A randomized trial evaluating spinal as compared with general anesthesia for hip-fracture surgery in adults 50 years of age or older did not show superiority of spinal anesthesia with respect to a ...composite of death or an inability to walk unassisted at 60 days. Postoperative delirium occurred in similar percentages of patients in the two groups.
Aims
The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network initiated a second observational cohort study—the Symptom Patterns Study (SPS)—to further investigate ...the underlying pathophysiology of Urologic Chronic Pelvic Pain Syndrome (UCPPS) and to discover factors associated with longitudinal symptom changes and responses to treatments.
Methods
This multisite cohort study of males and females with UCPPS features a run‐in period of four weekly web‐based symptom assessments before a baseline visit, followed by quarterly assessments up to 36 months. Controls were also recruited and assessed at baseline and 6 months. Extensive clinical data assessing urological symptoms, nonurological pain, chronic overlapping pain syndromes, and psychosocial factors were collected. Diverse biospecimens for biomarker and microbiome studies, quantitative sensory testing (QST) data under multiple stimuli, and structural and functional neuroimaging scans were obtained under a standardized protocol.
Results
Recruitment was initiated (July 2015) and completed (February 2019) at six discovery sites. A total of 620 males and females with UCPPS and 73 Controls were enrolled, including 83 UCPPS participants who re‐enrolled from the first MAPP Network cohort study (2009‐2012). Baseline neuroimaging scans, QST measures, and biospecimens were obtained on 578 UCPPS participants. The longitudinal follow‐up of the cohort is ongoing.
Conclusions
This comprehensive characterization of a large UCPPS cohort with extended follow‐up greatly expands upon earlier MAPP Network studies and provides unprecedented opportunities to increase our understanding of UCPPS pathophysiology, factors associated with symptom change, clinically relevant patient phenotypes, and novel targets for future interventions.
BACKGROUND/OBJECTIVES
Accurate estimates of clinically important difference (CID) are required for interpreting the clinical importance of treatments to improve physical function, but CID estimates ...vary in different disease populations. We determined the CID for two common measures of walking ability in mobility‐limited older men.
Design
Longitudinal, multisite placebo‐controlled trial.
Setting/Participants
Men enrolled in the Testosterone Trials who had self‐reported mobility limitation and gait speed less than 1.2 m/second (n = 429). Testosterone‐ and placebo‐allocated participants were combined for this study.
RESULTS
Mean changes from baseline, adjusting for time‐in‐intervention and site, were 29.6, 13.2, 12.5, −2.4, and −32.6 m for 6MWD, and 15.4, 7.2, 2.1, −3.4, and −7.2 for PF10 in men who reported their mobility was “very/much better,” “little better,” “no change,” “little worse,” or “much worse,” respectively. CID estimates using regression, ROC, and eCDF varied from 5.0–29.6 m for 6MWD, and 5.0–15.2 points for PF10.
CONCLUSION
CID estimates vary by the population studied and by the method and precision of measurement. Increases of 16 to 30 m for 6MWD and 5 to 15 points for PF10 over 12 months appear to be clinically meaningful in mobility‐limited, older hypogonadal men. These CID estimates may be useful in the design of efficacy trials of therapies to improve physical function.
