ABSTRACT
We investigated the prevalence, incidence, and rates of pharmacological treatment of delayed ejaculation using the TriNetX Diamond Network. We included all men evaluated in the inpatient, outpatient, and emergency settings. Prevalence was determined by comparing the number of men diagnosed with delayed ejaculation to the entire population. Incidence was determined by comparing the number of men diagnosed with delayed ejaculation without a prior diagnosis to the overall population without a prior diagnosis. Rates of pharmacologic treatment were calculated by comparing the number of men who received a prescription to the total number of men with delayed ejaculation. Trends in prevalence and incidence were compared using six-month intervals, while trends in pharmacologic treatment were compared using one-year intervals. A total of 23,164 adult males were diagnosed with delayed ejaculation from 2013 to 2019. During the final six-month interval (July to December 2019), 2,747 of 16,496,744 men received a delayed ejaculation diagnosis, and 1,375 of 16,488,270 men without a prior diagnosis were diagnosed with delayed ejaculation. In 2019, only 916 of 4,733 (19.4%) men diagnosed with delayed ejaculation received any prescription, with the most common being testosterone (9.5%), bupropion (6.6%), and buspirone (2.3%). Prevalence, incidence and pharmacologic treatment all had increasing trends.
ABSTRACT
Semaglutide was approved in June 2021 for weight loss in non-diabetic, obese patients. While package inserts include sexual dysfunction as a side effect, no study has assessed the degree of this risk. The objective of our study is to assess the risk of developing erectile dysfunction after semaglutide is prescribed for weight loss in obese, non-diabetic men. The TriNetX Research database was used to identify men without a diagnosis of diabetes ages 18 to 50 with BMI > 30 who were prescribed semaglutide after June 1st, 2021. Men were excluded if they had a prior erectile dysfunction diagnosis, any phosphodiesterase-5 inhibitors prescription, intracavernosal injections, penile prosthesis placement, history of testosterone deficiency, testosterone prescription, pelvic radiation, radical prostatectomy, pulmonary hypertension, or were deceased. We further restricted our cohort to non-diabetic, obese men by excluding men with a prior diabetes mellitus diagnosis, a hemoglobin A1c > 6.5%, or having ever received insulin or metformin. Men were then stratified into cohorts of those that did and did not receive a semaglutide prescription. The primary outcome was the risk of new ED diagnosis and/or new prescription of phosphodiesterase type 5 inhibitors at least one month after prescription of semaglutide. The secondary outcome was risk of testosterone deficiency diagnosis. Risk was reported using risk ratios with 95% confidence intervals (95% CI). 3,094 non-diabetic, obese men ages 18-50 who received a prescription of semaglutide were identified and subsequently matched to an equal number cohort of non-diabetic, obese men who never received a prescription of semaglutide. After matching, average age at index prescription for non-diabetic, obese men was 37.8 ± 7.8 and average BMI at index prescription was 38.6 ± 5.6. Non-diabetic men prescribed semaglutide were significantly more likely to develop erectile dysfunction and/or were prescribed phosphodiesterase type 5 inhibitors (1.47% vs 0.32%; RR: 4.5; 95% CI [2.3, 9.0]) and testosterone deficiency (1.53% vs 0.80%; RR: 1.9; 95% CI [1.2, 3.1]) when compared to the control cohort of non-diabetic men who never received a semaglutide prescription.
