Testosterone replacement in men with sexual dysfunction.

BACKGROUND: Clinical practice guidelines recommend testosterone replacement therapy (TRT) for men with sexual dysfunction and testosterone deficiency. However, TRT is commonly promoted in men without testosterone deficiency and existing trials often do not clearly report participants' testosterone levels or testosterone-related symptoms. This review assesses the potential benefits and harms of TRT in men presenting with complaints of sexual dysfunction. OBJECTIVES: To assess the effects of testosterone replacement therapy compared to placebo or other medical treatments in men with sexual dysfunction. SEARCH METHODS: We performed a comprehensive search of CENTRAL (the Cochrane Library), MEDLINE, EMBASE, and the trials registries ClinicalTrials.gov and World Health Organization International Clinical Trials Registry Platform, with no restrictions on language of publication or publication status, up to 29 August 2023. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in men (40 years or over) with sexual dysfunction. We excluded men with primary or secondary hypogonadism. We compared testosterone or testosterone with phosphodiesterase-5 inhibitors (PDEI5I) to placebo or PDE5I alone. DATA COLLECTION AND ANALYSIS: Two review authors independently screened the literature, assessed the risk of bias, extracted data, and rated the certainty of evidence (CoE) according to GRADE using a minimally contextualized approach. We performed statistical analyses using a random-effects model and interpreted them according to standard Cochrane methodology. Predefined primary outcomes were self-reported erectile dysfunction assessed by a validated instrument, sexual quality of life assessed by a validated instrument, and cardiovascular mortality. Secondary outcomes were treatment withdrawal due to adverse events, prostate-related events, and lower urinary tract symptoms (LUTS). We distinguished between short-term (up to 12 months) and long-term (> 12 months) outcomes. MAIN RESULTS: We identified 43 studies with 11,419 randomized participants across three comparisons: testosterone versus placebo, testosterone versus PDE5I, and testosterone with PDE5I versus PDE5I alone. This abstract focuses on the most relevant comparison of testosterone versus placebo. Testosterone versus placebo (up to 12 months) Based on a predefined sensitivity analysis of studies at low risk of bias, and an analysis combing data from the similar International Index of Erectile Function (IIEF-EF) and IIEF-5 instruments, TRT likely results in little to no difference in erectile function assessed with the IIEF-EF (mean difference (MD) 2.37, 95% confidence interval (CI) 1.67 to 3.08; I² = 0%; 6 RCTs, 2016 participants; moderate CoE) on a scale from 6 to 30 with larger values reflecting better erectile function. We assumed a minimal clinically important difference (MCID) of greater than or equal to 4. TRT likely results in little to no change in sexual quality of life assessed with the Aging Males' Symptoms scale (MD -2.31, 95% CI -3.63 to -1.00; I² = 0%; 5 RCTs, 1030 participants; moderate CoE) on a scale from 17 to 85 with larger values reflecting worse sexual quality of life. We assumed a MCID of greater than or equal to 10. TRT also likely results in little to no difference in cardiovascular mortality (risk ratio (RR) 0.83, 95% CI 0.21 to 3.26; I² = 0%; 10 RCTs, 3525 participants; moderate CoE). Based on two cardiovascular deaths in the placebo group and an assumed MCID of 3%, this would correspond to no additional deaths per 1000 men (95% CI 1 fewer to 4 more). TRT also likely results in little to no difference in treatment withdrawal due to adverse events, prostate-related events, or LUTS. Testosterone versus placebo (later than 12 months) We are very uncertain about the longer-term effects of TRT on erectile dysfunction assessed with the IIEF-EF (MD 4.20, 95% CI -2.03 to 10.43; 1 study, 42 participants; very low CoE). We did not find studies reporting on sexual quality of life or cardiovascular mortality. We are very uncertain about the effect of testosterone on treatment withdrawal due to adverse events. We found no studies reporting on prostate-related events or LUTS. AUTHORS' CONCLUSIONS: In the short term, TRT probably has little to no effect on erectile function, sexual quality of life, or cardiovascular mortality compared to a placebo. It likely results in little to no difference in treatment withdrawals due to adverse events, prostate-related events, or LUTS. In the long term, we are very uncertain about the effects of TRT on erectile function when compared to placebo; we did not find data on its effects on sexual quality of life or cardiovascular mortality. The certainty of evidence ranged from moderate (signaling that we are confident that the reported effect size is likely to be close to the true effect) to very low (indicating that the true effect is likely to be substantially different). The findings of this review should help to inform future guidelines and clinical decision-making at the point of care.

