Assessment of Mammalian Target of Rapamycin Pathway Activation in Basal Cell Carcinoma as a New Therapeutic Approach.

ABSTRACT: Targeting the mammalian target of rapamycin (mTOR) pathway represents a potentially novel approach to treat basal cell carcinoma (BCC), but activation of this pathway has not been well described in human BCCs. The purpose of this study was to assess whether mTOR pathway activation occurs in BCCs (both sporadic and syndromic) and report a case of a patient with Gorlin syndrome (GS) whose clinically suspicious BCCs responded to mTOR inhibition through topical sirolimus treatment. After Stanford Institutional Review Board Approval, archived BCCs from patients with GS (n = 25), sporadic BCCs (n = 35), and control tissues were subjected to immunohistochemical analysis for the activation of mTOR pathway, and immunohistochemical staining intensity was evaluated by a dermatopathologist. BCCs (compared with normal skin) had elevated levels of eIF4EBP1 (Padjusted = 0.0336), which is downstream of mTOR. a serine/threonine kinase Phospho-(AKT), which interacts with mTOR, was also significantly elevated (perinuclear: Padjusted < 0.0001; cytoplasmic: Padjusted = 0.0021). When off-label topical 1% sirolimus was used on a pediatric patient with GS, we noted reduction of new BCC development and decreased size of existing neoplasms clinically suspicious for BCCs. This treatment was well tolerated after 2 years of continuous use, with no other treatments needed during this period. Topical sirolimus is a promising therapeutic candidate against both sporadic and GS-associated BCC. Multicenter, prospective studies are needed to understand the efficacy and safety of topical mTOR inhibitors in BCC treatment, and ascertain whether the immunohistochemical markers downstream of mTOR could have predictive value in identifying BCCs most likely to respond to topical mTOR inhibitors, such as sirolimus.

The Impact of Venous Thromboembolism on Upper Tract Urothelial Carcinomas Undergoing Open or Minimally Invasive Radical Nephroureterectomy in the USA: Perioperative Outcomes and Health Care Costs from Insurance Claims Data.

BACKGROUND AND OBJECTIVE: Venous thromboembolism (VTE) is a significant predictor of worse postoperative morbidity in cancer surgeries. No data have been available for patients with preoperative VTE and upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy (RNU). Our aim was to assess the impact of a preoperative VTE diagnosis on perioperative outcomes in the RNU context. METHODS: Patients aged 18 yr or older with a UTUC diagnosis undergoing RNU were identified in the Merative Marketscan Research deidentified databases between 2007 and 2021. Multivariable logistic regression adjusted by relevant perioperative confounders was used to investigate the association between a diagnosis of VTE prior to RNU and 90-d complication rates, postoperative VTE, rehospitalization, and total costs. A sensitivity analysis on VTE severity (pulmonary embolism [PE] and/or deep venous thrombosis [DVT]) was examined. KEY FINDINGS AND LIMITATIONS: Within the investigated cohort of 6922 patients, history of any VTE preceding RNU was reported in 568 (8.21%) cases, including DVT (n = 290, 51.06%), PE (n = 169, 29.75%), and superficial VTE (n = 109, 19.19%). The history of VTE before RNU was predictive of higher rates of complications, the most prevalent being respiratory complications (odds ratio [OR]: 1.78, 95% confidence interval [CI]: 1.43-2.22). Preoperative VTE was found to be associated with an increased risk of VTE following RNU (OR: 14.3, 95% CI: 11.48-17.82), higher rehospitalization rates (OR: 1.26, 95% CI 1.01-1.56) other than home discharge status (OR: 1.44, 95% CI: 1.18-1.77), and higher costs (OR 1.42, 95% CI: 1.20-1.68). Limitations include the retrospective nature and the use of an insurance database that relies on accurate coding and does not include information such as pathologic staging. CONCLUSIONS AND CLINICAL IMPLICATIONS: The presented findings will contribute to the counseling process for patients. These patients may benefit from enhanced pre/postoperative anticoagulation. More research is needed before the following results can be used in the clinical setting. PATIENT SUMMARY: Patients aged 18 yr or older with an upper tract urothelial carcinoma (UTUC) diagnosis undergoing radical nephroureterectomy (RNU) were identified in the Merative Marketscan Research deidentified databases between 2007 and 2021. Multivariable logistic regression adjusted by relevant perioperative confounders was used to investigate the association between a diagnosis of venous thromboembolism (VTE) prior to RNU and 90-d complication rates, postoperative VTE, rehospitalization, and total costs. A sensitivity analysis on VTE severity (pulmonary embolism and/or deep venous thrombosis) was examined. The presented findings will contribute to the counseling of patients with UTUC and preoperative VTE.

