Quantitative trait locus mapping: fishing strategy or replicable results?

Genomewide scan, as shown by recently published linkage studies on the behavior of mice or in psychiatry, provides evidence for replicated quantitative trait loci (QTL). Several studies of Alzheimer's disease have demonstrated the promise of moving from clinical diagnoses to biological signs for psychiatric investigations. Empirical studies also demonstrate that genetic background, differences in environment, epistatic effects, and definition of the phenotype (including psychiatric diagnosis) all actively contribute to limit the duplication of QTL.     

Inequalities in enrollment of women and racial minorities in trials testing uric acid lowering drugs

AimsWe investigated sex and racial inequalities in clinical trials testing serum uric acid (SUA) lowering drugs and analyzed the temporal trends of participation among the pre-specified demographic groups.Data were collected from publications of clinical trials testing SUA-lowering drugs. Linear regression analysis was performed to assess the relation between drug approval year and proportion of women and minorities enrolled in clinical studies.Data synthesisThe mean percentage enrollment of women in clinical trials significantly decreased over the time (r = −0.43, P-value = 0.02). Moreover, there was a statistically significant difference in mean percentage enrollment of women among trials testing different SUA-lowering drugs, with the highest representation in rasburicase (71.1%) and the lowest representation of women in dotinurad (0.8%). Over the time, also the mean percentage enrollment of racial minorities decreased, passing from 8.7% to 2.2% in a 10-year period.Women were proportionally underrepresented compared with their share of the population with asymptomatic hyperuricemia, overall (participation-to-prevalence ratio (PPR) = 0.34), in trials testing xanthine oxiase inhibitors (PPR = 0.38) and uricosurics (PPR = 0.29), and in trials with febuxostat, allopurinol, pegloticase, halofenate/arhalofenate, verinurad, lesinurad and dotinurad. Women were proportionally underreppresented also compared with their share of the population with gout, overall (PPR = 0.69) and in trials testing XOIs (PPR = 0.69), uricosurics (PPR = 0.68), and all SUA-lowering drugs excepted for rasburicase, pegloticase and topiroxostat.ConclusionsOur analysis shows that women and racial and ethnical minorities are underrepresented in controlled clinical trials testing SUA-lowering drugs, with similar pattern across drug classes.     

Risk stratification for mortality in cardiovascular disease survivors: A survival conditional inference tree analysis

Background and aimsEfficient analysis strategies for complex network with cardiovascular disease (CVD) risk stratification remain lacking. We sought to identify an optimized model to study CVD prognosis using survival conditional inference tree (SCTREE), a machine-learning method.Methods and resultsWe identified 5379 new onset CVD from 2006 (baseline) to May, 2017 in the Kailuan I study including 101,510 participants (the training dataset). The second cohort composing 1,287 CVD survivors was used to validate the algorithm (the Kailuan II study, n = 57,511). All variables (e.g., age, sex, family history of CVD, metabolic risk factors, renal function indexes, heart rate, atrial fibrillation, and high sensitivity C-reactive protein) were measured at baseline and biennially during the follow-up period. Up to December 2017, we documented 1,104 deaths after CVD in the Kailuan I study and 170 deaths in the Kailuan II study. Older age, hyperglycemia and proteinuria were identified by the SCTREE as main predictors of post-CVD mortality. CVD survivors in the high risk group (presence of 2–3 of these top risk factors), had higher mortality risk in the training dataset (hazard ratio (HR): 5.41; 95% confidence Interval (CI): 4.49–6.52) and in the validation dataset (HR: 6.04; 95%CI: 3.59–10.2), than those in the lowest risk group (presence of 0–1 of these factors).ConclusionOlder age, hyperglycemia and proteinuria were the main predictors of post-CVD mortality.Trial registrationChiCTR-TNRC-11001489.     

Higher-risk breast cancer in women aged 80 and older: Exploring the effect of treatment on survival