Association Between Parental BMI and Offspring's Blood Pressure by Mediation Analysis: A Study Using Data From the Korean National Health and Nutrition Examination Survey.

OBJECTIVES: This study analyzed the relationship between parental body mass index (BMI; BMI_p) and hypertension in their adolescent offspring (HTN_a), focusing on the mediating effect of adolescents' BMI (BMI_a). METHODS: Utilizing data from the Korea National Health and Nutrition Examination Survey, including participants aged 12-18, we conducted a mediation analysis while controlling for confounding factors such as age, sex, physical activity, dietary habits, household income quartile, and parents' alcohol and smoking habits. RESULTS: The study included a total of 5731 participants, of whom 3381 and 5455 participants had data on fathers' and mothers' BMI, respectively. For adolescent systolic blood pressure (SBP_a), the father's BMI (BMI_f) had a significant total effect (ß, 0.23; 95% confidence interval [CI], 0.12 to 0.34) and average controlled mediated effect (ACME) (ß, 0.27; 95% CI, 0.23 to 0.32), but the average direct effect (ADE) was not significant. The mother's BMI (BMI_m) had a significant total effect (ß, 0.17; 95% CI, 0.09 to 0.25), ACME (ß, 0.25; 95% CI, 0.22 to 0.28) and ADE (ß, -0.08; 95% CI, -0.16 to 0.00). For adolescent diastolic blood pressure, both BMI_f and BMI_m had significant ACMEs (ß, 0.10; 95% CI, 0.08 to 0.12 and ß, 0.09; 95% CI, 0.07 to 0.12, respectively), BMI_m had a significant ADE (ß, -0.09; 95% CI, -0.16 to -0.02) but BMI_f had an insignificant ADE and total effect. CONCLUSIONS: The study found that parental BMI had a significant effect on SBP_a, mediated through BMI_a. Therefore, a high BMI in parents could be a risk factor, mediated through BMI_a, for systolic hypertension in adolescents, necessitating appropriate management.

Posterior musculofascial reconstruction in robot-assisted laparoscopic prostatectomy for the treatment of clinically localised prostate cancer: a Cochrane Review.

OBJECTIVES: To assess the effects of posterior musculofascial reconstruction robot-assisted laparoscopic prostatectomy (PR-RALP) compared to no PR during standard RALP (S-RALP) for the treatment of clinically localised prostate cancer. PATIENTS AND METHODS: We performed a systematic search with no restrictions including randomised controlled trials (RCTs) comparing variations of PR-RALP vs S-RALP for clinically localised prostate cancer. The quality of evidence was assessed on outcome basis according to Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. Our search identified 13 records of eight unique RCTs, of which six were published studies, and two were abstract proceedings. There were 1085 randomised patients, of whom 963 completed the trials. All patients had either cT1c or cT2 or cT3a disease. RESULTS: A PR-RALP may improve urinary continence 1 week after catheter removal compared to no PR (risk ratio [RR] 1.25, 95% confidence interval [CI] 0.90-1.73; I2 = 42%, five studies, 498 patients, low certainty of evidence [CoE]). A PR-RALP may have little to no effect on urinary continence 3 months after surgery compared to no PR (RR 0.98, 95% CI 0.84-1.14; I2 = 67%, six studies, 842 patients, low CoE). A PR-RALP probably results in little to no difference in serious adverse events compared to no PR (RR 0.75, 95% CI 0.29-1.92; I2 = 0%, six studies, 835 patients, moderate CoE). CONCLUSIONS: This review found evidence that PR-RALP may improve early continence 1 week after catheter removal but not thereafter. Meanwhile, adverse event rates are probably not impacted and positive surgical margin rates are likely similar. There was no difference in our subgroup analysis for all outcomes with anterior reconstruction technique when combined with PR vs only PR.