Use of phosphodiesterase 5 inhibitors is not associated with ocular adverse events.

BACKGROUND: Phosphodiesterase 5 inhibitor (PDE5i) use has been linked to a number of ocular side effects, such as serous retinal detachment (SRD), retinal vascular occlusion (RVO), and ischemic optic neuropathy (ION). AIM: We investigated the risk for SRD, RVO, and ION in patients using PDE5is. METHODS: We utilized the IBM MarketScan (2007-2021) Commercial and Medicare Supplemental Databases (version 2.0) for this analysis. To estimate overall events risk, Cox proportional hazard models were applied to calculate the hazard ratios (HRs) for erectile dysfunction (ED) diagnosis and the different treatments, adjusting for region, median age, obesity, diabetes mellitus, hyperlipidemia, smoking, hypertension, coronary artery disease, and sleep apnea. Additionally, the same analyses were performed to calculate the HRs for benign prostatic hyperplasia (BPH) diagnosis and the different treatments. OUTCOMES: HRs for SRD, RVO, and ION. RESULTS: In total, 1 938 262 men with an ED diagnosis were observed during the study period. Among them, 615 838 (31.8%) were treated with PDE5is. In total, 2 175 439 men with a BPH diagnosis were observed during the study period. Among them, 175 725 (8.1%) were treated with PDE5is. On adjusted Cox regression analysis, PDE5i use was not associated with SRD, RVO, ION, and any ocular event when compared with ED diagnosis and other ED treatments. Importantly, as the intensity of ED treatment increased, so did the risk of ocular events. In addition, PDE5i use was not associated with SRD and ION when compared with BPH diagnosis and other BPH treatments. In contrast, in patients with BPH, PDE5i use was associated with RVO (HR, 1.14; 95% CI, 1.06-1.23). Importantly, patients with BPH receiving other medical treatment (ie, 5a reductase/alpha blocker; HR, 1.11; 95% CI, 1.06-1.16) or surgical treatment (HR, 1.10; 95% CI, 1.02-1.19) had a higher risk of RVO. CLINICAL IMPLICATIONS: We did not observe any consistent association between PDE5i use and any ocular adverse events (SRD, RVO, and ION). STRENGTHS AND LIMITATIONS: Because we did not have access to the patients' medical records, we recorded outcome definitions using ICD-9 and ICD-10 coding. CONCLUSIONS: Patients using PDE5is for ED or BPH indications did not have an increased risk of ocular events, even when compared with other treatments for ED or BPH.

5-alpha reductase inhibitors (5-ARi) with or without alpha-blockers (α-B) for Benign Prostatic Hyperplasia do NOT lower the risk of incident Bladder Cancer: United States insurance claims data.

BACKGROUND: Chemoprotective effect of 5-alpha reductase inhibitors (5-ARi) on bladder cancer (BCa) risk in men with Benign Prostatic Hyperplasia (BPH) has been explored with conflicting results. We sought to examine the effect of 5-ARi on new BCa diagnoses in a large US database. METHODS: Men ≥ 50 y/o with a prescription for 5-ARi after BPH diagnosis were identified in the IBM® Marketscan® Research de-identified Databases between 2007 and 2016 and matched with paired controls. Incident BCa diagnoses were identified after BPH diagnosis and/or pharmacologic treatment. Multivariable regression modeling adjusting for relevant factors was implemented. Sub-group analyses by exposure risk were performed to explore the association between 5-ARi and BCa over time. Administration of alpha-blockers (α-B) w/o 5-ARi was also examined. RESULTS: In total, n = 24,036 men on 5-ARi, n = 107,086 on 5-ARi plus alpha-blockers, and n = 894,275 without medical therapy for BPH were identified. The percentage of men diagnosed with BCa was 0.8% for the 5-ARi, 1.4% for the 5-ARi + α-B, and 0.6% for the untreated BPH group of incident BCa (adjusted hazard ratio [aHR], 0.90, 95% confidence interval [CI] 0.56 - 1.47), and 1.08, 95%CI 0.89 - 1.30, respectively). This was also true at both shorter (≤ 2 yr) and longer-term (> 2 yr) follow up. In addition, α-B alone had no change in BCa risk (HR 1.06, 0.86-1.30). CONCLUSIONS: We did not find any diminished risk of new BCa in men treated with 5-ARi (i.e., chemoprotective effect). The current report suggests that 5-ARi do not change a man's bladder cancer risk.

Assessment of Comorbidities Associated With Allergic Contact Dermatitis in the United States: A Retrospective Claims-Based Study.

