A frequent concern of patients and physicians is the impact of diet quality over time and the related risks of mortality. In this retrospective cohort study, researchers assessed diet-quality using three rubrics: the Alternate Healthy Eating Index (AHEI), Alternate Mediterranean Diet score (AMD), and the Dietary Approaches to Stop Hypertension (DASH) diet scores, to develop adjusted hazard ratios for total and cardiovascular-cause related mortality. Specifically, 47,994 women from the Nurses’ Health Study and 25,745 men from the Health Professionals Follow-up Study were followed from 1998 to 2010, excluding those with history of cardiovascular disease or cancer before baseline, those with extremely high or low caloric intake, and those with missing information regarding diet and lifestyle. The pooled hazard ratios (HRs) over a 12-year period for participants with the greatest improvement in diet quality compared to those whose diet quality remained largely stable were 0.91 (95% CI 0.85 to 0.97), 0.84 (95% CI 0.78 to 0.91) and 0.89 (95% CI 0.84 to 0.95) as measured by the AHERI, AMD and DASH dietary rubrics, respectively. A 20% increase in diet-quality scores was associated with significant overall mortality reduction over a 12-year period using the AHEI (HR 0.85, 95% CI 0.76 to 0.96) and AMD (HR 0.93, 95% CI 0.88 to 0.99) scores, though not with the DASH (HR 0.96, 95%CI 0.88 to 1.05) score. Greater mortality improvements were found in patients who maintained improvements in dietary score over 16 years compared to those over 8 years. Of note, however, this study fails to be generalizable to the overall population as the sample set was largely white and of a higher socioeconomic status, and the study was also not randomized creating potential for residual confounding. Ultimately, this study shows that sustained improvement in diet are associated with a broad improvement in health outcomes.
One of the most popularly consumed beverages worldwide, coffee, has received notable attention in its links to lower mortality rates. In this prospective cohort study, researchers assessed 521,330 patients from 10 European countries with various coffee preparation methods to examine the relationship between coffee consumption and all-cause mortality. This study found an inverse relationship between coffee drinking and mortality, where compared to non-consumers, coffee-drinkers in the highest quartile of coffee consumption had significantly reduced all-cause mortality in both men (HR 0.88, 95% CI 0.82 to 0.95, p<0.001) and women (HR 0.93, 95% CI 0.87 to 0.98, p=0.009 ). Inverse associations between coffee drinkers and several disease-associated mortalities were also observed, including circulatory disease, digestive diseases using biomarkers for liver function, inflammation, metabolic health, and ovarian cancer mortality. Of note, while this study aimed to control for confounding variables, as this was not a randomized study there could be residual confounding. In addition, coffee-drinking habits were only assessed once and could have changed along the course of the study. Nonetheless, this study shows that coffee drinking may be associated with reduced risk of death from various causes, and did not vary by country.
Less than a third of patients with major depressive disorder (MDD) achieve remission with their first antidepressant. Common strategies include switching to bupropion and adjunctive use of either bupropion or aripiprazole. In the VAST-D randomized clinical trial, 1522 patients at 35 US Veterans Health Administration medical centers diagnosed with MDD without psychotic features and unresponsive to at least 1 course of antidepressants were randomly assigned to 1 of 3 treatments and evaluated for up to 36 weeks to determine the relative effectiveness and safety of 3 common alternate treatments for MDD. The interventions included switch to bupropion, augment current treatment with bupropion, or augment with aripiprazole, an atypical antipsychotic, with the primary outcome of remission during the acute treatment phase defined as a 16-item Quick Inventory of Depressive Symptomatology-Clinician Rated (QIDS-C16) score ≤ 5 at 2 visits. Secondary outcomes included ≥50% improvement in QIDS-C16 score or Clinical Global Impression Improvement scale, relapse and adverse effects. Remission rates at 12 weeks were 22.3% (n = 114) for the switch group, 26.9% (n = 136) for the augment-bupropion group, and 28.9% (n = 146) for the augment-aripiprazole group. The augment-aripiprazole group exceeded the switch group in remission (RR 1.30, 95% CI 1.05 to 1.60, p =0.02), but other remission comparisons were not significant. Response was greater in the augment-aripiprazole group compared to other groups. Anxiety was more frequent in the 2 bupropion groups. Of note, this study population was predominantly male which decreases its generalizability. Furthermore, the small effect size and adverse effects associated with aripiprazole warrants further analysis for the utility of this approach. Overall, the augmentation with aripiprazole did result in a statistically significant but modest increase in likelihood of remission for these patients.