Posterior musculofascial reconstruction in robotic-assisted laparoscopic prostatectomy for the treatment of clinically localized prostate cancer.

BACKGROUND: Delayed recovery of urinary continence is a major adverse effect of robotic-assisted laparoscopic prostatectomy (RALP) in men undergoing prostate cancer treatment. To address this issue, a number of surgical techniques have been designed to reconstruct the posterior aspect of the rhabdosphincter, which is responsible for urinary continence after removal of the prostate; however, it is unclear how well they work.  OBJECTIVES: To assess the effects of posterior musculofascial reconstruction RALP compared to no posterior reconstruction during RALP for the treatment of clinically localized prostate cancer. SEARCH METHODS: We performed a comprehensive search of the Cochrane Library, MEDLINE, Embase, three other databases, trials registries, other sources of the grey literature, and conference proceedings, up to 12 March 2021. We applied no restrictions on publication language or status. SELECTION CRITERIA: We included randomized controlled trials (RCTs) in which participants were randomized to undergo variations of posterior musculofascial reconstruction RALP versus no posterior reconstruction during RALP for clinically localized prostate cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently classified studies and abstracted data from the included studies. Primary outcomes were: urinary continence recovery within one week after catheter removal, at three months after surgery, and serious adverse events. Secondary outcomes were: urinary continence recovery at six and twelve months after surgery, potency recovery twelve months after surgery, positive surgical margins (PSM), and biochemical recurrence-free survival (BCRFS). We performed statistical analyses using a random-effects model. We rated the certainty of evidence (CoE) according to the GRADE approach. MAIN RESULTS: Our search identified 13 records of eight unique RCTs, of which six were published studies and two were abstract proceedings. We included 1085 randomized participants, of whom 963 completed the trials (88.8%). All participants had either cT1c or cT2 or cT3a disease, with a mean prostate-specific antigen level of 8.15 ng/mL. Primary outcomes Posterior reconstruction RALP (PR-RALP) may improve urinary continence one week after catheter removal compared to no posterior reconstruction during RALP (risk ratio (RR) 1.25, 95% confidence interval (CI) 0.90 to 1.73; I2 = 42%; studies = 5, participants = 498; low CoE) although the CI also includes the possibility of no effect. Assuming 335 per 1000 men undergoing standard RALP are continent at this time point, this corresponds to 84 more men per 1000 (33 fewer to 244 more) reporting urinary continence recovery.  Posterior reconstruction may have little to no effect on urinary continence three months after surgery compared to no posterior reconstruction during RALP (RR 0.98, 95% CI 0.84 to 1.14; I2 = 67%; studies = 6, participants = 842; low CoE). Assuming 701 per 1000 men undergoing standard RALP are continent at this time point, this corresponds to 14 fewer men per 1000 (112 fewer to 98 more) reporting urinary continence after three months. PR-RALP probably results in little to no difference in serious adverse events compared to no posterior reconstruction during RALP (RR 0.75, 95% CI 0.29 to 1.92; I2 = 0%; studies = 6, participants = 835; moderate CoE). Assuming 25 per 1000 men undergoing standard RALP experience a serious adverse event at this time point, this corresponds to six fewer men per 1000 (17 fewer to 23 more) reporting serious adverse events.  Secondary outcomes PR-RALP may result in little to no difference in recovery of continence 12 months after surgery compared to no posterior reconstruction during RALP (RR 1.02, 95% CI 0.98 to 1.07; I2 = 25%; studies = 3, participants = 602; low CoE). Assuming 918 per 1000 men undergoing standard RALP are continent at this time point, this corresponds to 18 more men per 1000 (18 fewer to 64 more) reporting urinary continence recovery.  We are very uncertain about the effects of PR-RALP on recovery of potency 12 months after surgery compared to no posterior reconstruction during RALP (RR 1.02, 95% CI 0.82 to 1.26; I2 = 3%; studies = 2, participants = 308; very low CoE). Assuming 433 per 1000 men undergoing standard RALP are potent at this time point, this corresponds to nine more men per 1000 (78 fewer to 113 more) reporting potency recovery.  PR-RALP may result in little to no difference in positive surgical margins compared to no posterior reconstruction during RALP (RR 1.24, 95% CI 0.65 to 2.33; I2 = 50%; studies = 3, participants = 517; low CoE). Assuming 130 per 1000 men undergoing standard RALP have a positive surgical margin, this corresponds to 31 more men per 1000 (46 fewer to 173 more) reporting positive surgical margins.  PR-RALP may result in little to no difference in biochemical recurrence compared to no posterior reconstruction during RALP (RR 1.36, 95% CI 0.74 to 2.52; I2 = 0%; studies = 2, participants = 468; low CoE). Assuming 70 per 1000 men undergoing standard RALP have experienced biochemical recurrence at this time point, this corresponds to 25 more men per 1000 (18 fewer to 107 more) reporting biochemical recurrence.  AUTHORS' CONCLUSIONS: This review found evidence that PR-RALP may improve early continence one week after catheter removal but not thereafter. Meanwhile, adverse event rates are probably not impacted and surgical margins rates are likely similar. This review was unable to determine if or how these findings may be impacted by the person's age, nerve-sparing status, or clinical stage. Study limitations, imprecision, and inconsistency lowered the certainty of evidence for the outcomes assessed.

