IMPORTANCE Alteration in lung microbes is associated with disease progression in idiopathic pulmonary fibrosis. OBJECTIVE To assess the effect of antimicrobial therapy on clinical outcomes. DESIGN, SETTING, AND PARTICIPANTS Pragmatic, randomized, unblinded clinical trial conducted across 35 US sites. A total of 513 patients older than 40 years were randomized from August 2017 to June 2019 (final follow-up was January 2020).INTERVENTIONS Patients were randomized in a 1:1 allocation ratio to receive antimicrobials (n = 254) or usual care alone (n = 259). Antimicrobials included co-trimoxazole (trimethoprim 160 mg/sulfamethoxazole 800 mg twice daily plus folic acid 5 mg daily, n = 128) or doxycycline (100 mg once daily if body weight <50 kg or 100 mg twice daily if Ն50 kg, n = 126). No placebo was administered in the usual care alone group. MAIN OUTCOMES AND MEASURESThe primary end point was time to first nonelective respiratory hospitalization or all-cause mortality. RESULTS Among the 513 patients who were randomized (mean age, 71 years; 23.6% women), all (100%) were included in the analysis. The study was terminated for futility on December 18, 2019. After a mean follow-up time of 13.1 months (median, 12.7 months), a total of 108 primary end point events occurred: 52 events (20.4 events per 100 patient-years [95% CI, 14.8-25.9]) in the usual care plus antimicrobial therapy group and 56 events (18.4 events per 100 patient-years [95% CI, 13.2-23.6]) in the usual care group, with no significant difference between groups (adjusted HR, 1.04 [95% CI, 0.71-1.53; P = .83]. There was no statistically significant interaction between the effect of the prespecified antimicrobial agent (co-trimoxazole vs doxycycline) on the primary end point (adjusted HR, 1.15 [95% CI 0.68-1.95] in the co-trimoxazole group vs 0.82 [95% CI, 0.46-1.47] in the doxycycline group; P = .66). Serious adverse events occurring at 5% or greater among those treated with usual care plus antimicrobials vs usual care alone included respiratory events (16.5% vs 10.0%) and infections (2.8% vs 6.6%); adverse events of special interest included diarrhea (10.2% vs 3.1%) and rash (6.7% vs 0%).CONCLUSIONS AND RELEVANCE Among adults with idiopathic pulmonary fibrosis, the addition of co-trimoxazole or doxycycline to usual care, compared with usual care alone, did not significantly improve time to nonelective respiratory hospitalization or death. These findings do not support treatment with these antibiotics for the underlying disease.

ObjectiveTo evaluate the efficacy, safety, and tolerability of fixed-dose agomelatine 25 and 50 mg/d in the treatment of outpatients with obsesive-compulsive disorder (OCD) compared to placebo.MethodIn this 8-week, multicenter, double-blind, parallel-group trial, patients with DSM-IV-defined OCD were randomly assigned (1:1:1) to receive a once-daily dose of agomelatine 25 mg, agomelatine 50 mg, or placebo. The primary efficacy measure was the change from baseline to week 8 in the clinician-rated 17-item Hamilton Depression Rating Scale (HDRS(17)); other efficacy measures were The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Clinical Global Impression scale. The study was conducted between December 2009 and January 2010.ResultsAgomelatine 25 mg/d was more efficacious based on the HDRS(17) total score (P = .01) compared to placebo throughout the treatment period, whereas for agomelatine 50 mg/d, statistically significant reduction in HDRS(17) total score could be observed from weeks 2 to 6 but not at week 8 (P = .144). A higher proportion of patients receiving agomelatine 25 mg/d showed clinical response (P = .013), clinical remission (P = .07), and improvement according to the Clinical Global Impressions-Improvement scale (P = .065) compared to those receiving placebo. No statistically significant difference between patients receiving agomelatine 50 mg/d compared to placebo on clinical response. Both agomelatine doses were safe and well tolerated, although clinically notable aminotransferase elevations were observed transiently in the agomelatine 50 mg/d group.ConclusionsAgomelatine 50 mg/d provided evidence for its antidepressant efficacy until week 6 and was also safe and well tolerated.

Introduction: Comparative studies prove that levetiracetam therapy presents a major frequency of behavioral disturbances, producing problems of impulsive aggressiveness with a relative frequency. Principally if a previous psychiatric history is associated. Objetives: Report a case of Impulsive homicide aggression in a patient treated with Levetiracetam.Extensive bibliographical review. Methods: We describe the case of a patient admitted in our Psychiatric acute unit because a major depressive disorder and mild cognitive impairment associated with vascular factors that developed strange impulsive aggressive behavior after the initiation of treatment with levetiracetam, even to try to assassinate his wife. Follow-up visits were performed at 6 and 12 months after discharge to assess aggressive behavior and the change in the Barratt impulsivity scale and the hostility inventory of Buss-Durkee. We conducted a literature review of behavioral and aggression problems associated with treatment with levetiracetam and its possible mechanisms. Results: After the phasing out of levetiracetam and replacement by oxcarbazepine, aggressive behaviors disappeared. No significant psychopathology was showed in the patient in the follow-up visits, except secondary to preexisting cognitive impairment. Conclusions: According to studies reviewed a 7-13% of patients treated with levetiracetam may develop behavioral disorders with impulsive aggression that usually resolve after discontinuation of drug. Comparative studies show that levetiracetam has a greater frequency of such effects, leading to problems of impulsive aggression relatively often, especially if there is a comorbid psychiatric pathology.

Objective: This study sought to evaluate the presence of the metabolic syndrome in a group of 171 patients with bipolar disorder who were consecutively recruited in our hospital in a year. Methods: Data were collected from participants in 2009-2010. The study focused on the presence of the metabolic syndrome, as defined by the National Cholesterol Education Program Expert Panel on Detection, Evaluation And Treatment of High Blood Cholesterol in Adults (NCEP ATP III). Results: Thirty percent of the sample met the NCEP ATP III criterion for the metabolic syndrome, 49% met the criterion for abdominal obesity, 41% met the criterion for hypertriglyceridemia, 48% met the criterion for hypertriglyceridemia or were on a cholesterol-lowering medication, 23% met the criterion for low high-density lipoprotein cholesterol, 39% met the criterion for hypertension and 8% met the criterion for high fasting glucose or antidiabetic medication use. Patients with the metabolic syndrome and patients endorsing the obesity criterion were more likely (p = 0.05 and p = 0.004, respectively). Conclusions: The prevalence of the metabolic syndrome in patients with bipolar disorder is alarmingly high. We need interventions specifically designed for preventing and treating the metabolic syndrome and its components in patients with bipolar disorder.

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