Exploring the experiences and perceptions of patients awaiting rotator cuff repair surgery: an integrated qualitative study within the POWER pilot and feasibility trial

Background: As waiting times for orthopaedic surgery increase, there have been calls to move from ‘waiting lists’ to ‘preparation lists’, to better prepare patients for surgery. In this context, a pilot randomised controlled trial (POWER) was conducted, comparing physiotherapist-led exercise to waiting-list control (usual care), for patients awaiting rotator cuff repair surgery. This qualitative study was integrated within the pilot trial.Objectives: ●Explore experiences of adults awaiting rotator cuff repair surgery in the NHS●Explore the acceptability of the physiotherapist-led exercise intervention●Explore barriers and enablers to recruitment, retention, and adherence Design: Integrated qualitative study with semi-structured telephone interviewsMethods: Adults awaiting rotator cuff repair, consenting to participate in the trial were eligible. Sampling was purposive regarding age, gender, randomised allocation, and hospital site. Interviews were audio-recorded and transcribed. Data were analysed using Reflexive Thematic Analysis.Results: 20 participants were recruited (age range 49 to 81 years; 12 male, 10 randomised to physiotherapist-led exercise). Many participants were unable to recall their experiences of trial processes; nonetheless, three themes were identified from the data: experience of shoulder pain and pathway to treatment; communication and decision-making in the context of rotator cuff repair surgery; and experiences of the POWER physiotherapist-led exercise intervention and processes. Conclusions: Patients experience significant burden due to shoulder pain. Their journey to surgery can be long, confusing, and associated with perceived abandonment. In a future trial, the intervention should offer opportunity for shared decision-making, optional exit from the surgical pathway, and an individualised exercise programme

Specialist community teams for adults with learning disabilities: referrals to a countywide service in England

Purpose – While “generic” community teams for adults with learning disabilities (CTs) are well-established in the UK, very little recent evidence is available about any aspect of their work. As part of a larger project about the role, structure and functioning of CTs, the purpose of this paper is to provide data about referrals. Design/methodology/approach – Over threemonths, the authors obtained data about 270 consecutive new referrals to five CTs in a countywide integrated health (NHS) and care management (local authority) service. Findings – The 270 referrals related to 255 individuals, mainly already service users, with almost a third (30 per cent, n=204) described as people with severe or profound disabilities. Consistent with the reported living arrangements (residential accommodation or with one or more family members (87 per cent, n=270)), referrals were most often made by social care staff, General Practitioners or carers. The referrals related to a wide range of issues including mental health and/or behavioural needs, physical health and skills, and independence. The major group, however, were requests about a person’s entitlement to specialist learning disability services and/or reviews of an existing social care package. Research limitations/implications – The focus on new referrals and the exclusion of intra-team referrals mean that the data are not representative of a CT’s caseload and cannot be used as a basis for resourcing. Nevertheless, the findings emphasise the heterogeneity of the population, and the long-term and varied nature of their needs, meaning that CTs require access to a range of expertise and, often, an inter-agency approach. The implications for service design are considered. Originality/value – This is the first empirical study of referrals to specialist integrated (health and care management) community learning disabilities teams in England

Hunt for Planet Nine: Atmosphere, Spectra, Evolution, and Detectability

We investigate the physical characteristics of the solar system\u27s proposed Planet Nine using modeling tools with a heritage of studying Uranus and Neptune. For a range of plausible masses and interior structures, we find upper limits on the intrinsic , from ~35 to 50 K for masses of 5–20 M ⊕, and we also explore lower values. Possible planetary radii could readily span from 2.7 to 6 R ⊕, depending on the mass fraction of any H/He envelope. Given its cold atmospheric temperatures, the planet encounters significant methane condensation, which dramatically alters the atmosphere away from simple Neptune-like expectations. We find that the atmosphere is strongly depleted in molecular absorption at visible wavelengths, suggesting a Rayleigh scattering atmosphere with a high geometric albedo approaching 0.75. We highlight two diagnostics for the atmosphere\u27s temperature structure: (1) the value of the methane mixing ratio above the methane cloud and (2) the wavelength at which cloud scattering can be seen, which yields the cloud-top pressure. Surface reflection may be seen if the atmosphere is thin. Due to collision-induced opacity of H2 in the infrared, the planet would be extremely blue instead of red in the shortest wavelength WISE colors if methane is depleted and would, in some cases, exist on the verge of detectability by WISE. For a range of models, thermal fluxes from ~3 to 5 μm are ~20 orders of magnitude larger than blackbody expectations. We report a search of the AllWISE Source Catalog for Planet Nine, but find no detection

