Quality of life role in risky alcohol use research: should it be a more relevant outcome in any study?

Alcohol; Calidad de vida; AUDITAlcohol; Qualitat de vida; AUDITAlcohol; Quality of life; AUDITA partir de los datos basales del estudio EFAR-Spain para la validación de una intervención breve en línea en consumidores de riesgo de alcohol facilitado desde atención primaria nos hemos propuesto explorar la relación entre la calidad de vida (medida a través de la escala EQ-5D-5L ) y el patrón de consumo de alcohol (a partir del AUDIT). Utilizamos como variable principal dependiente la calidad de vida y las seis diferentes dimensiones de la misma (ansiedad/depresión, escala analógica-visual, dolor/incomodidad, movilidad, autocuidado, actividades diarias), y como variables independientes la puntuación en el AUDIT y los datos sociodemográficos. El análisis multivariante confirmó la asociación estadística de la calidad de vida (regresión linear B-0.25 IC95%-0.01 a -0.04), la subescala de depresión/ansiedad (regresión logística: OR 1.10 IC95% 1.08-1.22), y la subescala analógica-visual (regresión lineal B-0.27 IC95% -1.25 a -0.500) con puntuación total del AUDIT de forma independiente de los factores sociodemográficos. Teniendo en cuenta que en la asistencia del paciente con problemas de alcohol la reducción de consumo de alcohol puede ser un objetivo terapéutico alcanzable y respetuoso con la ética profesional en los casos leves y moderados y que la auto-evaluación del patrón de consumo de alcohol por parte del paciente no está exenta de minimizaciones en las cantidades y frecuencias, tal vez podría ser adecuado evaluar la evolución de nuestros pacientes en función de los cambios en la calidad de vida como respuesta al tratamiento.Using basal data from EFAR-Spain (A randomised controlled non-inferiority trial of primary care-based facilitated access to an alcohol reduction website) we explored the relationship between quality of life (QoL, as evaluated by EQ-5D-5L) and pattern of alcohol use (as evaluated by AUDIT) . Multivariate regression analyses were conducted using total QoL index and QoL six dimensions (anxiety/depression, Visual Analogue Scale (VAS), pain, mobility, self-care, daily activities) as dependent variables and AUDIT score and sociodemographic data as independent variables. Adjusting for sociodemographic data, AUDIT score was a statiscally significant predictor of overall QoL (lineal regression B-0.25 95% CI -0.04 to -0.01), anxiety/depression (logistic regression OR 1.10 95% CI 1.08-1.22) and health VAS (lineal regression B-0.27 95% CI -1.25 to -0.500). Since reducing alcohol intake can be a reasonable and ethically correct therapeutic objective in mild and moderate alcohol use disorders and since alcohol use pattern self-assessment has several limitations, perhaps assessing changes in QoL over time could be useful to monitor our patients recovery.Este trabajo ha sido financiado por el proyecto PI042924 del Instituto de Salud Carlos III (Ministerio de Economía, Industria y Competitividad) I+D+R y cofinanciado por el Fondo Europeo de Desarrollo Regional (FEDER). Unión Europea. Una manera de hacer Europa (http://www.isciii.es)

Anticoagulation for atrial fibrillation in people with serious mental illness in the general hospital setting

