Estimated Familial Amyotrophic Lateral Sclerosis Proportion: A Literature Review and Meta-analysis.

Background and Objectives: Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disorder. Familial (fALS) cases are usually reported to constitute 5%-10% of all ALS cases; however, no recent literature review or meta-analysis of this proportion (referred to throughout as "proportion fALS") has been conducted. Our objective was to estimate the proportion fALS by geographic region and to assess the effect of study characteristics on the estimates. Methods: A comprehensive literature review was performed to identify all original studies reporting the number of fALS cases in an ALS cohort. The results were stratified by geographic region, study design (case series or population-based), and decade of study publication. Subgroup analyses were conducted according to family history criteria used to define fALS. We report pooled estimates of the proportion fALS from random-effects meta-analyses when >2 studies are available and I2 is < 90%; weighted averages and ranges are otherwise presented. Results: The overall pooled proportion fALS based on a total 165 studies was 8% (0%, 71%). The proportion fALS was 9% (0%, 71%) among 107 case series and 5% (4%, 6%) among 58 population-based studies. Among population-based studies, proportion fALS by geographic region was 6% (5%, 7%; N = 37) for Europe, 5% (3%, 7%; N = 5) for Latin America, and 5% (4%, 7%; N = 12) for North America. Criteria used to define fALS were reported by 21 population-based studies (36%), and proportion fALS was 5% (4%, 5%; N = 9) for first-degree relative, 7% (4%, 11%; N = 4) for first or second-degree relative, and 11% (N = 1) for more distant ALS family history. Population-based studies published in the 2000s or earlier generated a lower pooled proportion fALS than studies published in the 2010s or later. Discussion: The results suggest that variability in the reported proportion fALS in the literature may be, in part, due to the differences in geography, study design, fALS definition, and decade of case ascertainment. Few studies outside of European ancestral populations were available. The proportion fALS was marginally higher among case series compared with population-based studies, likely because of referral bias. Criteria used to define fALS were largely unreported. Consensus criteria for fALS and additional population-based studies in non-European ancestral populations are needed.

Increased Risk of Venous Thromboembolism in Patients With Amyotrophic Lateral Sclerosis: Results From a US Insurance Claims Database Study.

Background and Objectives: Reduced mobility in patients with amyotrophic lateral sclerosis (ALS) is hypothesized to increase the risk of venous thromboembolism (VTE). A few small, single-center studies have investigated the risk of VTE in patients with ALS. Given the high morbidity and mortality associated with VTE, further understanding of the risk in patients with ALS may inform clinical care. The objective of this study was to investigate the incidence of VTE in patients with ALS compared with controls without ALS. Methods: Patients were identified from a US health insurance claims database, Optum's deidentified Clinformatics Data Mart Database, between 2004 and 2019. ALS cases were defined as patients aged 18 years or older with (1) 2 or more ALS claims at least 27 days apart including at least 1 claim from a neurologist visit or (2) 1 or more ALS claims and a prescription for riluzole or edaravone. Each ALS case was matched on age and sex to 5 controls without ALS. VTE was defined as at least 1 claim for VTE and at least 1 anticoagulant prescription or VTE-related procedure within 7 days before and 30 days after a VTE claim date. Incidence rates were reported per 1,000 person-years. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using the Cox proportional hazards model. Results: Among 4,205 ALS cases and 21,025 controls, incident VTE occurred in 132 ALS cases (3.1%) and 244 controls (1.2%). Incidence rates of VTE were 19.9 per 1,000 person-years (95% CI 16.7-23.6) in ALS cases compared with 6.0 per 1,000 person-years (95% CI 5.0-7.1) in controls. ALS cases were about 3 times more likely to develop VTE (HR 3.3, 95% CI 2.6-4.0), with similar results among men and women. The median time to first VTE was 10 months from the initial ALS claim in ALS cases. Discussion: Consistent with previous smaller studies, a higher incidence rate of VTE was observed in a large sample of patients with ALS from across the United States, as compared to matched controls. The markedly increased risk underscores the importance of preventive efforts and careful monitoring for VTE in patients with ALS and may have implications for the management of ALS.

Incidence of Aicardi-Goutières syndrome and KCNT1-related epilepsy in Denmark.

