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.

Association between preconception paternal health and pregnancy loss in the USA: an analysis of US claims data.

STUDY QUESTION: Is preconception paternal health associated with pregnancy loss? SUMMARY ANSWER: Poor preconception paternal health is associated with a higher risk of pregnancy loss as confirmed in sensitivity analyses accounting for maternal age and health. WHAT IS KNOWN ALREADY: Preconception paternal health can negatively impact perinatal outcomes. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study of US insurance claims database from 2009 to 2016 covering 958 804 pregnancies. PARTICIPANTS/MATERIALS, SETTING, METHODS: US insurance claims database including women, men and pregnancies within the USA between 2007 and 2016. Paternal preconception health status (e.g. metabolic syndrome diagnoses (MetS), Charlson comorbidity index (CCI) and individual chronic disease diagnoses) was examined in relation to pregnancy loss (e.g. ectopic pregnancy, miscarriage and stillbirth). MAIN RESULTS AND THE ROLE OF CHANCE: In all, 958 804 pregnancies were analyzed. The average paternal age was 35.3 years (SD 5.3) and maternal age was 33.1 years (SD 4.4). Twenty-two percent of all pregnancies ended in a loss. After adjusting for maternal factors, the risk of pregnancy loss increased with increasing paternal comorbidity. For example, compared to men with no components of MetS, the risk of pregnancy loss increased for men with one (relative risk (RR) 1.10, 95% CI 1.09-1.12), two (RR 1.15, 95% CI 1.13-1.17) or three or more (RR 1.19, 95% CI 1.14-1.24) components. Specifically, less healthy men had a higher risk of siring a pregnancy ending in spontaneous abortion, stillbirth and ectopic pregnancies. Similar patterns remained with other measures of paternal health (e.g. CCI, chronic diseases, etc.). When stratifying by maternal age as well as maternal health, a similar pattern of increasing pregnancy loss risk for men with 1, 2 or 3+ MetS was observed. A statistically significant but weak association between timing of pregnancy loss and paternal health was found. LIMITATIONS, REASONS FOR CAUTION: Retrospective study design covering only employer insured individuals may limit generalizability. WIDER IMPLICATIONS OF THE FINDINGS: Optimization of a father's health may improve pregnancy outcomes. STUDY FUNDING/COMPETING INTERESTS: National Institutes of Health National Center for Advancing Translational Science Clinical and Translational Science Award (UL1 TR001085). M.L.E. is an advisor for Sandstone Diagnostics, Dadi, Hannah and Underdog. No other competing interests were declared. TRIAL REGISTRATION NUMBER: N/A.

Anatomical study of the prostatic urethra using vinyl polysiloxane casts.

BACKGROUND: There are limited studies describing the detailed nonhistologic anatomy of the prostatic urethra. We studied radical prostatectomy specimens to describe the ex vivo anatomical details of its shape and size. METHODS: We conducted an observational study examining the prostatic urethra anatomy. Prostatic urethra casts (molds) were made using vinyl polysiloxane immediately after fresh specimens had been retrieved following prostatectomy for organ-confined prostate cancer. The following measurements were taken from the casts: anterior length, posterior length, maximal diameter, bladder neck to verumontanum, verumontanum to apex length, and prostate urethral angle (PUA). Prostate volume was calculated using the ellipsoid formula: ((p/6) × transverse × length × height). RESULTS: Thirty-three prostatic urethral casts were obtained. The mean prostate volume was 38.59 cc. The mean PUA was 127.6°. The mean transverse, apex, and length of the prostate were 4.65, 4.06, and 3.63 cm, respectively. The mean distance from the verumontanum to sphincter was 1.2 cm. The ratio between the anterior and posterior length of the prostatic urethra was 0.82 cm and did not correlate with prostatic size (Figure 8). CONCLUSION: The distance from the verumontanum to the apex does not change with prostate size; it is uniform with a mean length of 1.2 cm. The anterior length, posterior length, and maximum diameter of the prostatic urethra increase with prostate size. The mean difference between the anterior and posterior length is 0.8 cm and did not correlate with prostate size. Urethral angulation decreased with prostate size but was not significant. Information obtained from this study is of value designing prostatic stents and devices for benign prostatic hyperplasia.