OBJECTIVE: People with serious mental illnesses (SMI) have an increased risk of stroke compared to the general population. This study aims to evaluate oral anticoagulation prescription trends in atrial fibrillation (AF) patients with and without a comorbid SMI. METHODS: An open-source retrieval system for clinical data (CogStack) was used to identify a cohort of AF patients with SMI who ever had an inpatient admission to King's College Hospital from 2011 to 2020. A Natural Language Processing pipeline was used to calculate CHA2DS2-VASc and HASBLED risk scores from Electronic Health Records free text. Antithrombotic prescriptions of warfarin and Direct acting oral anti-coagulants (DOACs) (apixaban, rivaroxaban, dabigatran, edoxaban) were extracted from discharge summaries. RESULTS: Among patients included in the study (n = 16 916), 2.7% had a recorded co-morbid SMI diagnosis. Compared to non-SMI patients, those with SMI had significantly higher CHA2DS2-VASc (mean (SD): 5.3 (1.96) vs 4.7 (2.08), p < 0.001) and HASBLED scores (mean (SD): 3.2 (1.27) vs 2.5 (1.29), p < 0.001). Among AF patients having a CHA2DS2-VASc ≥2, those with co-morbid SMI were less likely than non-SMI patients to be prescribed an OAC (44% vs 54%, p < 0.001). However, there was no evidence of a significant difference between the two groups since 2019. CONCLUSION: Over recent years, DOAC prescription rates have increased among AF patients with SMI in acute hospitals. More research is needed to confirm whether the introduction of DOACs has reduced OAC treatment gaps in people with serious mental illness and to assess whether the use of DOACs has improved health outcomes in this population

Digital brief interventions for risky drinkers are not the panacea: a pilot study exploring barriers for its implementation according to professionals' perceptions

Alcohol; Brief interventions; E-health; Implementation; Risky drinkersAlcohol; Intervencions breus; Salut electrònica; Implementació; Bevedors de riscAlcohol; Intervenciones breves; Salud electrónica; Implementación; Bebedores de riesgoDigital brief interventions have emerged as an instrument to improve the implementation of Screening, Brief Intervention and Referral to Treatment programs for risky drinkers. However, trials in Catalonia have been unsuccessful. This study was aimed at researching professionals' perceptions regarding the usefulness of digital brief interventions in overcoming traditional barriers of face-to-face Screening, Brief Intervention and Referral to Treatment and new barriers posed by the use of digital brief interventions. Professionals who participated in the Effectiveness of primary care based Facilitated Access to alcohol Reduction website (EFAR)digital brief intervention clinical trial were surveyed on April 2017 on the following areas: (1) satisfaction, (2) usefulness, (3) perceived ability of digital interventions on overcoming traditional barriers and (4) perceived new barriers of digital interventions. Sixty-eight professionals completed the survey. Univariate and multivariate analyses were performed using the level of professional engagement with the project as the dependent variable, barriers as independent variables and socio-demographic characteristics as covariables. Of all professionals, 79.4 percent were satisfied with their participation in the project, but only 26.5 percent perceived the website as useful. Low engagement was associated with the perceived lack of feedback (0.22; 95% confidence interval: 0.05 -0.88), perception that it was difficult to use among the elderly(0.22; 95 confidence interval: 0.05 -0.091) and among low socioeconomic population (0.14; 95% confidence interval: 0.03 -0.64). The majority of the participants indicated that digital brief intervention for risky drinkers succeeded in overcoming most of the traditional barriers. However, new barriers emerged as difficulties for implementing digital brief interventions in the Catalan Primary Health Care System. Usefulness perception is a key factor, which must be addressed in any proposed intervention in primary care.This work was funded by project PI042924 integrated in the National R+D+I and funded by the Carlos III Health Institute-Deputy General Assessment and the European Regional Development Fund (ERDF) (http://www.isciii.es). H.L.-P. received funding from the Spanish Ministry of Science, Innovation and Universities, Instituto de Salud Carlos III through a “Rıo Hortega” contract (CM17/00123, to Dr LópezPelayo), with the support of the European Social Fund

A randomised controlled non-inferiority trial of primary care-based facilitated access to an alcohol reduction website (EFAR Spain): the study protocol

