Does prophylactic antibiotics post pediatric pyeloplasty reduce the incidence of febrile UTIs?

PURPOSE: The use of postoperative prophylactic antibiotics in pediatric upper urinary tract reconstruction remains controversial. In this study, we examined whether low dose antibiotics administered following pediatric pyeloplasty reduce the incidence of febrile urinary tract infections at our institution. As a secondary outcome, in those patients with infection, additional analysis was performed to better quantify which patient population benefits the most from low dose prophylactic antibiotics. METHODS: Institutional review board approval (IRB) was obtained. All methods were carried out in accordance with relevant guidelines and regulations. A retrospective study was performed in patients who underwent pyeloplasty (2011-2017) at our institution. Surgical approach (laparoscopic versus robotic assisted versus open, with or without internal JJ ureteral stent) were based on surgeon preference. Patients of 8 fellowship trained pediatric urologists were included in the study period. Patients with prior history of urologic interventions or other congenital genitourinary tract abnormalities were excluded. Demographics (age, gender, ethnicity, insurance status), prior history of culture proven urinary tract infection, surgical details (administration of perioperative antibiotics), and postoperative outcomes including; 1) re-admission 30 days post-surgery, 2) any urine cultures collected due to suspected urinary tract infection. RESULTS: A total of 209 patients (149 boys, 60 girls) met our inclusion criteria with 55/209 (26%) receiving postoperative prophylactic antibiotics. The average age was 6 years (range: 2 months-18 years). Indwelling ureteral stent was used in 176 (84%) patients. Eleven patients (5%) had a culture-proven urinary tract infection within 30-days postoperatively. No significant differences were seen in postoperative complications or incidence of urinary tract infection when comparing surgical approaches, +/- ureteral stent, or the use of antibiotics. Secondary analysis noted statistically significant increase in post-operative urinary tract infection in younger children (2.8 v. 6.2 years, p = 0.02), those patients who had a positive preoperative urine culture (8/11, p = 0.01) and those with public health insurance (p = 0.038). CONCLUSION: The incidence of postoperative urinary tract infection following pyeloplasty in our cohort was relatively low. There was a higher incidence of urinary tract infection in patients less than 3 years old. The use of antibiotics in patients post pyeloplasty did not appear to affect the incidence of post-operative urinary tract infection, however, they may have a role in children who have not yet potty trained and in patients with positive preoperative urine culture.

Molecular and Immunophenotypic Correlates of Metastatic Epithelioid Angiomyolipoma Include Alterations of TP53, RB1, and ATRX.

CONTEXT.­: Epithelioid angiomyolipomas (eAMLs) are rare tumors of the kidney that occur in patients with tuberous sclerosis complex or in a sporadic setting; a subset of these tumors exhibit metastatic behavior. OBJECTIVE.­: To analyze molecular profiling data to identify pathogenic alterations in rare cases of metastatic eAML, and to identify immunohistochemistry (IHC)-based surrogate markers. DESIGN.­: Molecular profiling data from the American Association for Cancer Research GENIE registry was accessed for 23 patients with angiomyolipomas, and 9 of 16 patients with eAMLs in our institutional registry were evaluated with next-generation sequencing. IHC was performed to screen for alterations of P53, RB, and ATRX for all 16 institutional cases. RESULTS.­: Combined alterations of 5 tumor-suppressor genes (TP53, ATRX, RB1, APC, and NF1) were identified using next-generation sequencing in 7 of 8 (88%) patients with metastatic disease compared to a single patient with nonmetastatic disease (RB1 variant of uncertain significance; 1 of 24, 4%). No cases with abnormal IHC results were identified in 11 patients with nonmetastatic disease compared to 3 of 5 patients with metastatic disease. CONCLUSIONS.­: Our results show that the majority of metastatic eAMLs have mutations of 5 tumor-suppressor genes (TP53, ATRX, RB1, APC, and NF1), while these are rare in patients with nonmetastatic disease. Furthermore, IHC for P53, RB, and ATRX may serve as a screen for a subset of these alterations in resource-limited settings. These findings, if validated in larger data sets, have the potential to predict metastatic behavior in eAMLs.