Retzius-sparing versus standard robot-assisted laparoscopic prostatectomy for the treatment of clinically localized prostate cancer.

OBJECTIVES: To assess the effects of Retzius-sparing (RS) robotic-assisted laparoscopic prostatectomy (RALP) compared to standard RALP for the treatment of clinically localized prostate cancer. METHODS: We performed a systematic search of multiple databases and the grey literature with no restrictions on the language of publication or publication status, up until June 2020. We included randomized controlled trials (RCTs) comparing RS-RALP with standard RALP. We performed a meta-analysis using a random-effect model. The quality of evidence was assessed on an outcome basis according to the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) approach. RESULTS: Our search identified six records of five unique RCTs, of which two were published studies, one was in press, and two were abstract proceedings. There were 571 randomized participants, of whom 502 completed the trials. The mean age of participants was 64.6 years and the mean prostate-specific antigen level was 6.9 ng/mL. Approximately 54.2% of participants had cT1c disease, 38.6% had cT2a-b disease, and 7.1% had cT2c disease. RS-RALP probably improves continence within 1 week after catheter removal (risk ratio [RR] 1.74, 95% confidence interval [CI] 1.41-2.14; I2 = 0%; studies = 4; participants = 410; moderate-certainty evidence). Assuming 335 per 1000 men undergoing standard RALP are continent at this time point, this corresponds to 248 more men per 1000 (137 more to 382 more) reporting continence recovery. RS-RALP may increase continence at 3 months after surgery compared to standard RALP (RR 1.33, 95% CI 1.06-1.68; I2 = 86%; studies = 5; participants = 526; low-certainty evidence). Assuming 750 per 1000 men undergoing standard RALP are continent at this time point, this corresponds to 224 more men per 1000 (41 more to 462 more) reporting continence recovery. We are very uncertain about the effects of RS-RALP on serious adverse events compared to standard RALP (RR 1.40, 95% CI 0.47-4.17; studies = 2; participants = 230; very low-certainty evidence). CONCLUSIONS: The findings of this review indicate that RS-RALP may result in better continence outcomes than standard RALP up to 6 months after surgery. Continence outcomes at 12 months may be similar. The disadvantages of RS-RALP may be higher positive surgical margin rates. We are very uncertain about the effect on biochemical recurrence-free survival and potency outcomes. Longer-term oncological and functional outcomes are lacking, and no preplanned subgroup analyses could be performed to explore the observed heterogeneity. Surgeons should discuss these trade-offs and the limitations of the evidence with their patients when considering this approach.

Deep learning models for the prediction of intraoperative hypotension.