Detecció d'alcoholèmia; Intervenció breu; Atenció electrònicaDetección de alcoholemia; Intervención breve; Atención electrónicaAlcoholism detection; Brief intervention; Electronic attentionIntroduction: Early identification (EI) and brief interventions (BIs) for risky drinkers are effective tools in primary care. Lack of time in daily practice has been identified as one of the main barriers to implementation of BI. There is growing evidence that facilitated access by primary healthcare professionals (PHCPs) to a web-based BI can be a time-saving alternative to standard face-to-face BIs, but there is as yet no evidence about the effectiveness of this approach relative to conventional BI. The main aim of this study is to test non-inferiority of facilitation to a web-based BI for risky drinkers delivered by PHCP against face-to-face BI. Method and analysis: A randomised controlled non-inferiority trial comparing both interventions will be performed in primary care health centres in Catalonia, Spain. Unselected adult patients attending participating centres will be given a leaflet inviting them to log on to a website to complete the Alcohol Use Disorders Identification Test (AUDIT-C) alcohol screening questionnaire. Participants with positive results will be requested online to complete a trial module including consent, baseline assessment and randomisation to either face-to-face BI by the practitioner or BI via the alcohol reduction website. Follow-up assessment of risky drinking will be undertaken online at 3 months and 1 year using the full AUDIT and D5-EQD5 scale. Proportions of risky drinkers in each group will be calculated and non-inferiority assessed against a specified margin of 10%. Assuming reduction of 30% of risky drinkers receiving standard intervention, 1000 patients will be required to give 90% power to reject the null hypothesis. Ethics and dissemination: The protocol was approved by the Ethics Commmittee of IDIAP Jordi Gol i Gurina P14/028. The findings of the trial will be disseminated through peer-reviewed journals, national and international conference presentations.This work has been funded by project PI042924 integrated in theNational R+D+I and funded by the Carlos III Health Institute-Deputy GeneralAssessment and the European Regional Development Fund (ERDF)

Planning for the Lifecycle Management and Long-Term Preservation of Research Data: A Federated Approach

Outcomes of the grant are archived here.The “data deluge” is a recent but increasingly well-understood phenomenon of scientific and social inquiry. Large-scale research instruments extend our observational power by many orders of magnitude but at the same time generate massive amounts of data. Researchers work feverishly to document and preserve changing or disappearing habitats, cultures, languages, and artifacts resulting in volumes of media in various formats. New software tools mine a growing universe of historical and modern texts and connect the dots in our semantic environment. Libraries, archives, and museums undertake digitization programs creating broad access to unique cultural heritage resources for research. Global-scale research collaborations with hundreds or thousands of participants, drive the creation of massive amounts of data, most of which cannot be recreated if lost. The University of Kansas (KU) Libraries in collaboration with two partners, the Greater Western Library Alliance (GWLA) and the Great Plains Network (GPN), received an IMLS National Leadership Grant designed to leverage collective strengths and create a proposal for a scalable and federated approach to the lifecycle management of research data based on the needs of GPN and GWLA member institutions.Institute for Museum and Library Services LG-51-12-0695-1

Language and memory for object location

In three experiments, we investigated the influence of two types of language on memory for object location: demonstratives (this, that) and possessives (my, your). Participants first read instructions containing demonstratives/possessives to place objects at different locations, and then had to recall those object locations (following object removal). Experiments 1 and 2 tested contrasting predictions of two possible accounts of language on object location memory: the Expectation Model (Coventry, Griffiths, & Hamilton, 2014) and the congruence account (Bonfiglioli, Finocchiaro, Gesierich, Rositani, & Vescovi, 2009). In Experiment 3, the role of attention allocation as a possible mechanism was investigated. Results across all three experiments show striking effects of language on object location memory, with the pattern of data supporting the Expectation Model. In this model, the expected location cued by language and the actual location are concatenated leading to (mis)memory for object location, consistent with models of predictive coding (Bar, 2009; Friston, 2003)

Biomarkers of rapid chronic kidney disease progression in type 2 diabetes.