Parental comorbidity and medication use in the USA: a panel study of 785 000 live births.

STUDY QUESTION: How prevalent is paternal medication use and comorbidity, and are rates of these rising? SUMMARY ANSWER: Paternal medication use and comorbidity is common and rising, similar to trends previously described in mothers. WHAT IS KNOWN ALREADY: Maternal medication use and comorbidity has been rising for the past few decades. These trends have been linked to potential teratogenicity, maternal morbidity and mortality and poorer fetal outcomes. STUDY DESIGN, SIZE, DURATION: This is a Panel (trend) study of 785 809 live births from 2008 to 2016. PARTICIPANTS/MATERIALS, SETTING, METHODS: We used the IBM© Marketscan®™ database to gather data on demographic information and International Classification of Diseases codes and Charlson comorbidity index (CCI) during the 12 months prior to the estimated date of conception for mothers and fathers. We similarly examined claims of prescriptions in the 3 months prior to conception. We performed companion analyses of medications used for >90 days in the 12 months prior to conception and of any medication use in the 12 months prior to conception. MAIN RESULTS AND THE ROLE OF CHANCE: We confirmed that both maternal medication use and comorbidity (e.g. hypertension, diabetes, hyperlipidemia) rose over the study period, consistent with prior studies. We found a concurrent rise in both paternal medication use 3 months prior to conception (overall use, 31.5-34.9% during the study period; P < 0.0001) and comorbidity (CCI of ≥1 and 10.6-18.0% over study period; P < 0.0001). The most common conditions seen in the CCI were chronic obstructive pulmonary disease for mothers (6.6-11.6%) and hyperlipidemia for fathers (8.6-13.7%). Similar trends for individual medication classes and specific comorbidities such as hypertension, diabetes and hyperlipidemia were also seen. All primary result trends were statistically significant, making the role of chance minimal. LIMITATIONS, REASONS FOR CAUTION: As this is a descriptive study, the clinical impact is uncertain and no causal associations may be made. Though the study uses a large and curated database that includes patients from across the USA, our study population is an insured population and our findings may not be generalizable. Mean parental age was seen to slightly increase over the course of the study (<1 year) and may be associated with increased comorbidity and medication use. WIDER IMPLICATIONS OF THE FINDINGS: As parental comorbidity and certain medication use may impact fecundability, temporal declines in parental health may impact conception, pregnancy and fetal outcomes. STUDY FUNDING/COMPETING INTEREST(S): None. TRIAL REGISTRATION NUMBER: N/A.

The age of fathers in the USA is rising: an analysis of 168 867 480 births from 1972 to 2015.

STUDY QUESTION: How has the mean paternal age in the USA changed over the past 4 decades? SUMMARY ANSWER: The age at which men are fathering children in the USA has been increasing over time, although it varies by race, geographic region and paternal education level. WHAT IS KNOWN ALREADY: While the rise in mean maternal age and its implications for fertility, birth outcomes and public health have been well documented, little is known about paternal characteristics of births within the USA. STUDY DESIGN, SIZE, DURATION: A retrospective data analysis of paternal age and reporting patterns for 168 867 480 live births within the USA since 1972 was conducted. PARTICIPANTS/MATERIALS, SETTING, METHODS: All live births within the USA collected through the National Vital Statistics System (NVSS) of the Centers for Disease Control and Prevention (CDC) were evaluated. Inverse probability weighting (IPW) was used to reduce bias due to missing paternal records. MAIN RESULTS AND THE ROLE OF CHANCE: Mean paternal age has increased over the past 44 years from 27.4 to 30.9 years. College education and Northeastern birth states were associated with higher paternal age. Racial/ethnic differences were also identified, whereby Asian fathers were the oldest and Black fathers were the youngest. The parental age difference (paternal age minus maternal age) has decreased over the past 44 years. Births to Black and Native American mothers were most often lacking paternal data, implying low paternal reporting. Paternal reporting was higher for older and more educated women. LIMITATIONS, REASONS FOR CAUTION: Although we utilized IPW to reduce the impact of paternal reporting bias, our estimates may still be influenced by the missing data in the NVSS. WIDER IMPLICATIONS OF THE FINDINGS: Paternal age is rising within the USA among all regions, races and education levels. Given the implications for offspring health and demographic patterns, further research on this trend is warranted. STUDY FUNDING/COMPETING INTEREST(S): No funding was received for this study and there are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Validity of Claims Data for the Identification of Male Infertility.