Interoceptive deficits moderate the relationship between bulimia symptoms and suicide risk.

Objective: Interoceptive deficits have been linked to suicidality and eating disorders. The relationship between disordered eating symptoms and suicidality may depend on the level of interoceptive deficits. It was expected that interoceptive deficits would moderate the relationship between disordered eating symptoms (oral control, dieting, and bulimia) and suicidality (suicide attempts, ideation, and communication) when interoceptive deficits were high. Methods: University students (N = 417, Mage = 19.75, 78.2% white, 72.4% female) completed self-report measures that assessed disordered eating, interoceptive deficits, and suicide history. Results: Interoceptive deficits emerged as a significant moderator only in the association between bulimia symptoms and suicidality, when interoceptive deficits were high. Conclusions: The results of this study indicate that bulimia symptoms may have a unique interaction with interoceptive deficits and suicidality. Future research should focus on targeting interoceptive deficits in treatment to help reduce disordered eating symptoms and suicide risk, particularly for students with bulimia symptoms.

Progression of Chronic Kidney Disease Following Radical and Partial Nephrectomy.

OBJECTIVE: To compare renal functional outcomes, as determined by percent decline in estimated glomerular filtration rate (eGFR) and CKD stage progression following radical (RN) and partial nephrectomy (PN) stratified by preoperative CKD stage. MATERIALS AND METHODS: We retrospectively evaluated adults treated with RN or PN between 1980 and 2018 for unilateral, sporadic, solid renal masses. Multivariable linear models for percent change in eGFR (n = 3046) and competing-risk Cox proportional hazards models for increase in CKD staging (n = 5805) were used to determine if there was a significant interaction between type of surgery (RN vs PN) and preoperative CKD stage. RESULTS: Percent change in eGFR at 1 year was significantly worse for RN (n = 1724; 57%) compared with PN (n = 1322; 43%) for all preoperative CKD stages. RN (n = 3227; 56%) was more likely to result in CKD stage progression compared with PN (n = 2578; 44%) for preoperative CKD stages I-IIIb (P <.001) but not for CKD stage IV (P = .8). CONCLUSION: RN was more likely to result in decline in eGFR and CKD stage progression compared to PN for patients with preoperative CKD stage IIIb or less. Additionally, RN was associated with a significantly greater decline in eGFR at 1 year relative to PN in the CKD stage IV subset. Our data support performing PN for renal preservation when feasible.

Renin Production by Juxtaglomerular Cell Tumors and Clear Cell Renal Cell Carcinoma and the Role of Angiotensin Signaling Inhibitors.

OBJECTIVE: To profile juxtaglomerular cell tumors (JXG) and histologic mimics by analyzing renin expression; to identify non-JXG renin-producing tumors in The Cancer Genome Atlas (TCGA) data sets; and to define the prevalence of hypertension (HTN) and patient outcomes with angiotensin signaling inhibitor (ASI) use in tumors of interest. PATIENTS AND METHODS: Thirteen JXGs and 10 glomus tumors (GTs), a histologic mimic, were evaluated for clinicopathologic features; TCGA data were analyzed to identify non-JXG renin-overexpressing tumors. An institutional registry was queried to determine the incidence of HTN, the use of ASIs in hypertensive patients, and the impact of ASIs on outcomes including progression-free survival (PFS) in a tumor type with high renin expression (clear cell renal cell carcinoma [CC-RCC] diagnosed between January 1, 2005, and December 31, 2012). RESULTS: We found an association between renin production and HTN in JXG compared with GT. Analysis of TCGA data found that a subset of CC-RCCs overexpress renin relative to 29 other tumor types. Furthermore, analysis of our institutional registry revealed a high prevalence (64%) of HTN among 1203 patients treated with radical or partial nephrectomy for nonmetastatic CC-RCC. On multivariable Cox regression, patients with HTN treated with ASIs (34%) had improved PFS (hazard ratio, 0.76; 95% CI, 0.57 to 1.00; P=.05) compared with patients with HTN not treated with ASIs (30%). CONCLUSION: The identification of renin expression in a subset of CC-RCC may provide a biologic rationale for the high prevalence of HTN and improved PFS with ASI use in hypertensive patients with nonmetastatic CC-RCC.