Objective: To estimate the incidence of Aicardi-Goutières syndrome (AGS) and potassium sodium-activated channel subfamily T member 1 (KCNT1)-related epilepsy in Denmark and to characterize the patients diagnosed with AGS and KCNT1-related epilepsy. Background: AGS and KCNT1-related epilepsy are 2 distinct rare genetic disorders. Due to the rarity of AGS and KCNT1-related epilepsy, the epidemiology remains unclear. The incidences for these diseases or the carriers with disease-related genetic variants remain unknown. Materials and methods: This is a retrospective, non-interventional, population-based study using aggregate data from the Danish population register and hospital-based patient-level data in Denmark to identify persons with genetically confirmed AGS between January 2010 to December 2020 and KCNT1-related epilepsies between January 2012 to December 2020. Cases of these disorders were identified from in-hospital databases, and pathogenic variants were identified and confirmed by Sanger and/or whole exome (panel-based) sequencing. The incidence of AGS and KCNT1-related epilepsy were estimated in separate statistical analyses. Results: A total of 7 AGS patients were identified. The mean age at AGS diagnosis was 19.4 months (median age 14 months). TREX1 (n < 5) and RNASEH2B (n ≥ 5) genes were reported with confirmed pathogenic variants. The birth incidence of AGS was <0.7600 per 100,000 live births. The average annual incidence rate was calculated as 0.0539 (95% CI: 0.0217-0.1111) per 100,000 persons per year in the total population < 18 years (n = 7); the average annual incidence rate was <0.7538 per 100,000 persons per year (n < 5) in the population < 12 months, and the average annual incidence rate in the population ≥ 12 months and < 18 years was <0.0406 per 100,000 persons per year (n < 5). A total of 14 KCNT1-related epilepsy cases were identified during the study period (n = 5 in 2016, remaining 9 cases in 2013 and 2015). The mean age at diagnosis was 20.6 years (median 19 years) for KCNT1 cases. A total of 8 cases (57.1%) were ≥ 18 years, and 6 (42.9%) were < 18 years at diagnosis. The phenotype autosomal dominant or sporadic sleep-related hypermotor epilepsy (ADSHE) (n = 10, 71.4%) was most reported; the remaining 4 cases had either epilepsy of infancy with migrating focal seizures (EIMFS) or an unclassifiable developmental and epileptic encephalopathy (DEE). The birth incidence of KCNT1-related epilepsy was ≤1.1205 per 100,000 live births. The average annual incidence rates per 100,000 persons per year during the study period were 0.0431 (95% confidence interval [CI]: 0.0236-0.0723; n = 14) in the overall population ≤ 50 years, 0.0568 (95% CI: 0.0209-0.1237; n = 6) in the population < 18 years, and 0.0365 (95% CI: 0.0157-0.0718; n = 8) in the population ≥ 18 and ≤ 50 years. There were 3 families with at least 2 cases diagnosed with KCNT1-related epilepsies (on average 3.3 cases per family), indicating 10 cases in total within the 3 families. All KCNT1 cases of ADSHE phenotype came from the 3 families. The higher incidence of older ages and ADSHE cases compared with previous KCNT1 studies is likely due to the capture of prevalent and familial previously undiagnosed cases. Excluding these family cases, the average annual incidence was 0.0123 (95% CI: 0.0034-0.0315, n = 4) per 100,000 persons per year in the population ≤ 50 years during 2012-2020. Conclusions: AGS and KCNT1-related epilepsy are particularly rare diseases. The annual average incidence rate of AGS was 0.0539 per 100,000 persons per year in the population < 18 years and birth incidence was <0.7600 per 100,000 live births during 2010-2020. The average annual incidence rate of KCNT1-related epilepsy was 0.0431 per 100,000 persons per year in the population ≤ 50 years and the birth incidence was ≤1.1205 per 100,000 live births during 2012-2020. Given similar healthcare systems and genetic pools, these findings may provide insight on the incidence of these rare diseases in the Nordics.

Comparative All-Cause Mortality Among a Large Population of Patients with Spinal Muscular Atrophy Versus Matched Controls.