PURPOSE OF REVIEW: We sought to determine whether infertile men can accurately be identified within a large insurance claims database to validate its use for reproductive health research. RECENT FINDINGS: Prior literature suggests that men coded for infertility are at higher risk for chronic disease though it was previously unclear if these diagnostic codes correlated with true infertility. We found that the specificity of one International Classification of Disease (9th edition) code in predicting abnormal semen parameters was 92.4%, rising to 99.8% if a patient had three different codes for infertility. The positive predictive value was as high as 85%. The use of claims data for male infertility research has been rapidly progressing due to its high power and feasibility. The high specificity of ICD codes for men with abnormal semen parameters is reassuring and validates prior studies as well as future investigation into men's health.

Inhibition of leukemia cell engraftment and disease progression in mice by osteoblasts.

The bone marrow niche is thought to act as a permissive microenvironment required for emergence or progression of hematologic cancers. We hypothesized that osteoblasts, components of the niche involved in hematopoietic stem cell (HSC) function, influence the fate of leukemic blasts. We show that osteoblast numbers decrease by 55% in myelodysplasia and acute myeloid leukemia patients. Further, genetic depletion of osteoblasts in mouse models of acute leukemia increased circulating blasts and tumor engraftment in the marrow and spleen leading to higher tumor burden and shorter survival. Myelopoiesis increased and was coupled with a reduction in B lymphopoiesis and compromised erythropoiesis, suggesting that hematopoietic lineage/progression was altered. Treatment of mice with acute myeloid or lymphoblastic leukemia with a pharmacologic inhibitor of the synthesis of duodenal serotonin, a hormone suppressing osteoblast numbers, inhibited loss of osteoblasts. Maintenance of the osteoblast pool restored normal marrow function, reduced tumor burden, and prolonged survival. Leukemia prevention was attributable to maintenance of osteoblast numbers because inhibition of serotonin receptors alone in leukemic blasts did not affect leukemia progression. These results suggest that osteoblasts play a fundamental role in propagating leukemia in the marrow and may be a therapeutic target to induce hostility of the niche to leukemia blasts.

Femoral condyle insufficiency fractures: associated clinical and morphological findings and impact on outcome.

OBJECTIVE: To determine the characteristics of femoral condyle insufficiency fracture (FCIF) lesions and their relative associations with the risk of clinical progression. MATERIALS AND METHODS: This HIPAA-compliant retrospective study was approved by our Institutional Review Board. Seventy-three patients (age range, 19-95) were included after excluding patients with post-traumatic fractures, bone marrow infarct, osteochondritis dissecans, or underlying tumor. Two board-certified musculoskeletal radiologists classified morphologic findings including lesion diameter, associated bone marrow edema pattern, and associated cartilage/meniscus damage. Electronic medical charts were evaluated for symptoms, risk factors, and longitudinal outcomes, including total knee arthroplasty (TKA). Imaging characteristics were correlated with clinical findings, and comparison of outcome groups was performed using a regression model adjusted for age. RESULTS: The majority of patients with FCIF were women (64.4%, 47/73), on average 10 years older than men (66.28 ± 15.86 years vs. 56.54 ± 10.39 years, p = 0.005). The most common location for FCIF was the central weight-bearing surface of the medial femoral condyle; overlying full thickness cartilage loss (75.7%, 53/70) and ipsilateral meniscal injury (94.1%, 64/68) were frequently associated. Clinical outcomes were variable, with 23.9% (11/46) requiring TKA. Cartilage WORMS score, adjacent cartilage loss, and contralateral meniscal injury, in addition to decreased knee range of motion at presentation, were significantly associated with progression to TKA (p < 0.05). CONCLUSIONS: FCIF are frequently associated with overlying cartilage loss and ipsilateral meniscal injury. The extent of cartilage loss and meniscal damage, in addition to loss of knee range of motion at the time of presentation, are significantly associated with clinical progression.

