Net clinical benefit of antiplatelet therapy was affected by patient preferences:A personalized benefit-risk assessment

Objectives: To assess the effect of patient preferences on the net clinical benefit (NCB) of an antiplatelet therapy for the secondary prevention of cardiovascular complications. Study Design and Setting: Risk equations were developed to estimate the individual predicted risk of key outcomes of antiplatelet treatment in patients with a prior myocardial infarction using the Clinical Practice Research Datalink linked to the Hospital Episode Statistics and UK Office of National Statistics databases. Patient preferences for outcomes of antiplatelet therapies were elicited in a separate discrete choice experiment survey. Trial hazard ratios, relative to placebo, were used to calculate the per-patient NCB using equal or preference weighting of outcomes. Results: Risk equations were estimated using 31,941 adults in the Clinical Practice Research Datalink population, of which 22,125 were included in the benefit-risk assessment. The mean NCB was lower in the preference-weighted than in the equal-weighted analysis (0.040 vs. 0.057; P < 0.0001), but the direction of effect was unchanged by the weighting. In analyses stratified by the presence of bleeding risk factors, including preference weighting altered the ranking of subgroups by NCB. Conclusion: Patient preference weighting may have a significant effect on NCB and should be included in personalized benefit-risk assessments

Comparing Patient Preferences for Antithrombotic Treatment During the Acute and Chronic Phases of Myocardial Infarction:A Discrete-Choice Experiment

BACKGROUND: Antithrombotic drugs are used as preventive treatment in patients with a prior myocardial infarction (MI) in both the acute and chronic phases of the disease. To support patient-centered benefit–risk assessment, it is important to understand the influence of disease stage on patient preferences. OBJECTIVE: The aim of this study was to examine patient preferences for antithrombotic treatments and whether they differ by MI disease phase. METHODS: A discrete-choice experiment was used to elicit preferences of adults in the acute (≤ 365 days before enrolment) or chronic phase (> 365 days before enrolment) of MI for key ischemic events (risk of cardiovascular [CV] death, non-fatal MI, and non-fatal ischemic stroke) and bleeding events (risk of non-fatal intracranial hemorrhage and non-fatal other severe bleeding). Preference data were analyzed using the multinomial logit model. Trade-offs between attributes were calculated as the maximum acceptable increase in the risk of CV death for a decrease in the risk of the other outcomes. To assess the potential effect of sociodemographic and clinical characteristics on patient preferences, subgroups were introduced as interaction terms in logit models. RESULTS: The evaluable population included 155 patients with MI in the acute phase of disease and 180 in the chronic phase. The overall population was 82% male, mean age was 64.2 ± 9.6 years, and 93% had not experienced bleeding events or key ischemic events other than MI. Patients valued reduction in the risk of non-fatal intracranial hemorrhage more than CV death (p < 0.01) and CV death more than non-fatal ischemic events (p < 0.01). Preferences were similar in the acute and chronic populations (p = 0.17). However, older patients valued reduction in risk of MI more than younger patients (p = 0.04), and patients with bleeding risk factors valued reduction in the risk of CV death (p = 0.01) and MI (p = 0.01) less than patients without bleeding risk factors. Also, patients who were at high risk of future ischemic events valued reduction of the risk of CV death less than those at low risk (p = 0.01). CONCLUSION: Patient preferences for antithrombotic treatments were unaffected by disease stage but varied by bleeding risk and other factors. This heterogeneity in preferences is an important consideration because it can affect the benefit–risk balance and the acceptability of antithrombotic treatments to patients. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40271-021-00548-6

An Open Platform That Allows Non-Expert Users to Build and Deploy Speech-Enabled Online CALL Courses (demo description)

Abstract We demonstrate Open CALL-SLT, a framework which allows non-experts to design, implement and deploy online speechenabled CALL courses. The demo accompanies two long papers [1, 2] also appearing at the SLaTE 2015 workshop, which describe the platform in detail

The positive mental health instrument: development and validation of a culturally relevant scale in a multi-ethnic asian population

<p>Abstract</p> <p>Background</p> <p>Instruments to measure mental health and well-being are largely developed and often used within Western populations and this compromises their validity in other cultures. A previous qualitative study in Singapore demonstrated the relevance of spiritual and religious practices to mental health, a dimension currently not included in exiting multi-dimensional measures. The objective of this study was to develop a self-administered measure that covers all key and culturally appropriate domains of mental health, which can be applied to compare levels of mental health across different age, gender and ethnic groups. We present the item reduction and validation of the Positive Mental Health (PMH) instrument in a community-based adult sample in Singapore.</p> <p>Methods</p> <p>Surveys were conducted among adult (21-65 years) residents belonging to Chinese, Malay and Indian ethnicities. Exploratory and confirmatory factor analysis (EFA, CFA) were conducted and items were reduced using item response theory tests (IRT). The final version of the PMH instrument was tested for internal consistency and criterion validity. Items were tested for differential item functioning (DIF) to check if items functioned in the same way across all subgroups. <b>Results: </b>EFA and CFA identified six first-order factor structure (General coping, Personal growth and autonomy, Spirituality, Interpersonal skills, Emotional support, and Global affect) under one higher-order dimension of Positive Mental Health (RMSEA = 0.05, CFI = 0.96, TLI = 0.96). A 47-item self-administered multi-dimensional instrument with a six-point Likert response scale was constructed. The slope estimates and strength of the relation to the theta for all items in each six PMH subscales were high (range:1.39 to 5.69), suggesting good discrimination properties. The threshold estimates for the instrument ranged from -3.45 to 1.61 indicating that the instrument covers entire spectrums for the six dimensions. The instrument demonstrated high internal consistency and had significant and expected correlations with other well-being measures. Results confirmed absence of DIF.</p> <p>Conclusions</p> <p>The PMH instrument is a reliable and valid instrument that can be used to measure and compare level of mental health across different age, gender and ethnic groups in Singapore.</p

Associations with photoreceptor thickness measures in the UK Biobank.