APOBECs and Herpesviruses

The apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like (APOBEC) family of DNA cytosine deaminases provides a broad and overlapping defense against viral infections. Successful viral pathogens, by definition, have evolved strategies to escape restriction by the APOBEC enzymes of their hosts. HIV-1 and related retroviruses are thought to be the predominant natural substrates of APOBEC enzymes due to obligate single-stranded (ss)DNA replication intermediates, abundant evidence for cDNA strand C-to-U editing (genomic strand G-to-A hypermutation), and a potent APOBEC degradation mechanism. In contrast, much lower mutation rates are observed in double-stranded DNA herpesviruses and the evidence for APOBEC mutation has been less compelling. However, recent work has revealed that Epstein-Barr virus (EBV), Kaposi's sarcoma-associated herpesvirus (KSHV), and herpes simplex virus-1 (HSV-1) are potential substrates for cellular APOBEC enzymes. To prevent APOBEC-mediated restriction these viruses have repurposed their ribonucleotide reductase (RNR) large subunits to directly bind, inhibit, and relocalize at least two distinct APOBEC enzymes-APOBEC3B and APOBEC3A. The importance of this interaction is evidenced by genetic inactivation of the EBV RNR (BORF2), which results in lower viral infectivity and higher levels of C/G-to-T/A hypermutation. This RNR-mediated mechanism therefore likely functions to protect lytic phase viral DNA replication intermediates from APOBEC-catalyzed DNA C-to-U deamination. The RNR-APOBEC interaction defines a new pathogen-host conflict that the virus must win in real-time for transmission and pathogenesis. However, partial losses over evolutionary time may also benefit the virus by providing mutational fuel for adaptation

Variation in Structure and Process of Care in Traumatic Brain Injury: Provider Profiles of European Neurotrauma Centers Participating in the CENTER-TBI Study.

INTRODUCTION: The strength of evidence underpinning care and treatment recommendations in traumatic brain injury (TBI) is low. Comparative effectiveness research (CER) has been proposed as a framework to provide evidence for optimal care for TBI patients. The first step in CER is to map the existing variation. The aim of current study is to quantify variation in general structural and process characteristics among centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. METHODS: We designed a set of 11 provider profiling questionnaires with 321 questions about various aspects of TBI care, chosen based on literature and expert opinion. After pilot testing, questionnaires were disseminated to 71 centers from 20 countries participating in the CENTER-TBI study. Reliability of questionnaires was estimated by calculating a concordance rate among 5% duplicate questions. RESULTS: All 71 centers completed the questionnaires. Median concordance rate among duplicate questions was 0.85. The majority of centers were academic hospitals (n = 65, 92%), designated as a level I trauma center (n = 48, 68%) and situated in an urban location (n = 70, 99%). The availability of facilities for neuro-trauma care varied across centers; e.g. 40 (57%) had a dedicated neuro-intensive care unit (ICU), 36 (51%) had an in-hospital rehabilitation unit and the organization of the ICU was closed in 64% (n = 45) of the centers. In addition, we found wide variation in processes of care, such as the ICU admission policy and intracranial pressure monitoring policy among centers. CONCLUSION: Even among high-volume, specialized neurotrauma centers there is substantial variation in structures and processes of TBI care. This variation provides an opportunity to study effectiveness of specific aspects of TBI care and to identify best practices with CER approaches

Age at onset as stratifier in idiopathic Parkinson’s disease – effect of ageing and polygenic risk score on clinical phenotypes

Several phenotypic differences observed in Parkinson’s disease (PD) patients have been linked to age at onset (AAO). We endeavoured to find out whether these differences are due to the ageing process itself by using a combined dataset of idiopathic PD (n = 430) and healthy controls (HC; n = 556) excluding carriers of known PD-linked genetic mutations in both groups. We found several significant effects of AAO on motor and non-motor symptoms in PD, but when comparing the effects of age on these symptoms with HC (using age at assessment, AAA), only positive associations of AAA with burden of motor symptoms and cognitive impairment were significantly different between PD vs HC. Furthermore, we explored a potential effect of polygenic risk score (PRS) on clinical phenotype and identified a significant inverse correlation of AAO and PRS in PD. No significant association between PRS and severity of clinical symptoms was found. We conclude that the observed non-motor phenotypic differences in PD based on AAO are largely driven by the ageing process itself and not by a specific profile of neurodegeneration linked to AAO in the idiopathic PD patients