Body Investment as a Protective Factor in the Relationship Between Acquired Capability for Suicide and Suicide Attempts.

Acquired capability for suicide is associated with increased suicide risk and behaviors, but little research has examined factors that may qualify this relationship. Body investment is proposed as one such factor, as it may engage self-preservation instincts and serve as a buffer to capability for suicide. It was expected that facets of body investment (body feelings, body care, comfort with touch, and body protection) would moderate the relationship between acquired capability for suicide and suicide attempts. The current study included a sample of 1,150 undergraduate students with a mean age of 19.74 (3.44). The majority of the sample identified as female (71%) and White/Caucasian (78%). Participants completed self-report measures of body investment (Body Investment Scale [BIS]), acquired capability (Acquired Capability for Suicide Scale [ACSS]), suicide thoughts and attempt history (Self-Harm Behavior Questionnaire [SHBQ]), and demographic information. Four moderation analyses were run using the PROCESS macro; one for each body investment subscale. All facets of body investment showed significant moderation except for body care. Acquired capability was significantly associated with suicide attempts when body feelings, comfort with touch, and body protection were low, but not when they were high. Results indicate that fostering aspects of body investment may be important for suicide prevention.

Assessing the Impact of Hospital Dismissal Summary Readability on Patient Outcomes Following Prostatectomy.

PURPOSE: To assess the impact of decreasing the reading level of hospital dismissal summary information on the number of unplanned patient contacts with providers following robot-assisted radical prostatectomy. METHODS: A multidisciplinary team revised the hospital dismissal summary given to patients following prostatectomy to decrease the reading level from a 13th grade to seventh grade level. We conducted a retrospective cohort study comparing 30-day outcome measures including: patient-initiated telephone calls and online messages, unplanned clinic visits, readmission rates, and emergency department visits pre- and post-intervention. Other perioperative practices remained unchanged between the cohorts. RESULTS: A total of 110 patients were included in the study (pre-intervention n=60, post-intervention n=50). Patient age (P =.72), race (P =.59), marital status (P =.39), and education level (P = 1.0) were similar between the groups. Pre-intervention, 11.7% of patients had a self-reported education lever lower than the 13th grade, compared to 2% of patients post-intervention with an education level at or below the seventh grade. Following revision of the dismissal information, the number of patient-initiated messages (per patient) significantly decreased (mean 2.3 vs 1.4; P =.02). Patients who received the new dismissal information were significantly less likely to have an emergency department visit (20% vs 4%;P = .02). There were no differences in 30-day unplanned office visits (P =.75) or readmissions (P = 1.0). CONCLUSION: Reducing grade level readability of hospital dismissal information was associated with significantly lower rates of patient-initiated messages and emergency department visits. This intervention represents a valuable opportunity for improving the quality of patient care and decreasing postoperative care burden on the healthcare system.

Varicocele Repair Prior to Assisted Reproductive Technology: Patient Selection and Special Considerations.

Clinical varicoceles are one of the most commonly identified physical exam abnormalities in men presenting with infertility. Clinical varicoceles can cause impaired spermatogenesis and surgical correction can improve semen parameters in select men. Increasingly, andrologists are performing varicocele repairs prior to intrauterine insemination (IUI), in vitro fertilization (IVF), and intracytoplasmic sperm injection (ICSI) to boost male fertility potential. In this review, we evaluated the available literature 1) to determine if varicocelectomy prior to IUI or assisted reproductive technologies proved to improve sperm production or pregnancy outcomes; and 2) to identify who may be the ideal candidate for pre-IUI/ART varicocelectomy. Overall, few studies have explored this topic and little can be concluded about the impact of varicocelectomy prior to IUI. The evidence, however, does support that correcting a clinical varicocele can increase pregnancy outcomes in couples who plan to pursue IVF or ICSI. When selecting patients for varicocelectomy prior to IUI or ART, clinicians should evaluate female age as improvement in semen parameters can take 6 months after varicocelectomy and this duration of time may be deleterious in cases of advanced maternal age when each cycle becomes increasingly important. Overall, the currently limited literature regarding clinical varicoceles correction demonstrates that pregnancy rates can be increased when comparing patients who have undergone varicocelectomy prior to ART with those who had clinical varicocele but did not undergo surgery.

