Telephone-Based versus In-Person Delivery of Cognitive Behavioral Treatment for Veterans with Chronic Multisymptom Illness: A Controlled, Randomized Trial

Background:The goal of this randomized clinical trial was to examine the efficacy of a cognitive behavioral stress reduction treatment for reducing disability among veterans with chronic multisymptom illness (CMI).Method: Veterans (N=128) who endorsed symptoms of CMI were randomized to: usual care (n=43), in-person (n=42) or telephone-delivered cognitive behavioral stress management (n=43). Assessments were conducted at baseline, three months, and twelve months. The primary outcome was limitation in roles at work and home (i.e., ‘role physical’). Reductions in catastrophizing cognitions were evaluated as a mechanism of action. Results: Intent-to-treat analyses showed no statistically significant main effect (F(2, 164)=.58, p=.56) or interaction effect (F(4,164)=.94, p=.45) for role physical. Over time, veterans improved in their physical function (F(2,170)=5.34, p2partial=.06), PTSD symptoms (F(2,170)=9.39, p2partial=.10), depressive symptoms (F(2,170)=10.81, p2partial=.11), and physical symptoms (F(2, 172)=12.65, p2partial=.13), but these improvements did not differ across study arms over time. Completer analyses yielded similar results. There were no differences in catastrophizing between arms. Conclusion: Findings suggest stress reduction may not be the right target for improving disability among veterans with CMI. Veterans with CMI may need intervention that directly impacts medical self-management to improve disability

Polyglutamine disease: from pathogenesis to therapy

Polyglutamine diseases are inherited neurodegenerative conditions arising from expanded trinucleotide CAG repeats in the disease-causing gene, which are translated into polyglutamine tracts in the resultant protein. Although these diseases share a common type of mutation, emerging evidence suggests that pathogenesis is complex, involving disruption of key cellular pathways, and varying with the disease context. An understanding of polyglutamine disease mechanisms is critical for development of novel therapeutics. Here we summarise theories of molecular pathogenesis, and examine ways in which this knowledge is being harnessed for therapy, with reference to work under way at the University of Cape Town. Despite a plethora of preclinical data, clinical trials of therapies for polyglutamine diseases have had only limited success. However, recently initiated trials, including those using gene silencing approaches, should provide valuable insights into the safety and efficacy of therapies directly targeting polyglutamine pathogenesis. This is particularly relevant in the South African context, where the frequencies of two polyglutamine diseases, spinocerebellar ataxia types 1 and 7, are among the highest globally

High Healthcare Utilization at the Onset of Medically Unexplained Symptoms

Objective: Patients with medically unexplained syndromes (MUS) often do not receive appropriate healthcare. A critical time for effective healthcare is the inception of MUS. The current study examined data from a prospective longitudinal study of Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) veterans to understand the relationship of increasing physical symptom burden to healthcare utilization. Methods: Data was examined from a prospective study of OEF/OIF veterans assessed before and one year after deployment (n=335). Physical symptom burden was measured with the Patient Health Questionnaire (PHQ-15). Analyses were conducted with polynomial regression and response surface analysis (RSA). Results: Increases in physical symptom burden predicted greater healthcare utilization one year after deployment: primary care practitioner (slope = -0.26, F=4.07, p=0.04), specialist (slope = -.43, t=8.67, p=0.003), allied health therapy (e.g., physical therapy) (slope = -.41, t=5.71, p=0.02) and mental health (slope = -.32, F=4.04, p=0.05). There were no significant difference in utilization between those with consistently high levels and those with increases in physical symptom burden. Conclusion: This is the first prospective study to examine, and show, a relationship between onset of clinically significant physical symptoms and greater healthcare utilization. Our data suggest that patients with increasing physical symptom burden have the same level of healthcare as patients with chronic physical symptom burden. Needed next steps are to better understand the quality of care at inception and determine how to intervene so that recommended approaches to care are provided from the onset

Adding to the HIV Prevention Portfolio – the Achievement of Structural Changes by 13 Connect to Protect® Coalitions

Opportunities to control risk factors that contribute to HIV transmission and acquisition extend far beyond individuals and include addressing social and structural determinants of HIV risk, such as inadequate housing, poor access to healthcare and economic insecurity. The infrastructure within communities, including the policies and practices that guide institutions and organizations, should be considered crucial targets for change. This paper examines the extent to which 13 community coalitions across the U.S. and Puerto Rico were able to achieve “structural change” objectives (i.e., new or modified practices or policies) as an intermediate step toward the long-term goal of reducing HIV risk among adolescents and young adults (12-24 years old). The study resulted in the completion of 245 objectives with 70% categorized as structural in nature. Coalitions targeted social services, education and government as primary community sectors to adopt structural changes. A median of 12 key actors and six new key actors contributed to accomplishing structural changes. Structural change objectives required a median of seven months to complete. The structural changes achieved offer new ideas for community health educators and practitioners seeking to bolster their HIV prevention agenda