BackgroundTo understand the association between various treatments and survival for older women with higher-risk breast cancer when controlling for patient and tumor factors.Materials and methodsWe conducted a retrospective, population-based study. Women aged 80 years or older and diagnosed between 2004 and 2017 with non-metastatic, higher-risk breast cancer were identified form the provincial cancer registry in Alberta, Canada. Higher-risk was defined as any of following: T3/4, node positive, human epidermal factor receptor-2 (Her2) positive or triple negative disease. Treatments were surgery, radiotherapy and systemic therapy (hormonal therapy, and/or chemotherapy and/or trastuzumab) or a combination of the previous. Cox regression models were used to examine the association between treatments and breast cancer specific survival (BCSS) and overall survival (OS).Results1369 patients were included. The median age was 84 years. 332 (24%) of women had T3-T4 tumors, 792 (58%) had nodal involvement, 130 (10%) had Her2 positive tumors, 124 (9%) had triple negative tumors. After a median follow-up of 35 months, 29.5% of patients died of breast cancer whereas 34.2% died from other causes. Patients had a lower adjusted hazard for BCSS if they had surgery (hazard ratio [HR] = 0.37 95% confidence interval [CI]: 0.27, 0.51), or systemic therapy (HR = 0.75, 95%CI: 0.58, 0.98). Patients had an increased probability of breast cancer death in the first 5 years after diagnosis compared to death from other causes.ConclusionsSurgery and systemic therapy were associated with longer BCSS and OS. This suggests that maximizing treatments might benefit higher-risk patients.     

Trends in Use and Outcomes of Same-Day Discharge Following Elective Percutaneous Coronary Intervention

ObjectivesThe aims of this study were to describe trends and hospital variation in same-day discharge following elective percutaneous coronary intervention (PCI) and to evaluate the association between trends in same-day discharge and patient outcomes.BackgroundInsights on contemporary use of same-day discharge following elective PCI are limited.MethodsIn a sequential cross-sectional analysis of 819,091 patients undergoing elective PCI at 1,716 hospitals in the National Cardiovascular Data Registry CathPCI Registry from July 1, 2009, to December 31, 2017, overall and hospital-level trends in same-day discharge were assessed. Among the 212,369 patients who linked to Centers for Medicare and Medicaid Services data, the association between same-day discharge and 30-day mortality and rehospitalization was assessed.ResultsA total of 114,461 patients (14.0%) were discharged the same day as PCI. The proportion of patients with same-day discharge increased from 4.5% in the third quarter of 2009 to 28.6% in the fourth quarter of 2017. From 2009 to 2017, the rate of same-day discharge increased from 4.3% to 19.5% for femoral-access PCI and from 9.9% to 39.7% for radial-access PCI. Hospital-level variation in the use of same-day discharge persisted throughout (median odds ratio adjusted for year and radial access: 4.15). Risk-adjusted 30-day mortality did not change over time, while risk-adjusted rehospitalization decreased over time and more quickly for same-day discharge (P for interaction <0.001).ConclusionsIn the past decade, a large increase in the use of same-day discharge following elective PCI was not associated with worse 30-day mortality or rehospitalization. Hospital-level variation in same-day discharge may represent an opportunity to reduce costs without compromising patient outcomes.     

Reducing delirium and cognitive dysfunction after off-pump coronary bypass: A randomized trial

BackgroundNeuropsychiatric complications of surgical coronary revascularization are inconspicuous but frequent and clinically relevant. So far, attempts to reduce their occurrence, such as the introduction of off-pump coronary artery bypass (OPCAB) grafting method, have not brought the desired results. The aim of this trial was to determine whether using any of the 2 selected modifications of OPCAB could decrease the incidence of these undesired sequelae.MethodsIn this single-center, assessor- and patient-blinded, superiority, randomized controlled trial, 192 patients scheduled for elective isolated OPCAB were randomized to 3 parallel arms. The control arm underwent “conventional” OPCAB with vein grafts. The first study arm underwent anaortic OPCAB (ANA) with total arterial revascularization. The second study arm underwent OPCAB with vein grafts using carbon dioxide surgical field flooding (CO₂FF). Outcomes included the incidence of postoperative delirium (PD) and early postoperative cognitive dysfunction (ePOCD).ResultsThe incidence of PD was 35.9% in the control (OPCAB) arm, 32.8% in the CO₂FF arm, and 12.5% in the ANA arm (χ² [2, N = 191] = 10.17; P = .006). Post hoc tests revealed that the incidence of PD in the ANA arm differed from that in the OPCAB arm (odds ratio [OR], 0.26; 95% confidence interval [CI], 0.09-0.68; P = .002). The incidence of ePOCD was 34.4% in the OPCAB arm, 28.1% in the CO₂FF arm, and 9.5% in the ANA arm (χ² [2, N = 191] = 11.58; P = .003). Post hoc tests revealed that the incidence of ePOCD differed between the ANA and OPCAB arms (OR, 0.20; 95% CI, 0.06-0.58; P < .001).ConclusionsPerforming ANA significantly decreases the incidence of PD and ePOCD compared with “conventional” OPCAB with vein grafts, whereas CO₂FF is inconsequential in this regard. These results, which probably reflect decreased delivery of embolic load to the brain in ANA, may have practical applicability in daily practice to improve clinical outcomes.