Buprenorphine for the treatment of posttraumatic stress disorder.

BACKGROUND AND OBJECTIVES: The core pharmacological treatment of Post-Traumatic Stress Disorder (PTSD) is selective serotonin reuptake inhibitors (SSRIs), although remission is only around 30% with them. Many patients will self-treat with opioids and due to the opiate system involvement in dysphoric mood and anxiety/stress responses, it is likely that antagonism of the kappa opioid receptor (KOR) system represents a potential target for treatment of PTSD. The aim of this study is to compare response of PTSD symptoms when antagonizing KOR via buprenorphine/naloxone compared to SSRIs or opioid therapy. METHODS: A retrospective chart review of patients in the MEDVAMC between June 1, 2010 and June 30, 2016 was conducted. Inclusion criteria included patients with a documented diagnosis of PTSD with at least two documented PTSD scores (either PCLC or PC-PTSD). Exclusion criteria included patients not prescribed one of the study medications (ie, buprenorphine, SSRI, or opiate for chronic pain), and patients not on the study medication for at least 30 days. RESULTS: Buprenorphine patients exhibited the lowest final average PTSD score (2.47) and the largest change from baseline (-24.0%) compared to opioids (-16.1%) or SSRIs (1.16%). The average buprenorphine dose was 23.3 mg/day, and the average length of therapy was 860 days. CONCLUSIONS: Buprenorphine may help decrease PTSD symptoms more than SSRIs or opioids alone. Prospective studies are needed to determine whether these effects are reproducible. SCIENTIFIC SIGNIFICANCE: Pharmacotherapy advancements in PTSD treatment have been limited and the kappa opioid receptor system presents a new target that warrants further research. (Am J Addict 2019;XX:1-6).

Smoking-Related Stigma Expressed by Physiotherapists toward Individuals with Lung Disease.

Purpose: We determined the extent and nature of stigma exhibited by a sample of Canadian cardiorespiratory physiotherapists toward people with lung disease who had a smoking history. Method: A quantitative online survey was distributed to Canadian cardiorespiratory physiotherapists, and an anti-smoking attitudes questionnaire was used to measure explicit stigma. We used two case studies with questions to measure implicit stigma. The first involved a patient with chronic obstructive pulmonary disease (COPD) and a smoking history, and the second described a patient with COPD with no smoking history. Results: Of the respondents (n=50), 56% demonstrated mild explicit stigma and 44% demonstrated moderate to severe explicit stigma. The extent of explicit stigma was not associated with respondents' age, area of practice, personal smoking history, or family history of lung disease resulting from smoking. The results indicated no evidence of implicit stigma, and no significant differences were found between the participants' prospective treatments and their professional attitudes toward patient cases. Conclusions: Canadian cardiorespiratory physiotherapists demonstrated explicit stigma toward people with lung disease with a significant smoking history, but there was no evidence of implicit stigma. These findings suggest that further research is needed to investigate how stigma held by cardiorespiratory physiotherapists may affect the quality of care provided for patients with a smoking history.

Objectif : déterminer l'étendue et la nature de la réprobation dont fait preuve un échantillon de physiothérapeutes cardiorespiratoires canadiens envers les fumeurs atteints d'une maladie pulmonaire. Méthodologie : les physiothérapeutes cardiorespiratoires canadiens ont reçu un sondage quantitatif en ligne. Ils ont répondu à un questionnaire sur les attitudes négatives envers le tabagisme pour mesurer leur réprobation explicite. Deux études de cas accompagnées de questions mesuraient leur réprobation implicite. La première portait sur un patient fumeur atteint d'une maladie pulmonaire obstructive chronique (MPOC) et la deuxième, sur un patient non-fumeur atteint d'une MPOC. Résultats : au total, 56 % des 50 répondants ont démontré une légère réprobation explicite et 44 %, une réprobation explicite modérée à importante. L'étendue de leur réprobation explicite n'était pas associée à leur âge, à leur région de pratique, à leur propre tabagisme, ni à une histoire familiale de maladie pulmonaire causée par le tabagisme. Les résultats ne faisaient état d'aucune réprobation implicite, et il n'y avait pas de différence significative entre les traitements prospectifs des répondants et leur attitude professionnelle envers les cas des patients. Conclusions : les physiothérapeutes cardiorespiratoires canadiens faisaient preuve d'une réprobation explicite envers les fumeurs atteints d'une maladie pulmonaire, sans toutefois démontrer de réprobation implicite. Selon ces résultats, d'autres recherches s'imposent pour évaluer si la réprobation des physiothérapeutes cardiorespiratoires nuit à la qualité des soins aux patients fumeurs.

Transcatheter Versus Surgical Aortic Valve Replacement: Propensity-Matched Comparison.

BACKGROUND: Randomized trials support the use of transcatheter aortic valve replacement (TAVR) for the treatment of aortic stenosis in high- and intermediate-risk patients, but the generalizability of those results in clinical practice has been challenged. OBJECTIVES: The aim of this study was to determine the safety and effectiveness of TAVR versus surgical aortic valve replacement (SAVR), particularly in intermediate- and high-risk patients, in a nationally representative real-world cohort. METHODS: Using data from the Transcatheter Valve Therapy Registry and Society of Thoracic Surgeons National Database linked to Medicare administrative claims for follow-up, 9,464 propensity-matched intermediate- and high-risk (Society of Thoracic Surgeons Predicted Risk of Mortality score ≥3%) U.S. patients who underwent commercial TAVR or SAVR were examined. Death, stroke, and days alive and out of the hospital to 1 year were compared, as well as discharge home, with subgroup analyses by surgical risk, demographics, and comorbidities. RESULTS: In a propensity-matched cohort (median age 82 years, 48% women, median Society of Thoracic Surgeons Predicted Risk of Mortality score 5.6%), TAVR and SAVR patients experienced no difference in 1-year rates of death (17.3% vs. 17.9%; hazard ratio: 0.93; 95% confidence interval [CI]: 0.83 to 1.04) and stroke (4.2% vs. 3.3%; hazard ratio: 1.18; 95% CI: 0.95 to 1.47), and no difference was observed in the proportion of days alive and out of the hospital to 1 year (rate ratio: 1.00; 95% CI: 0.98 to 1.02). However, TAVR patients were more likely to be discharged home after treatment (69.9% vs. 41.2%; odds ratio: 3.19; 95% CI: 2.84 to 3.58). Results were consistent across most subgroups, including among intermediate- and high-risk patients. CONCLUSIONS: Among unselected intermediate- and high-risk patients, TAVR and SAVR resulted in similar rates of death, stroke, and DAOH to 1 year, but TAVR patients were more likely to be discharged home.