Prevalence of pediatric lower urinary tract symptoms in a national claims database of privately insured patients, 2003-2014.

BACKGROUND: We conducted this study to estimate the prevalence of pediatric lower urinary tract symptoms (pLUTS) in a US privately insured pediatric population who are 6-20 years old by age, sex, race/ethnicity from 2003-2014. This has not been previously described in the literature. METHODS: We retrospectively reviewed Optum's de-identified Clinformatics® Data Mart Database between 2003-2014. A pLUTS patient was defined by the presence of ≥ 1 pLUTS-related ICD-9 diagnosis code between the age of 6-20 years. Neurogenic bladder, renal transplant and structural urologic disease diagnoses were excluded. Prevalence by year was calculated as a proportion of pLUTS patients among the total population at risk. Variables reviewed included age, sex, race, geographic region, household factors and clinical comorbidities including attention-deficit/hyperactivity disorder (ADHD), constipation, and sleep apnea. Point of service (POS) was calculated as a proportion of pLUTS-related claims associated with a POS compared to the total claims at all POS in the time period. RESULTS: We identified 282,427 unique patients with ≥ 1 claim for pLUTS between the ages of 6-20 years from 2003 to 2014. Average prevalence during this period was 0.92%, increasing from 0.63% in 2003 to 1.13% in 2014. The median age group of patients was 6-10 years. More patients were female (59.80%), white (65.97%), between 6 and 10 years old (52.18%) and resided in the Southern US (44.97%). Within a single household, 81.71% reported ≤ 2 children, and 65.53% reported ≥ 3 adults. 16.88% had a diagnosis of ADHD, 19.49% had a diagnosis of constipation and 3.04% had a diagnosis of sleep apnea. 75% of pLUTS-related claims were recorded in an outpatient setting. CONCLUSIONS: Families consistently seek medical care in the outpatient setting for pLUTS. The demographic and clinical characteristics of our cohort reflect prior literature. Future studies can help define temporal relationships between household factors and onset of disease as well as characterize pLUTS-related healthcare resource utilization. Additional work is required in publicly insured populations.

The Association Between Insomnia, Insomnia Medications, and Erectile Dysfunction.

BACKGROUND: Sleep quality and duration have been investigated for their association with health. Insomnia affects up to one-third of adults and may impact male erectile function. In addition, medical treatments for insomnia (many of which are sedatives) may also affect erectile quality. OBJECTIVE: To investigate the association of erectile dysfunction (ED) in patients diagnosed with and treated for insomnia. DESIGN, SETTING, AND PARTICIPANTS: We utilized the IBM MarketScan (2007-2016) Commercial and Medicare Supplemental Databases (v 2.0). Age- and enrollment-matched controls were selected among patients without insomnia diagnosis or treatment. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Cox proportional hazard models were used to estimate the risk of incident ED (ie, diagnosis alone, or diagnosis and treatment with phosphodiesterase-5 inhibitors [PDE5i], intracavernous injection (ICI)/urethral suppositories, and penile prosthesis) after the diagnosis or treatment of insomnia while adjusting for relevant comorbidities. RESULTS AND LIMITATIONS: In total, 539 109 men with an insomnia diagnosis were identified. Of these men, 356 575 were also medically treated for insomnia. The mean (±standard deviation) follow-up times for patients diagnosed with insomnia and those diagnosed with and treated for insomnia were 2.8 ± 1.6 and 3.1 ± 1.8 yr, respectively. Men with insomnia were more commonly smokers and had a higher number of office visits and comorbidities than controls (p < 0.001). On an adjusted analysis, both untreated and treated insomnia were associated with increased risks of ED diagnosis (hazard ratio or HR [95% confidence interval {CI}]: 1.58 [1.54-1.62] and 1.66 [1.64-1.69], respectively; p < 0.001). Similarly, men with treated insomnia had a higher risk of having ED treated with PDE5i (HR [95% CI]: 1.52 [1.49-1.55]; p < 0.001) and ICI (HR [95% CI]: 1.32 [1.14-1.54]; p < 0.001) when compared with controls. A limitation of this study was that a lack of granularity regarding patient clinical characteristics (eg, severity of disease, laboratory data, etc.) is inherent to insurance claims data. In addition, the follow-up was limited and may affect associations at longer time points. CONCLUSIONS: In the current report, a consistent association between insomnia and ED diagnosis was identified. Men diagnosed with insomnia only were found to have a higher risk of developing ED. Moreover, men with pharmacological insomnia treatments were more often prescribed treatments for ED. Given the prevalence of insomnia, future studies are warranted to delineate the association of insomnia and its treatment with erectile function. PATIENT SUMMARY: Insomnia affects up to one-third of adults and impact male erectile function. Men only diagnosed with insomnia were found to have a higher risk of developing erectile dysfunction (ED). Moreover, men with pharmacological insomnia treatments were more often prescribed treatments for ED.

