Search

Iram Haq,1,2 Maryam Almulhem,1 Simone Soars,1 David Poulton,2,3 Malcolm Brodlie1,2 1Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK; 2Paediatric Respiratory Medicine, Great North Children’s Hospital, Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK; 3Paediatrics, Ninewells Hospital, NHS Tayside, Dundee, UKCorrespondence: Malcolm BrodliePaediatric Respiratory Medicine, Level 3, Clinical Resource Building, Royal Victoria Infirmary, Newcastle upon Tyne, NE1 4LP, UK, Tel +44 191 2336161, Email malcolm.brodlie@ncl.ac.ukAbstract: Cystic fibrosis (CF) is an autosomal recessive genetic condition that is caused by variants in the cystic fibrosis transmembrane conductance regulator gene. This causes multisystem disease due to dysfunction of the cystic fibrosis transmembrane conductance regulator (CFTR) ion channel at the apical surface of epithelia. Until recently, treatment was directed at managing the downstream effects in affected organs, principally improving airway clearance and treating infection in the lungs and improving malabsorption in the gastrointestinal tract. Care delivered by multidisciplinary teams has yielded incremental improvements in outcomes. However, the development of small-molecule CFTR modulator drugs over the last decade has heralded a new era of CF therapeutics. Modulators target the underlying defect and improve CFTR function. Either monotherapy or a combination of modulators is used depending on the specific genotype and class of CFTR disease-causing variants that an individual has. Both ivacaftor and the ivacaftor/tezacaftor/elexacaftor combination have been demonstrated to be associated with clinically very significant benefits in randomised trials and have rapidly been made available as part of standard care in many countries. CFTR modulators represent one of the best examples of precision medicine to date. They are expensive, however, and equity of access to them worldwide remains an issue. Studies and approvals are also ongoing for children under the age of 6 years for ivacaftor/tezacaftor/elexacaftor. Furthermore, no modulators are available for around 10% of the people with CF. In this review, we firstly summarise the genetics, pathophysiology and clinical problems associated with CF. We then discuss the development of CFTR modulators and key clinical trials to support their use along with other potential future therapeutic approaches.Keywords: CFTR, ivacaftor, modulator, elexacaftor, tezacaftor

Hoarding behavior is an unrecognized but increasing problem among older adults that seriously threatens the quality of their daily lives. This study describes four hoarding cases; how each was identified, processed and resolved. Written records and interviews were obtained from Adult Protective Services, Office of the Public Guardian and city Police Department. Two cases were single women, one was a single man and one a married couple. Both single women were relocated to independent subsidized housing. The single man was placed under guardianship of the state but died at a local hospital. The couple's home had to be destroyed, and they were placed in a nursing home by a court order. Recommendations are made for earlier identification, intervention, treatment, potential prevention and more effective communication between service agencies. [ABSTRACT FROM AUTHOR]

BSTRACT: Biological responses to physical-chemical processes were examined in Toronto and Hamilton Harbours of Lake Ontario. Nutrient loadings to the harbors are large and are of similar magnitude, yet the trophic conditions of the harbors were considerably different. Lake oscillations were found to determine the flushing rates and environmental stability of the harbors. LOW residence times (<10 days) resulted in homogenous chemical conditions in Toronto Harbour, and prevented the establishment of large phytoplankton crops. The longer retention time of Hamilton Harbour permitted the establishment of huger phytoplankton crops. There probably exists a critical retention time where nutrient input events persist for a sufficient period of time for the algal community to adapt to and exploit the environmental conditions of nearshore areas. [ABSTRACT FROM AUTHOR]

Background: There are increasing calls for neurodivergent peoples' involvement in research into neurodevelopmental conditions. So far, however, this has tended to be achieved only through membership of external patient and public involvement (PPI) panels. The Regulating Emotions - Strengthening Adolescent Resilience (RE-STAR) programme is building a new participatory model of translational research that places young people with diagnoses of attention-deficit hyperactivity disorder (ADHD) and autism at the heart of the research team so that they can contribute to shaping and delivering its research plan., Aims: To outline the principles on which the RE-STAR participatory model is based and describe its practical implementation and benefits, especially concerning the central role of members of the Youth Researcher Panel (Y-RPers)., Method: The model presented is a culmination of a 24-month process during which Y-RPers moved from advisors to co-researchers integrated within RE-STAR. It is shaped by the principles of co-intentionality. The account here was agreed following multiple iterative cycles of collaborative discussion between academic researchers, Y-RPers and other stakeholders., Results: Based on our collective reflections we offer general guidance on how to effectively integrate young people with diagnoses of ADHD and/or autism into the core of the translational research process. We also describe the specific theoretical, methodological and analytical benefits of Y-RPer involvement in RE-STAR., Conclusions: Although in its infancy, RE-STAR has demonstrated the model's potential to enrich translational science in a way that can change our understanding of the relationship between autism, ADHD and mental health. When appropriately adapted we believe the model can be applied to other types of neurodivergence and/or mental health conditions.

Objective: Assess the prevalence of nonalcoholic fatty liver disease (NAFLD) and of liver fibrosis associated with nonalcoholic steatohepatitis in unselected patients with type 2 diabetes mellitus (T2DM)., Research Design and Methods: A total of 561 patients with T2DM (age: 60 ± 11 years; BMI: 33.4 ± 6.2 kg/m 2 ; and HbA 1c : 7.5 ± 1.8%) attending primary care or endocrinology outpatient clinics and unaware of having NAFLD were recruited. At the visit, volunteers were invited to be screened by elastography for steatosis and fibrosis by controlled attenuation parameter (≥274 dB/m) and liver stiffness measurement (LSM; ≥7.0 kPa), respectively. Secondary causes of liver disease were ruled out. Diagnostic panels for prediction of advanced fibrosis, such as AST-to-platelet ratio index (APRI) and Fibrosis-4 (FIB-4) index, were also measured. A liver biopsy was performed if results were suggestive of fibrosis., Results: The prevalence of steatosis was 70% and of fibrosis 21% (LSM ≥7.0 kPa). Moderate fibrosis (F2: LSM ≥8.2 kPa) was present in 6% and severe fibrosis or cirrhosis (F3-4: LSM ≥9.7 kPa) in 9%, similar to that estimated by FIB-4 and APRI panels. Noninvasive testing was consistent with liver biopsy results. Elevated AST or ALT ≥40 units/L was present in a minority of patients with steatosis (8% and 13%, respectively) or with liver fibrosis (18% and 28%, respectively). This suggests that AST/ALT alone are insufficient as initial screening. However, performance may be enhanced by imaging (e.g., transient elastography) and plasma diagnostic panels (e.g., FIB-4 and APRI)., Conclusions: Moderate-to-advanced fibrosis (F2 or higher), an established risk factor for cirrhosis and overall mortality, affects at least one out of six (15%) patients with T2DM. These results support the American Diabetes Association guidelines to screen for clinically significant fibrosis in patients with T2DM with steatosis or elevated ALT., (© 2020 by the American Diabetes Association.)

Cases of children presenting with limb or joint pain are relatively common and are due mainly to benign conditions. Early diagnosis will help reduce unnecessary invasive investigations so, although a relatively rare condition, benign acute childhood myositis (BACM), which presents with acute lower limb pain and an isolated rise in creatine kinase, should be considered. BACM is characterised by an infiltration of viruses into calf muscle fibres, which may cause a subsequent inflammatory response leading to calf-muscle pain. Symptomatic and supportive management, along with explanation and reassurance, is all that is required in managing this condition. This article discusses the management of a 10-year-old boy with a classical presentation of BACM, alongside differentials and management for clinician consideration.