, and 1,412 were included post-matching (706 in each group). They comprised 53% females, 62% White, with a mean age of 62.5 ± 11.4 years. Over the 2-year follow-up period, patients on SGLT2i had lower rates of new-onset HF (hazard ratio 0.147, 95% confidence interval 0.073 to 0.294) and arrhythmia (hazard ratio 0.397, 95% confidence interval 0.227 to 0.692) compared with those not on SGLT2i. The incidence of all-cause mortality, myocardial infarction, all-cause hospitalization, and safety outcomes were similar between both groups. In conclusion, among patients with cancer receiving anthracycline therapy without preexisting HF, SGLT2i use demonstrates both safety and effectiveness in reducing anthracycline-induced cardiotoxicity, with a decreased incidence of new-onset HF, HF exacerbation, and arrhythmias.

Development of cardiac risk prediction model in patients with HER-2 positive breast cancer on trastuzumab therapy.

BACKGROUND: 25% of all breast cancer patients have HER-2 overexpression. Breast Cancer patients with HER-2 overexpression are typically treated with HER-2 inhibitors such as Trastuzumab. Trastuzumab is known to cause a decrease in left ventricular ejection fraction. The aim of this study is to create a cardiac risk prediction tool among women with Her-2 positive breast cancer to predict cardiotoxicity. METHOD: Using a split sample design, we created a risk prediction tool using patient level data from electronic medical records. The study included women 18 years of age and older diagnosed with HER-2 positive breast cancer who received Trastuzumab. Outcome measure was defined as a drop in LVEF by more than 10% to less than 53% at any time in the 1-year study period. Logistic regression was used to test predictors. RESULTS: The cumulative incidence of cardiac dysfunction in our study was 9.4%. The sensitivity and specificity of the model are 46% and 84%, respectively. Given a cumulative incidence of cardiotoxicity of 9%, the negative predictive value of the test was 94%. This suggests that in a low-risk population, the interval of screening for cardiotoxicity may be performed less frequently. CONCLUSION: Cardiac risk prediction tool can be used to identify Her-2 positive breast cancer patients at risk of developing cardiac dysfunction. Also, test characteristics in addition to disease prevalence may inform a rational strategy in performing cardiac ultrasound in Her-2 breast cancer patients. We have developed a cardiac risk prediction model with high NPV in a low-risk population which has an appealing cost-effectiveness profile.

Hypertensive events after the initiation of contemporary cancer therapies for breast cancer control.

BACKGROUND: Contemporary therapies improve breast cancer (BC) outcomes. Yet, many of these therapies have been increasingly linked with serious cardiotoxicity, including reports of profound hypertension. Yet, the incidence, predictors, and impacts of these events are largely unknown. METHODS: Leveraging two large U.S.-based registries, the National Inpatient Sample (NIS) and the Food and Drug Administration Adverse Event Reporting System (FAERS) databases, we assessed the incidence, factors, and outcomes of hypertensive events among BC patients from 2007 to 2015. Differences in baseline characteristics, hypertension-related discharges, and complications were examined over time. Further, we performed a disproportionality analysis using reporting-odds-ratios (ROR) to determine the association between individual BC drugs and hypertensive events. Utilizing an ROR cutoff of >1.0, we quantified associations by drug-class, and individual drugs with the likelihood of excess hypertension. RESULTS: Overall, there were 5,464,401 BC-admissions, of which 46,989 (0.8%) presented with hypertension. Hypertensive BC patients were older, and saw initially increased in-hospital mortality, which equilibrated over time. The mean incidence of hypertension-related admissions was 732 per 100,000 among BC patients, versus 96 per 100,000 among non-cancer patients (RR 7.71, p < 0.001). Moreover, in FAERS, those with hypertension versus other BC-treatment side-effects were more frequently hospitalized (40.1% vs. 36.7%, p < 0.001), and were most commonly associated with chemotherapy (45.9%). Outside of Eribulin (ROR 3.36; 95% CI 1.37-8.22), no specific drug was associated with a higher reporting of hypertension; however, collectively BC drugs were associated with a higher odds of hypertension (ROR 1.66; 95% CI 1.09-2.53). CONCLUSIONS: BC therapies are associated with a substantial increase in limiting hypertension.

The impact of increasing the minimum legal age for work on school attendance in low- and middle-income countries.

Several countries have increased their legal minimum age for work in line with international conventions on child labor. We evaluated the effect of increasing the legal minimum age for work on school attendance in 3 low- and middle-income countries using difference-in-differences analyses. Increasing the legal minimum age for work increased school attendance by 3.0 (0.2, 5.8) percentage-points in Malawi, and 2.0 (0.2, 3.6) percentage-points in Colombia. In Malawi, we found a greater policy effect among girls compared to boys. In Colombia, the poorest tercile experienced the greatest improvement in educational outcomes. We found no evidence of an impact of increasing the legal minimum age for work on school attendance in Burkina Faso. Our findings suggest that increasing the legal minimum age for work has had a positive effect on educational outcomes in some low and middle income countries.

Child labour and health: a systematic review.

OBJECTIVES: This study aimed to synthesise the available knowledge, identify unexplored areas and discuss general limits of the published evidence. We focused on outcomes commonly hypothesised to be affected by child labour: nutritional status, harmful exposures and injuries. METHODS: Four electronic databases (EMBASE, MEDLINE, Scopus, ISI Web of Science) were searched in November 2017. All articles published since 1996, without restrictions on language, were considered for inclusion. RESULTS: Out of the 1090 abstracts initially identified by the search, 78 articles were selected for inclusion and reviewed. Most of the studies were conducted in Asia and South America, and only a third of them compared working children to a control group of non-working children. Child labour appears to be associated with poor nutritional status, diseases due to harmful exposures, and a higher prevalence of injuries. CONCLUSIONS: Despite evidence for a negative relation between child work and health, the cross-sectional design of most studies limits the causal interpretation of existing findings. More rigorous observational studies are needed to confirm and better quantify these associations.