Orientation and verbal fluency in the English Longitudinal Study of Ageing: modifiable risk factors for falls?

Objectives:To determine the relationship between falls and deficits in specific cognitive domains in older adults.Design:An analysis of the English Longitudinal Study of Ageing (ELSA) cohort.Setting:United Kingdom community-based.Participants:5197 community-dwelling older adults recruited to a prospective longitudinal cohort study.Measurements:Data on the occurrence of falls and number of falls, which occurred during a 12-month follow-up period, were assessed against the specific cognitive domains of memory, numeracy skills, and executive function. Binomial logistic regression was performed to evaluate the association between each cognitive domain and the dichotomous outcome of falls in the preceding 12 months using unadjusted and adjusted models.Results:Of the 5197 participants included in the analysis, 1308 (25%) reported a fall in the preceding 12 months. There was no significant association between the occurrence of a fall and specific forms of cognitive dysfunction after adjusting for self-reported hearing, self-reported eyesight, and functional performance. After adjustment, only orientation (odds ratio [OR]: 0.80; 95% confidence intervals [CI]: 0.65-0.98, p = 0.03) and verbal fluency (adjusted OR: 0.98; 95% CI: 0.96-1.00; p = 0.05) remained significant for predicting recurrent falls.Conclusions:The cognitive phenotype rather than cognitive impairment per se may predict future falls in those presenting with more than one fall

Doctors are inconsistent in estimating survival after CPR and are not using such predictions consistently in determining DNACPR decisions

Background: It is unclear whether doctors base their resuscitation decisions solely on their perceived outcome. Through the use of theoretical scenarios, we aimed to examine the ‘do not attempt cardiopulmonary resuscitation’ (DNACPR) decision-making. Methods: A questionnaire survey was sent to consultants and specialty trainees across two Norfolk (UK) hospitals during December 2013. The survey included demographic questions and six clinical scenarios with varying prognosis. Participants were asked if they would resuscitate the patient or not. Identical scenarios were then shown in a different order and doctors were asked to quantify patients’ estimated chance of survival. Results: A total of 137 individuals (mean age 41 years (SD 7.9%)) responded. The response rate was 69%. Approximately 60% were consultants. We found considerable variation in clinician estimates of median chance of survival. In three out of six of our scenarios, the survival estimated varied from <1% to 95%. There was a statistically significant difference identified in the estimated median survival between those clinicians who would or would not resuscitate in four of the six scenarios presented. Conclusion: This study has highlighted the wide variation between clinicians in their estimates of likely survival and little concordance between clinicians over their resuscitation decisions. The diversity in clinician decision-making should be explored further

Acute hypertriglyceridemia induces platelet hyperactivity that is not attenuated by insulin in polycystic ovary syndrome.

Atherothrombosis is associated with platelet hyperactivity. Hypertriglyceridemia and insulin resistance (IR) are features of polycystic ovary syndrome (PCOS). The effect of induced hypertriglyceridemia on IR and platelet function was examined in young women with PCOS. Following overnight fasting, 13 PCOS and 12 healthy women were infused with saline or 20% intralipid for 5 hours on separate days. Insulin sensitivity was measured using a hyperinsulinemic euglycaemic clamp in the final 2 hours of each infusion. Platelet responses to adenosine diphosphate (ADP) and prostacyclin (PGI2) were measured by flow cytometric analysis of platelet fibrinogen binding and P-selectin expression using whole blood taken during each infusion (at 2 hours) and at the end of each clamp. Lipid infusion increased triglycerides and reduced insulin sensitivity in both controls (median, interquartile range ) (5.25 [3.3, 6.48] versus 2.60 [0.88, 3.88] mg kg(-1) min(-1), P<0.001) and PCOS (3.15 [2.94, 3.85] versus 1.06 [0.72, 1.43] mg kg(-1) min(-1), P<0.001). Platelet activation by ADP was enhanced and ability to suppress platelet activation by PGI2 diminished during lipid infusion in both groups when compared to saline. Importantly, insulin infusion decreased lipid-induced platelet hyperactivity by decreasing their response to 1 μmol/L ADP (78.7% [67.9, 82.3] versus 62.8% [51.8, 73.3], P=0.02) and increasing sensitivity to 0.01 μmol/L PGI2 (67.6% [39.5, 83.8] versus 40.9% [23.8, 60.9], P=0.01) in controls, but not in PCOS. Acute hypertriglyceridemia induced IR, and increased platelet activation in both groups that was not reversed by insulin in PCOS subjects compared to controls. This suggests that platelet hyperactivity induced by acute hypertriglyceridemia and IR could contribute athero-thrombotic risk. www.isrctn.org. Unique Identifier: ISRCTN42448814