IMPORTANCE: As men age, they experience decreased serum testosterone concentrations, decreased bone mineral density (BMD), and increased risk of fracture. OBJECTIVE: To determine whether testosterone ...treatment of older men with low testosterone increases volumetric BMD (vBMD) and estimated bone strength. DESIGN, SETTING, AND PARTICIPANTS: Placebo-controlled, double-blind trial with treatment allocation by minimization at 9 US academic medical centers of men 65 years or older with 2 testosterone concentrations averaging less than 275 ng/L participating in the Testosterone Trials from December 2011 to June 2014. The analysis was a modified intent-to-treat comparison of treatment groups by multivariable linear regression adjusted for balancing factors as required by minimization. INTERVENTIONS: Testosterone gel, adjusted to maintain the testosterone level within the normal range for young men, or placebo gel for 1 year. MAIN OUTCOMES AND MEASURES: Spine and hip vBMD was determined by quantitative computed tomography at baseline and 12 months. Bone strength was estimated by finite element analysis of quantitative computed tomography data. Areal BMD was assessed by dual energy x-ray absorptiometry at baseline and 12 months. RESULTS: There were 211 participants (mean SD age, 72.3 5.9 years; 86% white; mean SD body mass index, 31.2 3.4). Testosterone treatment was associated with significantly greater increases than placebo in mean spine trabecular vBMD (7.5%; 95% CI, 4.8% to 10.3% vs 0.8%; 95% CI, −1.9% to 3.4%; treatment effect, 6.8%; 95% CI, 4.8%-8.7%; P < .001), spine peripheral vBMD, hip trabecular and peripheral vBMD, and mean estimated strength of spine trabecular bone (10.8%; 95% CI, 7.4% to 14.3% vs 2.4%; 95% CI, −1.0% to 5.7%; treatment effect, 8.5%; 95% CI, 6.0%-10.9%; P < .001), spine peripheral bone, and hip trabecular and peripheral bone. The estimated strength increases were greater in trabecular than peripheral bone and greater in the spine than hip. Testosterone treatment increased spine areal BMD but less than vBMD. CONCLUSIONS AND RELEVANCE: Testosterone treatment for 1 year of older men with low testosterone significantly increased vBMD and estimated bone strength, more in trabecular than peripheral bone and more in the spine than hip. A larger, longer trial could determine whether this treatment also reduces fracture risk. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00799617
Effects of Testosterone Treatment in Older Men Snyder, Peter J; Bhasin, Shalender; Cunningham, Glenn R ...
The New England journal of medicine,
02/2016, Letnik:
374, Številka:
7
Journal Article
Recenzirano
Odprti dostop
In this study, men 65 years of age or older with low serum testosterone and symptoms of hypoandrogenism received testosterone or placebo for a year. Testosterone had a moderate benefit in sexual ...function and some benefit in mood but no benefit in vitality or walking distance.
Testosterone concentrations in men decrease with increasing age.
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Many symptoms and conditions similar to those that are caused by low testosterone levels in men with pituitary or testicular disease become more common with increasing age. Such symptoms include decreases in mobility, sexual function, and energy. These parallels suggest that the lower testosterone levels in older men may contribute to these conditions.
Previous trials of testosterone treatment in men 65 years of age or older, however, have yielded equivocal results. Although testosterone treatment consistently increased muscle mass and decreased fat mass,
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effects on physical performance,
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sexual function, . . .
Surgical site infections (SSIs) are a common complication in liver transplant(LT) recipients. Lack of pediatric prophylaxis guidelines results in variation in preventative antibiotic regimens.
We ...performed a retrospective observational study of LT recipients under 18 years using a merged dataset that included data from PHIS and UNOS between 2006 and 2017. The exposure was defined as the antibiotic(s) received within 24 hours of LT; with 6 categories, ranging from narrow (category 1: cefazolin), to broad). The primary outcome was presence or absence of SSI in the index admission. Mixed-effects logistic regression compared the effectiveness of each category relative to category 1 in preventing SSI.
Of the 2586 LT, 284 (11%) met SSI criteria. SSI rate was higher (16.2%) in the younger sub-cohort compared to older (8.6%), necessitating a stratified analysis. Antibiotics from category 5 were most commonly used. In the younger sub-cohort, the adjusted risk was increased in all categories compared to the reference, most notably in category 3 (OR 2.58; 0.69-9.59) and category 6 (OR 2.76; 0.66-11.56). In the older sub-cohort, estimated ORs were also increased for each category, most notably in category 4 (2.49; 0.99-6.27). None of the ORs suggested benefit from broader-spectrum prophylaxis. Our E value assessment suggests it's unlikely there is unmeasured confounding by indication to the degree necessary to revert ORs to protective.
There was wide variation in antibiotic prophylaxis. Adjusted analyses did not reveal a protective benefit of broader-spectrum prophylaxis in either sub-cohort, suggesting that narrower regimens may be adequate.
Lessons From the Testosterone Trials Snyder, Peter J; Bhasin, Shalender; Cunningham, Glenn R ...
