Seroprevalence of anti-N-methyl-d-aspartate receptor antibodies in women with ovarian teratoma

Recently antibodies against neuronal receptors have been identified as cause of a new type of encephalitis. The anti-N-methyl-d-aspartate receptor (anti-NMDA-R) encephalitis is the prototype of these disorders. Patients have a high incidence of teratomata. Removal of teratoma is considered the essential treatment of anti-NMDA-R encephalitis. Here, we aimed to investigate whether neurologically asymptomatic individuals suffering from ovarian teratomata may have positive anti-NMDA-R antibodies to be detected by an established assay. Over a time period of 15 months, all patients suffering from ovarian teratomata without neurological symptoms were included in this prospective study. Twenty consecutive patients were pair matched to patients with other benign ovarian disease and healthy controls. Preoperatively, patients had a gynaecological examination, transvaginal ultrasound, neurological examination and determination of anti-NMDA-R antibodies. None of the patients or controls presented with neurological symptoms. All tumours could be removed completely by laparoscopy. Anti-NMDA-R antibodies were absent in the group of patients with teratomata as well as in patients with benign ovarian tumours and healthy controls. Testing for anti-NMDA-R antibodies revealed negative findings in well-characterised patients with ovarian teratomata lacking neurological symptoms. Our data support the current clinical practice that a systematic screening for anti-NMDA-R antibodies in teratoma patients is not indicated.     

Controlled trial of the impact of a BC adult mental health practice support program (AMHPSP) on primary health care professionals’ management of depression

Background

Depression affects over 400 million people globally. The majority are seen in primary care. Barriers in providing adequate care are not solely related to physicians’ knowledge/skills deficits, but also time constraints, lack of confidence/avoidance, which need to be addressed in mental health-care redesign. We hypothesized that family physician (FP) training in the Adult Mental Health Practice Support Program (AMHPSP) would lead to greater improvements in patient depressive symptom ratings (a priori primary outcome) compared to treatment as usual.

Methods

From October 2013 to May 2015, in a controlled trial 77 FP practices were stratified on the total number of physicians/practice as well as urban/rural setting, and randomized to the British Columbia AMHPSP?a multi-component contact-based training to enhance FPs’ comfort/skills in treating mild-moderate depression (intervention), or no training (control) by an investigator not operationally involved in the trial. FPs with a valid license to practice in NS were eligible. FPs from both groups were asked to identify 3–4 consecutive patients >?18?years old, diagnosis of depression, Patient Health Questionnaire (PHQ-9) score ≥ 10, able to read English, intact cognitive functioning. Exclusion criteria: antidepressants within 5?weeks and psychotherapy within 3?months of enrollment, and clinically judged urgent/emergent medical/psychiatric condition. Patients were assigned to the same arm as their physician. Thirty-six practices recruited patients (intervention n =?23; control n =?13). The study was prematurely terminated at 6?months of enrollment start-date due to concomitant primary health-care transformation by health-system leaders which resulted in increased in-office demands, and recruitment failure. We used the PHQ-9 to assess between-group differences at baseline, 1, 2, 3, and 6?months follow-up. Outcome collectors and assessors were blind to group assignment.

Results

One hundred-and-twenty-nine patients (intervention n =?72; control n =?57) were analysed. A significant improvement in depression scores among intervention group patients emerged between 3 and 6?months, time by treatment interaction, likelihood ratio test (LR) chi2(3)?=?7.96, p =?.047.

Conclusions

This novel skill-based program shows promise in translating increased FP comfort and skills managing depressed patients into improved patient clinical outcomes?even in absence of mental health specialists availability.

Trial registration

#NCT01975948.

     

Permanent cardiac pacing for severe pallid breath-holding spells

We report the case of an infant affected by frequent episodes of loss of consciousness with the clinical features of pallid breath-holding attacks. Prolonged asystole, up to 26 seconds, was demonstrated by Holter monitoring. The patient was treated with permanent pacemaker implantation, followed by complete symptom resolution during a 26-month follow-up.     

Pharmacological Stimulation of the Brain Serotonin Receptor 7 as a Novel Therapeutic Approach for Rett Syndrome

Rett syndrome (RTT) is a rare neurodevelopmental disorder, characterized by severe behavioral and physiological symptoms. Mutations in the methyl CpG-binding protein 2 gene (MECP2) cause >95% of classic cases, and currently there is no cure for this devastating disorder. The serotonin receptor 7 (5-HT7R) is linked to neuro-physiological regulation of circadian rhythm, mood, cognition, and synaptic plasticity. We presently report that 5-HT7R density is consistently reduced in cortical and hippocampal brain areas of symptomatic MeCP2–308 male mice, a RTT model. Systemic repeated treatment with LP-211 (0.25 mg/kg once/day for 7 days), a brain-penetrant selective 5-HT7R agonist, was able to rescue RTT-related defective performance: anxiety-related profiles in a Light/Dark test, motor abilities in a Dowel test, the exploratory behavior in the Marble Burying test, as well as memory in the Novelty Preference task. In the brain of RTT mice, LP-211 also reversed the abnormal activation of PAK and cofilin (key regulators of actin cytoskeleton dynamics) and of the ribosomal protein (rp) S6, whose reduced activation in MECP2 mutant neurons by mTOR is responsible for the altered protein translational control. Present findings indicate that pharmacological targeting of 5-HT7R improves specific behavioral and molecular manifestations of RTT, thus representing a first step toward the validation of an innovative systemic treatment. Beyond RTT, the latter might be extended to other disorders associated with intellectual disability.     

Influence of weight reduction on blood pressure: a meta-analysis of randomized controlled trials

Increased body weight is a strong risk factor for hypertension. A meta-analysis of randomized controlled trials was performed to estimate the effect of weight reduction on blood pressure overall and in population subgroups. Twenty-five randomized, controlled trials (comprising 34 strata) published between 1966 and 2002 with a total of 4874 participants were included. A random-effects model was used to account for heterogeneity among trials. A net weight reduction of -5.1 kg (95% confidence interval [CI], -6.03 to -4.25) by means of energy restriction, increased physical activity, or both reduced systolic blood pressure by -4.44 mm Hg (95% CI, -5.93 to -2.95) and diastolic blood pressure by -3.57 mm Hg (95% CI, -4.88 to -2.25). Blood pressure reductions were -1.05 mm Hg (95% CI, -1.43 to -0.66) systolic and -0.92 mm Hg (95% CI, -1.28 to -0.55) diastolic when expressed per kilogram of weight loss. As expected, significantly larger blood pressure reductions were observed in populations with an average weight loss >5 kg than in populations with less weight loss, both for systolic (-6.63 mm Hg [95% CI, -8.43 to -4.82] vs -2.70 mm Hg [95% CI, -4.59 to -0.81]) and diastolic (-5.12 mm Hg [95% CI, -6.48 to -3.75] vs -2.01 mm Hg [95% CI, -3.47 to -0.54]) blood pressure. The effect on diastolic blood pressure was significantly larger in populations taking antihypertensive drugs than in untreated populations (-5.31 mm Hg [95% CI, -6.64 to -3.99] vs -2.91 mm Hg [95% CI, -3.66 to -2.16]). This meta-analysis clearly shows that weight loss is important for the prevention and treatment of hypertension.