Long-term efficacy and tolerability of TNFα inhibitors in the treatment of non-infectious ocular inflammation:an 8-year prospective surveillance study

BACKGROUND/AIM: To report the efficacy and tolerability of antitumour necrosis factor-alpha therapy (TNF inhibitors [TNFi]) in the management of non-infectious ocular inflammation, including uveitis and scleritis, in adult patients over an 8-year period. MATERIALS AND METHODS: This is a prospective cohort study of infliximab and adalimumab in the treatment of non-infectious ocular inflammatory disease. 43 of 85 adult patients on TNFi (34 infliximab, 9 adalimumab) for ≥1 year with non-infectious uveitis or scleritis were followed from 2006 to 2014. Clinical assessments, medication, adverse events and history of steroid rescues were collected at 6 monthly intervals. General quality of life (Short Form Health Survey (SF-36)) and visual quality of life (Vision-related quality of life Core Measure (VCM1)) were assessed annually. Outcome measures included rate of sustained remission, rate of relapse, systemic corticosteroid reduction, adverse events, and VCM1 and SF-36 scores. RESULTS: The median time on infliximab was 3.2 years (IQR 4.3) and on adalimumab was 2.4 years (IQR 1.8). Sustained remission was induced in 39 patients (91%) (0.5 per patient year) after a median of 1.2 years on a TNFi. 22 (51%) experienced one relapse, and 5 (12%) had two relapses. 23 (54%) had at least one adverse event; serious adverse events necessitating hospitalisation or cessation of medication occurred in four (9%) patients. 10 patients (23%) switched from the initiation of TNFi, at 1.7 years after starting, to another TNFi or another class of biologic therapy. CONCLUSION: TNFi treatment is associated with long-term drug-induced remission of ocular inflammation, visual stability and corticosteroid reduction. Adverse events were common and no new safety signals occurred. Relapse of inflammation occurs in half of the treated population

Understanding stakeholder views regarding the design of an intervention trial to reduce anticholinergic burden : a qualitative study

Funding statement This research was supported by the Chief Scientist Office under their Catalytic Research Grants Scheme, CSO reference number: CGA/18/47. Acknowledgments We gratefully acknowledge the support from the Alliance, the Glasgow Stroke Group and NKS in recruiting focus group participants and conducting the focus groups and Scottish Primary Care Research Network for recruiting patients from primary care. Special thanks to Irene Oldfather from Alliance and Naseem Suleman from NKS for their help in setting up interviews and focus groups. We gratefully acknowledge the research participants who provided their views and insights.Peer reviewedPublisher PD

Assessing risks of polypharmacy involving medications with anticholinergic properties

PURPOSE Anticholinergic burden (ACB), the cumulative effect of anticholinergic medications, is associated with adverse outcomes in older people but is less studied in middle-aged populations. Numerous scales exist to quantify ACB. The aims of this study were to quantify ACB in a large cohort using the 10 most common anticholinergic scales, to assess the association of each scale with adverse outcomes, and to assess overlap in populations identified by each scale. METHODS We performed a longitudinal analysis of the UK Biobank community cohort (502,538 participants, baseline age: 37-73 years, median years of follow-up: 6.2). The ACB was calculated at baseline using 10 scales. Baseline data were linked to national mortality register records and hospital episode statistics. The primary outcome was a composite of all-cause mortality and major adverse cardiovascular event (MACE). Secondary outcomes were all-cause mortality, MACE, hospital admission for fall/fracture, and hospital admission with dementia/delirium. Cox proportional hazards models (hazard ratio [HR], 95% CI) quantified associations between ACB scales and outcomes adjusted for age, sex, socioeconomic status, body mass index, smoking status, alcohol use, physical activity, and morbidity count. RESULTS Anticholinergic medication use varied from 8% to 17.6% depending on the scale used. For the primary outcome, ACB was significantly associated with all-cause mortality/MACE for each scale. The Anticholinergic Drug Scale was most strongly associated with mortality/MACE (HR = 1.12; 95% CI, 1.11-1.14 per 1-point increase in score). The ACB was significantly associated with all secondary outcomes. The Anticholinergic Effect on Cognition scale was most strongly associated with dementia/delirium (HR = 1.45; 95% CI, 1.3-1.61 per 1-point increase). CONCLUSIONS The ACB was associated with adverse outcomes in a middle- to older-aged population. Populations identified and effect size differed between scales. Scale choice influenced the population identified as potentially requiring reduction in ACB in clinical practice or intervention trials

Impact of hemoglobin levels and anemia on mortality in acute stroke: analysis of UK regional registry data, systematic review and meta-analysis