BACKGROUND: Allergic contact dermatitis (ACD) is a common dermatologic disease. Patch testing remains the criterion standard for diagnosis. In clinical practice, avoidance may be limited by patient occupation or noncompliance, the pervasive nature of the culprit agent, or barriers to expert care because of socioeconomic, cultural, or geographic factors. Thus, ACD is frequently chronic and/or recurrent; however, the comorbidities associated with ACD are not well characterized. OBJECTIVE: The aim of the study is to identify associations between ACD and psychiatric, sleep health, cardiovascular, and infectious conditions. METHODS: In this study, we used a large US claims database to identify comorbidities associated with ACD diagnosed after patch testing, including psychiatric, sleep health, cardiovascular, and infectious conditions. We also stratified these associations by chronicity of disease. RESULTS: We identified associations between ACD and psychiatric, sleep-related, cardiovascular, and infectious comorbidities. We also found that more chronic ACD was associated with more infectious comorbidities. All of these associations remained significant on further subanalysis when patients with AD and venous stasis were excluded. CONCLUSIONS: Allergic contact dermatitis is associated with multiple comorbidities. Further study is required to corroborate these findings, determine causality, and to explore the impact of possible interventions in the workup and management of this common and often debilitating disease.

A global, cross-sectional survey of patient-reported outcomes, disease burden, and quality of life in epidermolysis bullosa simplex.

BACKGROUND: Epidermolysis bullosa simplex (EBS) comprises a group of rare, blistering genodermatoses. Prior work has been limited by small sample sizes, and much remains unexplored about the disease burden and health-related quality of life (QOL) of patients with EBS. The aim of this study was to characterize the most common patient-reported clinical manifestations and the health-related impact of QOL in EBS, and to examine differences in disease burden by age. METHODS: Patients with a diagnosis of epidermolysis bullosa (EB) or their caregivers completed a one-time online survey administered by EBCare, an international online EB registry. Survey data from respondents self-reporting a diagnosis of EBS were analyzed for clinical and wound manifestations, medication use, and QOL (using Quality of Life in Epidermolysis Bullosa [QOLEB] scores). Differences across age groups were assessed using Kruskal-Wallis and Fisher's exact tests. RESULTS: There were 214 survey respondents with EBS. The mean age was 32.8 years (standard deviation = 19.2). Many respondents reported blisters (93%), recurrent wounds (89%), pain (74%), chronic wounds (59%), itch (55%), and difficulty walking (44%). Mean QOLEB score was 14.7 (standard deviation = 7.5) indicating a "moderate" impact on QOL, and 12% of respondents required regular use of opiates. Findings were consistent in subgroup analyses restricted to respondents with diagnostic confirmation via genetic testing or skin biopsy (n = 63 of 214). Age-stratified analyses revealed differences in disease burden: younger respondents were more likely to self-report severe disease (24% vs. 19% vs. 5% for respondents aged 0-9 vs. 10-17 vs. 18 + , p = 0.001), failure to thrive (9% vs. 15% vs. 3%, p = 0.02), and use of gastrostomy tubes (15% vs. 12% vs. 1%, p < 0.001) and topical antibiotics (67% vs. 69% vs. 34%, p < 0.001), while older respondents were more likely to be overweight or obese (6% vs. 0% vs. 51%, p < 0.001) and have difficulty walking (24% vs. 46% vs. 48%, p = 0.04). CONCLUSIONS: In the largest international cross-sectional survey of EBS patients conducted, respondents reported extensive disease burden including significant wounding, pain, itch, difficulty walking, and impact on QOL. Age stratified disease manifestations. These findings suggest significant unmet need, and treatment and counseling for EBS patients should consider age-specific differences.

Contemporary Trends of Systemic Neoadjuvant and Adjuvant Intravesical Chemotherapy in Patients With Upper Tract Urothelial Carcinomas Undergoing Minimally Invasive or Open Radical Nephroureterectomy: Analysis of US Claims on Perioperative Outcomes and Health Care Costs.

