Potential contribution of lifestyle and socioeconomic factors to healthy user bias in antihypertensives and lipidlowering drugs

Objectives Healthy user bias arises when users of preventive medications such as lipid-lowering drugs (LLDs), hormone replacement therapy and antihypertensive (AH) medications are healthier than non-users due to factors other than medication effects, making the medications appear more beneficial in observational studies of effectiveness and safety. The purpose of the study is to examine factors contributing to healthy user effect in patients taking AHs or LLDs.Methods: Among patients with hypertension or hyperlipidaemia in a population-based sample from the National Health and Nutrition Examination Survey (1999–2010), we assessed the association between socioeconomic and lifestyle factors and the use of AHs/LLDs by logistic regression with adjustment for demographics and comorbidities in a cross-sectional study.Results: When 9715 AH/LLD users were compared with 3725 non-users, AH/LLD users were more likely to be: highly educated (OR 1.2, 95% CI 1.2 to 1.3), non-impoverished (OR 1.3, 95% CI 1.2 to 1.4), current non-smokers (OR 1.2, 95% CI 1.1 to 1.4), physically active (OR 1.1, 95% CI 1.0 to 1.2) and consume more calcium (OR 1.1, 95% CI 1.0 to 1.3) but less likely to have normal body mass index (OR 0.6, 95% CI 0.6 to 0.7) or to meet dietary sodium recommendations (OR 0.8, 95% CI 0.7 to 0.9).Conclusions: We identified several salutary lifestyle factors associated with AH/LLD use in a representative US population. Healthy user effect may be partly explained by better socioeconomic profiles and lifestyles in AH/LLD users compared with non-users.</p

Clinical characteristics of DM-PM ILD

Background : Dermatomyositis (DM) and polymyositis (PM) often have association with interstitial lung disease (ILD) which have disease specific autoantibody. Methodology :We reviewed medical records of DM/PM associated ILD from January 2000 to December 2017 according to the autoantibody. Result : We identified 52 patients, of whom30 were antibody negative, 18 had anti aminoacyl-tRNA synthetases (ARS) antibodies and 4 had anti melanoma differentiation-associated gene (MDA)-5 antibody. In high resolution computed tomography (HRCT) of the chest, area of ground glass opacity (GGO), consolidation, and lung tip consolidation were more extensive in anti MDA-5 antibody positive patients (p=0.051, p=0.026, and p=0.027, respectively). Among laboratory findings, GOT had strong correlations with CPK (r=0.889, p<0.001), and LDH (r=0.910, p<0.001). Among roentgenographic findings, there were moderate correlations between GGO and consolidation (r=0.668, p<0.001), and between reticular shadow and traction bronchiectasis (p=0.633, p<0.001). ILD patients with anti MDA-5 antibodies had decreased survival (1.00 vs 84.3, 22.9 months, p<0.001). Conclusion : ILD patients with anti ARS antibody had intense inflammation, but reversible fibrosis and good prognosis. On the other hand, anti MDA-5 antibody positive ILD patients had shorter survival. Extent of parenchymal shadow and serum GOT were useful indicator of disease activity of PM/DM associated ILD patients in our cohort

Clinical characteristics of DM-PM ILD

Background : Dermatomyositis (DM) and polymyositis (PM) often have association with interstitial lung disease (ILD) which have disease specific autoantibody. Methodology :We reviewed medical records of DM/PM associated ILD from January 2000 to December 2017 according to the autoantibody. Result : We identified 52 patients, of whom30 were antibody negative, 18 had anti aminoacyl-tRNA synthetases (ARS) antibodies and 4 had anti melanoma differentiation-associated gene (MDA)-5 antibody. In high resolution computed tomography (HRCT) of the chest, area of ground glass opacity (GGO), consolidation, and lung tip consolidation were more extensive in anti MDA-5 antibody positive patients (p=0.051, p=0.026, and p=0.027, respectively). Among laboratory findings, GOT had strong correlations with CPK (r=0.889, p<0.001), and LDH (r=0.910, p<0.001). Among roentgenographic findings, there were moderate correlations between GGO and consolidation (r=0.668, p<0.001), and between reticular shadow and traction bronchiectasis (p=0.633, p<0.001). ILD patients with anti MDA-5 antibodies had decreased survival (1.00 vs 84.3, 22.9 months, p<0.001). Conclusion : ILD patients with anti ARS antibody had intense inflammation, but reversible fibrosis and good prognosis. On the other hand, anti MDA-5 antibody positive ILD patients had shorter survival. Extent of parenchymal shadow and serum GOT were useful indicator of disease activity of PM/DM associated ILD patients in our cohort

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

Acute mountain sickness.

