Real-world efficacy of deep TMS for obsessive-compulsive disorder: Post-marketing data collected from twenty-two clinical sites.

BACKGROUND: Deep transcranial magnetic stimulation (dTMS) with the H7-coil was FDA cleared for obsessive-compulsive disorder (OCD) in August 2018 based on multicenter sham-controlled studies. Here we look at the efficacy of dTMS for OCD in real world practices. METHODS: All dTMS clinics were asked to supply their data on treatment details and outcome measures. The primary outcome measure was response, defined by at least a 30% reduction in the Yale Brown Obsessive Compulsive Scale (YBOCS) score from baseline to endpoint. Secondary outcome measures included first response, defined as the first time the YBOCS score has met response criteria, and at least one-month sustained response. Analyses included response rate at the endpoint (after 29 dTMS sessions), number of sessions and days required to reach first response and sustained response. RESULTS: Twenty-two clinical sites with H7-coils provided data on details of treatment and outcome (YBOCS) measures from a total of 219 patients. One-hundred-sixty-seven patients who had at least one post-baseline YBOCS measure were included in the main analyses. Overall first and sustained response rates were 72.6% and 52.4%, respectively. The response rate was 57.9% in patients who had YBOCS scores after 29 dTMS sessions. First response was achieved in average after 18.5 sessions (SD = 9.4) or 31.6 days (SD = 25.2). Onset of sustained one-month response was achieved in average after 20 sessions (SD = 9.8) or 32.1 days (SD = 20.5). Average YBOCS scores demonstrated continuous reduction with increasing numbers of dTMS sessions. CONCLUSIONS: In real-world clinical practice, the majority of OCD patients benefitted from dTMS, and the onset of improvement usually occurs within 20 sessions. Extending the treatment course beyond 29 sessions results in continued reduction of OCD symptoms, raising the prospect of value for extended treatment protocols in non-responders.

Internet-enhanced management of fibromyalgia: a randomized controlled trial.

Both pharmacological and non-pharmacological interventions have demonstrated efficacy in the management of fibromyalgia (FM). Non-pharmacological interventions however are far less likely to be used in clinical settings, in part due to limited access. This manuscript presents the findings of a randomized controlled trail of an Internet-based exercise and behavioral self-management program for FM designed for use in the context of a routine clinical care. 118 individuals with FM were randomly assigned to either (a) standard care or (b) standard care plus access to a Web-Enhanced Behavioral Self-Management program (WEB-SM) grounded in cognitive and behavioral pain management principles. Individuals were assessed at baseline and again at 6 months for primary endpoints: reduction of pain and an improvement in physical functioning. Secondary outcomes included fatigue, sleep, anxiety and depressive symptoms, and a patient global impression of improvement. Individuals assigned to the WEB-SM condition reported significantly greater improvement in pain, physical functioning, and overall global improvement. Exercise and relaxation techniques were the most commonly used skills throughout the 6 month period. A no-contact, Internet-based, self-management intervention demonstrated efficacy on key outcomes for FM. While not everyone is expected to benefit from this approach, this study demonstrated that non-pharmacological interventions can be efficiently integrated into routine clinical practice with positive outcomes.

Expression of type 1 and 2A protein phosphatase subunits in the rat corpus luteum across pregnancy.

This study was undertaken to test the hypothesis that the reduction in protein phosphatase activity that had been observed at mid-pregnancy in the rat corpus luteum (CL) was due to a decrease in expression of one of the catalytic subunits or an increase in one of the B regulatory subunits of the type 2A protein phosphatase (PP2A). Ovaries were collected from rats on days (d) 1, 3, 7, 14, 20, and 21 of pregnancy, and on day 21 after progesterone treatment on day 20 (n = 6). Real-time RT-PCR was used to analyze the expression of the alpha and beta isoforms of the catalytic subunit, the structural A subunit, and three B regulatory subunits of PP2A, as well as the catalytic subunit of PP1. Expression of the alpha and beta catalytic subunits of PP2A was progesterone responsive. Expression of the PP1 catalytic subunit correlated with the previously reported protein phosphatase activity, but PP2A subunits did not. The data suggest that the decreased protein phosphatase activity at mid-pregnancy was due to a decline in expression of the catalytic subunits of PP1 rather than changes in expression of PP2A subunits.

Comparative potency of formulations of mometasone furoate in terms of inhibition of 'PIRHR' in the forearm skin of normal human subjects measured with laser doppler velocimetry.