INTRODUCTION: New evidence indicates that minimally invasive surgery (MIS) (laparoscopic or robotic-assisted [LNU, RANU]) reaches oncologic equivalence compared with Open Radical Nephroureterectomy (ORNU) for high-risk upper-tract urothelial carcinoma (UTUC). Recently, European Association of Urology (EAU) Guidelines suggested implementing neoadjuvant chemotherapy (NAC) to standard treatment to improve oncologic outcomes of high-risk UTUC. We aimed (1) To explore contemporary trends of MIS for RNU in the United States and to compare perioperative outcomes and costs with that of ORNU. (2) To determine the trends of NAC and postoperative intravesical chemotherapy (PIC) administration for high-risk UTUC and to assess their contribution to perioperative outcomes and costs. PATIENTS AND METHODS: The Optum Clinformatics Data Mart de-identified database was queried from 2003 to 2018 to retrospectively examine patients who had undergone LNU/RANU or ORNU with or without NAC and PIC. We evaluated temporal adoption trends, complications, and health care cost analyses. We obtained descriptive statistics and utilized multivariable regression modeling to assess outcomes. RESULTS: A total of n = 492 ORNU and n = 1618 LNU/RANU procedures were reviewed. The MIS approach was associated with a statistically significant lower risk of intraoperative complications (adjusted Odds Ratio [aOR], 0.48, 95% CI:0.24-0.96), risk of hospitalization costs (aOR: 0.62, 95% CI:0.49-0.78), and shorter hospital stay (aOR: 0.20, 95% CI:0.15-0.26) when compared to ORNU. Overall, adoption of NAC and PIC accounted for only n = 81 and n < 37 cases respectively. The implementation of NAC and higher number of cycles were associated with an increased probability of any complication rate (aOR: 2.06, 95% CI:1.26-3.36) and hospital costs (aOR: 2.12, 95% CI:1.33-3.38). CONCLUSION: MIS has become the approach of choice for RNU in the US. Although recommended by guidelines, neither NAC nor postoperative bladder instillation of chemotherapy has been routinely incorporated into the clinical practice of patients with UTUC.

Associations between Race and Erectile Dysfunction Treatment Patterns.

INTRODUCTION: While erectile dysfunction (ED) has many available and effective treatments, the decision to elect one therapy over another depends on many variables. Whether race plays a significant role in treatment decision making is uncertain. This study seeks to investigate whether there are racial differences between men receiving treatment for ED in the United States. METHODS: We performed a retrospective review using the Optum® De-identified Clinformatics® Data Mart database. Administrative diagnosis and procedural and pharmacy codes were used to identify male subjects 18 years and older with a diagnosis of ED between 2003 and 2018. Demographic and clinical variables were identified. Men with a history of prostate cancer were excluded. Types and patterns of ED treatment were analyzed after adjusting for age, income, education, frequency of urologist visits, smoking status and metabolic syndrome comorbidity diagnoses. RESULTS: During the observation period, 810,916 men were identified who met the inclusion criteria. After matching for demographic, clinical and health care utilization factors, differences in ED treatment persisted between racial groups. Compared to Caucasians, Asian and Hispanic men had a significantly lower probability of undergoing any ED treatment, while African Americans had a higher probability of ED treatment. African American and Hispanic men had higher probabilities to undergo surgical treatment for ED than Caucasian men. CONCLUSIONS: Differences in ED treatment patterns exist across racial groups even after accounting for socioeconomic variables. An opportunity exists to further investigate potential barriers to men receiving care for sexual dysfunction.

The Association Between Hemoglobin A1c Levels and Inflatable Penile Prosthesis Infection: Analysis of US Insurance Claims Data.

BACKGROUND: The association between elevated hemoglobin A1c (HbA1c) levels and the risk of postoperative infection after penile prosthesis surgery remains controversial. AIM: To examine the association between HbA1c levels and penile implant infections in men undergoing inflatable penile prosthesis (IPP) surgery for erectile dysfunction using a large insurance claims database. METHODS: This was a retrospective review using Optum's de-identified Clinformatics Data Mart Database. Male subjects 18 years and older with available laboratory data undergoing IPP insertion between 2003 and 2018 were included. Administrative diagnosis and procedural codes were used to assess subsequent penile implant revision surgery status for either infectious or noninfectious causes. Associated conditions were controlled for such as smoking status, hyperlipidemia, hypertension, obesity status, and Peyronie's disease. OUTCOMES: The main outcomes were risk of revision for infection and time to revision. RESULTS: A total of 2,363 individuals underwent initial IPP insertion and had available HbA1c data with a mean HbA1c of 6.9%. The overall IPP infection revision rate was 3.9% and the highest rate of 12.1% was seen in the highest HbA1c group (>10%). After adjusting for demographic and health factors, a higher HbA1c level was associated with a higher risk of revision for infection, with every 1 point increase in HbA1c conferring an increased risk of infection requiring revision by 29% (95% CI 17-42%). When infections did occur, they happened sooner in men with HbA1c > 10.0% with an average of 1.3 months vs 3.5 months in the HbA1c < 6.0% group. CLINICAL IMPLICATIONS: These findings provide insight into the potential relationship between HbA1c levels and postoperative risk of infection after penile prosthesis surgery and may aid in clinical decision-making. STRENGTHS AND LIMITATIONS: Strengths include the large sample size, length of data coverage, and real-world analysis of surgeries done across the United States. Limitations include the reliance on insurance claims data, the retrospective study design, and lack of additional relevant clinical variables that may impact infection rates. CONCLUSIONS: While the overall risk of penile prosthesis infection remains modest, the current report notes an increased risk of infection for diabetic men with poor glycemic control. Chen T, Li S, Eisenberg ML. The Association Between Hemoglobin A1c Levels and Inflatable Penile Prosthesis Infection: Analysis of US Insurance Claims Data. J Sex Med 2021;18:1104-1109.