INTRODUCTION: There is little information about survival of spinal muscular atrophy (SMA) patients into adulthood, in particular from population-based samples. We estimated and compared age-specific, all-cause mortality rates in patients with SMA and matched controls in a large, retrospective cohort study using electronic health records (EHRs) from the pre-treatment era. METHODS: The US Optum® de-identified EHR database contains EHRs for ~ 104 million persons (study period: January 1, 2007-December 22, 2016). SMA cases were identified by one or more International Classification of Diseases, Ninth/Tenth Edition codes for SMA. Controls with no SMA diagnosis code were matched 10:1 to SMA cases based on birth year, gender, and first diagnostic code date. For both groups, ≥ 1 month of observation and (if deceased) a valid date of death were required for inclusion. Age-specific mortality rates per person-year (PY) and hazard ratios were calculated. RESULTS: Five thousand one hundred seventy-nine SMA cases and 51,152 controls were analyzed. The overall hazard ratio comparing cases with controls was 1.76 (95% CI 1.63-1.90). In patients with SMA type III diagnostic codes only, the all-age mortality rate was 1059/100,000 PYs in cases and 603/100,000 PYs in controls. In older age groups (13-20, 21-30, 31-40, 41-50, 51-60, and > 60 years), age-specific mortality rates for cases consistently exceeded those of controls. Limitations of this study included the inability to confirm the SMA diagnosis or SMA type by genetic or clinical confirmation. CONCLUSION: Patients with SMA of all ages, including adults and type III patients, had a higher all-cause mortality rate as compared to age-matched controls during the pre-treatment era.

Estimated Prevalence and Incidence of Amyotrophic Lateral Sclerosis and SOD1 and C9orf72 Genetic Variants.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a rare neurological disorder characterized by progressive deterioration of motor neurons. Assessment of the size/geographic distribution of the ALS population, including ALS with genetic origin, is needed to understand the burden of the disease and the need for clinical intervention and therapy. OBJECTIVES: The main objective of this study was to estimate the number of prevalent and incident ALS cases overall and superoxide dismutase 1 (SOD1) and chromosome 9 open reading frame 72 (C9orf72) ALS in 22 countries across Europe (Belgium, France, Germany, Ireland, Italy, Netherlands, Norway, Russia, Spain, Sweden, and UK), North America (USA and Canada), Latin America (Argentina, Brazil, Colombia, Mexico, and Uruguay), and Asia (China, Japan, South Korea, and Taiwan). METHODS: A comprehensive literature search was conducted to identify population-based studies reporting ALS prevalence and/or incidence rates. Pooled prevalence and incidence rates were obtained using a meta-analysis approach at the country and regional geographic level. A country-level pooled estimate was used when ≥2 studies were available per country and geographic regional pooled estimates were used otherwise. The proportion of cases with a SOD1 or C9orf72 mutation among sporadic (sALS) and familial (fALS) cases were obtained from a previous systematic review and meta-analysis. RESULTS: Pooled prevalence rates (per 100,000 persons) and incidence rates (per 100,000 person-years) were 6.22 and 2.31 for Europe, 5.20 and 2.35 for North America, 3.41 and 1.25 for Latin America, 3.01 and 0.93 for Asian countries excluding Japan, and 7.96 and 1.76 for Japan, respectively. Significant heterogeneity in reported incidence and prevalence was observed within and between countries/geographic regions. The estimated number of 2020 ALS cases across the 22 countries is 121,028 prevalent and 41,128 incident cases. The total estimated number of prevalent SOD1 cases is 2,876 cases, of which, 1,342 (47%) were fALS and 1,534 (53%) were sALS, and the number of incident SOD1 cases is 946 (434 [46%] fALS and 512 [54%] sALS). The total estimated number of prevalent C9orf72 cases is 4,545 (1,198 [26%] fALS, 3,347 [74%] sALS), and the number of incident C9orf72 cases is 1,706 (450 [26%] fALS and 1,256 [74%] sALS). DISCUSSION: The estimated number of patients with SOD1 and C9orf72 ALS suggests that although the proportions of SOD1 and C9orf72 are higher among those with fALS, the majority of SOD1 and C9orf72 ALS cases may be found among those with sALS (about 53 and 74%, respectively). These results suggest that classification of fALS based on reported family history does not capture the full picture of ALS of genetic origin.

14-Year Changes in Plasma Neurofilament Levels Among Men: A Pilot Study.