Here we evaluated the performance of a large set of serum biomarkers for the prediction of rapid progression of chronic kidney disease (CKD) in patients with type 2 diabetes. We used a case-control design nested within a prospective cohort of patients with baseline eGFR 30-60 ml/min per 1.73 m(2). Within a 3.5-year period of Go-DARTS study patients, 154 had over a 40% eGFR decline and 153 controls maintained over 95% of baseline eGFR. A total of 207 serum biomarkers were measured and logistic regression was used with forward selection to choose a subset that were maximized on top of clinical variables including age, gender, hemoglobin A1c, eGFR, and albuminuria. Nested cross-validation determined the best number of biomarkers to retain and evaluate for predictive performance. Ultimately, 30 biomarkers showed significant associations with rapid progression and adjusted for clinical characteristics. A panel of 14 biomarkers increased the area under the ROC curve from 0.706 (clinical data alone) to 0.868. Biomarkers selected included fibroblast growth factor-21, the symmetric to asymmetric dimethylarginine ratio, β2-microglobulin, C16-acylcarnitine, and kidney injury molecule-1. Use of more extensive clinical data including prebaseline eGFR slope improved prediction but to a lesser extent than biomarkers (area under the ROC curve of 0.793). Thus we identified several novel associations of biomarkers with CKD progression and the utility of a small panel of biomarkers to improve prediction.We acknowledge all the SUMMIT partners (http://www.imi-summit.eu/) for their assistance with this project. This work was funded by the Innovative Medicine Initiative under grant agreement no. IMI/115006 (the SUMMIT consortium) and the Go-DARTS cohort was funded by the Chief Scientists Office Scotland.This is the accepted manuscript of a paper published in Kidney International (Looker et al., Kidney International, 2015 doi: 10.1038/ki.2015.199). The final version is available at http://dx.doi.org/10.1038/ki.2015.19

Apolipoprotein CIII and N-terminal prohormone b-type natriuretic peptide as independent predictors for cardiovascular disease in type 2 diabetes

Background and aims: Developing sparse panels of biomarkers for cardiovascular disease in type 2 diabetes would enable risk stratification for clinical decision making and selection into clinical trials. We examined the individual and joint performance of five candidate biomarkers for incident cardiovascular disease (CVD) in type 2 diabetes that an earlier discovery study had yielded. Methods: Apolipoprotein CIII (apoCIII), N-terminal prohormone B-type natriuretic peptide (NT-proBNP), high sensitivity Troponin T (hsTnT), Interleukin-6, and Interleukin-15 were measured in baseline serum samples from the Collaborative Atorvastatin Diabetes trial (CARDS) of atorvastatin versus placebo. Among 2105 persons with type 2 diabetes and median age of 62.9 years (range 39.2–77.3), there were 144 incident CVD (acute coronary heart disease or stroke) cases during the maximum 5-year follow up. We used Cox Proportional Hazards models to identify biomarkers associated with incident CVD and the area under the receiver operating characteristic curves (AUROC) to assess overall model prediction. Results: Three of the biomarkers were singly associated with incident CVD independently of other risk factors; NT-proBNP (Hazard Ratio per standardised unit 2.02, 95% Confidence Interval [CI] 1.63, 2.50), apoCIII (1.34, 95% CI 1.12, 1.60) and hsTnT (1.40, 95% CI 1.16, 1.69). When combined in a single model, only NT-proBNP and apoCIII were independent predictors of CVD, together increasing the AUROC using Framingham risk variables from 0.661 to 0.745. Conclusions: The biomarkers NT-proBNP and apoCIII substantially increment the prediction of CVD in type 2 diabetes beyond that obtained with the variables used in the Framingham risk score

Serum kidney injury molecule 1 and β2-microglobulin perform as well as larger biomarker panels for prediction of rapid decline in renal function in type 2 diabetes