Acute mountain sickness (AMS) is a clinical syndrome occurring in otherwise healthy normal individuals who ascend rapidly to high altitude. Symptoms develop over a period ofa few hours or days. The usual symptoms include headache, anorexia, nausea, vomiting, lethargy, unsteadiness of gait, undue dyspnoea on moderate exertion and interrupted sleep. AMS is unrelated to physical fitness, sex or age except that young children over two years of age are unduly susceptible. One of the striking features ofAMS is the wide variation in individual susceptibility which is to some extent consistent. Some subjects never experience symptoms at any altitude while others have repeated attacks on ascending to quite modest altitudes. Rapid ascent to altitudes of 2500 to 3000m will produce symptoms in some subjects while after ascent over 23 days to 5000m most subjects will be affected, some to a marked degree. In general, the more rapid the ascent, the higher the altitude reached and the greater the physical exertion involved, the more severe AMS will be. Ifthe subjects stay at the altitude reached there is a tendency for acclimatization to occur and symptoms to remit over 1-7 days

Language endangerment and language documentation in Africa

Non peer reviewe

Global wealth disparities drive adherence to COVID-safe pathways in head and neck cancer surgery

Peer reviewe

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Percutaneous revascularization for ischemic left ventricular dysfunction: Cost-effectiveness analysis of the REVIVED-BCIS2 trial

BACKGROUND: Percutaneous coronary intervention (PCI) is frequently undertaken in patients with ischemic left ventricular systolic dysfunction. The REVIVED (Revascularization for Ischemic Ventricular Dysfunction)-BCIS2 (British Cardiovascular Society-2) trial concluded that PCI did not reduce the incidence of all-cause death or heart failure hospitalization; however, patients assigned to PCI reported better initial health-related quality of life than those assigned to optimal medical therapy (OMT) alone. The aim of this study was to assess the cost-effectiveness of PCI+OMT compared with OMT alone. METHODS: REVIVED-BCIS2 was a prospective, multicenter UK trial, which randomized patients with severe ischemic left ventricular systolic dysfunction to either PCI+OMT or OMT alone. Health care resource use (including planned and unplanned revascularizations, medication, device implantation, and heart failure hospitalizations) and health outcomes data (EuroQol 5-dimension 5-level questionnaire) on each patient were collected at baseline and up to 8 years post-randomization. Resource use was costed using publicly available national unit costs. Within the trial, mean total costs and quality-adjusted life-years (QALYs) were estimated from the perspective of the UK health system. Cost-effectiveness was evaluated using estimated mean costs and QALYs in both groups. Regression analysis was used to adjust for clinically relevant predictors. RESULTS: Between 2013 and 2020, 700 patients were recruited (mean age: PCI+OMT=70 years, OMT=68 years; male (%): PCI+OMT=87, OMT=88); median follow-up was 3.4 years. Over all follow-ups, patients undergoing PCI yielded similar health benefits at higher costs compared with OMT alone (PCI+OMT: 4.14 QALYs, £22 352; OMT alone: 4.16 QALYs, £15 569; difference: −0.015, £6782). For both groups, most health resource consumption occurred in the first 2 years post-randomization. Probabilistic results showed that the probability of PCI being cost-effective was 0. CONCLUSIONS: A minimal difference in total QALYs was identified between arms, and PCI+OMT was not cost-effective compared with OMT, given its additional cost. A strategy of routine PCI to treat ischemic left ventricular systolic dysfunction does not seem to be a justifiable use of health care resources in the United Kingdom