Little is known about the feasibility of using long-term stored blood samples to measure neurofilament levels and about long-term changes in neurofilament levels among healthy individuals. We performed a pilot study among 26 adult men in preparation for a larger-scale study of the natural history of neurofilament levels. Median change over 14 years in pNf-H was 97.1 pg/mL (IQR: 5.0 to 242.0 pg/mL) and in Nf-L was 2.117 pg/mL (IQR: -2.691 to 3.393 pg/mL). We demonstrated the feasibility of measuring neurofilament concentrations in stored blood samples and found a trend between age and increases in Nf-L levels among adults.

Clinical and genetic predictors of atypical hemolytic uremic syndrome phenotype and outcome.

Atypical hemolytic uremic syndrome (aHUS) is a rare, genetic, life-threatening disease. The Global aHUS Registry collects real-world data on the natural history of the disease. Here we characterize end-stage renal disease (ESRD)-free survival, the rate of thrombotic microangiopathy, organ involvement and the genetic background of 851 patients in the registry, prior to eculizumab treatment. A sex-specific difference was apparent according to age at initial disease onset as the ratio of males to females was 1.3:1 for childhood presentation and 1:2 for adult presentation. Complement Factor I and Membrane Cofactor Protein mutations were more common in patients with initial presentation as adults and children, respectively. Initial presentation in childhood significantly predicted ESRD risk (adjusted hazard ratio 0.55 [95% confidence interval 0.41-0.73], whereas sex, race, family history of aHUS, and time from initial presentation to diagnosis, did not. Patients with a Complement Factor H mutation had reduced ESRD-free survival, whereas Membrane Cofactor Protein mutation was associated with longer ESRD-free survival. Additionally extrarenal organ manifestations occur in 19%-38% of patients within six months of initial disease presentation (dependent on organ). Thus, our real-world results provide novel insights regarding phenotypic variables and genotypes on the clinical manifestation and progression of aHUS.

Association of Glycemic Control With Reduced Risk for Large-Vessel Disease After More Than 50 Years of Type 1 Diabetes.

Context: Previously we demonstrated, in individuals who have had type 1 diabetes (T1D) for 50 or more years (Medalists), that glycemic control was unrelated to diabetic complications, with the exception of cardiovascular disease (CVD), contrary to what has been documented in registry-based studies. Objective: The purpose of this study is to validate these initial findings and identify contributors to mortality on an individual basis in a large cohort. Design: Cross-sectional and longitudinal study. Setting: Joslin Diabetes Center (JDC), Boston, Massachusetts. Patients: 50-year Medalists presenting to JDC for study participation. Interventions: None. Main Outcomes Measures: Microvascular and macrovascular complications of diabetes and mortality. Results: Glycemic control was not significantly associated with small-vessel complications in Medalists but was associated with CVD in the overall cohort, yet with varying effect by tertile of cohort duration. CVD was the largest contributor to mortality, whereas hemoglobin A1c was not an independent predictor of mortality either overall or substantially by diagnosis interval. Additionally, exercise mitigated mortality risk imparted by CVD. Conclusions: Few large populations with long duration of (T1D) have been available to examine the effects of long-term exposure to hyperglycemia. These data indicate that an association of glycemic control, complications, and mortality may change in an older population with T1D. These results suggest that careful control is still warranted in older populations with T1D.

Nocturia: Current Levels of Evidence and Recommendations From the International Consultation on Male Lower Urinary Tract Symptoms.

OBJECTIVE: To evaluate published evidence on nocturia in men and derive expert recommendations. METHODS: The International Consultations on Urological Diseases-Société Internationale d'Urologie convened a Consultation of experts on male lower urinary tract symptoms. The Consultation assigned standardized levels of evidence and grades of recommendation to various studies of nocturia epidemiology, pathophysiology, assessment, and treatment. RESULTS: Evidence review and consensus recommendations were made in the areas of epidemiology, pathophysiology, assessment, and treatment. CONCLUSION: The review presents a condensed summary of the International Consultations on Urological Diseases-Société Internationale d'Urologie evaluation of nocturia, which offers contemporaneous expert consensus on this topic, with an assessment algorithm emphasizing the potential contribution of systemic conditions to the symptom.

Changes in erectile dysfunction over time in relation to Framingham cardiovascular risk in the Boston Area Community Health (BACH) Survey.

