Fragility of cardiovascular outcome trials (CVOTs) examining nutrition interventions among patients with diabetes mellitus: a systematic review of randomized controlled trials.

PURPOSE: There is controversy regarding the optimal statistical method to interpret how robust is a statistically significant result. The fragility index (FI) and the reverse fragility index (RFI) are quantitative measures that can facilitate the appraisal of a clinical trial's robustness. This study was performed to evaluate the FI and RFI of randomized controlled trials (RCTs) examining nutritional interventions in patients with diabetes mellitus, focusing on cardiovascular outcomes. METHODS: A systematic search was conducted and relevant RCTs were identified in three databases. RCTs examining nutritional interventions (supplements or dietary patterns) in patients with DM with dichotomous primary endpoints involving cardiovascular outcomes were eligible. Data were extracted to compose 2 × 2 event tables and the FI and RFI were calculated for each comparison, using Fisher's exact test. Risk of bias (RoB) of the included RCTs was assessed with the Cochrane RoB 2.0 tool. RESULTS: A total of 14,315 records were screened and 10 RCTs were included in the analyses. The median FI of the paired comparisons was 3 (IQR: 2-4) and the median RFI was 8 (IQR: 4.5-17). RoB and heterogeneity were low. CONCLUSIONS: RCTs examining nutritional interventions and cardiovascular outcomes among patients with diabetes mellitus appear to be statistically fragile. Τhe FI and the RFI can be reported and interpreted as an additional perspective of a trial's robustness. HIGHLIGHTS: • In the evidence-healthcare era, assessing how robust statistically significant results are remains a matter of controversy. • Recently, the fragility index (FI) and reverse fragility index (RFI) were proposed to assess the robustness of randomized controlled trials (RCTs) with 2 × 2 comparisons. • When applying the FI and RFI, RCTs examining nutritional interventions and cardiovascular outcomes among patients with diabetes mellitus (DM) appear to be statistically fragile. • Τhe FI and the RFI can be reported and interpreted as an additional perspective of a trial's robustness. • RCTs implementing nutrition interventions among patients with DM can improve their methodology.

Gestational Hypertension and Preeclampsia: An Overview of National and International Guidelines.

IMPORTANCE: Gestational hypertension and preeclampsia are leading causes of maternal and perinatal morbidity and mortality worldwide. Τhe lack of effective screening and management policies appears to be one of the main reasons. OBJECTIVE: The aim of this study was to review and compare recommendations from published guidelines on these common pregnancy complications. EVIDENCE ACQUISITION: A descriptive review of guidelines from the National Institute for Health and Care Excellence, the Society of Obstetric Medicine of Australia and New Zealand, the International Society of Hypertension, the International Society for the Study of Hypertension in Pregnancy, the European Society of Cardiology, the International Federation of Gynecology and Obstetrics, the Society of Obstetricians and Gynaecologists of Canada, the American College of Obstetricians and Gynecologists, the International Society of Ultrasound in Obstetrics and Gynecology, the World Health Organization, and the US Preventive Services Task Force on gestational hypertension and preeclampsia was carried out. RESULTS: There is an overall agreement that, in case of suspected preeclampsia or new-onset hypertension, blood and urine tests should be carried out, including dipstick test for proteinuria, whereas placental growth factor-based testing is only recommended by the National Institute for Health and Care Excellence and the European Society of Cardiology. In addition, there is a consensus on the recommendations for the medical treatment of severe and nonsevere hypertension, the management of preeclampsia, the appropriate timing of delivery, the optimal method of anesthesia and the mode of delivery, the administration of antenatal corticosteroids and the use of magnesium sulfate for the treatment of eclamptic seizures, the prevention of eclampsia in cases of severe preeclampsia, and the neuroprotection of preterm neonates. The reviewed guidelines also state that, based on maternal risk factors, pregnant women identified to be at high risk for preeclampsia should receive low-dose aspirin starting ideally in the first trimester until labor or 36 to 37 weeks of gestation, although the recommended dose varies between 75 and 162 mg/d. Moreover, most guidelines recommend calcium supplementation for the prevention of preeclampsia and discourage the use of other agents. However, controversy exists regarding the definition and the optimal screening method for preeclampsia, the need for treating mild hypertension, the blood pressure treatment targets, and the postnatal blood pressure monitoring. CONCLUSIONS: The development and implementation of consistent international protocols will allow clinicians to adopt effective universal screening, as well as preventive and management strategies with the intention of improving maternal and neonatal outcomes.

Prediction of long-term survival in patients with transfusion-dependent hemoglobinopathies: Insights from cardiac imaging and ferritin.