A Study on the Efficacy of a Naloxone Training Program

Introduction: The use of naloxone to reverse a potentially fatal opioid overdose is a harm reduction strategy that reduces mortality and increases the potential for referral to substance use treatment for affected individuals. In the setting of outreach performed by a street medicine team, we aimed to determine the effectiveness of an educational intervention involving distribution of naloxone accompanied by a brief instructive session about opioids, opioid overdose, and medication administration. Methods: Our street medicine outreach team distributed 200 naloxone kits to clinicians and volunteers involved in caring for patients on ‘street rounds,’ as well as in shelters, soup kitchens, and street medicine clinic settings. Those receiving a naloxone kit engaged in a peer-reviewed presentation on how to safely use the medication to reverse a potentially fatal opioid overdose. The study team developed and administered a pre- and post-survey of 10 multiple choice questions on material covered in the educational training. The pre- and post-survey scores were compared to assess the effectiveness of implementing this training. Results were stratified by participant gender and age group. Results: Out of the 200 participants, six were excluded from the analysis due to completely missing data from one or both surveys. The mean age of participants was 40.2±12.5 years; 120 (65.6%) were female, 62 (33.9%) were male, and 1 (0.6%) identified as nonbinary. Every survey question had an increase in correct responses from pre-survey to post-survey (identified by an increase in the percentage of correct responses). The mean survey total score increased from 5.5±1.6 to 7.5±1.3. Within the sample of 194, the mean difference in scores from pre-survey to post-survey was 2.02 points (95% CI [1.77, 2.26]), p\u3c0.0001. Males had a mean increase in the total score from 5.6±1.8 to 7.4±1.1. Females had a mean increase in the total score from 5.5±1.5 to 7.5±1.3. The difference in total scores in males was 1.89 points (95% CI [1.42, 2.35]), p\u3c0.0001, and in females was 2.02 points (95% CI [1.71, 2.32]), p\u3c0.0001. Post-test scores improved in all age groups. Conclusion: The educational training on opioids, opioid overdose, and the use of naloxone was an effective adjunct to naloxone kit distribution to volunteers and clinicians caring for people experiencing homelessness

A Novel Bacterium Associated with Lymphadenitis in a Patient with Chronic Granulomatous Disease

Chronic granulomatous disease (CGD) is a rare inherited disease of the phagocyte NADPH oxidase system causing defective production of toxic oxygen metabolites, impaired bacterial and fungal killing, and recurrent life-threatening infections. We identified a novel gram-negative rod in excised lymph nodes from a patient with CGD. Gram-negative rods grew on charcoal-yeast extract, but conventional tests could not identify it. The best 50 matches of the 16S rRNA (using BLAST) were all members of the family Acetobacteraceae, with the closest match being Gluconobacter sacchari. Patient serum showed specific band recognition in whole lysate immunoblot. We used mouse models of CGD to determine whether this organism was a genuine CGD pathogen. Intraperitoneal injection of gp91(phox) (−/−) (X-linked) and p47 (phox −/−) (autosomal recessive) mice with this bacterium led to larger burdens of organism recovered from knockout compared with wild-type mice. Knockout mouse lymph nodes had histopathology that was similar to that seen in our patient. We recovered organisms with 16S rRNA sequence identical to the patient's original isolate from the infected mice. We identified a novel gram-negative rod from a patient with CGD. To confirm its pathogenicity, we demonstrated specific immune reaction by high titer antibody, showed that it was able to cause similar disease when introduced into CGD, but not wild-type mice, and we recovered the same organism from pathologic lesions in these mice. Therefore, we have fulfilled Koch's postulates for a new pathogen. This is the first reported case of invasive human disease caused by any of the Acetobacteraceae. Polyphasic taxonomic analysis shows this organism to be a new genus and species for which we propose the name Granulobacter bethesdensis

miRNA contributions to pediatric-onset multiple sclerosis inferred from GWAS.

ObjectiveOnset of multiple sclerosis (MS) occurs in childhood for approximately 5% of cases (pediatric MS, or ped-MS). Epigenetic influences are strongly implicated in MS pathogenesis in adults, including the contribution from microRNAs (miRNAs), small noncoding RNAs that affect gene expression by binding target gene mRNAs. Few studies have specifically examined miRNAs in ped-MS, but individuals developing MS at an early age may carry a relatively high burden of genetic risk factors, and miRNA dysregulation may therefore play a larger role in the development of ped-MS than in adult-onset MS. This study aimed to look for evidence of miRNA involvement in ped-MS pathogenesis.MethodsGWAS results from 486 ped-MS cases and 1362 controls from the U.S. Pediatric MS Network and Kaiser Permanente Northern California membership were investigated for miRNA-specific signals. First, enrichment of miRNA-target gene network signals was evaluated using MIGWAS software. Second, SNPs in miRNA genes and in target gene binding sites (miR-SNPs) were tested for association with ped-MS, and pathway analysis was performed on associated target genes.ResultsMIGWAS analysis showed that miRNA-target gene signals were enriched in GWAS (P = 0.038) and identified 39 candidate biomarker miRNA-target gene pairs, including immune and neuronal signaling genes. The miR-SNP analysis implicated dysregulation of miRNA binding to target genes in five pathways, mainly involved in immune signaling.InterpretationEvidence from GWAS suggests that miRNAs play a role in ped-MS pathogenesis by affecting immune signaling and other pathways. Candidate biomarker miRNA-target gene pairs should be further studied for diagnostic, prognostic, and/or therapeutic utility