Biochemical and Hematologic Reference Intervals for Aged Xenopus laevis in a Research Colony.

Xenopus laevis, the African clawed frog, is commonly used in developmental and toxicology research studies. Little information is available on aged X. laevis; however, with the complete mapping of the genome and the availability of transgenic animal models, the number of aged animals in research colonies is increasing. The goals of this study were to obtain biochemical and hematologic parameters to establish reference intervals for aged X. laevis and to compare results with those from young adult X. laevis. Blood samples were collected from laboratory reared, female frogs (n = 52) between the ages of 10 and 14 y. Reference intervals were generated for 30 biochemistry analytes and full hematologic analysis; these data were compared with prior results for young X. laevis from the same vendor. Parameters that were significantly higher in aged compared with young frogs included calcium, calcium:phosphorus ratio, total protein, albumin, HDL, amylase, potassium, CO2, and uric acid. Parameters found to be significantly lower in aged frogs included glucose, AST, ALT, cholesterol, BUN, BUN:creatinine ratio, phosphorus, triglycerides, LDL, lipase, sodium, chloride, sodium:potassium ratio, and anion gap. Hematology data did not differ between young and old frogs. These findings indicate that chemistry reference intervals for young X. laevis may be inappropriate for use with aged frogs.

Glucagon-Like Peptide 2 (GLP-2) Stimulates Postprandial Chylomicron Production and Postabsorptive Release of Intestinal Triglyceride Storage Pools via Induction of Nitric Oxide Signaling in Male Hamsters and Mice.

The intestinal overproduction of apolipoprotein B48 (apoB48)-containing chylomicron particles is a common feature of diabetic dyslipidemia and contributes to cardiovascular risk in insulin resistant states. We previously reported that glucagon-like peptide-2 (GLP-2) is a key endocrine stimulator of enterocyte fat absorption and chylomicron output in the postprandial state. GLP-2's stimulatory effect on chylomicron production in the postabsorptive state has been confirmed in human studies. The mechanism by which GLP-2 regulates chylomicron production is unclear, because its receptor is not expressed on enterocytes. We provide evidence for a key role of nitric oxide (NO) in mediating the stimulatory effects of GLP-2 during the postprandial and postabsorptive periods. Intestinal chylomicron production was assessed in GLP-2-treated hamsters administered the pan-specific NO synthase (NOS) inhibitor L-N(G)-nitroarginine methyl ester (L-NAME), and in GLP-2-treated endothelial NOS knockout mice. L-NAME blocked GLP-2-stimulated apoB48 secretion and reduced triglycerides (TGs) in the TG-rich lipoprotein (TRL) fraction of the plasma in the postprandial state. Endothelial NOS-deficient mice were resistant to GLP-2 stimulation and secreted fewer large apoB48-particles. When TG storage pools were allowed to accumulate, L-NAME mitigated the GLP-2-mediated increase in TRL-TG, suggesting that NO is required for early mobilization and secretion of stored TG and preformed chylomicrons. Importantly, the NO donor S-nitroso-L-glutathione was able to elicit an increase in TRL-TG in vivo and stimulate chylomicron release in vitro in primary enterocytes. We describe a novel role for GLP-2-mediated NO-signaling as a critical regulator of intestinal lipid handling and a potential contributor to postprandial dyslipidemia.

Apolipoprotein B100 quality control and the regulation of hepatic very low density lipoprotein secretion.

Apolipoprotein B (apoB) is the main protein component of very low density lipoprotein (VLDL) and is necessary for the assembly and secretion of these triglyceride (TG)-rich particles. Following release from the liver, VLDL is converted to low density lipoprotein (LDL) in the plasma and increased production of VLDL can therefore play a detrimental role in cardiovascular disease. Increasing evidence has helped to establish VLDL assembly as a target for the treatment of dyslipidemias. Multiple factors are involved in the folding of the apoB protein and the formation of a secretion-competent VLDL particle. Failed VLDL assembly can initiate quality control mechanisms in the hepatocyte that target apoB for degradation. ApoB is a substrate for endoplasmic reticulum associated degradation (ERAD) by the ubiquitin proteasome system and for autophagy. Efficient targeting and disposal of apoB is a regulated process that modulates VLDL secretion and partitioning of TG. Emerging evidence suggests that significant overlap exists between these degradative pathways. For example, the insulin-mediated targeting of apoB to autophagy and postprandial activation of the unfolded protein response (UPR) may employ the same cellular machinery and regulatory cues. Changes in the quality control mechanisms for apoB impact hepatic physiology and pathology states, including insulin resistance and fatty liver. Insulin signaling, lipid metabolism and the hepatic UPR may impact VLDL production, particularly during the postprandial state. In this review we summarize our current understanding of VLDL assembly, apoB degradation, quality control mechanisms and the role of these processes in liver physiology and in pathologic states.