People living with Parkinson’s disease and their caregivers: a systematic review of psychosocial interventions; and, Psychological adjustment in people living with Parkinson’s disease and their caregivers: the role of coping, illness beliefs and self-compassion

This thesis comprises of a systematic review and an empirical study aimed to gain a greater understanding of the psychological needs of both people living with Parkinson’s disease (PD), their caregivers, and how these needs can be met. The systematic review aimed to evaluate the effectiveness of psychosocial interventions, where people living with PD and their caregivers are involved in the intervention (dyad-based), on psychological and additional outcomes measured. The review included 13 studies which met predefined eligibility criteria. Due to varied methodological quality of the studies, this review to an extent suggests that dyad-based psychosocial interventions may provide psychological benefits for people living with PD. Whereas, there was no substantive evidence to suggest dyad-based psychosocial interventions are effective for caregivers. More high-quality research is required to conclusively establish the effectiveness of these interventions for both people living with PD and their caregivers. The empirical study extended previous research examining the relationship between illness beliefs and coping with psychological adjustment (in terms of anxiety, depression and quality of life) in people living with PD and caregivers, whilst developing research in to the role of self-compassion within this process. A cross-sectional survey design with participants living with PD (N=66) and their caregivers (N=24) with the following measures was utilised; Brief COPE, Brief-Illness Perception Questionnaire, Self-Compassion Scale, Hospital Anxiety and Depression Scale, Parkinson’s disease Questionnaire 8-item and Adult Carer Quality of Life Questionnaire. The results of the study provided further evidence for the relationship between illness beliefs and psychological adjustment outcomes in people living with PD. In addition, the study provided preliminary evidence of a relationship between self-compassion and psychological adjustment outcomes of psychological distress in people living with PD. Further research of a larger and more representative sample is required to establish the role of illness beliefs, coping responses and self-compassion in psychological adjustment in both people living with PD and their caregivers

Chromosomal instability in untreated primary prostate cancer as an indicator of metastatic potential.

BackgroundMetastatic prostate cancer (PC) is highly lethal. The ability to identify primary tumors capable of dissemination is an unmet need in the quest to understand lethal biology and improve patient outcomes. Previous studies have linked chromosomal instability (CIN), which generates aneuploidy following chromosomal missegregation during mitosis, to PC progression. Evidence of CIN includes broad copy number alterations (CNAs) spanning > 300 base pairs of DNA, which may also be measured via RNA expression signatures associated with CNA frequency. Signatures of CIN in metastatic PC, however, have not been interrogated or well defined. We examined a published 70-gene CIN signature (CIN70) in untreated and castration-resistant prostate cancer (CRPC) cohorts from The Cancer Genome Atlas (TCGA) and previously published reports. We also performed transcriptome and CNA analysis in a unique cohort of untreated primary tumors collected from diagnostic prostate needle biopsies (PNBX) of localized (M0) and metastatic (M1) cases to determine if CIN was linked to clinical stage and outcome.MethodsPNBX were collected from 99 patients treated in the VA Greater Los Angeles (GLA-VA) Healthcare System between 2000 and 2016. Total RNA was extracted from high-grade cancer areas in PNBX cores, followed by RNA sequencing and/or copy number analysis using OncoScan. Multivariate logistic regression analyses permitted calculation of odds ratios for CIN status (high versus low) in an expanded GLA-VA PNBX cohort (n = 121).ResultsThe CIN70 signature was significantly enriched in primary tumors and CRPC metastases from M1 PC cases. An intersection of gene signatures comprised of differentially expressed genes (DEGs) generated through comparison of M1 versus M0 PNBX and primary CRPC tumors versus metastases revealed a 157-gene "metastasis" signature that was further distilled to 7-genes (PC-CIN) regulating centrosomes, chromosomal segregation, and mitotic spindle assembly. High PC-CIN scores correlated with CRPC, PC-death and all-cause mortality in the expanded GLA-VA PNBX cohort. Interestingly, approximately 1/3 of M1 PNBX cases exhibited low CIN, illuminating differential pathways of lethal PC progression.ConclusionsMeasuring CIN in PNBX by transcriptome profiling is feasible, and the PC-CIN signature may identify patients with a high risk of lethal progression at the time of diagnosis

IQuaD dental trial; improving the quality of dentistry : a multicentre randomised controlled trial comparing oral hygiene advice and periodontal instrumentation for the prevention and management of periodontal disease in dentate adults attending dental primary care

Peer reviewedPublisher PD

Genome-wide association analysis identifies six new loci associated with forced vital capacity

