Associations of Menstrual Cycle and Progesterone-to-Estradiol Ratio With Alcohol Consumption in Alcohol Use Disorder: A Sex-Separated Multicenter Longitudinal Study.

OBJECTIVE: Alcohol use disorder (AUD) constitutes a critical public health issue and has sex-specific characteristics. Initial evidence suggests that progesterone and estradiol might reduce or increase alcohol intake, respectively. However, there is a need for a better understanding of how the menstrual cycle in females and the ratio of progesterone to estradiol in females and males influence alcohol use patterns in individuals with AUD. METHODS: In this sex-separated multicenter longitudinal study, the authors analyzed 12-month data on real-life alcohol use (from 21,460 smartphone entries), menstrual cycle, and serum progesterone-to-estradiol ratios (from 667 blood samples at four individual study visits) in 74 naturally cycling females and 278 males with AUD between 2020 and 2022, using generalized and general linear mixed modeling. RESULTS: Menstrual cycle phases were significantly associated with binge drinking and progesterone-to-estradiol ratio. During the late luteal phase, females showed a lower predicted binge drinking probability of 13% and a higher predicted marginal mean of progesterone-to-estradiol ratio of 95 compared with during the menstrual, follicular, and ovulatory phases (binge drinking probability and odds ratios vs. late luteal phase, respectively: 17%, odds ratio=1.340, 95% CI=1.031, 1.742; 19%, odds ratio=1.523, 95% CI=1.190, 1.949; and 20%, odds ratio=1.683, 95% CI=1.285, 2.206; difference in progesterone-to-estradiol ratios, respectively: -61, 95% CI=-105.492, -16.095; -78, 95% CI=-119.322, -37.039; and -71, 95% CI=-114.568, -27.534). In males, a higher progesterone-to-estradiol ratio was related to lower probabilities of binge drinking and of any alcohol use, with a 10-unit increase in the hormone ratio resulting in odds ratios of 0.918 (95% CI=0.843, 0.999) and 0.914 (95% CI=0.845, 0.988), respectively. CONCLUSIONS: These ecologically valid findings suggest that high progesterone-to-estradiol ratios can have a protective effect against problematic alcohol use in females and males with AUD, highlighting the progesterone-to-estradiol ratio as a promising treatment target. Moreover, the results indicate that females with AUD may benefit from menstrual cycle phase-tailored treatments.

Pavlovian-to-Instrumental Transfer across Mental Disorders: A Review.

A mechanism known as Pavlovian-to-instrumental transfer (PIT) describes a phenomenon by which the values of environmental cues acquired through Pavlovian conditioning can motivate instrumental behavior. PIT may be one basic mechanism of action control that can characterize mental disorders on a dimensional level beyond current classification systems. Therefore, we review human PIT studies investigating subclinical and clinical mental syndromes. The literature prevails an inhomogeneous picture concerning PIT. While enhanced PIT effects seem to be present in non-substance-related disorders, overweight people, and most studies with AUD patients, no altered PIT effects were reported in tobacco use disorder and obesity. Regarding AUD and relapsing alcohol-dependent patients, there is mixed evidence of enhanced or no PIT effects. Additionally, there is evidence for aberrant corticostriatal activation and genetic risk, e.g., in association with high-risk alcohol consumption and relapse after alcohol detoxification. In patients with anorexia nervosa, stronger PIT effects elicited by low caloric stimuli were associated with increased disease severity. In patients with depression, enhanced aversive PIT effects and a loss of action-specificity associated with poorer treatment outcomes were reported. Schizophrenic patients showed disrupted specific but intact general PIT effects. Patients with chronic back pain showed reduced PIT effects. We provide possible reasons to understand heterogeneity in PIT effects within and across mental disorders. Further, we strengthen the importance of reliable experimental tasks and provide test-retest data of a PIT task showing moderate to good reliability. Finally, we point toward stress as a possible underlying factor that may explain stronger PIT effects in mental disorders, as there is some evidence that stress per se interacts with the impact of environmental cues on behavior by selectively increasing cue-triggered wanting. To conclude, we discuss the results of the literature review in the light of Research Domain Criteria, suggesting future studies that comprehensively assess PIT across psychopathological dimensions.

Clinical characteristics and cardiovascular outcomes among young patients with acute myocardial infarction in Kerala, India: A secondary analysis of ACS QUIK trial.

