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A group-randomized trial of shared decision making for non-steroidal anti-inflammatory drug risk awareness: primary results and lessons learned

eScholarship@UMMS - Mon, 08/24/2015 - 3:24pm

RATIONALE, AIMS AND OBJECTIVES: Frequent use and serious adverse effects related to non-steroidal anti-inflammatory drugs (NSAIDs) underscore the need to raise patient awareness about potential risks. Partial success of patient- or provider-based interventions has recently led to interest in combined approaches focusing on both patient and physician. This research tested a shared decision-making intervention for increasing patient-reported awareness of NSAID risk.

METHODS: A group randomized trial was performed in Alabama from 2005 to 2007. Intervention group doctor practices received continuing medical education (CME) about NSAIDs and patient activation tools promoting risk assessment and communication during visits. Comparison group doctor practices received only CME. Cross-sectional data were collected before and after the intervention. Generalized linear latent and mixed models with logistic link tested relationships among the intervention, study phase, intervention by study phase interaction and patient-reported awareness of risks with either prescription or over-the-counter (OTC) NSAIDs.

RESULTS: Three hundred and forty-seven patients at baseline and 355 patients at follow-up participated in this study. The intervention [adjusted odds ratio (AOR)=0.74, P=0.248], follow-up study phase (AOR=1.31, P=0.300) and intervention by study phase interaction (AOR=0.98, P=0.942) were not significantly associated with patient-reported awareness of any prescription NSAID risk. Follow-up study phase was associated with increased odds of reporting any OTC NSAID risk awareness (AOR=2.99, P < 0.001), but the patient activation intervention and intervention by study phase interaction were not significantly associated with patient-reported awareness of any OTC NSAID risk (AOR=0.98, P=0.929; AOR=0.87, P=0.693, respectively).

CONCLUSIONS: Our point-of-care intervention encouraging shared decision making did not increase NSAID risk awareness.

Differential expression of APE1 and APE2 in germinal centers promotes error-prone repair and A:T mutations during somatic hypermutation

eScholarship@UMMS - Mon, 08/24/2015 - 3:24pm

Somatic hypermutation (SHM) of antibody variable region genes is initiated in germinal center B cells during an immune response by activation-induced cytidine deaminase (AID), which converts cytosines to uracils. During accurate repair in nonmutating cells, uracil is excised by uracil DNA glycosylase (UNG), leaving abasic sites that are incised by AP endonuclease (APE) to create single-strand breaks, and the correct nucleotide is reinserted by DNA polymerase beta. During SHM, for unknown reasons, repair is error prone. There are two APE homologs in mammals and, surprisingly, APE1, in contrast to its high expression in both resting and in vitro-activated splenic B cells, is expressed at very low levels in mouse germinal center B cells where SHM occurs, and APE1 haploinsufficiency has very little effect on SHM. In contrast, the less efficient homolog, APE2, is highly expressed and contributes not only to the frequency of mutations, but also to the generation of mutations at A:T base pair (bp), insertions, and deletions. In the absence of both UNG and APE2, mutations at A:T bp are dramatically reduced. Single-strand breaks generated by APE2 could provide entry points for exonuclease recruited by the mismatch repair proteins Msh2-Msh6, and the known association of APE2 with proliferating cell nuclear antigen could recruit translesion polymerases to create mutations at AID-induced lesions and also at A:T bp. Our data provide new insight into error-prone repair of AID-induced lesions, which we propose is facilitated by down-regulation of APE1 and up-regulation of APE2 expression in germinal center B cells.

Tweeting it off: characteristics of adults who tweet about a weight loss attempt

eScholarship@UMMS - Mon, 08/24/2015 - 3:24pm

OBJECTIVE: The purpose of this study was to describe adults who use Twitter during a weight loss attempt and to compare the positive and negative social influences they experience from their offline friends, online friends, and family members.

MATERIALS AND METHODS: Participants (N=100, 80% female, mean age=37.65, SD=8.42) were recruited from Twitter. They completed a brief survey about their experiences discussing their weight loss attempt with their online and offline friends and provided responses to open-ended questions on the benefits and drawbacks of discussing weight on Twitter, Facebook, and weight-specific social networks.

