Efficacy of minocycline in patients with amyotrophic lateral sclerosis: a phase III randomised trial.

BACKGROUND: Minocycline has anti-apoptotic and anti-inflammatory effects in vitro, and extends survival in mouse models of some neurological conditions. Several trials are planned or are in progress to assess whether minocycline slows human neurodegeneration. We aimed to test the efficacy of minocycline as a treatment for amyotrophic lateral sclerosis (ALS). METHODS: We did a multicentre, randomised placebo-controlled phase III trial. After a 4-month lead-in phase, 412 patients were randomly assigned to receive placebo or minocycline in escalating doses of up to 400 mg/day for 9 months. The primary outcome measure was the difference in rate of change in the revised ALS functional rating scale (ALSFRS-R). Secondary outcome measures were forced vital capacity (FVC), manual muscle testing (MMT), quality of life, survival, and safety. Analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00047723. FINDINGS: ALSFRS-R score deterioration was faster in the minocycline group than in the placebo group (-1.30 vs -1.04 units/month, 95% CI for difference -0.44 to -0.08; p=0.005). Patients on minocycline also had non-significant tendencies towards faster decline in FVC (-3.48 vs -3.01, -1.03 to 0.11; p=0.11) and MMT score (-0.30 vs -0.26, -0.08 to 0.01; p=0.11), and greater mortality during the 9-month treatment phase (hazard ratio=1.32, 95% CI 0.83 to 2.10; p=0.23) than did patients on placebo. Quality-of-life scores did not differ between the treatment groups. Non-serious gastrointestinal and neurological adverse events were more common in the minocycline group than in the placebo group, but these events were not significantly related to the decline in ALSFRS-R score. INTERPRETATION: Our finding that minocycline has a harmful effect on patients with ALS has implications for trials of minocycline in patients with other neurological disorders, and for how potential neuroprotective agents are screened for use in patients with ALS.

Obstructive lower urinary tract symptoms correlate with erectile dysfunction.

OBJECTIVES: To examine whether the severity of lower urinary tract symptoms (LUTS), when controlled for other factors, is related to erectile dysfunction (ED) in the male veteran population. Early evidence suggests that LUTS may be associated with ED in men. METHODS: A total of 181 male veterans were prospectively entered into the study. They completed the Sexual Health Inventory for Men (SHIM) and International Prostate Symptom Score (IPSS) questionnaires. Of the 181 men, 144 also underwent uroflowmetry, including determination of the postvoid residual urine volume. Demographic and medical history data were recorded. Pearson correlation coefficients and multiple linear regression analysis were used to examine the relationship between LUTS and ED, as well as the effects of age and comorbidities. RESULTS: The correlation coefficient (r) for the SHIM score with the total IPSS was -0.17 (P = 0.023); with the obstructive IPSS, it was -0.20 (P = 0.006); and with the irritative IPSS, -0.05 (P = 0.492). Age was the only other factor with a statistically significant correlation with the SHIM score (r = -0.23, P = 0.002). Multiple linear regression modeling showed obstructive IPSS (P = 0.001) and depression (P = 0.017) to be the only statistically significant predictors of the SHIM score. A consistent negative correlation was found between obstructive IPSS and the SHIM score across age groups, with the strongest effect for men aged 60 to 70 years (r = -0.412, P = 0.003). CONCLUSIONS: Obstructive LUTS correlated with, and were predictive of, ED, even after controlling for age and comorbidities. Although age correlated with ED, it did not add to the power of the multiple linear regression model composed of obstructive IPSS and depression.

Mental health in men treated for early stage prostate carcinoma: a posttreatment, longitudinal quality of life analysis from the Cancer of the Prostate Strategic Urologic Research Endeavor.

BACKGROUND: The current study was conducted to assess posttreatment changes in the mental components of health related quality of life in prostate carcinoma patients during the two years following diagnosis and management with radical prostatectomy, pelvic irradiation, or watchful waiting. METHODS: The authors studied the mental domains of general health related quality of life in 452 men recently diagnosed with early stage prostate carcinoma and treated with radical prostatectomy, pelvic radiation, or watchful waiting. Outcomes were assessed with the RAND 36-Item Health Survey, a validated health-related quality of life instrument that includes four mental domains. To minimize the influence of potentially confounding factors, the authors adjusted for age, comorbidity, prostate specific antigen (PSA) at diagnosis, and biopsy Gleason score. All subjects were drawn from CaPSURE, a national, longitudinal cohort. RESULTS: By 6-12 months after treatment, the active treatment groups began to show differences in mental health and vitality. By 15 months, surgery and radiation patients scored differently in all four mental domains. Over time, the gaps between mental domain scores grew wider among the treatment groups, with surgery patients performing the best, radiation patients performing the worst, and watchful waiting patients falling in between. CONCLUSIONS: The mental health profiles differ for patients undergoing surgery, radiation, or watchful waiting for early stage prostate carcinoma. Men with more serious disease, as evidenced by higher PSA levels or more aggressive histology, tended to worry more about it. Older men performed better, while sicker men performed worse, even though the older men tended to be sicker.