Association between infertility and all-cause mortality: analysis of US claims data.

BACKGROUND: The consequences of an infertility diagnosis extend beyond the pursuit of family building, because women with infertility also face increased risks for severe maternal morbidity, cancer, and chronic disease. OBJECTIVE: This study aimed to examine the association between female infertility and all-cause mortality. STUDY DESIGN: This retrospective analysis compared 72,786 women with infertility, identified in the Optum Clinformatics Datamart from 2003 to 2019 by infertility diagnosis, testing, and treatment codes, with 3,845,790 women without infertility seeking routine gynecologic care. The baseline comorbidities were assessed using the presence of ≥1 metabolic syndrome diagnoses and the Charlson Comorbidity Index. The primary outcome, which was all-cause mortality, was identified by linkage to the Social Security Administration Death Master File outcomes and medical claims. The association between infertility and mortality was examined using a Cox proportional hazard regression by adjusting for age, hypertension, hyperlipidemia, type II diabetes, year of evaluation, smoking, number of visits per year, nulliparity, obesity, region of the country, and race. RESULTS: Among 16,473,458 person-years of follow-ups, 13,934 women died. Women with infertility had a 32% higher relative risk for death from any cause (0.42% vs 0.35%, adjusted hazard ratio, 1.32; 95% confidence interval, 1.18-1.48) than women without infertility. The mean follow-up time per patient was 4.0±3.7 years vs 4.2±3.8 years for women with and without infertility, respectively. When stratified by age of <35 or ≥35 years or baseline medical comorbidity, the association between infertility and mortality remained. Women with infertility who delivered a child during the follow-up period faced a similar increased risk for mortality than the overall infertile group. Finally, receiving fertility treatment was not associated with a higher risk for death than receiving an infertility diagnosis or testing alone. CONCLUSION: Although the absolute risk for death was low in both groups, women with infertility faced a higher relative risk for mortality than women without infertility. The association remained across all age, race and ethnicity groups, morbidities, and delivery strata. Importantly, infertility treatment was not associated with an increased risk for death. These findings reinforce the disease burden associated with infertility and its potential for long-term sequelae.

Development and Assessment of Novel Lung Ultrasound Interpretation Criteria for the Detection of Interstitial Lung Disease in Systemic Sclerosis.

OBJECTIVE: Interstitial lung disease (ILD) is a frequent complication of systemic sclerosis (SSc), and ILD screening, characterization, and monitoring are important for therapeutic decision-making and prognostication. Lung ultrasonography (US) is a potential alternative imaging modality for ILD detection. In this study, our objective was to develop and test a novel lung US examination technique and interpretation criteria for detecting SSc-ILD. METHODS: Lung US acquisition was performed by collecting short US movies at 14 lung positions. Lung US interpretation criteria for SSc-ILD detection focused on visualized pleural changes. To assess the performance of our methodology for SSc-ILD detection, we prospectively enrolled SSc patients with high-resolution computed tomography (HRCT) imaging within 3 months of lung US. Lung US examinations were scored independently by 2 blinded readers (1 ultrasonographer and 1 nonultrasonographer). The sensitivity and specificity for SSc-ILD detection were assessed, and agreement was measured with Cohen's kappa statistic. RESULTS: To test the performance of our lung US acquisition technique and interpretation criteria, 20 SSc patients were evaluated by lung US (278 lung zones) and HRCT. HRCT confirmed ILD in 9 patients (45%). Lung US was positive for SSc-ILD in 11 patients (55%) with a sensitivity of 100% and specificity of 82% versus HRCT, with perfect agreement between the 2 readers (κ = 1). Analysis by individual lung zones found excellent agreement between readers, with 93.8% concordance and κ = 0.82. CONCLUSION: We developed a novel lung US examination technique and interpretation criteria that are highly sensitive and specific for SSc-ILD detection in an SSc cohort, affording perfect agreement between ultrasonographer and nonultrasonographer readers.

Increased Mortality Among Men Diagnosed With Impaired Fertility: Analysis of US Claims Data.