INTRODUCTION: Erectile dysfunction (ED) is associated with cardiovascular disease (CVD); however, the association between change in ED status over time and future underlying CVD risk is unclear. AIM: The aim of this study was to investigate the association between change in ED status and Framingham CVD risk, as well change in Framingham risk. METHODS: We studied 965 men free of CVD in the Boston Area Community Health (BACH) Survey, a longitudinal cohort study with three assessments. ED was assessed with the five-item International Index of Erectile Function at BACH I (2002-2005) and BACH II (2007-2010) and classified as no ED/transient ED/persistent ED. CVD risk was assessed with 10-year Framingham CVD risk algorithm at BACH I and BACH III (2010-2012). Linear regression models controlled for baseline age, socio-demographic and lifestyle factors, as well as baseline Framingham risk. Models were also stratified by age (≥/< 50 years). MAIN OUTCOME MEASURES: Framingham CVD risk and change in Framingham CVD risk were the main outcome measures. RESULTS: Transient and persistent ED was significantly associated with increased Framingham risk and change in risk over time in univariate and age-adjusted models. In younger men, persistent ED was associated with a Framingham risk that was 1.58 percentage points higher (95% confidence interval [CI]: 0.11, 3.06) and in older men, a Framingham risk that was 2.54 percentage points higher (95% CI: -1.5, 6.59), compared with those without ED. Change in Framingham risk over time was also associated with transient and persistent ED in men <50 years, but not in older men. CONCLUSIONS: Data suggest that even after taking into account other CVD risk factors, transient and persistent ED is associated with Framingham CVD risk and a greater increase in Framingham risk over time, particularly in younger men. Findings further support clinical assessment of CVD risk in men presenting with ED, especially those under 50 years.

Association of peripheral microvascular dysfunction and erectile dysfunction.

PURPOSE: Increasing evidence of a link between erectile dysfunction and cardiovascular disease suggests a shared vascular etiology with endothelial dysfunction as a plausible underlying biological mechanism. To our knowledge whether this association is different for large arterial endothelium compared to microvascular endothelium has not yet been established. We investigated the association of erectile dysfunction with macrovascular and microvascular endothelial function. MATERIALS AND METHODS: A sample of 390 men with a mean age of 55.5 years was recruited from the BACH survey, a population based survey of urological symptoms. Erectile dysfunction was assessed using IIEF-5. The percent of brachial artery flow mediated dilatation, a measure of macrovascular function, and hyperemic flow velocity in cm per second, a measure of microvascular function, were assessed by ultrasound. Linear regression was used to assess the association of erectile dysfunction and endothelial function, and adjust for potential confounders. RESULTS: Reactive hyperemia was lower in men with vs without erectile dysfunction (mean ± SE 97.1 ± 2.5 vs 106.0 ± 1.6 cm per second, p = 0.003). However, the difference in flow mediated dilatation between men with vs without erectile dysfunction was statistically nonsignificant (mean 6.6% ± 0.33% vs 7.2% ± 0.24%, p = 0.147). The association of erectile dysfunction with reactive hyperemia was attenuated but it remained statistically significant in men with moderate to severe erectile dysfunction (IIEF-5 less than 12) after adjusting for traditional cardiovascular risk factors (p = 0.038). CONCLUSIONS: These results provide evidence of greater microvascular than macrovascular endothelial dysfunction as a potential contributor to erectile dysfunction and an underlying mechanism linking erectile dysfunction and cardiovascular disease.

Association of moderate to severe lower urinary tract symptoms with incident type 2 diabetes and heart disease.

PURPOSE: Increasing evidence suggests a possible link between lower urinary tract symptoms and chronic illnesses. We determined whether lower urinary tract symptoms are associated with incident type 2 diabetes and heart disease in a population based study. MATERIALS AND METHODS: BACH is a population based epidemiological survey of urological symptoms. A multistage, stratified, cluster sample design was used to obtain a random sample of 4,144 men and women 30 to 79 years old at baseline. Median followup was 4.8 years between baseline (2002 to 2005) and followup (2006 to 2010). Type 2 diabetes and heart disease were assessed by self-report. Lower urinary tract symptoms were assessed by the AUA-SI, and voiding and storage subscores. Logistic regression was used to estimate the OR and 95% CI, and adjust for potential confounders. RESULTS: In participants with a body mass index of 30 kg/m(2) or greater the adjusted ORs for incident heart disease were 1.89 (95% CI 1.05, 3.39) for AUA-SI 8 or greater and 2.32 (95% CI 1.33, 4.05) for a storage score of 4 or greater. In participants with abdominal obesity the adjusted ORs for incident type 2 diabetes were 2.06 (95% CI 1.19, 3.55) for AUA-SI 8 or greater and 1.81 (95% CI 1.04, 3.15) for a storage score of 4 or greater. Lower urinary tract symptoms (AUA-SI 8 or greater) were also predictive of type 2 diabetes in men and women younger than 50 years (adjusted OR 2.37, 95% CI 1.18, 4.80). CONCLUSIONS: Longitudinal results of BACH suggest that lower urinary tract symptoms are a marker of increased risk for type 2 diabetes and heart disease in obese men and women. The increased risk in younger men and women suggests that lower urinary tract symptoms may be an indicator of impending disease.