ABSTRACT
IMPORTANCE: Although the use of perioperative pain medications is highly investigated, limited studies have examined the usage of pain medication for post hysterectomy prolapse repair and the few that have have been restricted to smaller sample sizes. OBJECTIVE: Our objective was to assess the association of perioperative opioid usage after posthysterectomy prolapse repairs with development of new persistent opioid usage. STUDY DESIGN: The TriNetX Diamond Research Network was queried to create our cohorts of opioid-naive adult women with vaginal repair or laparoscopic sacrocolpopexy. The primary study outcomes were (1) the rate of perioperative opioid usage and (2) development of new persistent opioid usage. All cohorts were matched on age, race, ethnicity, chronic kidney disease, hypertensive diseases, ischemic heart disease, diseases of the liver, obstructive sleep apnea, affective mood disorders, pelvic and perineal pain, obesity, tobacco use, and utilization of office/outpatient, inpatient, or emergency department services. RESULTS: We identified 10,414 opioid-naive women who underwent laparoscopic sacrocolpopexy and 13,305 opioid-naive women who underwent vaginal reconstruction. Rates of perioperative opioid usage were higher after laparoscopic sacrocolpopexy. Rates of developing new opioid usage were higher in both surgical-approach populations that received perioperative opioids compared with those that did not. Rates of new and persistent opioid usage did not differ by surgical approach when stratified by perioperative opioid usage. CONCLUSIONS: We identified that opioid dependence may occur after surgery if patients are given opioids within 7 days of either approach, associating opioid dependence with perioperative opioid usage rather than the approach taken.
Subject(s)
Analgesics, Opioid , Opioid-Related Disorders , Adult , Humans , Female , Analgesics, Opioid/adverse effects , Pain, Postoperative/drug therapy , Pain Management , Opioid-Related Disorders/drug therapy , ProlapseABSTRACT
Testicular adrenal rest tumors are a rare development of patients with congenital adrenal hyperplasia. It is difficult to diagnose due to similarities with Leydig cell tumors. Treatment can be conservative or surgical. We describe the case of a 56 year old male presenting with bilateral testicular pain and irregular growth that was managed with a unilateral orchiectomy. We analyzed the distinguishing factors of testicular adrenal rest tumors compared to Leydig cell tumors, as well as the diagnostic and treatment methods.
ABSTRACT
Synthesis gas was produced by methane oxidation on a NiO/YSZ cermet by interrupting the oxygen flow. Stopping the oxygen flow provoked the diffusion of lattice oxygen in the cermet, which in turn replenished the Ni-O bond that was consumed by methane. Resuming the oxygen flow brought about the activation of oxygen on the extrinsic vacancy site of YSZ. The activation, followed by the diffusion of oxygen and a Ni/NiO redox cycle, led to oscillatory syngas production. The infrared and mass spectroscopy results provide the reaction mechanism that governs the oxidation of methane on the NiO/YSZ cermet. This study presents a technique that can be applied to the catalysis of other metal/anion or cation conductor systems.
ABSTRACT
High-altitude environments present a range of biochemical and physiological challenges for organisms through decreases in oxygen, pressure, and temperature relative to lowland habitats. Protein-level adaptations to hypoxic high-altitude conditions have been identified in multiple terrestrial endotherms; however, comparable adaptations in aquatic ectotherms, such as fishes, have not been as extensively characterized. In enzyme proteins, cold adaptation is attained through functional trade-offs between stability and activity, often mediated by substitutions outside the active site. Little is known whether signaling proteins [e.g., G protein-coupled receptors (GPCRs)] exhibit natural variation in response to cold temperatures. Rhodopsin (RH1), the temperature-sensitive visual pigment mediating dim-light vision, offers an opportunity to enhance our understanding of thermal adaptation in a model GPCR. Here, we investigate the evolution of rhodopsin function in an Andean mountain catfish system spanning a range of elevations. Using molecular evolutionary analyses and site-directed mutagenesis experiments, we provide evidence for cold adaptation in RH1. We find that unique amino acid substitutions occur at sites under positive selection in high-altitude catfishes, located at opposite ends of the RH1 intramolecular hydrogen-bonding network. Natural high-altitude variants introduced into these sites via mutagenesis have limited effects on spectral tuning, yet decrease the stability of dark-state and light-activated rhodopsin, accelerating the decay of ligand-bound forms. As found in cold-adapted enzymes, this phenotype likely compensates for a cold-induced decrease in kinetic rates-properties of rhodopsin that mediate rod sensitivity and visual performance. Our results support a role for natural variation in enhancing the performance of GPCRs in response to cold temperatures.