Validation of a risk prediction model for COVID-19: the PERIL prospective cohort study.

Aim: This study aims to perform an external validation of a recently developed prognostic model for early prediction of the risk of progression to severe COVID-19. Patients & methods/materials: Patients were recruited at their initial diagnosis at two facilities within Hamad Medical Corporation in Qatar. 356 adults were included for analysis. Predictors for progression of COVID-19 were all measured at disease onset and first contact with the health system. Results: The C statistic was 83% (95% CI: 78%-87%) and the calibration plot showed that the model was well-calibrated. Conclusion: The published prognostic model for the progression of COVID-19 infection showed satisfactory discrimination and calibration and the model is easy to apply in clinical practice.d.

Income inequality and its association with COVID-19 cases and deaths: a cross-country analysis in the Eastern Mediterranean region.

INTRODUCTION: There is limited evidence on the associations between economic and social disparities in the Eastern Mediterranean region (EMR) with COVID-19 infections and deaths. This study aims to investigate the relationship between income inequalities using Gini coefficients and COVID-19 cases and deaths per million population in the EMR countries. METHODS: Country-level data on monthly COVID-19 cases and deaths between March 2020 and October 2021, along with data on selected confounders, were collected from publicly available databases. Mixed-effect negative binomial and inverse hyperbolic sine transformation regressions were estimated to examine the association. RESULTS: The study showed that, in the EMR, a unit increase in Gini coefficient is associated with approximately 7.2% and 3.9% increase in COVID-19 cases and deaths per million population, respectively. The magnitude and direction of the association between income inequality and COVID-19 cases and deaths per-million population still remain the same after excluding four warzone countries from the analysis. CONCLUSION: This increase in COVID-19 cases and deaths is underpinned by the fact that a large number of the population in the region is living in conditions of poverty, with inadequate housing, comorbidities and limited or virtually no access to essential healthcare services. Healthcare policy-makers across countries in the region need to implement effective interventions in areas of income inequality, where it may be linked to increasing the risk of COVID-19 cases and deaths.

Infliximab versus ciclosporin in steroid resistant acute severe ulcerative colitis: a model-based cost-utility analysis of data from CONSTRUCT pragmatic trial.

BACKGROUND: There is limited evidence in the literature on the long-term effectiveness and cost-effectiveness of treatments for Acute Severe Ulcerative Colitis (ASUC). The study aimed to perform decision analytic model-based long-term cost-utility analysis (CUA) of infliximab versus ciclosporin for steroid-resistant ASUC investigated in CONSTRUCT pragmatic trial. METHODS: A decision tree (DT) model was developed using two-year health effect, resource use and costs data from CONSTRUCT trial to estimate relative cost-effectiveness of two competing drugs from the United Kingdom (UK) National Health Services (NHS) perspective. Using short-term trial data, a Markov model (MM) was then developed and evaluated over further 18 years. Both DT and MM were combined to investigate cost-effectiveness of infliximab versus ciclosporin for ASUC patients over 20-year time horizon, with a rigorous multiple deterministic and probabilistic sensitivity analyses to address uncertainty in results. RESULTS: The decision tree mirrored trial-based results. Beyond 2-year trial follow-up, Markov model predicted a decrease in colectomy rate, but it remained slightly higher for ciclosporin. NHS costs and quality adjusted life years (QALYs) over base-case 20 year time horizon were £26,793 and 9.816 for ciclosporin and £34,185 and 9.106 for infliximab, suggesting ciclosporin dominates infliximab. Ciclosporin had 95% probability of being cost-effective at a willingness-to-pay (WTP) threshold value up to £20,000. CONCLUSION: Using data from a pragmatic RCT, the cost-effectiveness models produced incremental net health benefit in favour of ciclosporin relative to infliximab. Results from long-term modelling indicated that ciclosporin remains dominant compared with infliximab for the treatment of NHS ASUC patients, however, these need to be interpreted cautiously. TRIAL REGISTRATION: CONSTRUCT Trial registration number ISRCTN22663589; EudraCT number: 2008- 001968-36 (Date 27/08/2008).

The Economic Impact of Optimizing a COVID-19 Management Protocol in Pre-Existing Cardiovascular Disease Patients.