Renal Mass Biopsy is Associated with Reduction in Surgery for Early-Stage Kidney Cancer.

OBJECTIVE: To determine whether use of renal mass biopsy may be associated with a reduction in surgery for patients with small, localized renal cell carcinoma (cT1aN0M0), especially among older patients and patients with greater comorbidity burden. METHODS: A total of 106,258 patients with cT1aN0M0 renal cell carcinoma from 2004 to 2015 were analyzed in the National Cancer Data Base. Multivariable logistic regression identified independent associations with nonsurgical management, receipt of biopsy, and pathologic upstaging. Marginal effects were derived by age and comorbidity. A sensitivity analysis was conducted in years identifying patients undergoing active surveillance (2010-2015). RESULTS: There was increased use of biopsy (8.0%-15.3%) and nonsurgical management (11.7%-15.6%) over time. Biopsy was significantly associated with use of nonsurgical management (OR 4.80 [95%CI 4.58-5.02], P <.001) as well as active surveillance (OR 1.87 [1.69-2.07], P <.001) in the sensitivity analysis. Individual predicted probability of undergoing nonsurgical management ranged from 3% to 92% (median 31.4% with use of biopsy) and increased with age and comorbidity. Pathologic tumor upstaging (≥pT3a) occurred more frequently for patients receiving biopsy compared to no biopsy (5.8% vs 3.3%, P <.001). After adjustment, biopsy remained a statistically significant predictor of upstaging (OR 1.31 [95%CI 1.24-1.38], P <.001). CONCLUSION: Overall, biopsy demonstrated a strong, independent association with reduced use of surgery for cT1aN0M0 kidney cancer, especially with increasing age and comorbidity. The potential association of renal mass biopsy with upstaging warrants caution, but it is uncertain whether it impacts prognosis relative to true perinephric fat invasion.

Cytomegalovirus Infection in Allogeneic Hematopoietic Cell Transplantation Managed by the Preemptive Approach: Estimating the Impact on Healthcare Resource Utilization and Outcomes.

We quantified cytomegalovirus (CMV) antiviral use and hospital length of stay (LOS) associated with CMV infection in a contemporary cohort of conventional (CONV) and CD34-selected (T cell-depleted) hematopoietic cell transplantation (HCT) recipients managed by preemptive therapy (PET) in a single US center. Adults who received first allogeneic HCT at Memorial Sloan Kettering Cancer Center from June 2010 through December 2014 were analyzed. Days on PET, number of readmissions, and readmission LOS by day 180 post-HCT were summarized. Estimated unit value (EUV) was defined as the expected number of PET days for a cohort of 100 HCT with characteristics as the analyzed cohort. Standardized incidence ratio was calculated as the ratio of observed outcomes of patients with CMV viremia over the outcomes of patients without CMV viremia. Of 318 patients, 88 received CONV and 230 CD34-selected HCT. Rates of CMV viremia were 26.3% for CONV and 41.9% for CD34-selected (P = .003). Among patients with viremia 68.2% CONV and 97.9% CD34-selected received PET. EUV for PET was 852 days and 2821 days for CONV and CD34-selected, respectively. The standardized incidence ratios for number of readmission and readmission LOS were 1.7 (95% confidence interval [CI], 1.4 to 2.1) and 1.2 (95% CI, 1.1 to 1.3), respectively, for CONV HCT and 1.7 (95% CI, 1.3 to 2.1) and 1.6 (95% CI, 1.5 to 1.7), respectively, for CD34-selected HCT. Overall survival was similar between patients with and without CMV viremia by HCT type. CMV end-organ disease was associated with lower overall survival only in CD34-selected HCT (P = .0007). CMV infection managed by PET requires substantial antiviral use and is associated with longer readmission LOS more, particularly among CD34-selected HCT.