BACKGROUND AND AIMS: Topical glucocorticoid formulations are widely used for effective treatment and control of a variety of dermatoses. Mometasone furoate is a newer corticoid that has high potency but low systemic toxicity. Pharmaceutical factors are known to significantly influence potency and systemic absorption of topically applied glucocorticoids. We studied the potency of "Elocon", a topical formulation of mometasone furoate, compared with two other branded formulations of the same corticoid. METHODS: Corticoid potency was measured by employing a pharmacodynamic parameter of an inhibitory effect of the corticoid on post-ischemic-reactive-hyperemic-response (PIRHR) in human forearm skin under occlusive dressing. The PIRHR was expressed in terms of % increase in the skin blood flow (SBF) as measured with laser doppler velocimetry (LDV). RESULTS: All three active branded formulations of mometasone furoate produced significant inhibition of PIRHR. The AUC(0-2 min) of PIRHR was ( Mean +/- SEM ), Control = 213.52 +/- 11.80, Placebo = 209.77 +/- 19.31, Formulation A = 119.83 +/- 13.71, Formulation C = 53.67 +/- 4.85 and Formulation D = 111.46 +/- 22.87. Formulation "C" exhibited significantly higher topical anti-inflammatory potency than formulations "A" or "D". CONCLUSIONS: Thus, branded formulations of the same glucocorticoid, mometasone furoate significantly differed in their topical anti-inflammatory potency. "Elocon" was significantly more potent than the two other branded formulations studied.

Prolonged activated partial thromboplastin time in pregnancy: a brief report.

BACKGROUND: Limited data are available regarding causes of prolonged activated partial thromboplastin time (aPTT) in otherwise normal pregnancies. We retrospectively evaluated clinical data of pregnant women in whom an elevated aPTT was noted on routine prenatal testing. Our intent was to identify various causes of prolonged aPTT and to evaluate whether the pregnancies were adversely affected. METHODS: A retrospective review of medical records of 36 pregnant patients with a prolonged aPTT as the sole abnormal coagulation test seen in the outpatient department of a tertiary care hospital over a period of 4 years. RESULTS: Patients' median age was 26 (range, 19-41) years and median duration of gestation period was 19 (range, 8-38) weeks. Fifteen patients were primigravida. Of 36 patients, repeated aPTT values were normal in 24 (67%) patients, whereas 12 (33%) patients had persistently elevated aPTT values. Factor XI deficiency was found in 5 patients, lupus anticoagulant in 3 patients, elevated anticardiolipin antibody in 2 patients, and low von Willebrand Factor level in 1 patient. Overall, 23 patients delivered. No patients experienced excessive bleeding or thromboembolism. CONCLUSION: Factor XI deficiency and antiphospholipid antibody were 2 major abnormalities identified in patients with prolonged aPTT. These coagulopathies were not associated with excessive bleeding or thromboembolism. Repeat normal aPTT in approximately 2 thirds of patients suggests that proper sample collection and processing are important for coagulation assays to avoid erroneous clotting times.

Effect of low-dose warfarin on D-dimer levels during sickle cell vaso-occlusive crisis: a brief report.

OBJECTIVE: To evaluate the activation of clotting systems in patients with sickle cell disease (SCD) by measuring the plasma D-dimer level and to determine the effect of low-dose warfarin on D-dimer level during vaso-occlusive crisis. METHODS: Plasma D-dimer level was measured in 65 blood samples of 37 adult patients with SCD who were hospitalized for vaso-occlusive painful crisis. D-dimer level of patients who were on low-dose warfarin was compared with those patients who were not on any anticoagulation treatment. Analysis of variance (anova) was carried out to determine factors significantly associated with low D-dimer level in patients with SCD. The following factors were included in the anova model; warfarin, homozygous hemoglobin S, history of blood transfusion in past 3 months, hydroxyurea, hemoglobin S%, hemoglobin F%, white blood cell counts, hemoglobin level, platelet count, and plasma fibrinogen level. RESULTS: Overall median D-dimer level in 65 samples was 2.7 microg fibrinogen equivalent units (FEU)/mL (0.34-4). Patients who were on low-dose warfarin had a median D-dimer level of 0.81 microg FEU/mL (0.34-1.8) compared with 3.1 microg FEU/mL (0.94-4) in those patients who were not on anticoagulation treatment. Using anova to model D-dimer levels, only warfarin was significantly correlated with low D-dimer levels after controlling for other variables. CONCLUSIONS: Patients with SCD during vaso-occulsive painful crisis have an elevated D-dimer level. Low-dose anticoagulation treatment is associated with a significant reduction in the D-dimer levels.