Population-based patterns of prescription androgen use, 1976-2008.

PURPOSE: Prescription testosterone (T) has limited approved medical indications and is a controlled substance in Canada. Utilization studies in other Westernized countries have revealed sharp increases in T use in recent years. We examined medical use of androgens, including T, over a ≥30-year period among adult (18+) men in a population-based study set in a Canadian juridisdiction of universal health care. METHODS: Analyses were based on data from electronic records of dispensed prescriptions during 1976-2008 in Saskatchewan, Canada. All formulations of androgens listed in the provincial formulary (oral and injectable) were included. We examined demographics of users, androgen types used, switching patterns, and trends in the annual rate of use over time. RESULTS: There were 11 521 androgen users who were followed for an average of 11.8 years. Overall, 11 types of androgens were used, and there were 86 812 dispensing events. The mean age at first use was 56.4 years (median: 58). Men had 7.5 prescription dispensing events on average (median: 2). The most commonly used formulations were methyl-T (36.2% of users) followed by T-enanthate (32.5%), T-cypionate (22.3%), and T-undecanoate (20.0%). Most users (82%) did not switch among androgen types. The annual rate of use varied substantially over time, with a marked increase observed from 1994 to 1999 and a decrease from 2000 to 2008. CONCLUSIONS: Androgen users were largely middle aged and had relatively few dispensings. We hypothesize that observed secular trends in androgen use may align with drug treatment pattern changes for erectile dysfunction, including the advent of phosphodiesterase type 5 inhibitors.

Treatment status and progression or regression of lower urinary tract symptoms in a general adult population sample.

PURPOSE: We report progression and regression of lower urinary tract symptoms in a population based cohort by race/ethnicity, gender, age and lower urinary tract symptom medication use. MATERIALS AND METHODS: The BACH (Boston Area Community Health) Survey enrolled 5,502 participants 30 to 79 years old of black, Hispanic or white race/ethnicity. The 5-year followup interviews were completed by 1,610 men and 2,534 women for a conditional response rate of 80%. Population weighted estimates of lower urinary tract symptoms severity were assessed using the AUASI (American Urological Association symptom index) and analyzed using multivariate models. RESULTS: Symptom progression (increase in AUASI score of 3 or more points) was reported by 21% to 33% of participants and regression (decrease 3 or greater) by 30% to 44% of participants, most commonly women and Hispanic participants. Age and higher body mass index were associated with progression (p <0.01), but not with regression. Lower urinary tract symptom medication use at baseline only was associated with improved symptoms scores 5 years later (multivariate adjusted OR 3.10, 95% CI 1.28-7.51, compared to nonusers), whereas using medication at baseline and followup was associated with similar rates of progression and regression as observed among participants not using lower urinary tract symptom medication at either point. CONCLUSIONS: Lower urinary tract symptoms persisted at followup for approximately half of the population experiencing symptoms at baseline, including many men and women using lower urinary tract symptom medications. However, overall lower urinary tract symptom medication use and surgical treatment appeared beneficial for symptom control at 5-year followup. Age and body mass index were associated with symptom worsening, and Hispanic ethnicity was associated with greater symptom fluctuation. Clinicians should consider the higher likelihood of lower urinary tract symptom progression for older or heavier patients, and monitor responsiveness to lower urinary tract symptom medication.

Common prescription medication use and erectile dysfunction: results from the Boston Area Community Health (BACH) survey.

