Internet search analytics for shoulder arthroplasty: what questions are patients asking?

Background Common questions about shoulder arthroplasty (SA) searched online by patients and the quality of this content are unknown. The purpose of this study is to uncover questions SA patients search online and determine types and quality of webpages encountered. Methods The “People also ask” section of Google Search was queried to return 900 questions and associated webpages for general, anatomic, and reverse SA. Questions and webpages were categorized using the Rothwell classification of questions and assessed for quality using the Journal of the American Medical Association (JAMA) benchmark criteria. Results According to Rothwell classification, the composition of questions was fact (54.0%), value (24.7%), and policy (21.3%). The most common webpage categories were medical practice (24.6%), academic (23.2%), and medical information sites (14.4%). Journal articles represented 8.9% of results. The average JAMA score for all webpages was 1.69. Journals had the highest average JAMA score (3.91), while medical practice sites had the lowest (0.89). The most common question was, “How long does it take to recover from shoulder replacement?” Conclusions The most common questions SA patients ask online involve specific postoperative activities and the timeline of recovery. Most information is from low-quality, non-peer-reviewed websites, highlighting the need for improvement in online resources. By understanding the questions patients are asking online, surgeons can tailor preoperative education to common patient concerns and improve postoperative outcomes. Level of evidence IV

Current experiences and educational preferences of general practitioners and staff caring for people with dementia living in residential facilities

<p>Abstract</p> <p>Background</p> <p>Residential care is important for older adults, particularly for those with advanced dementia and their families. Education interventions that achieve sustainable improvement in the care of older adults are critical to quality care. There are few systematic data available regarding the educational needs of Residential Care Facility (RCF) staff and General Practitioners (GPs) relating to dementia, or the sustainability of educational interventions. We sought to determine participation in dementia education, perceived levels of current knowledge regarding dementia, perceived unmet educational needs, current barriers, facilitators and preferences for dementia education.</p> <p>Methods</p> <p>A mixed methods study design was utilised. A survey was distributed to a convenience sample of general practitioners, and staff in 223 consecutive residential care facilities in Perth, Western Australia. Responses were received from 102 RCF staff working in 10 facilities (out of 33 facilities who agreed to distribute the survey) and 202 GPs (19% of metropolitan GPs). Quantitative survey data were summarised descriptively and chi squared statistics were used to analyse the distribution of categorical variables. Qualitative data were collected from general practitioners, staff in residential care facilities and family carers of people with dementia utilizing individual interviews, surveys and focus groups. Qualitative data were analysed thematically.</p> <p>Results</p> <p>Among RCF staff and GPs attending RCF, participation in dementia education was high, and knowledge levels generally perceived as good. The individual experiences and needs of people with dementia and their families were emphasised. Participants identified the need for a person centred philosophy to underpin educational interventions. Limited time was a frequently mentioned barrier, especially in relation to attending dementia care education. Perceived educational needs relating to behaviours of concern, communication, knowledge regarding dementia, aspects of person centred care, system factors and the multidisciplinary team were consistently and frequently cited. Small group education which is flexible, individualized, practical and case based was sought.</p> <p>Conclusion</p> <p>The effectiveness and sustainability of an educational intervention based on these findings needs to be tested. In addition, future interventions should focus on supporting cultural change to facilitate sustainable improvements in care.</p

A missense mutation in Katnal1 underlies behavioural, neurological and ciliary anomalies

Microtubule severing enzymes implement a diverse range of tissue-specific molecular functions throughout development and into adulthood. Although microtubule severing is fundamental to many dynamic neural processes, little is known regarding the role of the family member Katanin p60 subunit A-like 1, KATNAL1, in central nervous system (CNS) function. Recent studies reporting that microdeletions incorporating the KATNAL1 locus in humans result in intellectual disability and microcephaly suggest that KATNAL1 may play a prominent role in the CNS; however, such associations lack the functional data required to highlight potential mechanisms which link the gene to disease symptoms. Here we identify and characterise a mouse line carrying a loss of function allele in Katnal1. We show that mutants express behavioural deficits including in circadian rhythms, sleep, anxiety and learning/memory. Furthermore, in the brains of Katnal1 mutant mice we reveal numerous morphological abnormalities and defects in neuronal migration and morphology. Furthermore we demonstrate defects in the motile cilia of the ventricular ependymal cells of mutants, suggesting a role for Katnal1 in the development of ciliary function. We believe the data we present here are the first to associate KATNAL1 with such phenotypes, demonstrating that the protein plays keys roles in a number of processes integral to the development of neuronal function and behaviour.Molecular Psychiatry advance online publication, 4 April 2017; doi:10.1038/mp.2017.54

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Effects of Anacetrapib in Patients with Atherosclerotic Vascular Disease

BACKGROUND: Patients with atherosclerotic vascular disease remain at high risk for cardiovascular events despite effective statin-based treatment of low-density lipoprotein (LDL) cholesterol levels. The inhibition of cholesteryl ester transfer protein (CETP) by anacetrapib reduces LDL cholesterol levels and increases high-density lipoprotein (HDL) cholesterol levels. However, trials of other CETP inhibitors have shown neutral or adverse effects on cardiovascular outcomes. METHODS: We conducted a randomized, double-blind, placebo-controlled trial involving 30,449 adults with atherosclerotic vascular disease who were receiving intensive atorvastatin therapy and who had a mean LDL cholesterol level of 61 mg per deciliter (1.58 mmol per liter), a mean non-HDL cholesterol level of 92 mg per deciliter (2.38 mmol per liter), and a mean HDL cholesterol level of 40 mg per deciliter (1.03 mmol per liter). The patients were assigned to receive either 100 mg of anacetrapib once daily (15,225 patients) or matching placebo (15,224 patients). The primary outcome was the first major coronary event, a composite of coronary death, myocardial infarction, or coronary revascularization. RESULTS: During the median follow-up period of 4.1 years, the primary outcome occurred in significantly fewer patients in the anacetrapib group than in the placebo group (1640 of 15,225 patients [10.8%] vs. 1803 of 15,224 patients [11.8%]; rate ratio, 0.91; 95% confidence interval, 0.85 to 0.97; P=0.004). The relative difference in risk was similar across multiple prespecified subgroups. At the trial midpoint, the mean level of HDL cholesterol was higher by 43 mg per deciliter (1.12 mmol per liter) in the anacetrapib group than in the placebo group (a relative difference of 104%), and the mean level of non-HDL cholesterol was lower by 17 mg per deciliter (0.44 mmol per liter), a relative difference of -18%. There were no significant between-group differences in the risk of death, cancer, or other serious adverse events. CONCLUSIONS: Among patients with atherosclerotic vascular disease who were receiving intensive statin therapy, the use of anacetrapib resulted in a lower incidence of major coronary events than the use of placebo. (Funded by Merck and others; Current Controlled Trials number, ISRCTN48678192 ; ClinicalTrials.gov number, NCT01252953 ; and EudraCT number, 2010-023467-18 .)

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease