Testosterone Treatment and Fractures in Men with Hypogonadism.

BACKGROUND: Testosterone treatment in men with hypogonadism improves bone density and quality, but trials with a sufficiently large sample and a sufficiently long duration to determine the effect of testosterone on the incidence of fractures are needed. METHODS: In a subtrial of a double-blind, randomized, placebo-controlled trial that assessed the cardiovascular safety of testosterone treatment in middle-aged and older men with hypogonadism, we examined the risk of clinical fracture in a time-to-event analysis. Eligible men were 45 to 80 years of age with preexisting, or high risk of, cardiovascular disease; one or more symptoms of hypogonadism; and two morning testosterone concentrations of less than 300 ng per deciliter (10.4 nmol per liter), in fasting plasma samples obtained at least 48 hours apart. Participants were randomly assigned to apply a testosterone or placebo gel daily. At every visit, participants were asked if they had had a fracture since the previous visit. If they had, medical records were obtained and adjudicated. RESULTS: The full-analysis population included 5204 participants (2601 in the testosterone group and 2603 in the placebo group). After a median follow-up of 3.19 years, a clinical fracture had occurred in 91 participants (3.50%) in the testosterone group and 64 participants (2.46%) in the placebo group (hazard ratio, 1.43; 95% confidence interval, 1.04 to 1.97). The fracture incidence also appeared to be higher in the testosterone group for all other fracture end points. CONCLUSIONS: Among middle-aged and older men with hypogonadism, testosterone treatment did not result in a lower incidence of clinical fracture than placebo. The fracture incidence was numerically higher among men who received testosterone than among those who received placebo. (Funded by AbbVie and others; TRAVERSE ClinicalTrials.gov number, NCT03518034.).

Results from a prospective longitudinal survey of employment and work outcomes in newly diagnosed cancer patients during and after curative-intent chemotherapy: A Wisconsin Oncology Network study.

BACKGROUND: Postcancer work limitations may affect a substantial proportion of patients and contribute to the "financial toxicity" of cancer treatment. The degree and nature of work limitations and employment outcomes are poorly understood for cancer patients, particularly in the immediate period of transition after active treatment. We prospectively examined employment, work ability, and work limitations during and after treatment. METHODS: A total of 120 patients receiving curative therapy who were employed prior to their cancer diagnosis and who intended to work during or after end of treatment (EOT) completed surveys at baseline (pretreatment), EOT, and 3, 6, and 12 months after EOT. Surveys included measures of employment, work ability, and work limitations. Descriptive statistics (frequencies, percentages, means with standard deviations) were calculated. RESULTS: A total of 111 participants completed the baseline survey. On average, participants were 48 years of age and were mostly white (95%) and female (82%) with a diagnosis of breast cancer (69%). Full-time employment decreased during therapy (from 88% to 50%) and returned to near prediagnosis levels by 12-month follow-up (78%). Work-related productivity loss due to health was high during treatment. CONCLUSIONS: This study is the first to report the effects of curative intent cancer therapy on employment, work ability, and work limitations both during and after treatment. Perceived work ability was generally high overall 12 months after EOT, although a minority reported persistent difficulty. A prospective analysis of factors (eg, job type, education, symptoms) most associated with work limitations is underway to assist in identifying at-risk patients.

Apabetalone and hospitalization for heart failure in patients following an acute coronary syndrome: a prespecified analysis of the BETonMACE study.