OBJECTIVE: To determine whether male infertility or impaired spermatogenesis is associated with mortality. METHODS: The Optum de-identified Clinformatics Data Mart database was queried from 2003 to 2017. Infertile men were compared to subjects undergoing semen analysis (ie, infertility testing). Infertile men with oligozoospermia or azoospermia were included. Mortality was determined by data linkage to the Social Security Administration Death Master File. Results were adjusted for age, smoking, obesity, year of evaluation, and health care visits as well as for most prevalent comorbidities. We separately examined men with prevalent or incident cardiovascular disease and cancer diagnoses to determine associations with mortality. RESULTS: A total of 134,796 infertile men and 242,282 controls were followed for a mean of 3.6 and 3.1 years respectively. Overall, infertile men had a higher risk of death (Hazard Ratio [HR]= 1.42, 95% CI: 1.27-1.60) The diagnosis of azoospermia was associated with a significantly increased risk of death (HR= 2.01, 95% CI: 1.60-2.53) with a higher trend among men with oligospermia (HR: 1.17, 95% CI: 0.92-1.49) compared to controls. Subanalysis was done excluding prevalent cardiovascular and malignant disease (alone and combined) showing similar hazard ratios. CONCLUSION: Male infertility is associated with a higher risk of mortality especially among azoospermic men. Prevalent disease (which is known to be higher among infertile men) did not explain the higher risk of death among infertile men. The implications for treatment and surveillance of infertile men require further study.

Increased risk of severe maternal morbidity among infertile women: analysis of US claims data.

BACKGROUND: Severe maternal morbidity continues to be an issue of national and global concern and is increasing in incidence. The incidence of infertility is also on the rise, and infertile women experience a higher risk of incident chronic medical disease and cancer, suggesting that fertility may serve as a window to a woman's overall health. OBJECTIVE: To investigate the risk of severe maternal morbidity by maternal fertility status. MATERIALS AND METHODS: This was a retrospective cohort analysis using Optum's de-identifed Clinformatics Data Mart Database between 2003 and 2015. Infertile women stratified by infertility diagnosis, testing, or treatment were compared to fertile women seeking routine gynecologic care. In both groups, only women who underwent pregnancy and delivery of a singleton during the follow-up period were included. Main outcomes were severe maternal morbidity indicators, defined by the Centers for Disease Control and Prevention and identified by International Classification of Diseases 10th Revision and Common Procedural Technology codes within 6 weeks of each delivery. Results were adjusted for maternal age, race, education, nulliparity, smoking, obesity, delivery mode, preterm birth, number of prenatal visits, and year of delivery. RESULTS: A total of 19,658 women comprised the infertile group and 525,695 women comprised the fertile group. The overall incidence of any severe maternal morbidity indicator was 7.0% among women receiving fertility treatment, 6.4% among women receiving a fertility diagnosis, 5.5% among women receiving fertility testing, and 4.3% among fertile women. Overall, infertile women had a significantly higher risk of developing any severe maternal morbidity indicator (adjusted odds ratio, 1.22; confidence interval, 1.14-1.31, P < .01) as well as a significantly higher risk of disseminated intravascular coagulation (adjusted odds ratio, 1.48; confidence interval, 1.26-1.73, P < .01), eclampsia (adjusted odds ratio, 1.37; confidence interval, 1.05-1.79, P < .01), heart failure during procedure or surgery (adjusted odds ratio, 1.54; confidence interval, 1.21-1.97, P < .01), internal injuries of the thorax, abdomen, or pelvis (adjusted odds ratio, 1.59; confidence interval, 1.12-2.26, P < .01), intracranial injuries (adjusted odds ratio, 1.77; confidence interval, 1.20-2.61, P < .01), pulmonary edema (adjusted odds ratio, 2.18; confidence interval, 1.54-3.10, P < .01), thrombotic embolism (adjusted odds ratio, 1.58; confidence interval, 1.14-2.17, P < .01), and blood transfusion (adjusted odds ratio, 1.50; confidence interval, 1.30-1.72, P < .01) compared to fertile women. Fertile women did not face a significantly higher risk of any maternal morbidity indicator compared to infertile women. In subgroup analysis by maternal race/ethnicity, the likelihood of severe morbidity was significantly higher among fertile black women compared to fertile white women. There was no difference between infertile black women and infertile white women after multivariable adjustment. CONCLUSION: Using an insurance claims database, we report that women diagnosed with infertility and women receiving fertility treatment experience a significantly higher risk of multiple indicators of severe maternal morbidity compared to fertile women. The increased risk of severe maternal morbidity noted among fertile black women compared to fertile white women is attenuated among infertile black women, who face risks similar to those of infertile white women.

Changing Trends in the Treatment of Nephrolithiasis in the Real World.