Endocrine reviews,
2018-June, Letnik:
39, Številka:
3
Journal Article
Recenzirano
Odprti dostop
Abstract
The Testosterone Trials (TTrials) were a coordinated set of seven placebo-controlled,
double-blind trials in 788 men with a mean age of 72 years to determine the efficacy of
increasing the ...testosterone levels of older men with low testosterone. Testosterone
treatment increased the median testosterone level from unequivocally low at baseline to
midnormal for young men after 3 months and maintained that level until month 12. In the
Sexual Function Trial, testosterone increased sexual activity, sexual desire, and erectile
function. In the Physical Function Trial, testosterone did not increase the distance
walked in 6 minutes in men whose walk speed was slow; however, in all TTrial participants,
testosterone did increase the distance walked. In the Vitality Trial, testosterone did not
increase energy but slightly improved mood and depressive symptoms. In the Cognitive
Function Trial, testosterone did not improve cognitive function. In the Anemia Trial,
testosterone increased hemoglobin in both men who had anemia of a known cause and in men
with unexplained anemia. In the Bone Trial, testosterone increased volumetric bone mineral
density and the estimated strength of the spine and hip. In the Cardiovascular Trial,
testosterone increased the coronary artery noncalcified plaque volume as assessed using
computed tomographic angiography. Although testosterone was not associated with more
cardiovascular or prostate adverse events than placebo, a trial of a much larger number of
men for a much longer period would be necessary to determine whether testosterone
increases cardiovascular or prostate risk.
The Testosterone Trials were conducted to determine if testosterone treatment would
benefit older men with low testosterone. This report describes the Trials' development and
results and the lessons learned.
IMPORTANCE: In one-third of older men with anemia, no recognized cause can be found. OBJECTIVE: To determine if testosterone treatment of men 65 years or older with unequivocally low testosterone ...levels and unexplained anemia would increase their hemoglobin concentration. DESIGN, SETTING, AND PARTICIPANTS: A double-blinded, placebo-controlled trial with treatment allocation by minimization using 788 men 65 years or older who have average testosterone levels of less than 275 ng/dL. Of 788 participants, 126 were anemic (hemoglobin ≤12.7 g/dL), 62 of whom had no known cause. The trial was conducted in 12 academic medical centers in the United States from June 2010 to June 2014. INTERVENTIONS: Testosterone gel, the dose adjusted to maintain the testosterone levels normal for young men, or placebo gel for 12 months. MAIN OUTCOMES AND MEASURES: The percent of men with unexplained anemia whose hemoglobin levels increased by 1.0 g/dL or more in response to testosterone compared with placebo. The statistical analysis was intent-to-treat by a logistic mixed effects model adjusted for balancing factors. RESULTS: The men had a mean age of 74.8 years and body mass index (BMI) (calculated as weight in kilograms divided by height in meters squared) of 30.7; 84.9% were white. Testosterone treatment resulted in a greater percentage of men with unexplained anemia whose month 12 hemoglobin levels had increased by 1.0 g/dL or more over baseline (54%) than did placebo (15%) (adjusted OR, 31.5; 95% CI, 3.7-277.8; P = .002) and a greater percentage of men who at month 12 were no longer anemic (58.3%) compared with placebo (22.2%) (adjusted OR, 17.0; 95% CI, 2.8-104.0; P = .002). Testosterone treatment also resulted in a greater percentage of men with anemia of known cause whose month 12 hemoglobin levels had increased by 1.0 g/dL or more (52%) than did placebo (19%) (adjusted OR, 8.2; 95% CI, 2.1-31.9; P = .003). Testosterone treatment resulted in a hemoglobin concentration of more than 17.5 g/dL in 6 men who had not been anemic at baseline. CONCLUSIONS AND RELEVANCE: Among older men with low testosterone levels, testosterone treatment significantly increased the hemoglobin levels of those with unexplained anemia as well as those with anemia from known causes. These increases may be of clinical value, as suggested by the magnitude of the changes and the correction of anemia in most men, but the overall health benefits remain to be established. Measurement of testosterone levels might be considered in men 65 years or older who have unexplained anemia and symptoms of low testosterone levels. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00799617
Many effects of testosterone are mediated through dihydrotestosterone (DHT) and estradiol.