BACKGROUND: Intraoperative hypotension is associated with a risk of postoperative organ dysfunction. In this study, we aimed to present deep learning algorithms for real-time predictions 5, 10, and 15 min before a hypotensive event. METHODS: In this retrospective observational study, deep learning algorithms were developed and validated using biosignal waveforms acquired from patient monitoring of noncardiac surgery. The classification model was a binary classifier of a hypotensive event (MAP <65 mm Hg) or a non-hypotensive event by analysing biosignal waveforms. The regression model was developed to directly estimate the MAP. The primary outcome was area under the receiver operating characteristic (AUROC) curve and the mean absolute error (MAE). RESULTS: In total, 3301 patients were included. For invasive models, the multichannel model with an arterial pressure waveform, electrocardiography, photoplethysmography, and capnography showed greater AUROC than the arterial-pressure-only models (AUROC15-min, 0.897 [95% confidence interval {CI}: 0.894-0.900] vs 0.891 [95% CI: 0.888-0.894]) and lesser MAE (MAE15-min, 7.76 mm Hg [95% CI: 7.64-7.87 mm Hg] vs 8.12 mm Hg [95% CI: 8.02-8.21 mm Hg]). For the noninvasive models, the multichannel model showed greater AUROCs than that of the photoplethysmography-only models (AUROC15-min, 0.762 [95% CI: 0.756-0.767] vs 0.694 [95% CI: 0.686-0.702]) and lesser MAEs (MAE15-min, 11.68 mm Hg [95% CI: 11.57-11.80 mm Hg] vs 12.67 [95% CI: 12.56-12.79 mm Hg]). CONCLUSIONS: Deep learning models can predict hypotensive events based on biosignals acquired using invasive and noninvasive patient monitoring. In addition, the model shows better performance when using combined rather than single signals.

Incidence, Risk Factors, and Prediction of Myocardial Infarction and Stroke in Farmers: A Korean Nationwide Population-based Study.

OBJECTIVES: This study was conducted to determine the incidence and risk factors of myocardial infarction (MI) and stroke in farmers compared to the general population and to establish 5-year prediction models. METHODS: The farmer cohort and the control cohort were generated using the customized database of the National Health Insurance Service of Korea database and the National Sample Cohort, respectively. The participants were followed from the day of the index general health examination until the events of MI, stroke, or death (up to 5 years). RESULTS: In total, 734 744 participants from the farmer cohort and 238 311 from the control cohort aged between 40 and 70 were included. The age-adjusted incidence of MI was 0.766 and 0.585 per 1000 person-years in the farmer and control cohorts, respectively. That of stroke was 0.559 and 0.321 per 1000 person-years in both cohorts, respectively. In farmers, the risk factors for MI included male sex, age, personal history of hypertension, diabetes, current smoking, creatinine, metabolic syndrome components (blood pressure, triglycerides, and high-density lipoprotein cholesterol). Those for stroke included male sex, age, personal history of hypertension, diabetes, current smoking, high γ-glutamyl transferase, and metabolic syndrome components (blood pressure, triglycerides, and high-density lipoprotein cholesterol). The prediction model showed an area under the receiver operating characteristic curve of 0.735 and 0.760 for MI and stroke, respectively, in the farmer cohort. CONCLUSIONS: Farmers had a higher age-adjusted incidence of MI and stroke. They also showed distinct patterns in cardiovascular risk factors compared to the general population.

Retzius-sparing versus standard robotic-assisted laparoscopic prostatectomy for the treatment of clinically localized prostate cancer.