RESULTS: Participants rated their connections on Twitter and weight loss-specific social networks to be significantly greater sources of positive social influence for their weight loss (F(3)=3.47; p < 0.001) and significantly lesser sources of negative social influence (F(3)=40.39 and F(3)=33.68 (both p < 0.001)) than their offline friends, family, and Facebook friends. Greater positive social influence from Twitter and Facebook friends was associated with greater weight loss in participants' most recent weight loss attempt (r=0.30, r=0.32; p < 0.01). The most commonly reported benefits of tweeting about weight loss include social support, information, and accountability. The most common drawbacks reported are that interactions were too brief and lacked personal connection.

DISCUSSION: People who discuss their weight loss on Twitter report more social support and less negativity from their Twitter friends than their Facebook friends and in-person relationships.

CONCLUSIONS: Online social networks should be explored as a tool for connecting patients who lack weight loss social support from their in-person relationships.

Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Lifestyle Medicine: Finding a Way to Prevent Diabetes

Headlines from MedPage Today® - Mon, 08/24/2015 - 3:07pm
(MedPage Today) -- Community programs work, so how can you utilize them?

Breast Cancer: Intervention Helpful for Weight Loss (CME/CE)

Headlines from MedPage Today® - Mon, 08/24/2015 - 2:42pm
(MedPage Today) -- Benefit diminished with time, but not eliminated

Combination Is Best for Maintenance Tx of Lupus Podocytopathy (CME/CE)

Headlines from MedPage Today® - Mon, 08/24/2015 - 2:31pm
(MedPage Today) -- Adding immunosuppressants to steroids made a big difference, study finds

RA: Lung Disease Risk Tracks Biomarkers (CME/CE)

Headlines from MedPage Today® - Mon, 08/24/2015 - 1:28pm
(MedPage Today) -- Standard RA biomarkers appear to raise risk of interstitial lung disease

Parental Feeding Habits Tied to Child's Weight Status (CME/CE)

Headlines from MedPage Today® - Mon, 08/24/2015 - 1:02pm
(MedPage Today) -- Obese adolescents tend to have food restrictions while healthy weight kids face pressure to eat

CardioBreak: Fitness Fights Afib, PICC Line Leg Clots

Headlines from MedPage Today® - Mon, 08/24/2015 - 12:36pm
(MedPage Today) -- Recent developments of interest in cardiovascular medicine

Developing El Niño could be strongest on record

news@nature - Mon, 08/24/2015 - 12:21pm

Event could bring rain to drought-stricken California and dry conditions to Australia.

Nature News doi: 10.1038/nature.2015.18184

Medicine in India: Rough Road to Physician Accountability

Headlines from MedPage Today® - Mon, 08/24/2015 - 11:59am
(MedPage Today) -- Second in a series

Wilderness Lab: An Exploration of Heat Loss After Avalanche Burial

Headlines from MedPage Today® - Mon, 08/24/2015 - 11:20am
(MedPage Today) -- Part 1 in a series on the world of wilderness medicine

Make the Diagnosis: Scuba Foot

Headlines from MedPage Today® - Mon, 08/24/2015 - 11:00am
(MedPage Today) -- Case Findings: A male scuba diver experiences memory loss and becomes unresponsive after surfacing from a dive. Red marks appear on his neck shortly after surfacing. He did not ascend rapidly. What is your diagnosis?

Consider Advance Care Planning Needs for LGBT Patients

Headlines from MedPage Today® - Mon, 08/24/2015 - 10:56am
(MedPage Today) -- What tools do we need to promote equality at the end of life?

An integrated approach in a case of facioscapulohumeral dystrophy

eScholarship@UMMS - Mon, 08/24/2015 - 10:45am

BACKGROUND: Muscle fatigue, weakness and atrophy are basilar clinical features that accompany facioscapulohumeral dystrophy (FSHD) the third most common muscular dystrophy.No therapy is available for FSHD.

CASE PRESENTATION: We describe the effects of 6mo exercise therapy and nutritional supplementation in a 43-year-old woman severely affected by FSHD.

CONCLUSION: A mixed exercise program combined with nutritional supplementation can be safely used with beneficial effects in selected patients with FSHD.

PLAAC: a web and command-line application to identify proteins with prion-like amino acid composition

eScholarship@UMMS - Mon, 08/24/2015 - 10:45am

Prions are self-templating protein aggregates that stably perpetuate distinct biological states and are of keen interest to researchers in both evolutionary and biomedical science. The best understood prions are from yeast and have a prion-forming domain with strongly biased amino acid composition, most notably enriched for Q or N. PLAAC is a web application that scans protein sequences for domains with P: rion- L: ike A: mino A: cid C: omposition. Users can upload sequence files, or paste sequences directly into a textbox. PLAAC ranks the input sequences by several summary scores and allows scores along sequences to be visualized. Text output files can be downloaded for further analyses, and visualizations saved in PDF and PNG formats.