Trabecular and cortical microarchitecture in postmenopausal HIV-infected women.

Our objective was to assess the effects of HIV infection and antiretroviral therapy on trabecular and cortical microarchitecture in postmenopausal minority women. A subgroup of 106 (46 HIV-infected, 60 uninfected) postmenopausal Hispanic and African American women from an established cohort had areal bone mineral density (aBMD) measured by dual-energy X-ray absorptiometry and trabecular and cortical volumetric BMD (vBMD) and microarchitecture measured by high-resolution peripheral quantitative computed tomography (HRpQCT) at the radius and tibia. HIV-infected women were slightly younger (58 ± 1 vs. 61 ± 1 years, p = 0.08), and had lower body mass index (BMI; 28 ± 1 vs. 32 ± 1 kg/m(2), p < 0.01). BMI-adjusted aBMD Z scores were lower in HIV-infected women at the lumbar spine, total hip, and ultradistal radius. Serum N-telopeptide and C-telopeptide levels were also higher in HIV-infected women. Trabecular and cortical vBMD were similar at the radius, but cortical area (105.5 ± 2.4 vs. 120.6 ± 2.0 mm(2), p < 0.01) and thickness (956 ± 33 vs. 1,075 ± 28 µm, p < 0.01) at the tibia were approximately 11-12 % lower in HIV-infected women. Differences remained significant after adjusting for age, BMI, and race/ethnicity. In contrast, cortical porosity was similar in the two groups. Although HIV-infected postmenopausal women had lower aBMD at the spine, total hip, and ultradistal radius and higher levels of bone resorption markers, the only differences detected by HRpQCT were lower cortical thickness and area at the tibia.

The association of preconception paternal metabolic syndrome on early childhood emergency department visits and hospitalizations.

BACKGROUND: Increasing preconception paternal comorbidity has been associated with adverse pregnancy outcomes. However, whether the father's health impacts the child after birth is uncertain. OBJECTIVES: In the present study, we examined the association of preconception paternal metabolic syndrome status with childhood emergency department visits and hospitalizations. MATERIALS AND METHODS: This is a longitudinal cohort study of children (295,355 boys and 278,735 girls) born to linked pairs of fathers and mothers in the United States between 2009 and 2016 within the IBM MarketScan Research database. Associations between paternal and maternal metabolic syndrome component diagnoses and subsequent hospitalizations and emergency department visits for offspring within the first 2 years of life were determined. RESULTS: Note that, 35.5% (203,617/574,090) of children had at least one emergency room visit and 6.1% (35,141/574,090) of children had an inpatient admission. After adjustment, the odds of inpatient admission and emergency department visits increased in a dose-dependent fashion among fathers with higher comorbidities. Similar trends were seen for emergency department visit utilization. DISCUSSION AND CONCLUSION: Increasing paternal preconception comorbidity is associated with a higher risk that a child requires the emergency department and inpatient care in the first years of life. An opportunity exists to engage men in preconception counseling to optimize their and their offspring's health.

Prevalence of pediatric lower urinary tract symptoms in a US population seeking medical care, 2003- 2014.