BACKGROUND: Robotic-assisted laparoscopic prostatectomy (RALP) is widely used to surgically treat clinically localized prostate cancer. It is typically performed using an approach (standard RALP) that mimics open retropubic prostatectomy by dissecting the so-called space of Retzius anterior to the bladder. An alternative, Retzius-sparing (or posterior approach) RALP (RS-RALP) has been described, which is reported to have better continence outcomes but may be associated with a higher risk of incomplete resection and positive surgical margins (PSM). OBJECTIVES: To assess the effects of RS-RALP compared to standard RALP for the treatment of clinically localized prostate cancer. SEARCH METHODS: We performed a comprehensive search of the Cochrane Library, MEDLINE, Embase, three other databases, trials registries, other sources of the grey literature, and conference proceedings, up to June 2020. We applied no restrictions on publication language or status. SELECTION CRITERIA: We included trials where participants were randomized to RS-RALP or standard RALP for clinically localized prostate cancer. DATA COLLECTION AND ANALYSIS: Two review authors independently classified and abstracted data from the included studies. Primary outcomes were: urinary continence recovery within one week after catheter removal, at three months after surgery, and serious adverse events. Secondary outcomes were: urinary continence recovery six and 12 months after surgery, potency recovery 12 months after surgery, positive surgical margins (PSM), biochemical recurrence-free survival (BCRFS), and urinary and sexual function quality of life. We performed statistical analyses using a random-effects model. We rated the certainty of evidence using the GRADE approach. MAIN RESULTS: Our search identified six records of five unique randomized controlled trials, of which two were published studies, one was in press, and two were abstract proceedings. There were 571 randomized participants, of whom 502 completed the trials. Mean age of participants was 64.6 years and mean prostate-specific antigen was 6.9 ng/mL. About 54.2% of participants had cT1c disease, 38.6% had cT2a-b disease, and 7.1 % had cT2c disease. Primary outcomes RS-RALP probably improves continence within one week after catheter removal (risk ratio (RR) 1.74, 95% confidence interval (CI) 1.41 to 2.14; I2 = 0%; studies = 4; participants = 410; moderate-certainty evidence). Assuming 335 per 1000 men undergoing standard RALP are continent at this time point, this corresponds to 248 more men per 1000 (137 more to 382 more) reporting continence recovery. RS-RALP may increase continence at three months after surgery compared to standard RALP (RR 1.33, 95% CI 1.06 to 1.68; I2 = 86%; studies = 5; participants = 526; low-certainty evidence). Assuming 750 per 1000 men undergoing standard RALP are continent at this time point, this corresponds to 224 more men per 1000 (41 more to 462 more) reporting continence recovery. We are very uncertain about the effects of RS-RALP on serious adverse events compared to standard RALP (RR 1.40, 95% CI 0.47 to 4.17; studies = 2; participants = 230; very low-certainty evidence). Secondary outcomes There is probably little to no difference in continence recovery at 12 months after surgery (RR 1.01, 95% CI 0.97 to 1.04; I2 = 0%; studies = 2; participants = 222; moderate-certainty evidence). Assuming 982 per 1000 men undergoing standard RALP are continent at this time point, this corresponds to 10 more men per 1000 (29 fewer to 39 more) reporting continence recovery.  We are very uncertain about the effect of RS-RALP on potency recovery 12 months after surgery (RR 0.98, 95% CI 0.54 to 1.80; studies = 1; participants = 55; very low-certainty evidence).  RS-RALP may increase PSMs (RR 1.95, 95% CI 1.19 to 3.20; I2 = 0%; studies = 3; participants = 308; low-certainty evidence) indicating a higher risk for prostate cancer recurrence. Assuming 129 per 1000 men undergoing standard RALP have positive margins, this corresponds to 123 more men per 1000 (25 more to 284 more) with PSMs. We are very uncertain about the effect of RS-RALP on BCRFS compared to standard RALP (hazard ratio (HR) 0.45, 95% CI 0.13 to 1.60; I2 = 32%; studies = 2; participants = 218; very low-certainty evidence). AUTHORS' CONCLUSIONS: Findings of this review indicate that RS-RALP may result in better continence outcomes than standard RALP up to six months after surgery. Continence outcomes at 12 months may be similar. Downsides of RS-RALP may be higher positive margin rates. We are very uncertain about the effect on BCRFS and potency outcomes. Longer-term oncologic and functional outcomes are lacking, and no preplanned subgroup analyses could be performed to explore the observed heterogeneity. Surgeons should discuss these trade-offs and the limitations of the evidence with their patients when considering this approach.