International Committee on Mental Health in Cystic Fibrosis: Cystic Fibrosis Foundation and European Cystic Fibrosis Society consensus statements for screening and treating depression and anxiety

Studies measuring psychological distress in individuals with cystic fibrosis (CF) have found high rates of both depression and anxiety. Psychological symptoms in both individuals with CF and parent caregivers have been associated with decreased lung function, lower body mass index, worse adherence, worse health-related quality of life, more frequent hospitalisations and increased healthcare costs. To identify and treat depression and anxiety in CF, the CF Foundation and the European CF Society invited a panel of experts, including physicians, psychologists, psychiatrists, nurses, social workers, a pharmacist, parents and an individual with CF, to develop consensus recommendations for clinical care. Over 18 months, this 22-member committee was divided into four workgroups: Screening; Psychological Interventions; Pharmacological Treatments and Implementation and Future Research, and used the Population, Intervention, Comparison, Outcome methodology to develop questions for literature search and review. Searches were conducted in PubMed, PsychINFO, ScienceDirect, Google Scholar, Psychiatry online and ABDATA by a methodologist at Dartmouth. The committee reviewed 344 articles, drafted statements and set an 80% acceptance for each recommendation statement as a consensus threshold prior to an anonymous voting process. Fifteen guideline recommendation statements for screening and treatment of depression and anxiety in individuals with CF and parent caregivers were finalised by vote. As these recommendations are implemented in CF centres internationally, the process of dissemination, implementation and resource provision should be closely monitored to assess barriers and concerns, validity and use

An exploration of neighbourhood team members experiences of the transition from traditional health and social care teams to integrated care systems, within a defined health and social care economy

The UK is undergoing changes in the demographics and epidemiology of the population. To tackle this, successive UK governments have introduced policies focused on transforming health and social care from its traditional forms into integrated care systems. Previous research has demonstrated that people are essential in the transformation process which is often complex and requires structural, practical, and cultural change. Despite this focus, there has been a lack of frontline research on the real-time experiences of practitioners tasked with making integration real from the outset.This study attempts to address this gap. It presents a faithful representation of the experiences of two teams, one from health, one from social work, as they moved through the initial stages of integration. The study uses an adapted institutional ethnographic approach (Smith, 2005), which involved observing two teams as they came together to form an integrated neighbourhood team over a nine-month period. The use of this approach ensured that the reporting of the team’s experience was from their perspectives and considered the wider external factors that influenced those experiences.The analysis of the findings identifies several key factors in how teams experience integration that could influence future policy. These areas included: the imperative of a local narrative for integration; the place of hope and hopefulness in uniting teams; the importance of ‘Bottom-up’ action; the imperative of joint leadership. The process of integration was not a linear one but one where teams move through a process of converging and separating from each other. Based on the findings a framework has been developed to assist organisations in the development of integrated teams

Validity and reliability of the multidimensional health locus of control scale for college students

<p>Abstract</p> <p>Background</p> <p>The purpose of the present study was to assess the validity and reliability of Form A of Multidimensional Health Locus of Control scales in Iran. Health locus of control is one of the most widely measured parameters of health belief for the planning of health education programs.</p> <p>Methods</p> <p>496 university students participated in this study. The reliability coefficients were calculated in three different methods: test-retest, parallel forms and Cronbach alpha. In order to survey validity of the scale we used three methods including content validity, concurrent validity and construct validity.</p> <p>Results</p> <p>We established the content validity of the Persian translation by translating (and then back-translating) each item from the English version into the Persian version. The concurrent validity of the questionnaire, as measured by Levenson's IPC scale was .57 (P < .001), .49 (P < .01) and .53 (P < .001) for IPC, respectively. Exploratory principal components analysis supported a three-factor structure that items loading adequately on each factor. Moreover, the approximate orthogonal of the dimensions were obtained through correlation analyses. In addition, the reliability results were acceptable, too.</p> <p>Conclusion</p> <p>The results showed that the reliability and validity of Persian Form A of MHLC was acceptable and respectable and is suggested as an applicable criterion for similar studies in Iran.</p

Plasticity of the human visual system after retinal gene therapy in patients with Leber's congenital amaurosis.