BACKGROUND: Patients with diabetes and acute coronary syndrome (ACS) are at high risk for subsequent heart failure. Apabetalone is a selective inhibitor of bromodomain and extra-terminal (BET) proteins, epigenetic regulators of gene expression. Preclinical data suggest that apabetalone exerts favorable effects on pathways related to myocardial structure and function and therefore could impact subsequent heart failure events. The effect of apabetalone on heart failure events after an ACS is not currently known. METHODS: The phase 3 BETonMACE trial was a double-blind, randomized comparison of apabetalone versus placebo on the incidence of major adverse cardiovascular events (MACE) in 2425 patients with a recent ACS and diabetes. This prespecified secondary analysis investigated the impact of apabetalone on hospitalization for congestive heart failure, not previously studied. RESULTS: Patients (age 62 years, 74.4% males, 90% high-intensity statin use, LDL-C 70.3 mg/dL, HDL-C 33.3 mg/dL and HbA1c 7.3%) were followed for an average 26 months. Apabetalone treated patients experienced the nominal finding of a lower rate of first hospitalization for heart failure (2.4% vs. 4.0%, HR 0.59 [95%CI 0.38-0.94], P = 0.03), total number of hospitalizations for heart failure (35 vs. 70, HR 0.47 [95%CI 0.27-0.83], P = 0.01) and the combination of cardiovascular death or hospitalization for heart failure (5.7% vs. 7.8%, HR 0.72 [95%CI 0.53-0.98], P = 0.04). CONCLUSION: Apabetalone treatment was associated with fewer hospitalizations for heart failure in patients with type 2 diabetes and recent ACS. Future studies are warranted to define the potential for BET inhibition with apabetalone to prevent heart failure in patients with diabetes and ACS.

Impact of endotracheal tube size and cuff pressure on tracheal and laryngeal mucosa of adult horses.

OBJECTIVE: To assess the effects of two sizes of silicone endotracheal tubes with internal diameter 26 mm (ETT26) and 30 mm (ETT30) inflated to minimum occlusive volume on tracheal and laryngeal mucosa of adult horses anesthetized for 2 hours with isoflurane. STUDY DESIGN: Prospective, randomized, blinded, crossover experimental study. ANIMALS: A total of eight healthy adult mares. METHODS: Upper airway endoscopy and ultrasound measurements of internal tracheal diameter were performed the day before anesthesia. Horses were anesthetized and orotracheally intubated with ETT26 or ETT30. Ease of intubation was scored. The cuff was inflated in 10 mL increments to produce a seal. Final volume of air used and intracuff (IC) pressure (measured by pressure transducer) were recorded. At the end of anesthesia, a manometer was used to measure IC pressure and these measurements compared against measurements from the pressure transducer. Laryngeal and tracheal mucosa were assessed via endoscopy and assigned a score 0-3 before anesthesia, and at 2 and 24 hours following extubation. RESULTS: Data are from seven horses because one horse with laryngeal hemiplegia was excluded. Mean tracheal ultrasound measurement was 3.5 ± 0.4 cm. No significant differences were noted between endotracheal tube sizes for intubation score, IC pressures, inflation volumes or tracheal or laryngeal injury scores at any time point. IC pressure measured by manometer was slightly higher than that by transducer (+1.0 ± 2.8 mmHg). CONCLUSIONS AND CLINICAL RELEVANCE: Results identified no clear advantage of one endotracheal tube size over the other in the population of horses studied, when endotracheal intubation is properly applied and IC pressure is carefully monitored. However, given that ETT26 was associated with the highest observed IC pressures and the only observed incidents of tracheal circumferential erythema, the larger ETT30 may be the better choice in most cases where tracheal size is sufficient.

Effect of Apabetalone Added to Standard Therapy on Major Adverse Cardiovascular Events in Patients With Recent Acute Coronary Syndrome and Type 2 Diabetes: A Randomized Clinical Trial.

