Primary care patients in psychiatric clinical trials: a pilot study using videoconferencing

Background  

While primary care physicians play a pivotal role in the treatment of depression, collaboration between primary care and psychiatry in clinical research has been limited. Primary care settings provide unique opportunities to improve the methodology of psychiatric clinical trials, by providing more generalizable and less treatment-resistant patients. We examined the feasibility of identifying, recruiting, screening and assessing primary care patients for psychiatric clinical trials using high-quality videoconferencing in a mock clinical trial.     

Chronic low back pain in primary care: a prospective study on the management and course

BACKGROUND: There is little evidence about the management and course of chronic low back pain in primary care. OBJECTIVES: Our aim was to describe the course of chronic low back pain and the performed diagnostic and therapeutic procedures for patients with chronic low back pain in general practice. METHODS: Twenty-six GPs involved in the Registration Network Family Practices participated in this prospective follow-up study. All patients and GPs were asked to complete questionnaires at baseline and at 4, 8 and 12 months follow-up. RESULTS: The GPs provided information about diagnostic and therapeutic procedures concerning 524 patients with chronic low back pain. Diagnostic tests other than history-taking and physical examination were not frequently used. Medication, mostly NSAIDs, was the most frequently used type of treatment (21.6%). The most frequent referrals concerned physiotherapy (16.3%) and neurology or neurologic surgery (6.3%). Information about the course of their chronic low back pain was provided by 368 patients participating in our study. The course of chronic low back pain appeared to be quite stable, as there was only a slight improvement in pain intensity and physical functioning over the 12 months of follow-up. CONCLUSIONS: A variety of options for the treatment and referral of chronic low back pain patients is available for and used by GPs. Efforts should be made to establish which diagnostic and therapeutic procedures are the most effective for chronic low back pain.      

The accuracy of single serum progesterone measurement in the diagnosis of ectopic pregnancy: a meta-analysis

Serum progesterone measurement has been advocated as a diagnostic tool in the non-invasive diagnosis of ectopic pregnancy. To assess the accuracy of a single serum progesterone measurement in the diagnosis of ectopic pregnancy, a meta-analysis was performed incorporating 26 studies evaluating the performance of single serum progesterone measurement in the diagnosis of ectopic pregnancy. A distinction was made in the diagnosis of pregnancy failure of any type versus viable intrauterine pregnancy and the diagnosis of ectopic pregnancy versus non-ectopic pregnancy. The reported sensitivity and specificity differed between the studies. Since there was a clear negative correlation between sensitivity and specificity, summary receiver- operating characteristic (ROC) curves could be estimated. The ROC curve for the diagnosis of pregnancy failure versus viable intrauterine pregnancy showed a good discriminative capacity. Single serum progesterone measurement could not discriminate between ectopic pregnancy and non-ectopic pregnancy. It is concluded that serum progesterone measurement can identify patients at risk for ectopic pregnancy, who need further evaluation, but its discriminative capacity is insufficient to diagnose ectopic pregnancy with certainty.      

WAY-318068: a novel, potent and selective noradrenaline re-uptake inhibitor with activity in rodent models of pain and depression

Background and purpose:

Antidepressants, which raise the CNS concentrations of 5-HT and noradrenaline, are frequently used in the treatment of chronic pain; however, it is not known if increasing CNS noradrenaline levels alone is sufficient for efficacy, in part resulting from a lack of small molecules with sufficient selectivity.

Experimental approach:

In this report, we present the in vitro pharmacological and in vivo pharmacokinetic and pharmacological properties of the novel, orally available and CNS penetrant inhibitor of the noradrenaline transporter (NET), WAY-318068 (1-[(1S,2R)-1-(3,5-difluorophenyl)-2-hydroxy-3-(methylamino)propyl]-7-fluoro-3,3-dimethyl-1,3-dihydro-2H-indol-2-one).

Key results:

WAY-318068 is a potent and effective inhibitor of the NET with a K_i of 8.7 nM in a binding assay, and an IC₅₀ of 6.8 nM in an assay of transporter function, without significant binding to the dopamine transporter. Furthermore, the compound has only weak activity at the 5-HT transporter, leading to a functional selectivity of greater than 2500-fold. It is orally bioavailable with substantial quantities of the compound found in the CNS after oral dosing. As measured by microdialysis in rats, the compound causes a robust and significant increase in cortical noradrenaline levels without affecting 5-HT. WAY-318068 was effective in models of acute, visceral, inflammatory, osteoarthritic, neuropathic, diabetic and bone cancer pain, as well as in traditional models of depression at doses that do not cause motor deficits.

Conclusions and implications:

Collectively, the present results support the conclusion that selectively increasing CNS levels of noradrenaline is sufficient for efficacy in models of depression and pain.