INTRODUCTION: Changes in the surgical treatment of nephrolithiasis, owing to recent technical advances and innovations, have made treatments more effective and less invasive. In this retrospective, observational cohort study, we identified the changing trends in the treatment of nephrolithiasis. MATERIALS AND METHODS: We included patients with newly diagnosed nephrolithiasis who received any treatment in the United States, including extracorporeal shockwave lithotripsy (SWL), retrograde intrarenal surgery (RIRS), percutaneous nephrolithotomy (PCNL), and open surgery, from January 2007 to December 2014. Demographic factors, such as age, sex, region, surgical treatment type, and cost data, were analyzed. RESULTS: The median age of patients at treatment was 52 years, and the ratio of men and women was similar. There were definite changes in the trends of all treatment modalities (p < 0.01). Both the number and percentage tended to increase for RIRS, whereas for SWL, the number increased, but the percentage showed a steady decrease. In PCNL, both number and percentage increased to a minor degree. The overall cost of nephrolithiasis treatments during the study period nearly doubled (from $30,998,726 to $57,310,956). The number of treatments and average cost per treatment increased annually for each treatment modality. RIRS was the least expensive; the other procedures in decreasing order of their mean costs were as follows: SWL, PCNL, and open surgery. CONCLUSIONS: There was a gradual but constant change in treatment trends of nephrolithiasis, with an increasing trend for RIRS and a decreasing trend for SWL. Although PCNL has relatively invasive characteristics, it is still in steady demand.

Racial and Sociodemographic Differences of Semen Parameters Among US Men Undergoing a Semen Analysis.

OBJECTIVE: To characterize sociodemographic differences in semen parameters among US men undergoing a semen analysis. MATERIALS AND METHODS: Men who provided a semen sample were identified from insurance claims between 2007 and 2016. Differences in semen parameters were characterized according to age, race, education, and region. Mean semen parameters and proportions of men with suboptimal parameters were compared and risks of oligospermia and azoospermia were assessed by logistic regression. RESULTS: Of the 7263 men included, most men were white (55.1%), Hispanic (20.2%), or Asian (10.2%). Asians had the highest mean semen concentrations (69.2 × 106/mL), whereas blacks had the lowest (51.3 × 106/mL). Men from the Midwest were more likely to have oligospermia (odds ratio [OR] 1.62; 95% confidence interval [CI] 1.34-1.94), whereas men from the West were less likely (OR 0.82; 95% CI 0.82-0.94) when compared with men from South. An association between education and sperm concentration was observed. For example, men with a high school diploma or less were more likely to have oligospermia (OR 1.09; 95% CI 0.95-1.26), whereas men with at least a bachelor degree were less likely (OR 0.87; 95% CI 0.76-1.0) when compared with men with less than a bachelor degree. CONCLUSION: As we observed differences in semen quality based on sociodemographic factors, these findings may have clinical implications as relying on a single reference value when guiding infertile couples may be problematic given these variations. Further work is warranted to understand the etiology of such differences and determine if different normative reference values may apply for different populations.

The Impact of Clostridium Histolyticum Collagenase on the Prevalence and Management of Peyronie's Disease in the United States.

PURPOSE: We evaluated the impact of collagenase clostridium histolyticum (CCH) on rates of diagnosis, treatment, and corporal rupture in Peyronie's disease (PD). We examined the impact of CCH on cost of PD treatment. MATERIALS AND METHODS: We extracted data on PD diagnosis (ICD-9 607.95 and ICD-10 N48.6), corporal rupture (ICD-9 959.13 and ICD-10 S39.840A), CCH use (J0775), penile injections (CPT 54200), and corporal rupture repair from 2008 to 2016 in men over 40 years old using the Clinformatics® Data Mart Database (3.7 to 4.9 million males). We analyzed for prevalence of PD, rates of PD treatments, cost associated with treatment, and rates of corporal rupture and repair by year. RESULTS: The prevalence of PD was 0.29% in 2013 and did not increase after CCH entered the market in 2014. An average of 2.52% of men with PD received treatment before CCH, compared with 3.75% after (p<0.0001). Penile injection rates increased (1.34% vs. 2.61%, p<0.0001), while rates of surgical treatments decreased between these periods. There was no change in rate of corporal rupture in men with PD before (0.024%) and after (0.024%) CCH. Overall, only 20.0% of corporal ruptures were repaired. After CCH entered practice, a significant increase in cost occurred (p=0.013). CONCLUSIONS: The prevalence of men with PD did not change after CCH. However, more men with PD received treatment due to an increase in penile injections. The cost of treating PD increased after CCH became available. The overall prevalence of corporal rupture did not change after CCH entered the market.

