Effects of oral contraceptives on spatial cognition depend on pharmacological properties and phase of the contraceptive cycle.

The central nervous system effects of oral contraceptives (OCs) are not well-documented. In a set of 3 studies, we investigated a specific cognitive function, mental rotation, in healthy women currently using OCs for contraceptive purposes (n = 201) and in medication-free controls not using OCs (n = 44). Mental rotation was measured using a well-standardized and extensively validated psychometric test, the Vandenberg Mental Rotations Test (MRT). In an initial study (Study 1), current OC users (n = 63) were tested during the active or inactive phases of the contraceptive cycle in a parallel-groups design. Studies 2 and 3 were based on an archival dataset (n = 201 current OC users) that consisted of data on the MRT collected in real-time over a 30-year period and compiled for purposes of the present work. The OCs were combined formulations containing ethinyl estradiol (10-35 ug/day) plus a synthetic progestin. All 4 families of synthetic progestins historically used in OCs were represented in the dataset. Cognitive performance was evaluated during either active OC use ('active phase') or during the washout week of the contraceptive cycle ('inactive phase') when OC steroids are not used. The results showed a significant phase-of-cycle (POC) effect. Accuracy on the MRT was mildly diminished during the active phase of OC use, while scores on verbal fluency and speeded motor tasks were modestly improved. The POC effect was most evident in women using OCs that contained first- or second-generation progestins (the estrane family of progestins or OCs containing levonorgestrel), but not in women using OCs containing recently developed progestins and lower doses of ethinyl estradiol. Using independently established ratings of the estrogenic, androgenic, and progestogenic intensities of the different OC formulations, each brand of OC was classified according to its distinct endocrine profile. Multiple regression revealed that the effects of OC use on the MRT could be predicted based on the estrogenic strength of the contraceptives used. Estrogenic potency, not androgenic or anti-androgenic effects of the OC pill, may underlie the effects of OC usage on spatial cognition.

Effect of Perioperative Active Body Surface Warming Systems on Analgesic and Clinical Outcomes: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Inadvertent perioperative hypothermia is a common complication of surgery, and active body surface warming (ABSW) systems are used to prevent adverse clinical outcomes. Prior data on certain outcomes are equivocal (ie, blood loss) or limited (ie, pain and opioid consumption). The objective of this study was to provide an updated review on the effect of ABSW on clinical outcomes and temperature maintenance. METHODS: We conducted a systematic review of randomized controlled trials evaluating ABSW systems compared to nonactive warming controls in noncardiac surgeries. Outcomes studied included postoperative pain scores and opioid consumption (primary outcomes) and other perioperative clinical variables such as temperature changes, blood loss, and wound infection (secondary outcomes). We searched Ovid MEDLINE daily, Ovid MEDLINE, EMBASE, CINHAL, Cochrane CENTRAL, and Web of Science from inception to June 2019. Quality of evidence (QoE) was rated according to the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. Subgroup analysis sought to determine the effect of preoperative + intraoperative warming versus intraoperative warming alone. Metaregression evaluated the effect of year of publication, use of neuromuscular blockers, anesthesia, and surgery type on outcomes. RESULTS: Fifty-four articles (3976 patients) were included. Pooled results demonstrated that ABSW maintained normothermia compared to controls, during surgery (30 minutes postinduction [mean difference {MD}: 0.3°C, 95% confidence interval {CI}, 0.2-0.4, moderate QoE]), end of surgery (MD: 1.1°C, 95% CI, 0.9-1.3, high QoE), and up to 4 hours postoperatively (MD: 0.3°C, 95% CI, 0.2-0.5, high QoE). ABSW was not associated with difference in pain scores (<24 hours postoperatively, moderate to low QoE) or perioperative opioid consumption (very low QoE). ABSW increased patient satisfaction (MD: 2.2 points, 95% CI, 0.9-3.6, moderate QoE), reduced blood transfusions (odds ratio [OR] = 0.6, 95% CI, 0.4-1.0, moderate QoE), shivering (OR = 0.2, 95% CI, 0.1-0.4, high QoE), and wound infections (OR = 0.3, 95% CI, 0.2-0.7, high QoE). No significant differences were found for fluid administration (low QoE), blood loss (very low QoE), major adverse cardiovascular events (very low QoE), or mortality (very low QoE). Subgroup analysis and metaregression suggested increased temperature benefit with pre + intraoperative warming, use of neuromuscular blockers, and recent publication year. ABSW seemed to confer less temperature benefit in cesarean deliveries and neurosurgical/spinal cases compared to abdominal surgeries. CONCLUSIONS: ABSW is effective in maintaining physiological normothermia, decreasing wound infections, shivering, blood transfusions, and increasing patient satisfaction but does not appear to affect postoperative pain and opioid use.