Importance: Bromodomain and extraterminal proteins are epigenetic regulators of gene transcription. Apabetalone is a selective bromodomain and extraterminal protein inhibitor targeting bromodomain 2 and is hypothesized to have potentially favorable effects on pathways related to atherothrombosis. Pooled phase 2 data suggest favorable effects on clinical outcomes. Objective: To test whether apabetalone significantly reduces major adverse cardiovascular events. Design, Setting, and Participants: A randomized, double-blind, placebo-controlled trial, conducted at 190 sites in 13 countries. Patients with an acute coronary syndrome in the preceding 7 to 90 days, type 2 diabetes, and low high-density lipoprotein cholesterol levels were eligible for enrollment, which started November 11, 2015, and ended July 4, 2018, with end of follow-up on July 3, 2019. Interventions: Patients were randomized (1:1) to receive apabetalone, 100 mg orally twice daily (n = 1215), or matching placebo (n = 1210) in addition to standard care. Main Outcomes and Measures: The primary outcome was a composite of time to the first occurrence of cardiovascular death, nonfatal myocardial infarction, or stroke. Results: Among 2425 patients who were randomized (mean age, 62 years; 618 women [25.6%]), 2320 (95.7%) had full ascertainment of the primary outcome. During a median follow-up of 26.5 months, 274 primary end points occurred: 125 (10.3%) in apabetalone-treated patients and 149 (12.4%) in placebo-treated patients (hazard ratio, 0.82 [95% CI, 0.65-1.04]; P = .11). More patients allocated to apabetalone than placebo discontinued study drug (114 [9.4%] vs 69 [5.7%]) for reasons including elevations of liver enzyme levels (35 [2.9%] vs 11 [0.9%]). Conclusions and Relevance: Among patients with recent acute coronary syndrome, type 2 diabetes, and low high-density lipoprotein cholesterol levels, the selective bromodomain and extraterminal protein inhibitor apabetalone added to standard therapy did not significantly reduce the risk of major adverse cardiovascular events. Trial Registration: ClinicalTrials.gov Identifier: NCT02586155.

A randomized trial of immediate versus delayed survivorship care plan receipt on patient satisfaction and knowledge of diagnosis and treatment.

BACKGROUND: Survivorship care plans (SCPs) and care-planning sessions have been recommended for over a decade, yet evidence for their benefit remains mixed. In a randomized trial, changes in survivor knowledge and satisfaction before and after the receipt of an SCP were assessed. METHODS: Patients with breast cancer who had completed curative-intent treatment were randomized to immediate versus delayed receipt of an individualized SCP. All participants completed the modified Wisconsin Survey of Cancer Diagnosis and Management in Breast Cancer and the Preparing for Life As a New Survivor survey to assess individual knowledge about cancer diagnosis, treatment, side effects, and follow-up as well as satisfaction with communication and care coordination. Surveys were completed at baseline, at 4 weeks (before delayed receipt), and again at 12 weeks (after all participants had received SCPs); the primary outcome was change in knowledge at 4 weeks. RESULTS: In total, 127 eligible women were randomized. An improvement in individual knowledge was observed between baseline and week 12 for both arms combined (+1.6; 95% confidence interval, 0.9-2.3; P < .001). There was no statistically significant difference in the change in knowledge from baseline through week 4 between the arms. No significant change occurred for satisfaction scores over time. CONCLUSIONS: This randomized trial of immediate versus delayed SCP receipt demonstrated a small improvement (4%) in survivor knowledge. However, this improvement did not appear to be related to SCP provision. The authors hypothesized that the improvement was because of repeated administration of the knowledge survey. If improved survivor knowledge is a goal, then strategies beyond the 1-time provision and review of an SCP should be explored.

Integrated Care: Should It Count as Community Psychiatry Training for Psychiatry Residents?

Psychiatry residents are required to be exposed to community psychiatry. Historically, this occurred in public hospitals or assertive community treatment (ACT) teams. A new model of psychiatric care delivery, integrated care, has become prevalent. While integrated care shares some features with traditional community psychiatry rotations, no research exists to demonstrate if integrated care rotations can accomplish the aims of traditional rotations. This pilot study compared learning outcomes in ACT team rotations versus integrated care rotations. Pre- and post-rotation surveys were disseminated to third-year psychiatry residents (N = 8) who were randomized to complete a rotation with an ACT team or an integrated care team. By rotation end, many in both settings changed how conservative they were in treatment philosophies, but this did not result in a difference between groups. Residents in both groups were satisfied with their rotations. Training in integrated care may be a reasonable alternative to traditional community psychiatry rotations.

A survey of stereotactic radiation therapy in veterinary medicine.

