Bapineuzumab for mild to moderate Alzheimer’s disease in two global, randomized, phase 3 trials

Background Our objective was to evaluate the efficacy (clinical and biomarker) and safety of intravenous bapineuzumab in patients with mild to moderate Alzheimer’s disease (AD). Methods Two of four phase 3, multicenter, randomized, double-blind, placebo-controlled, 18-month trials were conducted globally: one in apolipoprotein E ε4 carriers and another in noncarriers. Patients received bapineuzumab 0.5 mg/kg (both trials) or 1.0 mg/kg (noncarrier trial) or placebo every 13 weeks. Coprimary endpoints were change from baseline to week 78 on the 11-item Alzheimer’s Disease Assessment Scale–Cognitive subscale and the Disability Assessment for Dementia. Results A total of 683 and 329 patients completed the current carrier and noncarrier trials, respectively, which were terminated prematurely owing to lack of efficacy in the two other phase 3 trials of bapineuzumab in AD. The current trials showed no significant difference between bapineuzumab and placebo for the coprimary endpoints and no effect of bapineuzumab on amyloid load or cerebrospinal fluid phosphorylated tau. (Both measures were stable over time in the placebo group.) Amyloid-related imaging abnormalities with edema or effusion were confirmed as the most notable adverse event. Conclusions These phase 3 global trials confirmed lack of efficacy of bapineuzumab at tested doses on clinical endpoints in patients with mild to moderate AD. Some differences in the biomarker results were seen compared with the other phase 3 bapineuzumab trials. No unexpected adverse events were observed. Trial registration Noncarriers (3000) ClinicalTrials.gov identifier NCT00667810; registered 24 Apr 2008. Carriers (3001) ClinicalTrials.gov identifier NCT00676143; registered 2 May 2008

Parents' perception of self-advocacy of children with myositis: an anonymous online survey

<p>Abstract</p> <p>Background</p> <p>Children with complex medical issues experience barriers to the transition of care from pediatric to adult providers. We sought to identify these barriers by elucidating the experiences of patients with idiopathic inflammatory muscle disorders.</p> <p>Methods</p> <p>We collected anonymous survey data using an online website. Patients and their families were solicited from the US and Canada through established clinics for children with idiopathic inflammatory muscle diseases as well as with the aid of a nonprofit organization for the benefit of such individuals. The parents of 45 older children/young adults suffering from idiopathic inflammatory muscle diseases were surveyed. As a basis of comparison, we similarly collected data from the parents of 207 younger children with inflammatory muscle diseases. The survey assessed transition of care issues confronting families of children and young adults with chronic juvenile myositis.</p> <p>Results</p> <p>Regardless of age of the patient, respondents were unlikely to have a designated health care provider assigned to aid in transition of care and were unlikely to be aware of a posted policy concerning transition of care at their pediatrician's office. Additionally, regardless of age, patients and their families were unlikely to have a written plan for moving to adult care.</p> <p>Conclusions</p> <p>We identified deficiencies in the health care experiences of families as pertain to knowledge, self-advocacy, policy, and vocational readiness. Moreover, as children with complex medical issues grow up, parents attribute less self-advocacy to their children's level of independence.</p

An integrated approach to the interpretation of Single Amino Acid Polymorphisms within the framework of CATH and Gene3D

Background The phenotypic effects of sequence variations in protein-coding regions come about primarily via their effects on the resulting structures, for example by disrupting active sites or affecting structural stability. In order better to understand the mechanisms behind known mutant phenotypes, and predict the effects of novel variations, biologists need tools to gauge the impacts of DNA mutations in terms of their structural manifestation. Although many mutations occur within domains whose structure has been solved, many more occur within genes whose protein products have not been structurally characterized.&lt;p&gt;&lt;/p&gt; Results Here we present 3DSim (3D Structural Implication of Mutations), a database and web application facilitating the localization and visualization of single amino acid polymorphisms (SAAPs) mapped to protein structures even where the structure of the protein of interest is unknown. The server displays information on 6514 point mutations, 4865 of them known to be associated with disease. These polymorphisms are drawn from SAAPdb, which aggregates data from various sources including dbSNP and several pathogenic mutation databases. While the SAAPdb interface displays mutations on known structures, 3DSim projects mutations onto known sequence domains in Gene3D. This resource contains sequences annotated with domains predicted to belong to structural families in the CATH database. Mappings between domain sequences in Gene3D and known structures in CATH are obtained using a MUSCLE alignment. 1210 three-dimensional structures corresponding to CATH structural domains are currently included in 3DSim; these domains are distributed across 396 CATH superfamilies, and provide a comprehensive overview of the distribution of mutations in structural space.&lt;p&gt;&lt;/p&gt; Conclusion The server is publicly available at http://3DSim.bioinfo.cnio.es/ webcite. In addition, the database containing the mapping between SAAPdb, Gene3D and CATH is available on request and most of the functionality is available through programmatic web service access.&lt;p&gt;&lt;/p&gt

UK guideline on transition of adolescent and young persons with chronic digestive diseases from paediatric to adult care