To determine the relative contributions of each hormone to the observed effects of testosterone treatment in ...older men with hypogonadism.
Using data from the Testosterone Trials, we assessed the association of changes in total testosterone, estradiol, and DHT levels over 12 months of testosterone treatment with hemoglobin, high-density lipoprotein (HDL) cholesterol, volumetric bone mineral density (vBMD) of lumbar spine, sexual desire, and prostate-specific antigen (PSA). We used random forests to model the associations of predicted mean changes in outcomes with change in each hormone at low, mean, or high change in the other 2 hormones. Stepwise regression models were run to confirm the findings of random forests.
Predicted increases in hemoglobin and sexual desire were greater with larger increases in estradiol and were larger with high change in DHT compared with low change in DHT. Greater increases in estradiol were associated with larger decreases in HDL cholesterol; this association did not vary according to changes in DHT or testosterone. Change in vBMD was most robustly associated with change in estradiol and was greater with high change in testosterone and DHT. There was no consistent relation between change in PSA and change in any hormone.
Change in estradiol level was the best predictor not only of the change in vBMD and sexual desire but also of the changes in hemoglobin and HDL cholesterol. Consideration of testosterone, estradiol, and DHT together offers a superior prediction of treatment response in older hypogonadal men than testosterone alone.
IMPORTANCE: Most cognitive functions decline with age. Prior studies suggest that testosterone treatment may improve these functions. OBJECTIVE: To determine if testosterone treatment compared with ...placebo is associated with improved verbal memory and other cognitive functions in older men with low testosterone and age-associated memory impairment (AAMI). DESIGN, SETTING, AND PARTICIPANTS: The Testosterone Trials (TTrials) were 7 trials to assess the efficacy of testosterone treatment in older men with low testosterone levels. The Cognitive Function Trial evaluated cognitive function in all TTrials participants. In 12 US academic medical centers, 788 men who were 65 years or older with a serum testosterone level less than 275 ng/mL and impaired sexual function, physical function, or vitality were allocated to testosterone treatment (n = 394) or placebo (n = 394). A subgroup of 493 men met criteria for AAMI based on baseline subjective memory complaints and objective memory performance. Enrollment in the TTrials began June 24, 2010; the final participant completed treatment and assessment in June 2014. INTERVENTIONS: Testosterone gel (adjusted to maintain the testosterone level within the normal range for young men) or placebo gel for 1 year. MAIN OUTCOMES AND MEASURES: The primary outcome was the mean change from baseline to 6 months and 12 months for delayed paragraph recall (score range, 0 to 50) among men with AAMI. Secondary outcomes were mean changes in visual memory (Benton Visual Retention Test; score range, 0 to −26), executive function (Trail-Making Test B minus A; range, −290 to 290), and spatial ability (Card Rotation Test; score range, −80 to 80) among men with AAMI. Tests were administered at baseline, 6 months, and 12 months. RESULTS: Among the 493 men with AAMI (mean age, 72.3 years SD, 5.8; mean baseline testosterone, 234 ng/dL SD, 65.1), 247 were assigned to receive testosterone and 246 to receive placebo. Of these groups, 247 men in the testosterone group and 245 men in the placebo completed the memory study. There was no significant mean change from baseline to 6 and 12 months in delayed paragraph recall score among men with AAMI in the testosterone and placebo groups (adjusted estimated difference, −0.07 95% CI, −0.92 to 0.79; P = .88). Mean scores for delayed paragraph recall were 14.0 at baseline, 16.0 at 6 months, and 16.2 at 12 months in the testosterone group and 14.4 at baseline, 16.0 at 6 months, and 16.5 at 12 months in the placebo group. Testosterone was also not associated with significant differences in visual memory (−0.28 95% CI, −0.76 to 0.19; P = .24), executive function (−5.51 95% CI, −12.91 to 1.88; P = .14), or spatial ability (−0.12 95% CI, −1.89 to 1.65; P = .89). CONCLUSIONS AND RELEVANCE: Among older men with low testosterone and age-associated memory impairment, treatment with testosterone for 1 year compared with placebo was not associated with improved memory or other cognitive functions. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00799617
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