Radiotherapy plays an important role in curative and palliative cancer treatment. As a novel radiation delivery technique, stereotactic radiotherapy utilizes three-dimensional-conformal treatment planning, high-precision beam delivery technology, and patient specific position verification to target tumors, often in one to five high-dose fractions. Currently, there is no consensus about best stereotactic radiotherapy practices in veterinary radiotherapy. The objective of this study was to document the breadth of perspectives, techniques, and applications of stereotactic radiotherapy in veterinary medicine. We conducted an online survey of American College of Veterinary Radiology members specializing in radiation oncology to assess how, when, and why stereotactic radiotherapy is being used. Both stereotactic radiotherapy users and nonusers completed the survey. The overall response and survey completion rates were 54% (67/123) and 87% (58/67), respectively. Overall, 55% of respondents reported providing stereotactic radiotherapy at their facility, with a median of 4.5 canine cases and one feline case per month. Delivery methods included C-arm linear accelerator with multi-leaf collimator, helical tomotherapy, and CyberKnife. Nonpituitary intracranial tumors, pituitary tumors, and sinonasal tumors were the most common cancers treated using stereotactic radiotherapy in both species. The most common fractionation scheme was three fractions of 10 Gy/fraction. The results of this survey suggest common availability of stereotactic radiotherapy in veterinary radiation facilities. These results provide valuable information regarding current stereotactic radiotherapy practices in veterinary medicine, and may provide an initial step toward standardizing methods and establishing consensus guidelines.

Effect of PR Interval on Outcomes Following Cardiac Resynchronization Therapy: A Secondary Analysis of the COMPANION Trial.

BACKGROUND: Prolonged PR intervals may impair atrioventricular mechanical coupling and adversely affect cardiac performance. We hypothesize that patients with advanced systolic heart failure, wide QRS complexes, and prolonged PR intervals will have improved survival from CRT-D regardless of whether left bundle branch block (LBBB) or non-LBBB is present. METHODS AND RESULTS: A total of 308 patients enrolled in the optimal pharmacologic therapy (OPT) and 595 patients in the cardiac resynchronization therapy with defibrillation (CRT-D) arms of the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure trial were stratified according to normal (≤230 ms) or prolonged PR interval (>230 ms). The incidence of all-cause mortality (ACM) or hospitalization (primary endpoint) and ACM (secondary endpoint) was compared using Kaplan-Meier curves. Cox proportional hazards models for the primary and secondary endpoints were fit with LBBB status and baseline PR interval. CRT-D treatment reduced both hospitalization/ACM (P = 0.002) and ACM (P = 0.003) compared to OPT. However, CRT-D was increasingly more effective in reducing ACM hazard in patients with longer baseline PR intervals (P = 0.002) regardless of LBBB status. In particular, in the prolonged baseline PR interval subgroup, ACM was reduced with CRT-D compared to OPT (P = 0.001) with little evidence of ACM reduction in the normal PR subgroup (P = 0.07). CONCLUSIONS: In patients with advanced systolic heart failure, wide QRS complexes, and prolonged PR intervals, restoration of atrioventricular mechanical coupling with CRT-D may improve survival regardless of LBBB status. In patients with non-LBBB, a benefit from CRT-D may occur with prolonged PR intervals.

Retinal detachment postphacoemulsification in Bichon Frises: a retrospective study of 54 dogs.

