Recommendations for buprenorphine and methadone therapy in opioid use disorder: a European consensus

Introduction: Management of patients with opioid use disorder (OUD) commonly includes opioid agonist therapy (OAT) as a part of an integrated treatment plan. These interventions are associated with proven benefits to the individual and society.

Areas covered: The use of methadone and buprenorphine within an integrated treatment plan in the management of patients with OUD: this work provides consensus recommendation on pharmacotherapy in OUD to assist clinicians with practical decision making in this field.

Expert opinion: Pharmacotherapy is recommended as part of an integrated OUD treatment approach with psychosocial interventions, with the goal of reducing risks of illicit opioid use, overdose mortality, infection with HIV or HCV, improving health, psychological and social outcomes. Access to OAT should be prioritised in the treatment of OUD. Treatment choices in OUD pharmacotherapy should be based on the needs of the individual and characteristics of medications. Recommendations for choices of OAT are based on clinical efficacy, safety, patient preference, side effects, pharmacological interactions, quality of life, dose titration potential and outcomes (control craving, ongoing opioids consumption or other drugs, and potentially psychiatric comorbidities). Special groups, pregnant women, prisoners, patients with mental health problems have specific needs which must be addressed with expert input.     

Obstructive sleep apnea is associated with worse clinical‐radiological risk scores of pulmonary embolism

Obstructive sleep apnea is a risk factor for pulmonary embolism, although its association with pulmonary embolism severity is unknown. Our objective was to study if obstructive sleep apnea is associated with worse pulmonary embolism severity scores and greater extent of arterial obstruction. In consecutive pulmonary embolism patients, we performed respiratory polygraphy and recorded sleep characteristics, classical risk factors for pulmonary embolism and physical activity 6–12 months after the pulmonary embolism episode. Simplified Geneva Prognostic Score and Pulmonary Embolism Severity Index were calculated at the time of the pulmonary embolism diagnosis. The Pulmonary Artery Obstruction Index and the right ventricle to left ventricle diameter ratio were measured by computed tomography pulmonary angiography. We included 120 patients, of whom 45.8% had moderate‐severe obstructive sleep apnea (apnea–hypopnea index > 15 hr^?1). There was a larger proportion of moderate‐severe obstructive sleep apnea patients in the third and fourth Pulmonary Artery Obstruction Index quartiles and in the III‐V Pulmonary Embolism Severity Index levels compared with apnea–hypopnea index < 15 hr^?1 group. However, no differences were found between the proportion of patients with or without moderate‐severe obstructive sleep apnea in their stratification by simplified Geneva Prognostic Score. The mean adjusted values of the simplified Geneva Prognostic Score, Pulmonary Embolism Severity Index and Pulmonary Artery Obstruction Index scores were higher in the apnea–hypopnea index > 15 hr^?1 group (p < .05). Multiple linear regression analysis identified apnea–hypopnea index as the only independent factor related to Pulmonary Artery Obstruction Index and Pulmonary Embolism Severity Index, whereas desaturation index was associated with simplified Geneva Prognostic Score. Patients with pulmonary embolism and moderate‐severe obstructive sleep apnea had greater pulmonary artery obstruction as well as more pulmonary embolism severity, assessed by both the simplified Geneva Prognostic Score and the Pulmonary Embolism Severity Index, compared with patients with apnea–hypopnea index ≤ 15 hr^?1. Moreover, these prognostic indices were independently related to sleep parameters.     

