Efficacy of repetitive transcranial magnetic stimulation in depression: A review of the evidence

Repetitive transcranial magnetic stimulation (rTMS) is a novel treatment in psychiatry. We reviewed all published evidence on the efficacy of this treatment option in depressive disorders. An extensive electronic and manual search for eligible research reports identified only 12 studies that met the predetermined criteria for inclusion. rTMS was administered differently in most studies, and patient characteristics varied widely. A formal meta-analysis of the studies was thus not possible. Instead, we conducted a qualitative evaluation of the included studies. The antidepressive efficacy was not consistent, and where efficacy was demonstrated, it was modest in most studies. Some patients had good but transient responses to rTMS. Treatment gains were not maintained beyond the treatment period. Comparisons with electroconvulsive therapy (ECT) indicated the superiority of ECT. More, larger and more carefully designed studies are needed to demonstrate convincingly a clinically relevant effect of rTMS. We conclude that there is insufficient evidence for rTMS as a valid treatment for depression at present.     

The epidemiology of hyperuricaemia and gout in Taiwan aborigines

To determine the prevalence of hyperuricaemia, gout and gout-related factors in Central Taiwan Atayal aborigines, 342 subjects over 18 yr old were interviewed and examined. A questionnaire was designed to screen for signs and symptoms of gout and gout-related risk factors. Serum uric acid, triglyceride and creatinine were measured in all subjects. The prevalence of hyperuricaemia was 41.4% and that of gout 11.7% in aborigines. The uric acid level was 7.9+/-1.7 mg/dl in males and 5.7+/-1.5 in females, and differed significantly under age 70 yr (P < 0.001). Significantly increased triglyceride, creatinine and alcoholism was found in gouty patients compared with non-gouty patients. In 40 cases with gout, 54% had tophi and 35% of their first- degree relatives had gout. The high prevalence of hyperuricaemia and gout in Taiwan Atayal aborigines, a significant family predisposition, increased creatinine level and alcoholism suggest multiple factors affecting the hyperuricaemia.      

Complications attributable to rotavirus-induced diarrhoea in a Swedish paediatric population: report from an 11-year surveillance

The aim of this retrospective observational study was to evaluate age, length of hospital stay and development of complications in children hospitalized with community- or nosocomially- acquired rotavirus gastroenteritis (RV GE). In total, medical records of 984 children with RV GE were analysed retrospectively. The median age was 13.8 months (3 weeks to 99 months) in children with community acquired RV GE (n=723) and 9.0 months (range 3 weeks to 82 months) in children with nosocomially acquired RV GE (n=261). During this 11-y surveillance, only 2 children were admitted twice for a RV GE, suggesting development of subsequent protective immunity against severe rotavirus gastroenteritis after the first episode. Complications occurred in 16.5% of the children with community acquired RV GE and only in 1.9% of the nosocomially acquired RV GE. Identified complications in children with community acquired RV GE were: severe dehydration resulting in intensive care (1.7%), death (0.1%), hypertonic dehydration (9.1%), seizures (4.0%) and encephalitis with abnormal EEG (1.7%). The median age of children in need of intensive care was 9.1 months and in those developing hypertonic dehydration 10.8 months, both significantly lower than in children with no complications (p<0.05). Interestingly, the age of children developing seizures and signs of encephalitis was significantly higher than in children with no complications (p<0.01).     

Intestinal pseudo-obstruction as an initial presentation of systemic sclerosis in two children

Two children are reported in whom intestinal pseudo-obstruction was the initial manifestation of systemic sclerosis. Gastrointestinal symptoms and skin changes resolved or improved in both children following treatment with prednisone and penicillamine (case 1) or methotrexate (case 2), although radiological changes of the gastrointestinal tract persisted at 3 and 2 yr of follow-up, respectively.      

Preclinical pharmacokinetics and biodistribution of subcutaneously administered glycoPEGylated recombinant factor VIII (N8‐GP) and development of a human pharmacokinetic prediction model

Essentials

• N8‐GP is an extended half‐life recombinant factor VIII (FVIII) for the treatment of hemophilia A.
• Subcutaneous (SC) FVIII dosing might reduce the treatment burden of prophylaxis.
• SC N8‐GP has a favorable PK profile in animal models and disappears from skin injection sites.
• Combined animal (SC) and clinical (IV) data suggest that daily SC dosing may provide prophylaxis.

Summary

Background

N8‐GP is an extended half‐life recombinant factor VIII (FVIII) for the treatment of hemophilia A. Subcutaneous administration of FVIII may reduce the treatment burden of prophylaxis; however, standard FVIII products have low bioavailability after subcutaneous dosing in animals.

Objective

To evaluate the pharmacokinetics, effectiveness and local distribution of subcutaneously administered N8‐GP in preclinical models and predict the human pharmacokinetic (PK) profile.

Methods

The pharmacokinetics of subcutaneously administered N8‐GP were evaluated in FVIII knockout (F8‐KO) mice and cynomolgus monkeys; a human PK prediction model in hemophilia A patients was developed. The hemostatic effect was evaluated in a tail vein bleeding model in F8‐KO mice. The injection‐site distribution and absorption of subcutaneously administered N8‐GP were assessed in F8‐KO mice by the use of temporal fluorescence imaging and immunohistochemistry.

Results

Subcutaneously administered N8‐GP had a bioavailability, a first‐order absorption rate and a half‐life, respectively, of 24%, 0.094 h^?1 and 14 h in F8‐KO mice, and 26%, 0.33 h^?1 and 15 h in cynomolgus monkeys. A dose‐dependent effect of subcutaneously administered N8‐GP on blood loss was observed in mice. A minimal amount of N8‐GP was detected at the injection site 48–72 h after single or multiple dose(s) in F8‐KO mice. Subcutaneously administered N8‐GP was localized to the skin around the injection site, with time‐dependent disappearance from the depot. PK modeling predicted that subcutaneously administered N8‐GP at a daily dose of 12.5 IU kg^?1 will provide FVIII trough levels of 2.5–10% in 95% of patients with severe hemophilia A.

Conclusions

Subcutaneously administered N8‐GP may provide effective hemophilia A prophylaxis. A phase I clinical trial is underway to investigate this possibility.