In a previous open-label study, we found that patients with bipolar disorder improved in symptom level when taking micronutrients and fish oil. We planned a randomized, double-blind, controlled trial to explore the feasibility and parameters needed for a larger clinical trial.

We aimed to determine the parameters necessary to conduct a large-scale clinical trial through completing a feasibility study.

Patients were screened for having the diagnosis of bipolar disorder and being willing to take up to 16 micronutrient capsules and 3 fish oil capsules per day. Patients were randomized in a 3:2 ratio to micronutrients or placebo. Patients were seen monthly with assessment of the Clinical Global Impression Scale, the UKU Side Effects Scale, and a review of their medication doses. On a quarterly basis, patients completed the BASIS-24, the MYMOP-2, the Young Mania Scale, and the MADRS questionnaire

The setting was a primary care clinic in Maine in the United States. The patient population was low-income and primarily rural. Disease severity was mild to moderate as only 2 patients were hospitalized during the study. All were symptomatic. One hundred twenty-five patients were screened and accepted randomization. The attrition rate was high and only 52 subjects completed 6 months of treatment. No differences were found between the two groups. We calculated that a minimum of 250 subjects would be needed to have 80% power to detect a difference. All patients improved dramatically in all measures.

Bipolar patients in primary care remain moderately symptomatic and will improve dramatically with monthly visits.

No significant relationships.

To assess the effect of individual compared to clinic-level feedback on guideline-concordant care for 3 acute respiratory tract infections (ARTIs) among family medicine clinicians caring for pediatric patients.

Cluster randomized controlled trial with a 22-month baseline, 26-month intervention period, and 12-month postintervention period.

In total, 26 family medicine practices (39 clinics) caring for pediatric patients in Virginia, North Carolina, and South Carolina were selected based upon performance on guideline-concordance for 3 ARTIs, stratified by practice size. These were randomly allocated to a control group (17 clinics in 13 practices) or to an intervention group (22 clinics in 13 practices).

All clinicians received an education session and baseline then monthly clinic-level rates for guideline-concordant antibiotic prescribing for ARTIs: upper respiratory tract infection (URI), acute bacterial sinusitis (ABS), and acute otitis media (AOM). For the intervention group only, individual clinician performance was provided.

Both intervention and control groups demonstrated improvement from baseline, but the intervention group had significantly greater improvement compared with the control group: URI (odds ratio [OR], 1.62; 95% confidence interval [CI], 1.37–1.92; P < 0.01); ABS (OR, 1.45; 95% CI, 1.11–1.88; P < 0.01); and AOM (OR, 1.59; 95% CI, 1.24–2.03; P < 0.01). The intervention group also showed significantly greater reduction in broad-spectrum antibiotic prescribing percentage (BSAP%): odds ratio 0.80, 95% CI 0.74-0.87, P < 0.01. During the postintervention year, gains were maintained in the intervention group for each ARTI and for URI and AOM in the control group.

Monthly individual peer feedback is superior to clinic-level only feedback in family medicine clinics for 3 pediatric ARTIs and for BSAP% reduction.

ClinicalTrials.gov identifier: NCT04588376, Improving Antibiotic Prescribing for Pediatric Respiratory Infection by Family Physicians with Peer Comparison.

Comparisons of antipsychotics with placebo can be biased by unblinding due to side effects. Therefore, this meta-analysis compared the efficacy of antipsychotics for acute schizophrenia in trials using barbiturates or benzodiazepines as active placebos.

Randomized controlled trials (RCTs) in acute schizophrenia with at least 3 weeks duration and comparing any antipsychotic with barbiturates or benzodiazepines were eligible. ClinicalTrials.gov, CENTRAL, EMBASE, MEDLINE, PsycINFO, PubMed, WHO-ICTRP as well as previous reviews were searched up to 9 January 2018. Two separate meta-analyses, one for barbiturates and one for benzodiazepines, were conducted using random-effects models. The primary outcome was response to treatment, and mean values of schizophrenia rating scales and dropouts were analyzed as secondary outcomes. This study is registered with PROSPERO (CRD42018086263).

Seven barbiturate-RCTs (number of participants n = 1736), and two benzodiazepine-RCTs (n = 76) were included in the analysis. The studies were published between 1960 and 1968 and involved mainly chronically ill patients. More patients on antipsychotics in comparison to barbiturates achieved a ‘good’ response (36.2% v. 16.8%; RR 2.15; 95% CI 1.36–3.41; I2 = 48.9) and ‘any’ response (57.4% v. 27.8%; RR 2.07; 95% CI 1.35–3.18; I2 = 68.2). In a single small trial (n = 60), there was no difference between antipsychotics and benzodiazepines on ‘any’ response (74.7% v. 65%; RR 1.15; 95% CI 0.82–1.62).

Antipsychotic drugs were more efficacious than barbiturates, based on a large sample size. Response ratios were similar to those observed in placebo-controlled trials. The results on benzodiazepines were inconclusive due to the small number of studies and participants.

Mirtazapine is an antidepressant first approved in the Netherlands in 1994 for the treatment of major depressive disorder. However, evidence suggests its effectiveness in a variety of other psychiatric disorders and non-psychiatric medical conditions.