Patient Decision-making and Predictors of Genital Satisfaction Associated With Testicular Prostheses After Radical Orchiectomy: A Questionnaire-based Study of Men With Germ Cell Tumors of the Testicle.

OBJECTIVE: To better understand patient decision-making and genital satisfaction associated with postorchiectomy testicular prosthesis (TP) implantation in patients with germ cell tumors of the testicle. MATERIALS AND METHODS: An electronic survey to assess TP decision-making and genital satisfaction was distributed to patients via an institutional database (n = 70) and social media outlets (n = 167). Statistical analyses were performed using chi-square tests for categorical variables, Wilcoxon-Mann-Whitney tests for continuous variables, and multivariate regression analyses to identify independent predictors of receiving a prosthesis, genital satisfaction, and prosthesis satisfaction. RESULTS: 24.9% of respondents elected to receive a TP, but 42% of men without a prosthesis reported never being offered one. Identifying as a heterosexual man (2.86) and receiving a TP (odds ratio = 3.29) were both positive predictors of overall genital satisfaction. Having the orchiectomy performed at an academic institution (odds ratio = 2.87) was a positive predictor of testicular prosthesis TP placement. 89.8% of TP recipients were satisfied with the look of their prosthetic, but only 59.3% of respondents were satisfied with prosthetic feel. CONCLUSION: There are high levels of genital satisfaction in those who elect to receive a TP postorchiectomy. Associations between TP placement, genital satisfaction, and sexuality merit further investigation. Our results also indicate that patients who pursue an orchiectomy at an academic institution are more likely to receive a TP. The use of social media to recruit study participants in urology should be explored further.

Access to Urological Care and Internet Connectivity in the United States: A Geospatial Analysis.

INTRODUCTION: Telemedicine video visits have been suggested as a mechanism to improve access to urological care in geographically isolated communities. However, Internet availability is not consistent across the United States. This study aims to better understand the interplay of broadband Internet, urologist density and county demographics to inform the strategic deployment of urological telemedicine. METHODS: A geospatial analysis was conducted to assess associations between broadband Internet and urologist density. Adequate broadband Internet availability was determined to be greater than 50% county coverage. Data were obtained from 2015 Federal Communications Commission filings. Physician density in 2015 was obtained from 2016-2017 Area Health Resources Files. A univariate regression was performed to estimate the associations of county demographics with broadband availability and urologist density. RESULTS: More than 10.9 million Americans lack access to local urology care and broadband Internet. Overall 31.7 million Americans lack access to a urologist but have reliable broadband Internet coverage. Counties with no urologists were associated with having less accessibility to broadband Internet and greater distance to the nearest county with a urologist. Counties without Internet availability or urologists were more likely to be rural (OR 9.93) and be designated as a whole county health professional shortage area (OR 10.05). CONCLUSIONS: A quarter of communities that lack access to local urologists also lack access to broadband Internet. Telemedicine cannot address poor access to urology care in communities without high-speed Internet. Future studies are needed to establish whether, pending expanded access to broadband Internet coverage, telemedicine will improve patient outcomes in geographically isolated communities.

The Effect of Adjunct Mechanical Traction on Penile Length in Men Undergoing Primary Treatment for Peyronie's Disease: A Systematic Review and Meta-analysis.

OBJECTIVE: To accurately characterize the effect of penile traction therapy (PTT) on stretched penile length (SPL) after primary treatment for men with PD. MATERIALS AND METHODS: A systematic search was performed for studies that evaluated the correction of PD using penile traction as secondary treatment published through January 2018. Studies were included if (1) a singular primary treatment of PD (injection or surgical treatment) was performed for all included men, (2) if there was a control group with no adjunct traction, and (3) if patients were required to wear the traction device for greater than 2 h/d. Estimates were pooled using random-effects meta-analysis. RESULTS: Data were obtained from 4 studies involving 348 men with an average age of 55.7 ± 2.0 years. Men who used PTT after primary intervention had SPLs 1.02 cm greater [95% CI: 0.64 to 1.40; I2=0%] when compared with men who did not use traction after primary intervention (p = 0.009). When performing subgroup analysis by primary therapy, no difference was seen in men undergoing penile traction after surgical correction when compared with men undergoing penile traction after injection therapy (1.01 vs 1.29 cm, p = 0.84). CONCLUSION: PTT may be a promising technique to reduce length loss in men undergoing PD treatment. Future work should be done to determine the ideal timing and subpopulations who would benefit from PTT.