Background: We conducted this study to estimate the prevalence of pediatric lower urinary tract symptoms (pLUTS) in a US privately-insured pediatric population who are 18 years of age or older by age, sex, race/ethnicity from 2003-2014. This has not been previously described in the literature. Methods: We retrospectively reviewed Optum's de-identifed Clinformatics® Data Mart Database database between 2003-2014. A pLUTS patient was defined by the presence of ≥ 1 pLUTS-related ICD-9 diagnosis code between the age of 6-20 years. Neurogenic bladder, renal transplant and structural urologic disease diagnoses were excluded. Prevalence by year was calculated as a proportion of pLUTS patients among the total population at risk. Variables reviewed included age, sex, race, geographic region, household factors and clinical comorbidities including attention-deficit/hyperactivity disorder (ADHD), constipation, and sleep apnea. Point of service (POS) was calculated as a proportion of pLUTS-related claims associated with a POS compared to the total claims at all POS in the time period. Results: We identified 282,427 unique patients with ≥ 1 claim for pLUTS between the ages of 6-20 years from 2003-2014. Average prevalence during this period was 0.92%, increasing from 0.63% in 2003 to 1.13% in 2014. Mean age was 12.15 years. More patients were female (59.80%), white (65.97%), between 6-10 years old (52.18%) and resided in the Southern US (44.97%). Within a single household, 81.71% reported ≤ 2 children, and 65.53% reported ≥ 3 adults. 16.88% had a diagnosis of ADHD, 19.49% had a diagnosis of constipation and 3.04% had a diagnosis of sleep apnea. 75% of pLUTS-related claims were recorded in an outpatient setting. Conclusions: Families consistently seek medical care in the outpatient setting for pLUTS. The demographic and clinical characteristics of our cohort reflect prior literature. Future studies can help define temporal relationships between household factors and onset of disease as well as characterize pLUTS-related healthcare resource utilization. Additional work is required in publicly-insured populations.

Delayed Ejaculation After Lumbar Spine Surgery: A Claims Database Analysis.

STUDY DESIGN: Retrospective cohort. OBJECTIVES: Delayed ejaculation (DE) is a distressing condition characterized by a notable delay in ejaculation or complete inability to achieve ejaculation, and there are no existing reports of DE following lumbar spine surgery. Inspired by our institutional experience, we sought to assess national rates of DE following surgery of the lumbar spine. METHODS: We queried the Optum De-identified Clinformatics Database for adult men undergoing surgery of the lumbar spine between 2003 and 2017. The primary outcome was the development of DE within 2 years of surgery. Multivariable logistic regression was performed to identify factors associated with the development of DE. RESULTS: We identified 117 918 men who underwent 162 646 lumbar spine surgeries, including anterior lumbar interbody fusion (ALIF), posterior lumbar fusion (PLF), and more. The overall incidence of DE was 0.09%, with the highest rate among ALIF surgeries at 0.13%. In multivariable analysis, the odds of developing DE did not vary between anterior/lateral lumbar interbody fusion, PLF, and other spine surgeries. A history of tobacco smoking (OR = 1.47, 95% CI 1.00-2.16, P = .05) and obesity (OR = 1.56, 95% CI 1.00-2.44, P = .05) were associated with development of DE. CONCLUSIONS: DE is a rare but distressing complication of thoracolumbar spine surgery, and patients should be queried for relevant symptoms at postoperative visits when indicated.

Risk of Postpartum Urinary Stone Disease in Women with History of Urinary Stone Disease During Pregnancy.

Objective: To determine the risk of postpartum urinary stone disease in women with a history of stone disease during pregnancy. Methods: Using the Optum® de-identified Clinformatics® Datamart we identified pregnant women with urinary stone disease in the United States between January 2003 to December 2017 by standardized International Classification of Diseases Ninth and Tenth Editions (ICD-9 and ICD-10), and Current Procedural Terminology code criteria. We limited the cohort to include women without evidence of urinary stone disease before pregnancy. We abstracted patient demographic characteristics, clinical risk factors for stone disease, and data for urinary stone disease encounters and related procedures after pregnancy. Encounters occurring within 1 year of pregnancy were excluded. Cox proportional hazard models were used to analyze for significance. Results: We identified a total of 1,395,783 pregnant women with a median postpartum follow-up of 4.0 years, including 5971 (0.4%) women with a urinary stone during pregnancy. Of these, 736 (12.3%) had an additional urinary stone diagnosis claim after pregnancy, compared with 13,275 (0.95%) women without a history of stone disease during pregnancy (p < 0.0001). In multivariable proportional hazards models urinary stone disease during pregnancy (hazards ratio 12.8, 95% confidence interval [11.8-13.8]) was independently associated with a higher hazard of urinary stone disease after pregnancy. Conclusion: Women with urinary stone disease during pregnancy were more likely to present with recurrent urinary stone disease after pregnancy. Given the one in eight chance of needing further care, women with history of stone disease during pregnancy may benefit from risk counseling, surveillance, or secondary prevention efforts in the postpartum period.