Aims/hypothesis: As part of the Surrogate Markers for Micro- and Macrovascular Hard Endpoints for Innovative Diabetes Tools (SUMMIT) programme we previously reported that large panels of biomarkers derived from three analytical platforms maximised prediction of progression of renal decline in type 2 diabetes. Here, we hypothesised that smaller (n ≤ 5), platform-specific combinations of biomarkers selected from these larger panels might achieve similar prediction performance when tested in three additional type 2 diabetes cohorts. Methods: We used 657 serum samples, held under differing storage conditions, from the Scania Diabetes Registry (SDR) and Genetics of Diabetes Audit and Research Tayside (GoDARTS), and a further 183 nested case–control sample set from the Collaborative Atorvastatin in Diabetes Study (CARDS). We analysed 42 biomarkers measured on the SDR and GoDARTS samples by a variety of methods including standard ELISA, multiplexed ELISA (Luminex) and mass spectrometry. The subset of 21 Luminex biomarkers was also measured on the CARDS samples. We used the event definition of loss of >20% of baseline eGFR during follow-up from a baseline eGFR of 30–75 ml min−1 [1.73 m]−2. A total of 403 individuals experienced an event during a median follow-up of 7 years. We used discrete-time logistic regression models with tenfold cross-validation to assess association of biomarker panels with loss of kidney function. Results: Twelve biomarkers showed significant association with eGFR decline adjusted for covariates in one or more of the sample sets when evaluated singly. Kidney injury molecule 1 (KIM-1) and β2-microglobulin (B2M) showed the most consistent effects, with standardised odds ratios for progression of at least 1.4 (p < 0.0003) in all cohorts. A combination of B2M and KIM-1 added to clinical covariates, including baseline eGFR and albuminuria, modestly improved prediction, increasing the area under the curve in the SDR, Go-DARTS and CARDS by 0.079, 0.073 and 0.239, respectively. Neither the inclusion of additional Luminex biomarkers on top of B2M and KIM-1 nor a sparse mass spectrometry panel, nor the larger multiplatform panels previously identified, consistently improved prediction further across all validation sets. Conclusions/interpretation: Serum KIM-1 and B2M independently improve prediction of renal decline from an eGFR of 30–75 ml min−1 [1.73 m]−2 in type 2 diabetes beyond clinical factors and prior eGFR and are robust to varying sample storage conditions. Larger panels of biomarkers did not improve prediction beyond these two biomarkers

Risk of acute kidney injury and survival in patients treated with Metformin:an observational cohort study

Background: Whether metformin precipitates lactic acidosis in patients with chronic kidney disease (CKD) remains under debate. We examined whether metformin use was associated with an increased risk of acute kidney injury (AKI) as a proxy for lactic acidosis and whether survival among those with AKI varied by metformin exposure. Methods: All individuals with type 2 diabetes and available prescribing data between 2004 and 2013 in Tayside, Scotland were included. The electronic health record for diabetes which includes issued prescriptions was linked to laboratory biochemistry, hospital admission, death register and Scottish Renal Registry data. AKI events were defined using the Kidney Disease Improving Global Outcomes criteria with a rise in serum creatinine of at least 26.5 μmol/l or a rise of greater than 150% from baseline for all hospital admissions. Cox Regression Analyses were used to examine whether person-time periods in which current metformin exposure occurred were associated with an increased rate of first AKI compared to unexposed periods. Cox regression was also used to compare 28 day survival rates following first AKI events in those exposed to metformin versus those not exposed. Results: Twenty-five thousand one-hundred fourty-eight patients were included with a total person-time of 126,904 person years. 4944 (19.7%) people had at least one episode of AKI during the study period. There were 32.4 cases of first AKI/1000pyrs in current metformin exposed person-time periods compared to 44.9 cases/1000pyrs in unexposed periods. After adjustment for age, sex, diabetes duration, calendar time, number of diabetes drugs and baseline renal function, current metformin use was not associated with AKI incidence, HR 0.94 (95% CI 0.87, 1.02, p = 0.15). Among those with incident AKI, being on metformin at admission was associated with a higher rate of survival at 28 days (HR 0.81, 95% CI 0.69, 0.94, p = 0.006) even after adjustment for age, sex, pre-admission eGFR, HbA1c and diabetes duration. Conclusions: Contrary to common perceptions, we found no evidence that metformin increases incidence of AKI and was associated with higher 28 day survival following incident AKI