OBJECTIVE: To compare rates of retinal detachment (RD) postphacoemulsification in American Bichon Frises with and without prophylactic retinopexy. PROCEDURES: Medical records of 54 Bichon Frises undergoing phacoemulsification with or without prophylactic retinopexy between 2003 and 2013 in one or both eyes were reviewed from five Midwestern university veterinary teaching hospitals. Inclusion criteria were preoperative ERG, at least 6 months of follow-up postphacoemulsification, and the absence of preexisting RD as determined by ophthalmic examination and/or ultrasound. Statistical analyses were performed using chi-squared test, and Wilcoxon rank-sum tests and Wilson confidence intervals with the P-value <0.05 were considered significant. RESULTS: Phacoemulsification was performed without retinopexy in 79 eyes (42 dogs, non-PR group) and with prophylactic retinopexy in 23 eyes (12 dogs, PR group). Incidence of diabetes mellitus was 10/42 and 3/12 in the non-PR and the PR groups, respectively (P = 0.93). Intraocular lens implantation was performed in 40/42 non-PR dogs and 11/12 PR dogs (P = 0.63, 73/79 vs. 21/23 eyes). At final re-examination, RD occurred in 4/79 eyes without retinopexy, compared to 0/23 RD in the retinopexy group. There was no statistically significant difference in RD rates between the two groups (P = 0.27). CONCLUSIONS: These data provide no statistical evidence to support prophylactic retinopexy in Bichon Frises. Due to the low rate of retinal detachment following phacoemulsification without prophylactic retinopexy, the procedure appears to offer limited benefit to offset cost, procedural risk, and risk of extended or repeated anesthesia in Bichon Frises.

Daptomycin dosing based on ideal body weight versus actual body weight: comparison of clinical outcomes.

Daptomycin use at our institution changed to ideal body weight dosing based on a published analysis of pharmacokinetic-pharmacodynamic efficacy target attainment, bacterial ecology, and a desire to reduce drug toxicity. The current study compared outcomes between actual body weight and ideal body weight dosing of daptomycin before and after this intervention. In the evaluable group, 69 patients received doses based on actual body weight and 48 patients received doses based on ideal body weight. Patients were treated for documented Enterococcus species, Staphylococcus aureus, or coagulase-negative Staphylococcus infections, including bloodstream, intraabdominal, skin and soft tissue, urinary, and bone. There was no statistically significant difference in clinical success between the groups (88.9% for actual body weight compared to 89.1% for ideal body weight, P = 0.97). After we adjusted for gender, age, body mass index, concomitant 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors, infection type, and organism type, clinical success rates remained similar between groups (adjusted odds ratio of 0.68 in favor of actual body weight, 95% confidence interval [CI] of 0.13 to 3.55). Microbiological outcomes, length of stay, mortality, and adverse effects were also similar between groups. Further studies are warranted to confirm that ideal body weight dosing provides similar outcomes to actual body weight dosing for all patients and types of infections and organisms.

Quantifying optic nerve axons in a cat glaucoma model by a semi-automated targeted counting method.

PURPOSE: To describe and validate a semi-automated targeted sampling (SATS) method for quantifying optic nerve axons in a feline glaucoma model. METHODS: Optic nerve cross sections were obtained from 15 cats, nine with mild to severe glaucoma and six with normal eyes. Optic nerves were dissected, fixed in paraformaldehyde and glutaraldehyde, and processed for light microscopy by resin embedding, sectioning, and staining of axon myelin sheaths with 1% p-phenylenediamine before axon quantification. Commercially available image analysis software was used as a semi-automated axon counting tool (SCT) and was first validated by comparison with a manual axon count (MAC). This counting tool was then used in a SATS method performed by three masked raters and in a semi-automated full count (SAFC) method performed by a single observer. Correlation was assessed between the SCT and MAC using a linear model and analysis of covariance (ANCOVA). Correlation between the SATS and SAFC methods was calculated and the bias, systematic errors, and variance component assessed. The intraclass correlation coefficient (ICC) was determined to establish inter-rater agreement. In addition, the time required to perform the SATS and SAFC methods was evaluated. RESULTS: Correlation between the axon counts obtained by the SCT and MAC was strong (r = 0.9985). There was evidence of an overcounting of axons by the SCT compared to the MAC with a percentage error rate of 13.0% (95% confidence interval [CI] 11.0%, 15.1%). Both the correlation of SATS count (average per rater) to SAFC (r = 0.9891) and inter-rater agreement (ICC = 0.986) were high. The SATS method presented an overall positive counting error (p<0.001) when compared to the SAFC, consistent with a fixed percentage overestimation of 11.2% (95% CI 8.3%, 14.2%) of the full count. The average time required to quantify axons by the SATS method was 10.9 min, only 27% of that required to conduct the SAFC. CONCLUSIONS: Our data demonstrate that the SATS method provides a practical, rapid, and reliable means of estimating axon counts in the optic nerves of cats with glaucoma.