Co-Infections by Double-Stranded DNA Viruses after Ex Vivo T Cell-Depleted, CD34+ Selected Hematopoietic Cell Transplantation.

Recipients of ex vivo T cell-depleted (TCD) hematopoietic cell transplantation (HCT) are at risk of infection by double-stranded (ds) DNA viruses. We report rates of dsDNA viremia, end-organ disease (EOD), infection-related mortality, and overall survival (OS) in a contemporary cohort of adult TCD HCT recipients routinely monitored for cytomegalovirus (CMV), adenovirus (ADV), human herpesvirus 6 (HHV6), and Epstein-Barr virus (EBV). Healthcare utilization in the first 6 months post-HCT was compared between patients with dsDNA viremia versus no viremia. This was an observational study of adult patients with acute leukemia and myelodysplastic syndrome who received CD34+ selected, peripheral blood HCT at Memorial Sloan Kettering Cancer Center from March 2012 through December 2014. Patients were prospectively monitored by quantitative PCR assays for CMV, ADV, HHV6, and EBV in whole blood or plasma. The cumulative incidence of viremia(s) at day +180, EOD at 1 year, and OS at 1 year were estimated by the Kaplan-Meier method and compared by the log-rank test among patient with and without viremia/EOD. Standardized incidence ratios were used to compare overall length of hospital stay (LOS), number of readmissions after HCT, and length of readmissions through day +180. Of 156 patients, 96 (62%) were CMV recipient seropositive. Forty-two patients received grafts from matched related (27%), 86 from matched unrelated (55%), and 28 from mismatched (18%) donors. Overall, 132 patients (85%) had ≥1 viremia and 52 (33%) ≥2 viremias by day +180. The cumulative incidences for CMV, HHV6, ADV, and EBV viremia were 44%, 61%, 7%, and 16%, respectively, with median times of onset 28 days (interquartile range [IQR], 25 to 33), 33 days (IQR, 25 to 47), 60 days (IQR, 19 to 84), and 79 days (IQR, 54 to 106) post-HCT, respectively. Twenty-eight patients (18%) developed EOD by dsDNA viruses at 1 year post-HCT. Treatment for CMV accounted for 91% total antiviral treatment-days. Compared with patients with no viremia, patients with CMV viremia, HHV6 viremia, or ≥2 viremias experienced longer LOS (P <.001) and a higher number of readmissions (P <.001) by day +180. OS rate at 1 year was 79% and was similar between patients with or without dsDNA viremias. EOD was associated with lower 1-year OS rates (63.4%) versus without EOD (81.1%) (P = .02). Of 33 patients who died, 10 died due to infection, and 7 of these infection-related deaths were due to dsDNA viruses. Viremia by dsDNA viruses occurred in 85% of TCD HCT recipients by day +100 and 33% of patients experienced ≥2 viremias by day +180. CMV accounted for most antiviral use. CMV, HHV6, or ≥2 viremias were associated with more readmissions and longer LOS. One year OS rate was 78%. EOD by dsDNA viruses was associated with decreased 1-year OS. Infections by dsDNA viruses pose a substantial burden after TCD HCT.

Emerging immunotherapies in ovarian cancer.

Despite a global effort to significantly reduce mortality, ovarian cancer remains the fifth leading cause of cancer death among American women, and five-year survival rates remain discouragingly low at 45%. Novel therapies are urgently needed. Notably, higher infiltration of activated immune cells into the tumor microenvironment correlates with improved ovarian cancer survival, suggesting that promoting their activity could favorably impact clinical outcomes. Immunotherapy has recently demonstrated impressive clinical benefit in a variety of solid tumors. Immunotherapy strategies tested in ovarian cancer include vaccines, adoptive T cell therapy, and immune checkpoint blockade. Ultimately, a combination immunotherapy approach that integrates immunotherapy with other cancer treatment modalities in additive or synergistic ways will most effectively improve survival.