Consumption of cruciferous vegetables and the risk of bladder cancer in a prospective US cohort: data from the NIH-AARP diet and health study.

BACKGROUND: Abundant pre-clinical data suggest that consumption of cruciferous vegetables might protect against bladder cancer. While small-scale clinical evidence supports this hypothesis, population-level data is lacking. We tested the hypothesis that consumption of cruciferous vegetables is associated with a lower risk of bladder cancer in a large population-based study. METHODS: We investigated the association between dietary consumption of cruciferous vegetables and the risk of bladder cancer in the NIH-American Association of Retired Persons (AARP) Diet and Health Study. Diet at baseline was collected with self-administered food-frequency questionnaires. Bladder cancer diagnoses were identified through linkage with state cancer registries. Hazard ratio (HR) and 95% confidence intervals (CI) were estimated with Cox proportional hazards models. RESULTS: Our analysis included 515,628 individuals. Higher intake of cruciferous vegetables, both overall and when stratified by variety (broccoli vs. brussels sprouts vs. cauliflower), were not associated with bladder cancer risk for men or women. A history of smoking did not affect the results. CONCLUSIONS: Our study shows no association between dietary consumption of cruciferous vegetables and incident bladder cancer.

In Vivo Imaging of Methionine Aminopeptidase II for Prostate Cancer Risk Stratification.

Prostate cancer is one of the most common malignancies worldwide, yet limited tools exist for prognostic risk stratification of the disease. Identification of new biomarkers representing intrinsic features of malignant transformation and development of prognostic imaging technologies are critical for improving treatment decisions and patient survival. In this study, we analyzed radical prostatectomy specimens from 422 patients with localized disease to define the expression pattern of methionine aminopeptidase II (MetAP2), a cytosolic metalloprotease that has been identified as a druggable target in cancer. MetAP2 was highly expressed in 54% of low-grade and 59% of high-grade cancers. Elevated levels of MetAP2 at diagnosis were associated with shorter time to recurrence. Controlled self-assembly of a synthetic small molecule enabled design of the first MetAP2-activated PET imaging tracer for monitoring MetAP2 activity in vivo. The nanoparticles assembled upon MetAP2 activation were imaged in single prostate cancer cells with post-click fluorescence labeling. The fluorine-18-labeled tracers successfully differentiated MetAP2 activity in both MetAP2-knockdown and inhibitor-treated human prostate cancer xenografts by micro-PET/CT scanning. This highly sensitive imaging technology may provide a new tool for noninvasive early-risk stratification of prostate cancer and monitoring the therapeutic effect of MetAP2 inhibitors as anticancer drugs. SIGNIFICANCE: This study defines MetAP2 as an early-risk stratifier for molecular imaging of aggressive prostate cancer and describes a MetAP2-activated self-assembly small-molecule PET tracer for imaging MetAP2 activity in vivo.

Racial and Socioeconomic Factors Influence Utilization of Advanced Therapies in Commercially Insured OAB Patients: An Analysis of Over 800,000 OAB Patients.