OBJECTIVE: To investigate the association of erectile dysfunction (ED) with commonly used medications including antihypertensive treatment (AHT), psychoactive medication and pain and anti-inflammatory medication. SUBJECTS AND METHODS: The Boston Area Community Health (BACH) survey used a multistage stratified design to recruit a random sample of 2301 men aged 30-79 years. ED was assessed using the five-item International Index of Erectile Function (IIEF-5). Prescription medications, captured using a combination of drug inventory and self-report with a prompt by indication, included in this analysis comprised AHT, psychoactive medication, and pain and anti-inflammatory medication. Logistic regression was used to estimate the odds ratios (ORs) of the association of medication use with ED and to adjust for potential confounders including age, comorbid conditions and sociodemographic and lifestyle factors. RESULTS: Multivariable analyses showed benzodiazepines (adjusted OR = 2.34, 95% confidence interval [CI]: 1.03, 5.31) and tricyclic antidepressants (adjusted OR = 3.35, 95% CI: 1.09, 10.27) were associated with ED, while no association was observed for serotonin reuptake inhibitors/serotonin-norepinephrine reuptake inhibitors and atypical antipsychotics. The use of AHT, whether in monotherapy or in conjunction with other AHTs, and pain or anti-inflammatory medications were not associated with ED after accounting for confounding factors. CONCLUSIONS: Results of the BACH survey suggest adverse effects of some psychoactive medications (benzodiazepines and tricyclic antidepressants). No evidence of an association of AHT or pain and anti-inflammatory medication with ED was observed.

Incidence of lower urinary tract symptoms in a population-based study of men and women.

OBJECTIVE: To report the incidence of lower urinary tract symptoms (LUTS) in a racially and ethnically and age-diverse U.S. population-based sample of men and women. MATERIALS AND METHODS: We conducted a prospective cohort study with 5 years of follow-up. A stratified 2-stage cluster random sampling method was used to recruit 5502 Boston residents aged 30-79 years of black, Hispanic, or white race or ethnicity. Of these, 4144 (1610 men and 2534 women) completed the follow-up protocol. The American Urological Association Symptom Index was used to define moderate-to-severe LUTS. RESULTS: Of the 3301 men and women with no or mild LUTS at baseline, the 5-year incidence of moderate-to-severe LUTS (American Urological Association Symptom Index ≥8) was 11.4% overall and was higher for women than for men (13.9% vs 8.5%, P = .02). Although the incidence increased with age (P <.001), it had a plateau among women aged 50-70 years and then doubled to 35.0% among women aged ≥70 years. White men had a distinctly lower incidence (7%) than all other sex and race subgroups (13%). CONCLUSION: Approximately 1 in 10 adults had newly developed LUTS at 5 years follow-up of in our study, with differences by sex and race or ethnicity, indicating a greater occurrence of urologic problems among black and Hispanic participants and women.

Association of lower urinary tract symptoms and the metabolic syndrome: results from the Boston area community health survey.

PURPOSE: In this study we investigated the relationship between lower urinary tract symptoms as defined by the American Urological Association symptom index and the metabolic syndrome, and determined the relationship between individual symptoms comprising the American Urological Association symptom index and the metabolic syndrome. MATERIALS AND METHODS: The Boston Area Community Health Survey used a 2-stage cluster design to recruit a random sample of 2,301 men 30 to 79 years old. Analyses were conducted on 1,899 men who provided blood samples. Urological symptoms comprising the American Urological Association symptom index were included in the analysis. The metabolic syndrome was defined using a modification of the Adult Treatment Panel III guidelines. The association between lower urinary tract symptoms and the metabolic syndrome was assessed using odds ratios and 95% confidence intervals estimated using logistic regression models. RESULTS: Increased odds of the metabolic syndrome were observed in men with mild to severe symptoms (American Urological Association symptom index 2 to 35) compared to those with an American Urological Association symptom index score of 0 or 1 (multivariate OR 1.68, 95% CI 1.21-2.35). A statistically significant association was observed between the metabolic syndrome and a voiding symptom score of 5 or greater (multivariate adjusted OR 1.73, 95% CI 1.06-2.80) but not for a storage symptom score of 4 or greater (multivariate adjusted OR 0.94, 95% CI 0.66-1.33). Increased odds of the metabolic syndrome were observed even with mild symptoms, primarily for incomplete emptying, intermittency and nocturia. These associations were observed primarily in younger men (younger than 60 years) and were null in older men (60 years old or older). CONCLUSIONS: The observed association between urological symptoms and the metabolic syndrome provides further evidence of common underlying factors between lower urinary tract symptoms and chronic conditions outside the urinary tract.