Natural history of Huntington disease.

IMPORTANCE: Understanding the natural history of Huntington disease will inform patients and clinicians on the disease course and researchers on the design of clinical trials. OBJECTIVE: To determine the longitudinal change in clinical features among individuals with Huntington disease compared with controls. DESIGN, SETTING, AND PARTICIPANTS: Prospective, longitudinal cohort study at 44 research sites in Australia (n = 2), Canada (n =4), and the United States (n = 38). Three hundred thirty-four individuals with clinically manifest Huntington disease who had at least 3 years of annually accrued longitudinal data and 142 controls consisting of caregivers and spouses who had no genetic risk of Huntington disease. MAIN OUTCOMES AND MEASURES: Change in movement, cognition, behavior, and function as measured by the Unified Huntington's Disease Rating Scale, the Mini-Mental State Examination, and vital signs. RESULTS: Total motor score worsened by 3.0 points (95% CI, 2.5-3.4) per year and chorea worsened by 0.3 point per year (95% CI, 0.1-0.5). Cognition declined by 0.7 point (95% CI, 0.6-0.8) per year on the Mini-Mental State Examination. Behavior, as measured by the product of frequency and severity score on the Unified Huntington's Disease Rating Scale, worsened by 0.6 point per year (95% CI, 0.0-1.2). Total functional capacity declined by 0.6 point per year (95% CI, 0.5-0.7). Compared with controls, baseline body mass index was lower in those with Huntington disease (25.8 vs 28.8; P < .001), and average pulse was higher (74.2 vs 69.6 beats/min; P < .001). CONCLUSIONS AND RELEVANCE: Over 3 years, the cardinal features of Huntington disease all declined in a monotonic manner. These data quantify the natural history of the disease and may inform the design of trials aimed at reducing its burden. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00313495.

Depressed mood and suicidality in individuals exposed to tetrabenazine in a large Huntington disease observational study.

BACKGROUND: Tetrabenazine, a treatment for chorea in Huntington disease, carries a boxed warning due to safety, especially related to suicidality. OBJECTIVE: To compare the frequency of depressed mood and suicidality among a closely monitored cohort of individuals with Huntington disease who were exposed and not exposed to tetrabenazine. METHODS: A longitudinal prospective study involving 1360 individuals with HD evaluated at 48 research centers in Australia, Canada, and the United States was examined for frequency of depressed mood that triggered a risk assessment, suicidal thoughts, suicide attempts, and completed suicide among individuals with prior, new, and no exposure to tetrabenazine.. Seventy-seven individuals were on tetrabenazine at study enrollment (prior exposure), 64 individuals were exposed to tetrabenazine during the study's course (new exposure), and 1219 individuals had no exposure to tetrabenazine. RESULTS: The hazard ratio for depressed mood among those with prior exposure to tetrabenazine compared to no exposure was 0.9 (95% CI, 0.5-1.6) and for those with new exposure compared to no exposure was 1.2 (95% CI, 0.8-1.9). One individual (1.3%) with prior exposure, one individual (1.6%) with new exposure, and 35 individuals (2.9%) with no exposure to tetrabenazine reported suicidal thoughts. The hazard ratio for suicidal ideation among those with prior exposure to tetrabenazine compared to no exposure was 0.5 (95% CI, 0.1-3.8) and for those with new exposure to tetrabenazine compared to no exposure was 0.6 (95% CI, 0.1-4.4). Among individuals with prior or new exposure to tetrabenazine, no suicide attempts or suicides occurred. Among those with no exposure to tetrabenazine 17 suicide attempts (1.4%) and four suicides (0.3%) occurred. CONCLUSIONS: In a large observational study with close clinical supervision, tetrabenazine treatment was not associated with an increased risk of depressed mood, suicidal ideation, suicide attempts, or suicide.