Risk of Melanoma With Phosphodiesterase Type 5 Inhibitor Use Among Patients With Erectile Dysfunction, Pulmonary Hypertension, and Lower Urinary Tract Symptoms.

BACKGROUND: Phosphodiesterase type 5 inhibitors (PDE5is), a treatment for erectile dysfunction, pulmonary hypertension (pHTN), and lower urinary tract symptoms (LUTS), have been implicated in melanoma development. AIM: We sought to determine the association between PDE5i use and melanoma development among patients with erectile dysfunction, pHTN, and LUTS. METHODS: This was a retrospective cohort study of subjects contained within the Truven Health MarketScan claims database, which provides information on insurance claims in the United States for privately insured individuals, from 2007-2015. Individuals taking PDE5i were identified through pharmacy claims. A comparison group of men diagnosed with conditions for which PDE5i are prescribed was assembled. OUTCOMES: Cox proportional hazard models were used to estimate the hazard ratio (HR) (95% CI) of incident melanoma, basal cell carcinoma, and squamous cell carcinoma. RESULTS: Of 610,881 subjects prescribed PDE5i, 636 developed melanoma (0.10%). The control group had 8,711 diagnoses of melanoma. There was an association between increased PDE5i tablet use and melanoma (HR 1.05, 95% CI 1.05-1.09). This association was also present between PDE5i use and basal cell carcinoma (HR 1.04, 95% CI 1.02-1.07) and squamous cell carcinoma (HR 1.04, 95% CI 1.01-1.07). In patients with pHTN and LUTS prescribed PDE5is, there was no relationship between exposure and melanoma incidence (HR 0.74, 95% CI 0.48-1.13; and HR 1.03, 95% CI 0.97-1.10, respectively). CLINICAL IMPLICATIONS: There is little evidence for a clinically relevant association between PDE5i use and melanoma incidence. STRENGTHS & LIMITATIONS: Our current work represents the largest study to date evaluating the relationship between PDE5i use and melanoma risk, and the first to examine all current indications of PDE5i use among men and women. Limitations include a patient population limited to commercially insured individuals, unknown patient medication compliance, and lack of information on patient skin type, lifestyle, and sun-exposure habits. CONCLUSION: There is a slight association between higher-volume PDE5i use and development of melanoma, basal cell carcinoma, and squamous cell carcinoma. This association among all skin cancers implies that confounding may account for the observed association. Shkolyar E, Li S, Tang J, et al. Risk of Melanoma With Phosphodiesterase Type 5 Inhibitor Use Among Patients With Erectile Dysfunction, Pulmonary Hypertension, and Lower Urinary Tract Symptoms. J Sex Med 2018;15:982-989.

Long-Term Outcomes in Systemic Sclerosis-Associated Pulmonary Arterial Hypertension From the Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma Registry (PHAROS).

BACKGROUND: Pulmonary arterial hypertension (PAH) is a leading cause of death in patients with systemic sclerosis (SSc). The purpose of this study was to assess long-term outcomes in patients with SSc-PAH. METHODS: Pulmonary Hypertension Assessment and Recognition of Outcomes in Scleroderma is a prospective registry of patients with SSc at high risk for or with incident pulmonary hypertension from right heart catheterization. Incident World Health Organization group I PAH patients were analyzed. Kaplan-Meier survival curves were generated for the overall cohort and those who died of PAH. Multivariate Cox regression models identified predictors of mortality. RESULTS: Survival in 160 patients with incident SSc-PAH at 1, 3, 5, and 8 years was 95%, 75%, 63%, and 49%, respectively. PAH accounted for 52% of all deaths. When restricted to deaths from PAH, respective survival rates were 97%, 83%, 76%, and 76%, with 93% of PAH-related deaths occurring within 4 years of diagnosis. Men (hazard ratio [HR], 3.11; 95% CI, 1.38-6.98), diffuse disease (HR, 2.12; 95% CI, 1.13-3.93), systolic pulmonary artery pressure (PAP) on ECG (HR, 1.06 95% CI, 1.01-1.11), mean PAP on right heart catheterization (HR, 1.03; 95% CI, 1.001-1.07), 6-min walk distance (HR, 0.92; 95% CI, 0.86-0.99), and diffusing capacity for carbon monoxide (HR, 0.65; 95% CI, 0.46-0.92) significantly affected survival on multivariate analysis. CONCLUSIONS: Overall survival in PHAROS was higher than other SSc-PAH cohorts. PAH accounted for more than one-half of deaths and primarily within the first few years after PAH diagnosis. Optimization of treatment for those at greatest risk of early PAH-related death is crucial.