Background: The impact of hemoglobin levels and anemia on stroke mortality remains controversial. We aimed to systematically assess this association and quantify the evidence. Methods and Results: We analysed data from a cohort of 8,013 stroke patients (mean (sd) 77.81±11.83 years) consecutively admitted over 11 years (January 2003–May 2015) using a UK Regional Stroke Register. The impact of hemoglobin levels and anemia on mortality was assessed by sex-specific values at different time points (7-day, 14-day, 1-month, 3-month, 6-month, 1 year), using multiple regression models controlling for confounders. Anemia was present in 24.5% of the cohort on admission and was associated with increased odds of mortality at most of the time points examined up to 1 year following stroke. The association was less consistent for males with hemorrhagic stroke. Elevated haemoglobin was also associated with increased mortality, mainly within the first month. We then conducted a systematic review using the EMBASE and Medline databases. Twenty studies met the inclusion criteria. When combined with the cohort from the current study, this gave a pooled population of 29,943 patients with stroke. The evidence base was quantified in a meta-analysis. Anemia on admission was found to be associated with an increased risk of mortality in both ischemic stroke (8 studies); OR 1.97(1.56– 2.47) and hemorrhagic stroke (4 studies); OR 1.46(1.23–1.74). Conclusions: There is strong evidence that patients with anemia have increased mortality in stroke. Targeted interventions in this patient population may improve outcomes and therefore require further evaluation

Infective endocarditis is associated with worse outcomes in stroke : A Thailand National Database Study

Acknowledgements We thank the administrative staff of Insurance Schemes who prepared the anonymized dataset Funding No project specific funding was obtained for this study. KAR received the Aberdeen Summer Research Scholarship funded by the NHS Grampian Department of Medicine for the Elderly Endowment Funds.Peer reviewedPublisher PD

Barriers and facilitators to reducing anticholinergic burden: a qualitative systematic review

Background: Despite common use, anticholinergic medications have been associated with serious health risks. Interventions to reduce their use are being developed and there is a need to understand their implementation into clinical care. Aim of review: This systematic review aims to identify and analyse qualitative research studies exploring the barriers and facilitators to reducing anticholinergic burden. Methods: Medline (OVID), EMBASE (OVID), CINAHL (EMBSCO) and PsycINFO (OVID) were searched using comprehensive search terms. Peer reviewed studies published in English presenting qualitative research in relation to the barriers and facilitators of deprescribing anticholinergic medications, involving patients, carers or health professionals were eligible. Normalization Process Theory was used to explore and explain the data. Results: Of 1764 identified studies, two were eligible and both involved healthcare professionals (23 general practitioners, 13 specialist clinicians and 12 pharmacists). No studies were identified that involved patients or carers. Barriers to collaborative working often resulted in poor motivation to reduce anticholinergic use. Low confidence, system resources and organisation of care also hindered anticholinergic burden reduction. Good communication and relationships with patients, carers and other healthcare professionals were reported as important for successful anticholinergic burden reduction. Having a named person for prescribing decisions, and clear role boundaries, were also important facilitators. Conclusions: This review identified important barriers and facilitators to anticholinergic burden reduction from healthcare provider perspectives which can inform implementation of such deprescribing interventions. Studies exploring patient and carer perspectives are presently absent but are required to ensure person-centeredness and feasibility of future interventions

Barriers and facilitators to reducing anticholinergic burden from the perspectives of patients, their carers, and healthcare professionals: A protocol for qualitative evidence synthesis

Anticholinergic drugs are prescribed for a range of conditions including gastrointestinal disorders, overactive bladder, allergies, and depression. While in some circumstances anticholinergic effects are therapeutic, they also pose many undesired or adverse effects. The overall impact from concomitant use of multiple medications with anticholinergic properties is termed “anticholinergic burden” (ACB). Greater ACB is associated with increased risks of impaired physical and cognitive function, falls, cardiovascular events and mortality. This has led to the development of interventions aimed at reducing ACB through the deprescribing of anticholinergic drugs. However, little is known about the implementation issues that may influence successful embedding and integration of such interventions into routine clinical practice. In this paper we present the protocol for our systematic review that aims to identify the qualitative evidence for the barriers and facilitators to reducing ACB from the perspectives of patients, carers and healthcare professionals. A comprehensive search strategy will be conducted across OVID Medline, EMBASE, PsycInfo and CINAHL. The review will be conducted in accordance with ENTREQ (Enhancing Transparency in Reporting the Synthesis of Qualitative Research) and has been registered with PROSPERO (Registration CRD42018109084). Normalization Process Theory (NPT) will be used to explore, understand and explain qualitative data in relation to factors that act as barriers or facilitators to ACB reduction