AVAILABILITY AND IMPLEMENTATION: http://plaac.wi.mit.edu/. The Ruby-based web framework and the command-line software (implemented in Java, with visualization routines in R) are available at http://github.com/whitehead/plaac under the MIT license. All software can be run under OS X, Windows and Unix.

Gene therapy for the nervous system: challenges and new strategies

eScholarship@UMMS - Mon, 08/24/2015 - 10:45am

Current clinical treatments for central nervous system (CNS) diseases, such as Parkinson's disease and glioblastoma do not halt disease progression and have significant treatment morbidities. Gene therapy has the potential to "permanently" correct disease by bringing in a normal gene to correct a mutant gene deficiency, knocking down mRNA of mutant alleles, and inducing cell-death in cancer cells using transgenes encoding apoptosis-inducing proteins. Promising results in clinical trials of eye disease (Leber's congenital aumorosis) and Parkinson's disease have shown that gene-based neurotherapeutics have great potential. The recent development of genome editing technology, such as zinc finger nucleases, TALENS, and CRISPR, has made the ultimate goal of gene correction a step closer. This review summarizes the challenges faced by gene-based neurotherapeutics and the current and recent strategies designed to overcome these barriers. We have chosen the following challenges to focus on in this review: (1) delivery vehicles (both virus and nonviral), (2) use of promoters for vector-mediated gene expression in CNS, and (3) delivery across the blood-brain barrier. The final section (4) focuses on promising pre-clinical/clinical studies of neurotherapeutics.

Biomarkers for disease progression and AAV therapeutic efficacy in feline Sandhoff disease

eScholarship@UMMS - Mon, 08/24/2015 - 10:45am

The GM2 gangliosidoses, Tay-Sachs disease (TSD) and Sandhoff disease (SD), are progressive neurodegenerative disorders that are caused by a mutation in the enzyme beta-N-acetylhexosaminidase (Hex). Due to the recent emergence of novel experimental treatments, biomarker development has become particularly relevant in GM2 gangliosidosis as an objective means to measure therapeutic efficacy. Here we describe blood, cerebrospinal fluid (CSF), magnetic resonance imaging (MRI), and electrodiagnostic methods for evaluating disease progression in the feline SD model and application of these approaches to assess AAV-mediated gene therapy. SD cats were treated by intracranial injections of the thalami combined with either the deep cerebellar nuclei or a single lateral ventricle using AAVrh8 vectors encoding feline Hex. Significantly altered in untreated SD cats, blood and CSF based biomarkers were largely normalized after AAV gene therapy. Also reduced after treatment were expansion of the lysosomal compartment in peripheral blood mononuclear cells and elevated activity of secondary lysosomal enzymes. MRI changes characteristic of the gangliosidoses were documented in SD cats and normalized after AAV gene therapy. The minimally invasive biomarkers reported herein should be useful to assess disease progression of untreated SD patients and those in future clinical trials.

Novel mutations support a role for Profilin 1 in the pathogenesis of ALS

eScholarship@UMMS - Mon, 08/24/2015 - 10:45am

Mutations in the gene encoding profilin 1 (PFN1) have recently been shown to cause amyotrophic lateral sclerosis (ALS), a fatal neurodegenerative disorder. We sequenced the PFN1 gene in a cohort of ALS patients (n = 485) and detected 2 novel variants (A20T and Q139L), as well as 4 cases with the previously identified E117G rare variant ( approximately 1.2%). A case-control meta-analysis of all published E117G ALS+/- frontotemporal dementia cases including those identified in this report was significant p = 0.001, odds ratio = 3.26 (95% confidence interval, 1.6-6.7), demonstrating this variant to be a susceptibility allele. Postmortem tissue from available patients displayed classic TAR DNA-binding protein 43 pathology. In both transient transfections and in fibroblasts from a patient with the A20T change, we showed that this novel PFN1 mutation causes protein aggregation and the formation of insoluble high molecular weight species which is a hallmark of ALS pathology. Our findings show that PFN1 is a rare cause of ALS and adds further weight to the underlying genetic heterogeneity of this disease.

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