OBJECTIVE: To determine if racial and/or socioeconomic factors influence advanced therapy utilization for refractory overactive bladder (OAB) among the commercially insured. METHODS: We queried Optum, a national claims database, between 2003 and 2017. Non-neurogenic OAB patients were identified using ICD-9/10 diagnosis codes. Demographic and treatment data were collected, including oral medication therapies (anticholinergic, beta3 agonists), and advanced therapies (OnabotulinumtoxinA [BTX], Sacral Nerve Stimulation [SNS], percutaneous tibial nerve stimulation [PTNS]). Associations between patient sociodemographic factors and advanced therapy utilization were explored. RESULTS: Of 4,229,617 OAB patients, 807,612 (19%) received medical therapies, of which 95% received oral medications only and only 4.7% received advanced therapies. Asians had the lowest use of oral therapy use (14% vs 18%-19% in other races/ethnicities, P <0.05), and advanced therapy use (0.44% vs 0.71%-0.93%, P <0.05). Asians and Hispanics were least likely to utilize SNS therapy and most likely to use PTNS compared to Blacks and Whites. BTX use was similar between races/ethnicities (P <0.05). Female gender (OR 1.65 [CI 1.61,1.69]), younger age (<65) (OR 1.28 [1.25,1.31]), higher annual income ≥$40K (OR 1.09 [1.06,1.12]) and prior use of oral medications (OR 3.30 [3.21,3.38] for 1 medication) were significantly associated with receiving advanced therapies. Non-white race (OR 0.89 [0.87,0.91]), lower education level (less than a bachelor's degree) (OR 0.97 [0.94,0.99]), and Northeast region were associated with a lower likelihood of receiving advanced therapies (P <0.05 for all). CONCLUSION: Among commercially insured, racial and socioeconomic factors predict utilization of advanced OAB therapies, including race/ethnicity, age, gender, education level, and region.

The Most Common Reasons for Health Care Provider Visits in Reproductive Aged Men Differ by Race and Age Stratification.

INTRODUCTION: We assessed common reasons for health care provider visits among reproductive aged men. METHODS: We used the Optum® Clinformatics® Data Mart, a de-identified insurance claims database encompassing commercial and Medicare Advantage health plan data from all 50 states, to analyze men 20 to 49 years old who were enrolled between January 1 and December 31, 2017. Men with at least 1 health care provider visit were included and were stratified into age groups of 20 to 29, 30 to 39 and 40 to 49 years old. For each age group the top 100 urological and nonurological ICD-10 diagnosis codes were aggregated and assessed per unit of observation. Groups were further stratified by race. Descriptive statistics are presented in counts and percentages. RESULTS: A total of 3,027,585 men 20 to 49 years old were enrolled in Optum Data Mart in 2017. Of these men 1,915,027 (63%) had at least 1 visit with a health care provider. Musculoskeletal pain was the top reason for visits across all age groups. Sexually transmitted diseases were the top urological complaint in men 20 to 29 and 30 to 39 years old. Sterilization was among the top reasons for visits in white men and was less common in black, Hispanic and Asian men. Testicular hypofunction was the most common urological complaint in men 40 to 49 years old and erectile dysfunction was also noted. CONCLUSIONS: We identified urological concerns as common drivers for reproductive aged men to visit providers. Urological issues including sexually transmitted diseases, testicular hypofunction and erectile dysfunction motivate these men to seek medical attention, with rates differing based on age and race.

Association between infertility and mental health of offspring in the United States: a population based cohort study.

There exist conflicting data in regard to the health outcomes of offspring born to infertile couples and follow up of offspring can be challenging. The objective of the study was to determine the association between infertility in men and women and the mental health of their offspring. The present study analyzes data obtained from the IBM Marketscan™ Commercial Claims and Encounters database from 2007 through 2015. Overall, 271,603 children of males with male factor infertility, 328,571 children of females with female factor infertility, 663,568 children of males who later underwent vasectomy were identified. The odds of psychosis were increased in offspring of those with male factor infertility (OR 1.25, 95% CI 1.22-1.29) and female factor infertility (OR 1.20, 95% CI 1.17-1.23). Offspring of infertile males (OR 1.19, 95% CI 1.13-1.26) and infertile females (OR 1.20, 95% CI 1.14-1.26) had an increased odds of autism compared to the reference group. In addition, offspring of infertile males (OR 1.48, 95% CI 1.28-1.7) and infertile females (OR 1.52, 95% CI 1.33-1.73) had higher odds of being diagnosed with an intellectual disability. Therefore, offspring of infertile men or women may have an increased risk of developing psychosis, autism, or intellectual disability.