Withholding versus Continuing Angiotensin-converting Enzyme Inhibitors or Angiotensin II Receptor Blockers before Noncardiac Surgery: An Analysis of the Vascular events In noncardiac Surgery patIents cOhort evaluatioN Prospective Cohort.

BACKGROUND: The effect on cardiovascular outcomes of withholding angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers in chronic users before noncardiac surgery is unknown. METHODS: In this international prospective cohort study, the authors analyzed data from 14,687 patients (including 4,802 angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users) at least 45 yr old who had in-patient noncardiac surgery from 2007 to 2011. Using multivariable regression models, the authors studied the relationship between withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers and a primary composite outcome of all-cause death, stroke, or myocardial injury after noncardiac surgery at 30 days, with intraoperative and postoperative clinically important hypotension as secondary outcomes. RESULTS: Compared to patients who continued their angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, the 1,245 (26%) angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker users who withheld their angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers in the 24 h before surgery were less likely to suffer the primary composite outcome of all-cause death, stroke, or myocardial injury (150/1,245 [12.0%] vs. 459/3,557 [12.9%]; adjusted relative risk, 0.82; 95% CI, 0.70 to 0.96; P = 0.01) and intraoperative hypotension (adjusted relative risk, 0.80; 95% CI, 0.72 to 0.93; P < 0.001). The risk of postoperative hypotension was similar between the two groups (adjusted relative risk, 0.92; 95% CI, 0.77 to 1.10; P = 0.36). Results were consistent across the range of preoperative blood pressures. The practice of withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers was only modestly correlated with patient characteristics and the type and timing of surgery. CONCLUSIONS: Withholding angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers before major noncardiac surgery was associated with a lower risk of death and postoperative vascular events. A large randomized trial is needed to confirm this finding. In the interim, clinicians should consider recommending that patients withhold angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers 24 h before surgery.

Estradiol concentrations and working memory performance in women of reproductive age.

OBJECTIVE: Estrogen has been proposed to exert a regulatory influence on the working memory system via actions in the female prefrontal cortex. Tests of this hypothesis have been limited almost exclusively to postmenopausal women and pharmacological interventions. We explored whether estradiol discernibly influences working memory within the natural range of variation in concentrations characteristic of the menstrual cycle. METHOD: The performance of healthy women (n=39) not using hormonal contraceptives, and a control group of age- and education-matched men (n=31), was compared on a spatial working memory task. Cognitive testing was done blind to ovarian status. Women were retrospectively classified into low- or high-estradiol groups based on the results of radioimmunoassays of saliva collected immediately before and after the cognitive testing. RESULTS: Women with higher levels of circulating estradiol made significantly fewer errors on the working memory task than women tested under low estradiol. Pearson's correlations showed that the level of salivary estradiol but not progesterone was correlated inversely with the number of working memory errors produced. Women tested at high levels of circulating estradiol tended to be more accurate than men. Superior performance by the high estradiol group was seen on the working memory task but not on two control tasks, indicating selectivity of the effects. CONCLUSIONS: Consistent with previous studies of postmenopausal women, higher levels of circulating estradiol were associated with better working memory performance. These results add further support to the hypothesis that the working memory system is modulated by estradiol in women, and show that the effects can be observed under non-pharmacological conditions.