The risks of poor transition include delayed and inappropriate transfer that can result in disengagement with healthcare. Structured transition care can improve control of chronic digestive diseases and long-term health-related outcomes. These are the first nationally developed guidelines on the transition of adolescent and young persons (AYP) with chronic digestive diseases from paediatric to adult care. They were commissioned by the Clinical Services and Standards Committee of the British Society of Gastroenterology under the auspices of the Adolescent and Young Persons (A&YP) Section. Electronic searches for English-language articles were performed with keywords relating to digestive system diseases and transition to adult care in the Medline (via Ovid), PsycInfo (via Ovid), Web of Science and CINAHL databases for studies published from 1980 to September 2014. The quality of evidence and grading of recommendations was appraised using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The limited number of studies in gastroenterology and hepatology required the addition of relevant studies from other chronic diseases to be included. These guidelines deal specifically with the transition of AYP living with a diagnosis of chronic digestive disease and/or liver disease from paediatric to adult healthcare under the following headings; 1. Patient populations involved in AYP transition 2. Risks of failing transition or poor transition 3. Models of AYP transition 4. Patient and carer/parent perspective in AYP transition 5. Surgical perspectiv

Preparedness of the CTSA's Structural and Scientific Assets to Support the Mission of the National Center for Advancing Translational Sciences (NCATS)

The formation of the National Center for Advancing Translational Sciences (NCATS) brings new promise for moving basic and discoveries to clinical practice, ultimately improving the health of the nation. The CTSA sites, now housed with NCATS, are organized and prepared to support in this endeavor. The CTSAs provide a foundation for capitalizing on such promise through provision of a disease-agnostic infrastructure devoted to C&T science, maintenance of training programs designed for C&T investigators of the future, by incentivizing institutional reorganization and by cultivating institutional support

European Cystic Fibrosis Society Standards of Care: Framework for the Cystic Fibrosis Centre

A significant increase in life expectancy in successive birth cohorts of people with cystic fibrosis (CF) is a result of more effective treatment for the disease. It is also now widely recognized that outcomes for patients cared for in specialist CF Centres are better than for those who are not. Key to the effectiveness of the specialist CF Centre is the multidisciplinary team (MDT), which should include consultants, clinical nurse specialist, microbiologist, physiotherapist, dietitian, pharmacist, clinical psychologist, social worker, clinical geneticist and allied healthcare professionals, all of whom should be experienced in CF care. Members of the MDT are also expected to keep up to date with developments in CF through continued professional development, attendance at conferences, auditing and involvement in research. Specialists CF Centres should also network with other Centres both nationally and internationally, and feed Centre data to registries in order to further the understanding of the disease. This paper provides a framework for the specialist CF Centre, including the organisation of the Centre and the individual roles of MDT members, as well as highlighting the value of CF organisations and disease registries

Characterizing the Unmet Mental Health Needs of Urban Adolescents

Background: Untreated mental illness among adolescents is a major public health concern. Nationwide, 80% of youth with mental illness are not receiving mental health services. Methods: Medical records (546 total) were abstracted for patients 16-22 years old with a diagnosis of serious mental illness/serious emotional disturbance (SMI/SED) seen between May 2014 and July 2015. A retrospective review of randomized (n=100) eligible charts was performed to abstract demographics, psychotropic medication use, history of mental health referrals, past hospitalization(s), and resource utilization. Based on the criteria outlined by the 1992 Alcohol, Drug Abuse and Mental Health Services Administration Reorganization Act, patients were categorized into mild, moderate, and severe categories. They were considered “mild” if they had a diagnosis of ADHD, ADD, anxiety, dysthymia, or substance use disorder only; “moderate” if they had a SMI/SED (e.g. bipolar affective disorder, major depression), or a “mild” diagnosis with a comorbid intellectual disability, and/or a previous psychiatric hospitalization; “severe” if they had multiple SMI/SEDs or a hospitalization within the past year. Descriptive statistics were performed. Results: Our patient sample had a median age of 18.9 years (SD ±1.87) with the majority self-identifying as African American (94%) and publically insured (86%). Thirty-four percent were found to have “mild” mental illness, 55% “moderate”, and 11% “severe”. Forty-two percent of the patients sampled had two or more mental illness comorbidities. Forty-eight percent were currently on psychotropic medication (“mild” 41%, “moderate” 51%, “severe” 55%, respectively) and 30% had a reported Individualized Education Program (IEP) or 504 plan (38%, 25%, 27%, respectively). Fourteen percent had been previously hospitalized for mental illness (0%,15%, 55%, respectively). While 83% of patients were offered referrals (82%, 85%, 73%, respectively), only 40% were being followed by a certified mental health provider (35%, 42%, 46%, respectively). Conclusion: In our population of largely minority, publicly insured youth, a large proportion of patients are not receiving needed mental health services. Studies have shown that untreated SMI/SED in adolescence leads to more intensive and costly treatment, and increases morbidity in adulthood. Our research demonstrates that despite primary care providers\u27 documented referrals, many adolescents with SMI/SED are not connected to ongoing mental healthcare. There are many barriers to accessing mental health services, including stigma and difficulty navigating a complex health system. Future efforts should focus on care coordination between primary care and mental health services to encourage adolescents with SMI/SED to meet their healthcare needs