Variation in general supportive and preventive intensive care management of traumatic brain injury: a survey in 66 neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study

Abstract Background General supportive and preventive measures in the intensive care management of traumatic brain injury (TBI) aim to prevent or limit secondary brain injury and optimize recovery. The aim of this survey was to assess and quantify variation in perceptions on intensive care unit (ICU) management of patients with TBI in European neurotrauma centers. Methods We performed a survey as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. We analyzed 23 questions focused on: 1) circulatory and respiratory management; 2) fever control; 3) use of corticosteroids; 4) nutrition and glucose management; and 5) seizure prophylaxis and treatment. Results The survey was completed predominantly by intensivists (n = 33, 50%) and neurosurgeons (n = 23, 35%) from 66 centers (97% response rate). The most common cerebral perfusion pressure (CPP) target was > 60 mmHg (n = 39, 60%) and/or an individualized target (n = 25, 38%). To support CPP, crystalloid fluid loading (n = 60, 91%) was generally preferred over albumin (n = 15, 23%), and vasopressors (n = 63, 96%) over inotropes (n = 29, 44%). The most commonly reported target of partial pressure of carbon dioxide in arterial blood (PaCO2) was 36–40 mmHg (4.8–5.3 kPa) in case of controlled intracranial pressure (ICP) < 20 mmHg (n = 45, 69%) and PaCO2 target of 30–35 mmHg (4–4.7 kPa) in case of raised ICP (n = 40, 62%). Almost all respondents indicated to generally treat fever (n = 65, 98%) with paracetamol (n = 61, 92%) and/or external cooling (n = 49, 74%). Conventional glucose management (n = 43, 66%) was preferred over tight glycemic control (n = 18, 28%). More than half of the respondents indicated to aim for full caloric replacement within 7 days (n = 43, 66%) using enteral nutrition (n = 60, 92%). Indications for and duration of seizure prophylaxis varied, and levetiracetam was mostly reported as the agent of choice for both seizure prophylaxis (n = 32, 49%) and treatment (n = 40, 61%). Conclusions Practice preferences vary substantially regarding general supportive and preventive measures in TBI patients at ICUs of European neurotrauma centers. These results provide an opportunity for future comparative effectiveness research, since a more evidence-based uniformity in good practices in general ICU management could have a major impact on TBI outcome

Variation in neurosurgical management of traumatic brain injury

Background: Neurosurgical management of traumatic brain injury (TBI) is challenging, with only low-quality evidence. We aimed to explore differences in neurosurgical strategies for TBI across Europe. Methods: A survey was sent to 68 centers participating in the Collaborative European Neurotrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. The questionnaire contained 21 questions, including the decision when to operate (or not) on traumatic acute subdural hematoma (ASDH) and intracerebral hematoma (ICH), and when to perform a decompressive craniectomy (DC) in raised intracranial pressure (ICP). Results: The survey was completed by 68 centers (100%). On average, 10 neurosurgeons work in each trauma center. In all centers, a neurosurgeon was available within 30 min. Forty percent of responders reported a thickness or volume threshold for evacuation of an ASDH. Most responders (78%) decide on a primary DC in evacuating an ASDH during the operation, when swelling is present. For ICH, 3% would perform an evacuation directly to prevent secondary deterioration and 66% only in case of clinical deterioration. Most respondents (91%) reported to consider a DC for refractory high ICP. The reported cut-off ICP for DC in refractory high ICP, however, differed: 60% uses 25 mmHg, 18% 30 mmHg, and 17% 20 mmHg. Treatment strategies varied substantially between regions, specifically for the threshold for ASDH surgery and DC for refractory raised ICP. Also within center variation was present: 31% reported variation within the hospital for inserting an ICP monitor and 43% for evacuating mass lesions. Conclusion: Despite a homogeneous organization, considerable practice variation exists of neurosurgical strategies for TBI in Europe. These results provide an incentive for comparative effectiveness research to determine elements of effective neurosurgical care

Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes

publisher: Elsevier articletitle: Genomic Dissection of Bipolar Disorder and Schizophrenia, Including 28 Subphenotypes journaltitle: Cell articlelink: https://doi.org/10.1016/j.cell.2018.05.046 content_type: article copyright: © 2018 Elsevier Inc