Development and evaluation of a survey to assess survivor knowledge change after survivorship care plans: WiSDOM-B (Wisconsin Survey of cancer DiagnOsis and Management in Breast cancer).

The oncology community has increased efforts to inform survivors about long-term risks and planned follow-up after cancer treatment. Survivorship care plans (SCPs) have been recommended since 2005, yet the benefits of implementation are only now being emphasized. SCPs are hypothesized to enhance patient knowledge. The Wisconsin Survey of Diagnosis and Management in Breast Cancer (WiSDOM-B) was developed to measure changes in breast cancer survivor knowledge pre- and postdelivery of an SCP. The WiSDOM-B was developed with input from oncologists (medical, radiation, and surgical), patient advocates, cancer survivors, and survey design experts. Initially, nine patients evaluated survey content, and modifications were made to enhance clarity. Subsequently, 38 patients were enrolled in a randomized pilot trial assessing SCP impact on knowledge of diagnosis, treatment, late effects, and follow-up (WiSDOM-B) and satisfaction with knowledge (existing survey). The WiSDOM-B was developed using feedback from multiple stakeholders. Baseline knowledge was poor and remained stable in the control arm. There was a suggestion of increased survivor knowledge following receipt of SCPs in the intervention arm (68.4 vs. 74.4%). Change was not statistically significant compared with the control arm. Despite knowledge deficits, baseline satisfaction with knowledge was high for both groups, with 100% of patients being satisfied/very satisfied with information provided. Satisfaction did not change significantly following SCP receipt. The WiSDOM-B assesses survivor knowledge of cancer diagnosis, treatment, follow-up, and side effects. It will be a useful tool for future studies assessing the impact of care plans on survivor knowledge.

Vowel Production in Children and Adults With Down Syndrome: Fundamental and Formant Frequencies of the Corner Vowels.

PURPOSE: Atypical vowel production contributes to reduced speech intelligibility in children and adults with Down syndrome (DS). This study compares the acoustic data of the corner vowels /i/, /u/, /æ/, and /ɑ/ from speakers with DS against typically developing/developed (TD) speakers. METHOD: Measurements of the fundamental frequency (f o) and first four formant frequencies (F1-F4) were obtained from single word recordings containing the target vowels from 81 participants with DS (ages 3-54 years) and 293 TD speakers (ages 4-92 years), all native speakers of English. The data were used to construct developmental trajectories and to determine interspeaker and intraspeaker variability. RESULTS: Trajectories for DS differed from TD based on age and sex, but the groups were similar with the striking change in f o and F1-F4 frequencies around age 10 years. Findings confirm higher f o in DS, and vowel-specific differences between DS and TD in F1 and F2 frequencies, but not F3 and F4. The measure of F2 differences of front-versus-back vowels was more sensitive of compression than reduced vowel space area/centralization across age and sex. Low vowels had more pronounced F2 compression as related to reduced speech intelligibility. Intraspeaker variability was significantly greater for DS than TD for nearly all frequency values across age. DISCUSSION: Vowel production differences between DS and TD are age- and sex-specific, which helps explain contradictory results in previous studies. Increased intraspeaker variability across age in DS confirms the presence of a persisting motor speech disorder. Atypical vowel production in DS is common and related to dysmorphology, delayed development, and disordered motor control.

Prostate Safety Events During Testosterone Replacement Therapy in Men With Hypogonadism: A Randomized Clinical Trial.