Forced vital capacity (FVC), a spirometric measure of pulmonary function, reflects lung volume and is used to diagnose and monitor lung diseases. We performed genome-wide association study meta-analysis of FVC in 52,253 individuals from 26 studies and followed up the top associations in 32,917 additional individuals of European ancestry. We found six new regions associated at genome-wide significance (P < 5 × 10−8) with FVC in or near EFEMP1, BMP6, MIR129-2–HSD17B12, PRDM11, WWOX and KCNJ2. Two loci previously associated with spirometric measures (GSTCD and PTCH1) were related to FVC. Newly implicated regions were followed up in samples from African-American, Korean, Chinese and Hispanic individuals. We detected transcripts for all six newly implicated genes in human lung tissue. The new loci may inform mechanisms involved in lung development and the pathogenesis of restrictive lung disease

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Neurodiversify your curriculum

Neurodiversity is the naturally-occurring variation in the human brain regarding movement, sociability, learning, attention, mood, and other mental functions (Armstrong, 2011). However, neurodivergence is often deemed a disorder as it is still largely seen through the lenses of the medical model shaped by the normative approach to science. According to this model, the difficulties that neurodivergent individuals face are inherent to the diagnosed disorder, rather than stemming from a misalignment between individual characteristics and non-inclusive environments, as well as the structures within the society that marginalise those who do not fit into the accepted norm. Diagnostic decisions are made on the basis of identifying specific atypical behaviours through observation. They are, therefore, influenced by cultural values and expectations of standard behaviours together with skewed norms as research into behaviour is conducted mainly on Rich, Educated, Western, Industrious, Democratic, Elite and Neurotypical (REWIDEN) individuals. Additionally, whether a specific behaviour is seen as atypical depends on existing social power relations, public perceptions and narratives and at present, the language used to discuss neurodivergence is often discriminatory, othering those who do not fall into the normative standard. Some of the main values of Open Scholarship are accessibility, diversity, equity, inclusivity and social justice. However, neurodivergent academics and students are rarely included in the discussion. Academics should aim to change the status quo by raising awareness of neurodiversity, de-pathologising language and promoting participatory research. Validating the neurodivergent community will allow science to benefit from increased epistemic diversity. Applied to the classroom setting, barriers arise when educators are not attuned to the diverse needs of their students, and/or when the demands of the hidden curriculum prevent some students from fully engaging with the learning experience. Lack of awareness of different neurotypes in the classroom may lead to what Milton (2012) calls the double empathy problem, which refers to the reciprocal deficits in understanding that occur when people have different communication preferences, social norms and expectations of each other, particularly across neurotypes. As educators, we can critically reflect on our assumptions and practice to eliminate double empathy barriers in the classroom. In this workshop, we will explore ways in which we can “neurodiversify” the open scholarship curriculum and work towards neurodiversity-affirming education. We will consider how educators can bring awareness of neurodiversity into their teaching, for example through the purposeful use of non-pathologising terminology in relation to cognitive and learning differences. Using practical examples, we will demonstrate the promise of inclusive pedagogical approaches, such as Universal Design for Learning (UDL) and strength-based assessment, to improve the learning experience for all. Finally, we will consider how collaborative team-working within open science practice may be particularly beneficial for neurodivergent students and researchers and, conversely, how science can be improved by the inclusion of all neurotypes. The workshop will be complemented by a resource pack that can be adapted and used in teaching practice

The Transfusion Alternatives Preoperatively in Sickle Cell Disease (TAPS) study: a randomised, controlled, multicentre clinical trial

No consensus exists on whether preoperative blood transfusions are beneficial in patients with sickle-cell disease. We assessed whether perioperative complication rates would be altered by preoperative transfusion. We did a multicentre, randomised trial. Eligible patients were aged at least 1 year, had haemoglobin SS or Sβ(0)thalassaemia sickle-cell-disease subtypes, and were scheduled for low-risk or medium-risk operations. Patients were randomly assigned no transfusion or transfusion no more than 10 days before surgery. The primary outcome was the proportion of clinically important complications between randomisation and 30 days after surgery. Analysis was by intention to treat. 67 (96%) of 70 enrolled patients-33 no preoperative transfusion and 34 preoperative transfusion-were assessed. 65 (97%) of 67 patients had the haemoglobin SS subtype and 54 (81%) were scheduled to undergo medium-risk surgery. 13 (39%) of 33 patients in the no-preoperative-transfusion group had clinically important complications, compared with five (15%) in the preoperative-transfusion group (p=0.023). Of these, 10 (30%) and one (3%), respectively, had serious adverse events. The unadjusted odds ratio of clinically important complications was 3.8 (95% CI 1.2-12.2, p=0.027). 10 (91%) of 11 serious adverse events were acute chest syndrome (nine in the no-preoperative-transfusion group and one in the preoperative-transfusion group). Duration of hospital stay and readmission rates did not differ between study groups. Preoperative transfusion was associated with decreased perioperative complications in patients with sickle-cell disease in this trial. This approach could, therefore, be beneficial for patients with the haemoglobin SS subtype who are scheduled to undergo low-risk and medium-risk surgeries. NHS Blood and Transplan