Much of our knowledge of the mechanisms underlying plasticity in the visual cortex in response to visual impairment, vision restoration, and environmental interactions comes from animal studies. We evaluated human brain plasticity in a group of patients with Leber's congenital amaurosis (LCA), who regained vision through gene therapy. Using non-invasive multimodal neuroimaging methods, we demonstrated that reversing blindness with gene therapy promoted long-term structural plasticity in the visual pathways emanating from the treated retina of LCA patients. The data revealed improvements and normalization along the visual fibers corresponding to the site of retinal injection of the gene therapy vector carrying the therapeutic gene in the treated eye compared to the visual pathway for the untreated eye of LCA patients. After gene therapy, the primary visual pathways (for example, geniculostriate fibers) in the treated retina were similar to those of sighted control subjects, whereas the primary visual pathways of the untreated retina continued to deteriorate. Our results suggest that visual experience, enhanced by gene therapy, may be responsible for the reorganization and maturation of synaptic connectivity in the visual pathways of the treated eye in LCA patients. The interactions between the eye and the brain enabled improved and sustained long-term visual function in patients with LCA after gene therapy

Mutation-Independent Allele-Specific Editing by CRISPR-Cas9, a Novel Approach to Treat Autosomal Dominant Disease

CRISPR-Cas9 provides a tool to treat autosomal dominant disease by non-homologous end joining (NHEJ) gene disruption of the mutant allele. In order to discriminate between wild-type and mutant alleles, Streptococcus pyogenes Cas9 (SpCas9) must be able to detect a single nucleotide change. Allele-specific editing can be achieved by using either a guide-specific approach, in which the missense mutation is found within the guide sequence, or a protospacer-adjacent motif (PAM)-specific approach, in which the missense mutation generates a novel PAM. While both approaches have been shown to offer allele specificity in certain contexts, in cases where numerous missense mutations are associated with a particular disease, such as TGFBI (transforming growth factor β-induced) corneal dystrophies, it is neither possible nor realistic to target each mutation individually. In this study, we demonstrate allele-specific CRISPR gene editing independent of the disease-causing mutation that is capable of achieving complete allele discrimination, and we propose it as a targeting approach for autosomal dominant disease. Our approach utilizes natural variants in the target region that contain a PAM on one allele that lies in cis with the causative mutation, removing the constraints of a mutation-dependent approach. Our innovative patient-specific guide design approach takes into account the patient’s individual genetic make-up, allowing on- and off-target activity to be assessed in a personalized manner

The Classic: A Morphogenetic Matrix for Differentiation of Bone Tissue

This Classic Article is a reprint of the original work by Marshall R. Urist, A Morphogenetic Matrix for Differentiation of Bone Tissue. An accompanying biographical sketch of Marshall R. Urist, MD is available at DOI 10.1007/s11999-009-1067-4; a second Classic Article is available at DOI 10.1007/s11999-009-1068-3; and a third Classic Article is available at DOI 10.1007/s11999-009-1069-2. The Classic Article is © 1970 by Springer and is reprinted with permission from Urist MR. A morphogenetic matrix for differentiation of bone tissue. Calc Tiss Res. 1970:4(Suppl);98–101

Etiology of Childhood Bacteremia and Timely Antibiotics Administration in the Emergency Department

BACKGROUND: Bacteremia is now an uncommon presentation to the children’s emergency department (ED) but is associated with significant morbidity and mortality. Its evolving etiology may affect the ability of clinicians to initiate timely, appropriate antimicrobial therapy. METHODS: A retrospective time series analysis of bacteremia was conducted in the Alder Hey Children’s Hospital ED between 2001 and 2011. Data on significant comorbidities, time to empirical therapy, and antibiotic susceptibility were recorded. RESULTS: A total of 575 clinical episodes were identified, and Streptococcus pneumoniae (n = 109), Neisseria meningitidis (n = 96), and Staphylococcus aureus (n = 89) were commonly isolated. The rate of bacteremia was 1.42 per 1000 ED attendances (95% confidence interval: 1.31–1.53). There was an annual reduction of 10.6% (6.6%–14.5%) in vaccine-preventable infections, and an annual increase of 6.7% (1.2%–12.5%) in Gram-negative infections. The pneumococcal conjugate vaccine was associated with a 49% (32%–74%) reduction in pneumococcal bacteremia. The rate of health care–associated bacteremia increased from 0.17 to 0.43 per 1000 ED attendances (P = .002). Susceptibility to empirical antibiotics was reduced (96.3%–82.6%; P < .001). Health care–associated bacteremia was associated with an increased length of stay of 3.9 days (95% confidence interval: 2.3–5.8). Median time to antibiotics was 184 minutes (interquartile range: 63–331) and 57 (interquartile range: 27–97) minutes longer in Gram-negative bacteremia than in vaccine-preventable bacteremia. CONCLUSIONS: Changes in the etiology of pediatric bacteremia have implications for prompt, appropriate empirical treatment. Increasingly, pediatric bacteremia in the ED is health care associated, which increases length of inpatient stay. Prompt, effective antimicrobial administration requires new tools to improve recognition, in addition to continued etiological surveillance