Pain and the blood-brain barrier: obstacles to drug delivery

Delivery of drugs across the blood-brain barrier has been shown to be altered during pathological states involving pain. Pain is a complex phenomenon involving immune and centrally mediated responses, as well as activation of the hypothalamic-pituitary-adrenal axis. Mediators released in response to pain have been shown to affect the structure and function of the blood-brain barrier in vitro and in vivo. These alterations in blood-brain barrier permeability and cytoarchitecture have implications in terms of drug delivery to the central nervous system, since pain and inflammation have the capacity to alter drug uptake and efflux across the blood-brain barrier. An understanding of how blood-brain barrier and central nervous system drug delivery mechanisms are altered during pathological conditions involving pain and/or inflammation is important in designing effective therapeutic regimens to treat disease.     

Developing and validating a new nomogram for diagnosing bladder outlet obstruction in women

Objective

To develop and validate a nomogram for assessing bladder outlet obstruction (BOO) in women derived from concurrent P_det.Qmax and Q_max based on radiographic evidence of increased urethral resistance.

Patients and Methods

Retrospective analysis of prospectively acquired video‐urodynamics and clinical data of 185 women (development cohort) was performed. The P_det.Qmax were plotted against Q_max and cluster analysis was performed to determine an axis that best divided the definitively obstructed and unobstructed. Using data from a further 350 women (validation cohort), the sensitivity and specificity of the derived criterion was calculated. Finally, the data from both groups was pooled together and using binary logistic regression analysis, a nomogram was produced.

Results

Of the 535 patients in the two cohorts, (122 [22.8%]) demonstrated radiographic evidence of BOO. Cluster analysis identified the axis that best separates the radiographically obstructed and unobstructed as P_det.Qmax = 2*Q_max. Using the data from the validation cohort, the sensitivity and specificity for this was calculated as 0.94 and 0.93, respectively. A nomogram, representing the probability of BOO for concurrent P_det.Qmax and Q_max measurements was derived by pooling data from both cohorts. Alternatively, a female BOO index (BOOIf) may be calculated mathematically using the formula BOOIf = P_det.Qmax ? 2.2*Q_{max, that is,} BOOIf < 0, <10% probability of obstruction, BOOIf > 5 likely obstructed (50%) and If BOOIf > 18, obstruction almost certain (>90%).

Conclusion

A female BOO nomogram (the SG nomogram) with high sensitivity and specificity is proposed. The nomogram can be used to stratify the degree of BOO or assess response to treatment.     

Cost-effectiveness analysis of rituximab treatment in patients in Germany with rheumatoid arthritis after etanercept-failure

Objective  

The present health economic analysis investigated the cost-effectiveness-ratios of either (1) rituximab or (2) an alternative TNF-alpha-inhibiting agent as second line biological treatment in patients with active rheumatoid arthritis (RA) and an inadequate response to etanercept therapy.     

Prevalence of depression among women with obstetric fistula in low-income African countries: a systematic review and meta-analysis

Depression is one of mental health consequences that present in women with obstetric fistula. It is estimated that over 264 million people of all ages suffer from depression globally. The objective of this systematic review and meta-analysis was to synthesize the epidemiologic evidence from previous studies on the prevalence of depression among women with obstetric fistula in low-income African countries. We followed the preferred reporting items for systematic review and meta-analysis (PRISMA) guidelines to conduct this meta-analysis. The common databases (PubMed, SCOPUS, EMBASE, Psych INFO, Google Scholar, African Index Medicus, and African Journals Online (AJOL)) were searched for the relevant literature. We used a random-effect meta-analysis model to estimate the overall prevalence of depression and the Q -and I² -statistics were used to assess the heterogeneity between the studies included in the meta-analysis. Egger’s test and visual inspection of the symmetry in funnel plots were used to check for the presence of publication bias. The pooled estimated prevalence of depression among women with obstetric fistula in low-income African countries was 56.2% (95% CI 43.1–68.4). The prevalence of depression among women with obstetric fistula was 74.4% in Ethiopia, 72.9% in Kenya, 46.0% in Malawi, 41.0% in Sudan, 34.8% in Nigeria, and 27.7% in Tanzania. Furthermore, the prevalence of depression was higher (97.0%) when it was measured by using Beck’s Depression Inventory (BDI) when compared with Patient Health Questionnaire (PHQ9) (62.7%), General Health Questionnaire (GHQ-28) (36.7%), Hamilton Depression Rating Scale (HDRS) (41.0%), and Center for Epidemiologic Studies Depression Scale (CES-D) (27.7%). Moreover, the pooled estimated prevalence of depression among women with obstetric fistula was ranged from 48.1 to 57.7% in a leave-one-out sensitivity analysis. The prevalence of depression among women with obstetric fistula in low-income African countries was high. Screening and appropriate management of depression among women with obstetric fistula are warranted.

     

Sensitivity of alpha-adrenoceptor agonists to the calcium channel activator, Bay K 8644, in canine saphenous vein

The purpose of the present study was to determine if the calcium channel activator, Bay K 8644, enhances the vasoconstrictor actions of selective alpha 1- and alpha 2-adrenoceptor agonists in canine saphenous vein. Phenylephrine (PE) and St 587 were used as fully and partially selective alpha 1-adrenoceptor agonists, B-HT 920 and B-HT 958 were used as fully and partially selective alpha 2-adrenoceptor agonists. Bay K 8644 (10(-8) M) markedly potentiated B-HT-958-mediated vasoconstrictor responses with a leftward shift and an increase in the maximum response of the logarithmic dose-response curve. Bay K 8644 produced less potentiation of responses to B-HT 920 and had minimal effects on responses to St 587 and PE. The intrinsic activities of the alpha-adrenoceptor agonists, as compared to the maximum response obtained by norepinephrine, in decreasing order, were PE greater than St 587 greater than B-HT 920 greater than B-HT 958, whereas the susceptibility of alpha-adrenoceptor agonists to potentiation by Bay K 8644 in decreasing order were B-HT 958 greater than B-HT 920 greater than St 587 greater than PE. These results suggest that Bay K 8644 preferentially improves the receptor-response coupling of alpha-adrenoceptor agonists with low intrinsic activity (alpha 2-agonists) versus agonists with high intrinsic activity (alpha-agonists) in canine saphenous vein.     

The Prevalence of Alcohol Consumption Among Pregnant Women in Ethiopia: A Systematic Review and Meta-Analysis

Maternal and Child Health Journal - Evidence indicates that a significant proportion of women drink alcohol during pregnancy. Studies have also suggested that prenatal alcohol consumption was...