Background: Limited data exist on the risk profile and outcomes among young patients with acute myocardial infarction(AMI) in low-and middle-income countries(LMICs). This study explored differences in the clinical characteristics, medical care, and outcomes of AMI in young adults in India with a subanalysis focusing on sex disparities amongst the young. Methods: Using the Acute Coronary Syndrome Quality Improvement in Kerala trial database, we compared baseline characteristics, management, and outcomes amongst the young patients(≤50 years) and their older counterparts. The primary outcomes were the rates of in-hospital and 30-day composite of in-hospital major adverse cardiovascular events(MACE). Results: Of the 21,374 adults enrolled, 4762(22%) were young, of which 614 (12.9%) were females. Young patients with AMI were more likely to be smokers(41.9% vs. 27.8%;P < 0.001) and undergo coronary angiography (66.3%vs.57.3%;P < 0.001) and percutaneous coronary intervention (PCI)(57.5% vs. 47.0%;P < 0.001), compared to older patients. After adjustment for potential confounders, younger patients had a lower likelihood of in-hospital (RR = 0.49; 95%CI 0.40-0.61;P < 0.001) and 30-day MACE (RR = 0.54; 95%CI 0.46-0.64;P < 0.001). Subgroup analysis comparing young males and females revealed worse cardiovascular risk profile among young women except for smoking. In-hospital MACE(RR = 1.60; 95%CI, 1.0-2.45;P = 0.048) were higher for young women compared to men. Conclusion: Young AMI patients had higher prevalence of modifiable risk factors, were more likely to receive reperfusion therapy, and had better short and intermediate outcomes, compared to older patients. Compared to young men with AMI, young women had worse cardiovascular risk profile, were less likely to be treated with diagnostic angiography or PCI and experienced higher in-hospital death and MACE.

Caprini score and surgical times linked to the risk for venous thromboembolism after robotic-assisted radical prostatectomy.

OBJECTIVE: To evaluate the Caprini score as an independent predictor of venous thromboembolism (VTE) in patients undergoing robotic-assisted radical prostatectomy (RARP) and to identify appropriate cut-points for clinical use. MATERIAL AND METHODS: We performed a retrospective review of patients who underwent RARP for prostate cancer between December 2003 and February 2016. VTE cases developed the condition within 90 days of discharge. The control group was comprised of patients whose RARP most closely preceded and followed each VTE case in time and who were matched on lymph node dissection and surgeon. The Caprini score was calculated for each patient, and the groups were compared on a number of clinical variables. Multiple logistic regression was used to evaluate whether the Caprini score was an independent predictor of VTE. Receiver operating characteristics (ROC) curves were used to establish appropriate clinical cutpoints. RESULTS: A total of 3719 patients underwent RARP during the study period. A total of 52 (1.4%) of patients met the criteria for cases. Data were available for 97 patients who met the criteria for controls. Multiple logistic regression indicated that the Caprini score and operative time were independently both significant predictors of VTE (p=0.005 and p=0.044, respectively). ROC indicated that the Caprini score showed a significant but moderate relationship to VTE (area under curve [AOC]=0.64; p=0.004). A Caprini score >6 was the best arithmetic balance for sensitivity (61.5; 95% confidence interval [CI]: 47.0-74.7) and specificity (59.8; 95% CI: 49.3-69.6). CONCLUSION: The Caprini score predicts postoperative VTE in patients undergoing RARP.

National Comprehensive Cancer Network® Favorable Intermediate Risk Prostate Cancer-Is Active Surveillance Appropriate?

PURPOSE: We compared pathological and biochemical outcomes after radical prostatectomy in patients at favorable intermediate risk who fulfilled current NCCN® (National Comprehensive Cancer Network®) Guidelines® for active surveillance criteria to outcomes in patients who met more traditional criteria for active surveillance. MATERIALS AND METHODS: We queried our institutional review board approved prostate cancer database for patients who met NCCN criteria for very low risk (T1c, Grade Group 1, 3 or fewer of 12 cores, 50% or less core volume and prostate specific antigen density less than 0.15 ng/ml), low risk (T1-T2a, Grade Group 1 and prostate specific antigen less than 10 ng/ml) or favorable intermediate risk (major pattern grade 3 and less than 50% positive biopsy cores) and who had 1 intermediate risk factor, including T2b/c, Grade Group 2 or prostate specific antigen 10 to 20 ng/ml. Men at intermediate risk who did not meet favorable criteria were labeled as being at unfavorable intermediate risk. Patients at favorable intermediate risk were compared to those at very low and low risk, and those at unfavorable intermediate risk to identify differences in rates of adverse pathological findings at radical prostatectomy, including Gleason score Grade Group 3-5, nonorgan confined disease or nodal involvement. Time to biochemical recurrence was compared among the groups using Cox regression. RESULTS: A total of 3,686 patients underwent radical prostatectomy between January 1, 2014 and December 31, 2015. Of these men 1,454, 250 and 1,362 fulfilled the criteria for low, favorable intermediate and unfavorable intermediate risk, respectively. The rate of adverse pathological findings in favorable intermediate risk cases was significantly higher than in low risk cases and significantly lower than in unfavorable intermediate risk cases (27.4% vs 14.8% and 48.5%, respectively, each p <0.001). Time to biochemical recurrence differed significantly among the risk groups (p <0.001). CONCLUSIONS: Relative to men at low risk those at favorable intermediate risk represent a distinct group. Care should be taken when selecting these patients for active surveillance and monitoring them once they are in an active surveillance program.