Acute heart failure (AHF) remains a significant cause of hospitalization in the US, with high inpatient morbidity and mortality. Persistent congestion is associated with worse outcomes in AHF. Mineralocorticoid receptor antagonists given at high doses are thought to relieve congestion, overcome diuretic resistance, and reduce the effects of adverse neurohormonal activation in AHF. In the ATHENA-HF double-blind placebo controlled randomized trial, 360 patients with AHF previously receiving no or low-dose (12.5 mg or 25 mg daily) spironolactone with NT-proBNP levels of 1000 pg/mL or more or B-type natriuretic peptide levels of 250 pg/mL or more were randomized to receive either high-dose 100 mg spironolactone or 25 mg spironolactone (usual care) daily for 96 hours. Primary outcomes were change in NT-proBNP levels from baseline in 96 hours. Secondary outcomes included clinical congestion score, dyspnea assessment, net urine output, and net weight change. Baseline median NT-proBNP levels were 4601 pg/mL (IQR 2697-9596 pg/mL) in the high-dose spironolactone group and 3753 pg/mL (IQR 1968-7633 pg/mL) in the usual care group. There was no significant difference in the log NT-proBNP reduction between the 2 groups, -0.55 (95% CI -0.92 to -0.18) with high-dose spironolactone and -0.49 (95% CI -0.98 to -0.14) with usual care (p =0.57). None of the secondary outcomes, 30-day all-cause mortality or heart failure hospitalization rates differed between the 2 groups. Limitations included the relatively short duration of treatment, which may not be sufficient for spironolactone to convert into its active metabolites. In clinical practice, this study reveals that high-dose spironolactone in AHF is not recommended, as it does not improve AHF biomarkers, hospitalization rate, or mortality.
Total plasma tau protein levels have been found to be elevated in patients with Alzheimer disease (AD) dementia or mild cognitive impairment (MCI), but few studies have evaluated the use of total plasma tau levels as prognostic markers or risk factors for cognitive decline and dementia. In this retrospective cohort study, plasma total tau levels were measured in 458 participants between the ages 70 and 89 years. Aβ positron emission tomography imaging, and a complete neuropsychological exam were also conducted with at least 1 follow-up visit to assess the relationship between plasma total tau levels and the primary outcome of AD dementia or MCI risk and global and domain-specific cognitive decline. In a follow-up of up to 15 months, plasma tau did not predict decline among cognitively normal (CN) patients. However, among all participants, higher levels of plasma total tau, examined as a continuous variable, were associated with significant declines in global cognition (p=0.009), memory, attention, and visuospatial ability (p<0.001) over a median follow-up of 3.0 years (range 1.1 to 4.9 years). In CN patients with elevated brain Aβ, patients in the highest (HR 2.02, 95% CI 1.01 to 4.06) and middle (HR 2.43, 95% CI 1.25 to 4.72) tertiles of plasma total tau levels had an increased risk of MCI. There was no association between plasma tau levels and brain Aβ for prognosis of any outcome. This study did not adjust for other brain pathologies that can attenuate the association. Overall, this study suggests that elevated plasma total tau levels are associated with cognitive decline, but differ based on cognitive status and duration of follow-up and is independent of elevated brain Aβ.
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