Importance: The effect of testosterone replacement therapy (TRT) on the risk of prostate cancer and other adverse prostate events is unknown. Objective: To compare the effect of TRT vs placebo on the incidences of high-grade prostate cancers (Gleason score ≥4 + 3), any prostate cancer, acute urinary retention, invasive prostate procedures, and pharmacologic treatment for lower urinary tract symptoms in men with hypogonadism. Design, Setting, and Participants: This placebo-controlled, double-blind randomized clinical trial enrolled 5246 men (aged 45-80 years) from 316 US trial sites who had 2 testosterone concentrations less than 300 ng/dL, hypogonadal symptoms, and cardiovascular disease (CVD) or increased CVD risk. Men with prostate-specific antigen (PSA) concentrations greater than 3.0 ng/mL and International Prostate Symptom Score (IPSS) greater than 19 were excluded. Enrollment took place between May 23, 2018, and February 1, 2022, and end-of-study visits were conducted between May 31, 2022, and January 19, 2023. Intervention: Participants were randomized, with stratification for prior CVD, to topical 1.62% testosterone gel or placebo. Main Outcomes and Measures: The primary prostate safety end point was the incidence of adjudicated high-grade prostate cancer. Secondary end points included incidence of any adjudicated prostate cancer, acute urinary retention, invasive prostate surgical procedure, prostate biopsy, and new pharmacologic treatment. Intervention effect was analyzed using a discrete-time proportional hazards model. Results: A total of 5204 men (mean [SD] age, 63.3 [7.9] years) were analyzed. At baseline, the mean (SD) PSA concentration was 0.92 (0.67) ng/mL, and the mean (SD) IPSS was 7.1 (5.6). The mean (SD) treatment duration as 21.8 (14.2) months in the TRT group and 21.6 (14.0) months in the placebo group. During 14 304 person-years of follow-up, the incidence of high-grade prostate cancer (5 of 2596 [0.19%] in the TRT group vs 3 of 2602 [0.12%] in the placebo group; hazard ratio, 1.62; 95% CI, 0.39-6.77; P = .51) did not differ significantly between groups; the incidences of any prostate cancer, acute urinary retention, invasive surgical procedures, prostate biopsy, and new pharmacologic treatment also did not differ significantly. Change in IPSS did not differ between groups. The PSA concentrations increased more in testosterone-treated than placebo-treated men. Conclusions and Relevance: In a population of middle-aged and older men with hypogonadism, carefully evaluated to exclude those at high risk of prostate cancer, the incidences of high-grade or any prostate cancer and other prostate events were low and did not differ significantly between testosterone- and placebo-treated men. The study's findings may facilitate a more informed appraisal of the potential risks of TRT. Trial Registration: ClinicalTrials.gov Identifier: NCT03518034.

Effect of lateral epicondylosis on grip force development.

STUDY DESIGN: Case-Control. INTRODUCTION: Although it is well known that grip strength is adversely affected by lateral epicondylosis (LE), the effect of LE on rapid grip force generation is unclear. PURPOSE OF THE STUDY: To evaluate the effect of LE on the ability to rapidly generate grip force. METHODS: Twenty-eight participants with LE (13 unilateral and 15 bilateral LE) and 13 healthy controls participated in this study. A multiaxis profile dynamometer was used to evaluate grip strength and rapid grip force generation. The ability to rapidly produce force is composed of the electromechanical delay and rate of force development. Electromechanical delay is defined as the time between the onset of electrical activity and the onset of muscle force production. The Patient-rated Tennis Elbow Evaluation (PRTEE) questionnaire was used to assess pain and functional disability. Magnetic resonance imaging was used to evaluate tendon degeneration. RESULTS: LE-injured upper extremities had lower rate of force development (50 lb/sec, confidence interval [CI]: 17, 84) and less grip strength (7.8 lb, CI: 3.3, 12.4) than nonnjured extremities. Participants in the LE group had a longer electromechanical delay (- 59% , CI: 29, 97) than controls. Peak rate of force development had a higher correlation (r = 0.56; p<0.05) with PRTEE function than grip strength (r = 0.47; p<0.05) and electromechanical delay (r = 0.30; p>0.05) for participants with LE. In addition to a reduction in grip strength, those with LE had a reduction in rate of force development and an increase in electromechanical delay. CONCLUSIONS: Collectively, these changes may contribute to an increase in reaction time, which may affect risk for recurrent symptoms. These findings suggest that therapists may need to address both strength and rapid force development deficits in patients with LE. LEVEL OF EVIDENCE: 3B.