The present paper reviews the published literature on the off-label indications of Mirtazapine.

A search of the relevant literature from MEDLINE, PsycLIT and EMBASE databases, included in the Science Citation Index and available up to March 2006, was conducted using the terms mirtazapine, case-reports, open-label trials and randomized controlled trials. Only articles referring to conditions other than major depression were included in this present review.

Off-label use of mirtazapine has been reported in panic disorder, post-traumatic stress disorder, generalized anxiety disorder, social phobia, obsessive-compulsive disorder, dysthymia, menopausal depression, poststroke depression, depression as a result of infection with human immunodeficiency virus, elderly depression, Methylenedioxymethamphetamine (MDMA)-induced depression, hot flashes, alcohol and other substance use disorders, sleep disorders, sexual disorders, tension-type headaches, cancer pain, fibromyalgia, schizophrenia and other less frequent conditions.

So far, data on the off-label usefulness of mirtazapine are limited and mainly based on observations from case reports or open-label studies. However, positive cues suggest that confirmation of these preliminary data with randomized controlled trials may give sufficient evidence to warrant the use of mirtazapine in a broad range of disorders.

After de-escalation techniques have failed, restraints, seclusion and/or rapid tranquillization may be used for people whose aggression is due to psychosis. Most coercive acts of health care have not been evaluated in trials.

People admitted to the emergency room of Instituto Philippe Pinel, Rio de Janeiro, Brazil, whose aggression/agitation was thought due to psychosis and for whom staff were unsure if best to restrict using physical restraints or a seclusion room, were randomly allocated to one or the other and followed up to 14 days. The primary outcomes were ‘no need to change intervention early – within 1 h’ and ‘not restricted by 4 h’.

A total of 105 people were randomized. Two-thirds of the people secluded were able to be fully managed in this way. Even taking into account the move out of seclusion into restraints, this study provides evidence that embarking on the less restrictive care pathway (seclusion) does not increase overall time in restriction of some sort [not restricted by 4 h: relative risk 1.09, 95% confidence interval 0.75–1.58; mean time to release: restraints 337.6 (s.d.=298.2) min, seclusion room 316.3 (s.d.=264.5) min, p=0.48]. Participants tended to be more satisfied with their care in the seclusion group (17.0% v. 11.1%) but this did not reach conventional levels of statistical significance (p=0.42).

This study should be replicated, but suggests that opting for the least restrictive option in circumstances where there is clinical doubt does not harm or prolong coercion.

We sought to determine whether inhaled 3% hypertonic saline (HS) reduces admission to hospital in ambulatory children with moderately severe viral bronchiolitis. Secondary objectives compared changes in respiratory scores before and after treatment and assessed the need for unscheduled medical intervention within 7 days.

Children under the age of 2 years presenting with moderately severe viral bronchiolitis to the emergency department of 4 general hospitals from November 2008 to March 2009 were randomly assigned to receive 3 consecutive 4-mL doses of nebulized 3% HS (treatment group) or 0.9% normal saline (NS; control group) in a double blind fashion, each coadministered with 1 mg salbutamol. Outcome measures included the difference in hospital admission rate and changes in respiratory distress scores.

A total of 81 children (mean age 8.9 mo, range 0.7–22 mo) were assessed over 88 visits on an intention-to-treat basis. No statistically significant differences were found between treatment groups. Children in the HS group had a nonsignificant trend toward greater improvement compared with NS controls with a same-day admission rate of 18% (95% confidence interval [CI] 9%–32%) versus 27% (95% CI 16%–42%), respectively. Respiratory Assessment Change Scores (RACS) favoured the HS group over NS controls (mean RACS 4.7 [95% CI 3.6–5.8] v. 3.7 [95% CI 2.5–4.9], respectively), although the CIs overlap and these differences were not statistically significant.

The short-term use of nebulized 3% HS did not result in any statistically significant benefits, although a nonsignificant trend toward a decrease in admission rate and improvement in respiratory distress was found. A larger study would be required to determine whether these trends arise from a clinically relevant treatment effect.

The aim was to reduce non-attendance for first-time consultations at psychiatric out-patient clinics.

The study was a pragmatic randomized controlled trial; the setting was seven inner-city UK out-patient clinics in Leeds. The participants were 764 subjects of working age with an appointment to attend a psychiatric out-patient clinic for the first time. The intervention was an ‘orientation statement’ letter delivered 24–48 h before the first appointment compared with standard care. The primary outcome measure was attendance at the first appointment; secondary outcomes included hospitalization, transfer of care, continuing attendance, discharge, presentation at accident and emergency and death by 1 year.

Follow-up was for 763 out of 764 subjects (>99%) for primary and for 755 out of 764 subjects (98.8%) of secondary outcome data. The orientation statement significantly reduced the numbers of people failing to attend [79 out of 388 v. 101 out of 376 subjects, relative risk 0.76, 95% confidence interval (CI) 0.59–0.98, number needed to treat 16, 95% CI 10–187].

Prompting people to go to psychiatric out-patient clinics for the first time encourages them to attend. Pragmatic trials within a busy working environment are possible and informative.