AIMS: The current study evaluated the association of echocardiography, cardiac magnetic resonance (CMR), and ferritin data with 10-year survival in thalassemia patients. METHODS: Demographics, ferritin, echocardiography, and CMR parameters of stable consecutive thalassemia patients were prospectively collected. RESULTS: In total, 75 patients (mean age 37 ± 11 years, 45% male) with thalassemia were included and dichotomized based on their survival status after a median follow-up period of 10.3 [9.6-10.9] years. Older age (HR: 1.071, p = 0.001), ferritin ≥2000 ng/ml (HR: 4.682, p = 0.007) and ≥1700 ng/ml (HR: 7.817, p = 0.002), elevated LV end-diastolic pressure (HR: 1.019, p = 0.044), TR Vmax >2.8 m/s (HR: 6.845, p = 0.005), and CMR T2∗ ≤20 msec (HR: 3.602, p = 0.043) and ≤34 msec (HR: 5.854, p = 0.026) were associated with increased all-cause mortality (primary endpoint). A baseline model including age was created and became more predictive of worse survival by adding TR Vmax >2.8 m/s instead of elevated LV end-diastolic pressure (C index 0.767 vs. 0.760, respectively), ferritin ≥1700 ng/ml instead of ≥2000 ng/ml (C index 0.890 vs. 0.807, respectively), or CMR T2∗≤34 msec instead of ≤20 msec (C index 0.845 vs. 0.839, respectively). Parameters associated with the combined endpoint of cardiac mortality/cardiac hospitalization (secondary endpoint) after adjusting for age were ferritin ≥1700 ng/ml (HR 3.770, p = 0.014), ratio E/A wave >2 (HR 3.565, p = 0.04), TR Vmax >2.8 m/s (HR 4.541, p = 0.049), CMR T2∗ ≤20 ms (HR 9.462, p = 0.001), and CMR T2∗ ≤34 ms (HR 11.735, p = 0.002). The model including age and T2∗ ≤34 ms instead of T2∗ ≤20 ms was more predictive of the secondary endpoint (C-index 0.844 vs 0.838, respectively). CONCLUSIONS: In thalassemia patients, TR Vmax >2.8 m/s, ferritin ≥2000 ng/ml, and CMR T2∗ ≤20 ms were associated with worse long-term survival. In the current era of advanced chelation therapy, aiming for ferritin ≤1700 ng/ml and CMR T2∗ ≥34 ms may improve their prognosis.

Cost-Effectiveness Analysis of Rivaroxaban for Treatment of Deep Vein Thrombosis and Pulmonary Embolism in Greece.

BACKGROUND AND OBJECTIVE: Venous thromboembolism (VTE), comprising deep-vein thrombosis (DVT) and pulmonary embolism (PE), is a major healthcare concern that results in substantial morbidity and mortality with great economic burden for healthcare systems. Hence, the need for effective and efficient treatment of patients with VTE is important for both clinical and economic reasons. The objective of this study was to evaluate the cost effectiveness of rivaroxaban compared to standard of care (SoC) with enoxaparin followed by dose-adjusted vitamin-K antagonists for the treatment of DVT and PE in Greece. METHODS: An existing Markov model was locally adapted from a third-party payer perspective to reflect the management and complications of DVT and PE in the course of 3-month cycles, up to death. The clinical inputs and utility values were extracted from published studies. Direct medical costs, obtained from local resources, were incorporated in the model and refer to year 2017. Both costs and outcomes were discounted at 3.5%. The incremental cost-effectiveness ratio (ICER) per quality-adjusted life year (QALY) gained was calculated. Probabilistic sensitivity analysis (PSA) was carried out to deal with uncertainty. RESULTS: The base-case analysis showed that rivaroxaban in 3- and 6-month treatment duration for DVT and PE, respectively, as this is the common clinical practice in Greece, was associated with a 0.02 and 0.01 increment in QALYs compared to SoC, respectively. Rivaroxaban was associated with a reduced total cost in DVT (€85) but with an additional total cost in PE (€2) compared to SoC. Therefore, rivaroxaban was a dominant (less costly, more effective) and cost-effective (ICER: €177) alternative over SoC for the management of DVT and PE, respectively. PSA revealed that the probability of rivaroxaban being cost effective at a threshold of €34,000 per QALY gained was 99% and 81% for DVT and PE, respectively. CONCLUSION: Rivaroxaban may represent a cost-effective option relative to SoC for the management of DVT and PE in Greece.

Adult congenital heart disease: A paradigm of epidemiological change.

Increasing survival rates for patients with congenital heart disease (CHD) represent a major achievement of modern medicine. Despite incredible progress been made in diagnosis, follow-up, early treatment and management in adulthood, many patients are faced with long-term complications, such as arrhythmia, thromboembolism, heart failure, pulmonary hypertension, endocarditis and/or the need for reoperation. In parallel, half of the patients are female, most of childbearing age, and, thus warrant specialist reproductive counseling and appropriate obstetric care. It is not surprising therefore, that healthcare utilization has steadily increased for CHD in recent years. Furthermore, cardiology and other medical disciplines are now faced with new challenges, namely the provision of expert care and optimal, lifelong medical surveillance for these patients.