Estradiol promotes proliferation of dopaminergic precursors resulting in a higher proportion of dopamine neurons derived from mouse embryonic stem cells

Estradiol protects dopamine neurons of the substantia nigra from toxic insults. Such neurons succumb in Parkinson's disease; one strategy for restoring dopamine deficiency is cell therapy with neurons differentiated from embryonic stem cells. We investigated the effects of 17β-estradiol on dopaminergic induction of embryonic stem cells using the 5-stage protocol. Cells were incubated with different steroid concentrations during the proliferation (stage 4) or differentiation (stage 5) phases. Estradiol added at nM concentrations only during stage 4 increases the proliferation of dopaminergic precursors expressing Lmx1a, inducing a higher proportion of dopamine neurons at stage 5. These actions were mediated by activation of estrogen receptors, because co-incubation of cells with estradiol and ICI 182,780 completely abolished the positive effect on both proliferation of committed precursors, and subsequent differentiation to dopaminergic neurons. Our results suggest that estradiol should be useful in producing higher proportions of dopamine neurons from embryonic stem cells aimed for treating Parkinson's disease.     

Effect of probiotic supplementation on immunoglobulins, isoagglutinins and antibody response in children of low socio-economic status

Background  

Antigen exposure is one of the major exogenous factors modulating human immunocompetence acquisition. Decline in family size and improvements in public health and hygiene in developed countries, may deprive the immune system of appropriate antigen input by diminishing infectious stimuli. Probiotics are a large group of microorganisms defined by their beneficial effects on human health and with stimulating effects on different functions of the immune system.     

Axon responses of embryonic stem cell‐derived dopaminergic neurons to semaphorins 3A and 3C

Class 3 Semaphorins are a subfamily of chemotropic molecules implicated in the projection of dopaminergic neurons from the ventral mesencephalon and in the formation of the nigrostriatal pathway (NSP) during embryonic development. In humans, loss of mesencephalic dopaminergic neurons leads to Parkinson's disease (PD). Cell replacement therapy with dopaminergic neurons generated from embryonic stem cells (ES‐TH⁺) is being actively explored in models of PD. Among several requisites for this approach to work are adequate reconstruction of the NSP and correct innervation of normal striatal targets by dopaminergic axons. In this work, we characterized the response of ES‐TH⁺ neurons to semaphorins 3A, 3C, and 3F and compared it with that of tyrosine hidroxylase‐positive neurons (TH⁺) obtained from embryonic ventral mesencephalon (VM‐TH⁺). We observed that similar proportions of ES‐TH⁺ and VM‐TH⁺ neurons express semaphorin receptors neuropilins 1 and 2. Furthermore, the axons of both populations responded very similarly to semaphorin exposure: semaphorin 3A increased axon length, and semaphorin 3C attracted axons and increased their length. These effects were mediated by neuropilins, insofar as addition of blocking antibodies against these proteins reduced the effects on axonal growth and attraction, and only TH⁺ axons expressing neuropilins responded to the semaphorins analyzed. The observations reported here show phenotypic similarities between VM‐TH⁺ and ES‐TH⁺ neurons and suggest that semaphorins 3A and 3C could be employed to guide axons of grafted ES‐TH⁺ in therapeutic protocols for PD. © 2009 Wiley‐Liss, Inc.     

Cyclospora cayetanensis in patients with AIDS and chronic diarrhea

Cyclospora spp. is a protozoan parasite responsible for significant gastrointestinal disease in patients infected with the human immunodeficiency virus. We report the clinical features of two patients with chronic diarrhea and intestinal cyclosporosis caused by Cyclospora cayetanensis. The average value for CD4 count in these patients was lower than or equal to 100 cells/mm3. The oocysts were detected in smears from stool samples stained with modified acid-fast or safranin technique. Light microscopy revealed parasites in the enterocytes and these parasites were associated with villous atrophy. Cyclospora cayetanensis infection might be an important cause of diarrhea in patients with AIDS in Argentina.     

Una nueva generación de triacetato de celulosa adecuado para hemodiafiltración on-line

Background

Online haemodiafiltration (OL-HDF) is currently the most effective dialysis technique that also improves survival. To date, high permeability membranes with low albumin loss, such as polysulfone, polyamide and polyacrylonitrile membranes have been the most widely used. However, the initially restricted use of cellulose triacetate (CTA) membranes in OL-HDF has expanded. The aim of the study was to ascertain whether the latest generation asymmetric CTA membranes are more effective in obtaining high convective transport.