Spectral-domain OCT (SD-OCT) provides high resolution images enabling identification of individual retinal layers. We included 32,923 participants aged 40-69 years old from UK Biobank. Questionnaires, physical examination, and eye examination including SD-OCT imaging were performed. SD OCT measured photoreceptor layer thickness includes photoreceptor layer thickness: inner nuclear layer-retinal pigment epithelium (INL-RPE) and the specific sublayers of the photoreceptor: inner nuclear layer-external limiting membrane (INL-ELM); external limiting membrane-inner segment outer segment (ELM-ISOS); and inner segment outer segment-retinal pigment epithelium (ISOS-RPE). In multivariate regression models, the total average INL-RPE was observed to be thinner in older aged, females, Black ethnicity, smokers, participants with higher systolic blood pressure, more negative refractive error, lower IOPcc and lower corneal hysteresis. The overall INL-ELM, ELM-ISOS and ISOS-RPE thickness was significantly associated with sex and race. Total average of INL-ELM thickness was additionally associated with age and refractive error, while ELM-ISOS was additionally associated with age, smoking status, SBP and refractive error; and ISOS-RPE was additionally associated with smoking status, IOPcc and corneal hysteresis. Hence, we found novel associations of ethnicity, smoking, systolic blood pressure, refraction, IOPcc and corneal hysteresis with photoreceptor thickness

The Relationship Between Ambient Atmospheric Fine Particulate Matter (PM2.5) and Glaucoma in a Large Community Cohort.

Purpose: Glaucoma is more common in urban populations than in others. Ninety percent of the world's population are exposed to air pollution above World Health Organization (WHO) recommended limits. Few studies have examined the association between air pollution and glaucoma. Methods: Questionnaire data, ophthalmic measures, and ambient residential area air quality data for 111,370 UK Biobank participants were analyzed. Particulate matter with an aerodynamic diameter < 2.5 μm (PM2.5) was selected as the air quality exposure of interest. Eye measures included self-reported glaucoma, intraocular pressure (IOP), and average thickness of macular ganglion cell-inner plexiform layer (GCIPL) across nine Early Treatment Diabetic Retinopathy Study (ETDRS) retinal subfields as obtained from spectral-domain optical coherence tomography. We examined the associations of PM2.5 concentration with self-reported glaucoma, IOP, and GCIPL. Results: Participants resident in areas with higher PM2.5 concentration were more likely to report a diagnosis of glaucoma (odds ratio = 1.06, 95% confidence interval [CI] = 1.01-1.12, per interquartile range [IQR] increase P = 0.02). Higher PM2.5 concentration was also associated with thinner GCIPL (β = -0.56 μm, 95% CI = -0.63 to -0.49, per IQR increase, P = 1.2 × 10-53). A dose-response relationship was observed between higher levels of PM2.5 and thinner GCIPL (P < 0.001). There was no clinically relevant relationship between PM2.5 concentration and IOP. Conclusions: Greater exposure to PM2.5 is associated with both self-reported glaucoma and adverse structural characteristics of the disease. The absence of an association between PM2.5 and IOP suggests the relationship may occur through a non-pressure-dependent mechanism, possibly neurotoxic and/or vascular effects

Retinal asymmetry in multiple sclerosis.

The diagnosis of multiple sclerosis is based on a combination of clinical and paraclinical tests. The potential contribution of retinal optical coherence tomography (OCT) has been recognized. We tested the feasibility of OCT measures of retinal asymmetry as a diagnostic test for multiple sclerosis at the community level. In this community-based study of 72 120 subjects, we examined the diagnostic potential of the inter-eye difference of inner retinal OCT data for multiple sclerosis using the UK Biobank data collected at 22 sites between 2007 and 2010. OCT reporting and quality control guidelines were followed. The inter-eye percentage difference (IEPD) and inter-eye absolute difference (IEAD) were calculated for the macular retinal nerve fibre layer (RNFL), ganglion cell inner plexiform layer (GCIPL) complex and ganglion cell complex. Area under the receiver operating characteristic curve (AUROC) comparisons were followed by univariate and multivariable comparisons accounting for a large range of diseases and co-morbidities. Cut-off levels were optimized by ROC and the Youden index. The prevalence of multiple sclerosis was 0.0023 [95% confidence interval (CI) 0.00229-0.00231]. Overall the discriminatory power of diagnosing multiple sclerosis with the IEPD AUROC curve (0.71, 95% CI 0.67-0.76) and IEAD (0.71, 95% CI 0.67-0.75) for the macular GCIPL complex were significantly higher if compared to the macular ganglion cell complex IEPD AUROC curve (0.64, 95% CI 0.59-0.69, P = 0.0017); IEAD AUROC curve (0.63, 95% CI 0.58-0.68, P  0.14) with narrow confidence intervals. In conclusion, the OCT macular GCIPL complex IEPD and IEAD may be considered as supportive measurements for multiple sclerosis diagnostic criteria in a young patient without relevant co-morbidity. The metric does not allow separation of multiple sclerosis from neuromyelitis optica. Retinal OCT imaging is accurate, rapid, non-invasive, widely available and may therefore help to reduce need for invasive and more costly procedures. To be viable, higher sensitivity and specificity levels are needed