Anatomic development of the upper airway during the first five years of life: A three-dimensional imaging study.

PURPOSE: Normative data on the growth and development of the upper airway across the sexes is needed for the diagnosis and treatment of congenital and acquired respiratory anomalies and to gain insight on developmental changes in speech acoustics and disorders with craniofacial anomalies. METHODS: The growth of the upper airway in children ages birth to 5 years, as compared to adults, was quantified using an imaging database with computed tomography studies from typically developing individuals. Methodological criteria for scan inclusion and airway measurements included: head position, histogram-based airway segmentation, anatomic landmark placement, and development of a semi-automatic centerline for data extraction. A comprehensive set of 2D and 3D supra- and sub-glottal measurements from the choanae to tracheal opening were obtained including: naso-oro-laryngo-pharynx subregion volume and length, each subregion's superior and inferior cross-sectional-area, and antero-posterior and transverse/width distances. RESULTS: Growth of the upper airway during the first 5 years of life was more pronounced in the vertical and transverse/lateral dimensions than in the antero-posterior dimension. By age 5 years, females have larger pharyngeal measurement than males. Prepubertal sex-differences were identified in the subglottal region. CONCLUSIONS: Our findings demonstrate the importance of studying the growth of the upper airway in 3D. As the lumen length increases, its shape changes, becoming increasingly elliptical during the first 5 years of life. This study also emphasizes the importance of methodological considerations for both image acquisition and data extraction, as well as the use of consistent anatomic structures in defining pharyngeal regions.

Effect of Apabetalone on Cardiovascular Events in Diabetes, CKD, and Recent Acute Coronary Syndrome: Results from the BETonMACE Randomized Controlled Trial.

BACKGROUND AND OBJECTIVES: CKD and type 2 diabetes mellitus interact to increase the risk of major adverse cardiovascular events (i.e., cardiovascular death, nonfatal myocardial infarction, or stroke) and congestive heart failure. A maladaptive epigenetic response may be a cardiovascular risk driver and amenable to modification with apabetalone, a selective modulator of the bromodomain and extraterminal domain transcription system. We examined this question in a prespecified analysis of BETonMACE, a phase 3 trial. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: BETonMACE was an event-driven, randomized, double-blind, placebo-controlled trial comparing effects of apabetalone versus placebo on major adverse cardiovascular events and heart failure hospitalizations in 2425 participants with type 2 diabetes and a recent acute coronary syndrome, including 288 participants with CKD with eGFR <60 ml/min per 1.73 m2 at baseline. The primary end point in BETonMACE was the time to the first major adverse cardiovascular event, with a secondary end point of time to hospitalization for heart failure. RESULTS: Median follow-up was 27 months (interquartile range, 20-32 months). In participants with CKD, apabetalone compared with placebo was associated with fewer major adverse cardiovascular events (13 events in 124 patients [11%] versus 35 events in 164 patients [21%]; hazard ratio, 0.50; 95% confidence interval, 0.26 to 0.96) and fewer heart failure-related hospitalizations (three hospitalizations in 124 patients [3%] versus 14 hospitalizations in 164 patients [9%]; hazard ratio, 0.48; 95% confidence interval, 0.26 to 0.86). In the non-CKD group, the corresponding hazard ratio values were 0.96 (95% confidence interval, 0.74 to 1.24) for major adverse cardiovascular events, and 0.76 (95% confidence interval, 0.46 to 1.27) for heart failure-related hospitalization. Interaction of CKD on treatment effect was P=0.03 for major adverse cardiovascular events, and P=0.12 for heart failure-related hospitalization. Participants with CKD showed similar numbers of adverse events, regardless of randomization to apabetalone or placebo (119 [73%] versus 88 [71%] patients), and there were fewer serious adverse events (29% versus 43%; P=0.02) in the apabetalone group. CONCLUSIONS: Apabetalone may reduce the incidence of major adverse cardiovascular events in patients with CKD and type 2 diabetes who have a high burden of cardiovascular disease.