This study answers the question of whether the health care costs of managing COVID-19 in preexisting cardiovascular diseases (CVD) patients increased or decreased as a consequence of evidence-based efforts to optimize the initial COVID-19 management protocol in a CVD group of patients. A retrospective cohort study was conducted in preexisting CVD patients with COVID-19 in Hamad Medical Corporation, Qatar. From the health care perspective, only direct medical costs were considered, adjusted to their 2021 values. The impact of revising the protocol was a reduction in the overall costs in non-critically ill patients from QAR15,447 (USD 4243) to QAR4337 (USD 1191) per patient, with an economic benefit of QAR11,110 (USD 3051). In the critically ill patients, however, the cost increased from QAR202,094 (USD 55,505) to QAR292,856 (USD 80,433) per patient, with added cost of QAR90,762 (USD 24,928). Overall, regardless of critical care status, the optimization of the initial COVID-19 protocols in patients with preexisting CVD did not reduce overall health care costs, but increased it by QAR80,529 (USD 22,117) per patient.

The effectiveness and safety of palbociclib and ribociclib in stage IV HR+/HER-2 negative breast cancer: a nationwide real world comparative retrospective cohort study.

Introduction: Palbociclib and ribociclib are indicated in the first-line treatment of hormonal receptor-positive HER-2 negative (HR+/HER2- negative) advanced breast cancer. Although randomized-controlled trials (RCTs) proved their clinical efficacy, there are no observational studies yet to validate the clinical findings in the real-world. Therefore, this study aimed to evaluate and compare the clinical effectiveness and safety profiles of palbociclib and ribociclib in Qatar. Materials and methods: A retrospective observational study was conducted on HR+/HER-2-negative stage-IV breast cancer patients receiving palbociclib or ribociclib in the state of Qatar. Clinical data were collected from the National Center for Cancer Care and Research (NCCCR) in Qatar using Cerner®. Primary outcomes were progression-free-survival (PFS) and overall-survival (OS) generated by Kaplan-Meier curves. Moreover, safety profiles of both two treatments were evaluated. Results: The data from 108 patients were included in the final analysis. There was no statistically significant difference in PFS between the palbociclib and ribociclib groups; PFS was 17.85 versus 13.55 months, respectively(p> 0.05). Similarly, there was no statistically significant difference in OS between the two medications, 29.82 versus 31.72 months, respectively(p>0.05). Adverse events were similar between the two groups. Neutropenia was the most common side effect in the study population accounting for 59.3% of the patients. Conclusions: Therefore, both treatments have similar efficacy and safety profiles. Further research on a larger-scale population and longer follow-up period is recommeneded.

Effectiveness and cost-effectiveness of face-to-face and electronic brief interventions versus screening alone to reduce alcohol consumption among high-risk adolescents presenting to emergency departments: three-arm pragmatic randomized trial (SIPS Junior high risk trial).

BACKGROUND AND AIMS: Alcohol use increases throughout adolescence. Emergency department (ED) attendance is an opportunity for alcohol screening and brief intervention (ASBI), which is effective for adults. This trial evaluated the effectiveness and cost-effectiveness of ASBI compared with screening alone (SA) in high-risk adolescents. DESIGN, SETTING AND PARTICIPANTS: Multi-centre, three-group, single-blind, individually randomized trial with follow-ups after 6 and 12 months in 10 ED settings in England. From October 2014 to May 2015 we screened 3327 adolescents aged 14 to 18 years, of whom 756 (22.7%) scored at least 3 on the Alcohol Use Disorders Identification Test: consumption (AUDIT-C) and consented to participate in this trial. Mean age was 16.1 years; 50.2% were female and 84.9% were white. INTERVENTIONS: Interventions were personalized feedback and brief advice (PFBA), personalized feedback plus electronic brief intervention (eBI) and SA. MEASURES: The primary outcome was the weekly alcohol consumed in standard UK units (8 g ethanol) at 12 months post-randomization, derived from extended AUDIT-C. Economic outcomes included quality of life and service use, from perspectives of both the National Health Service and personal social services (NHS&PSS) and society. FINDINGS: At 12 months, mean weekly consumption was 2.99 [95% confidence interval (CI) = 2.38-3.70] standard units for the SA group, 3.56 (95% CI = 2.90, 4.32) for PFBA and 3.18 (95% CI = 2.50, 3.97) for eBI, showing no significant differences. The PFBA group consumed mean 0.57 (-0.36, 1.70) units more than SA; and eBIs consumed 0.19 (-0.71, 1.30) more. Bayes factors suggested lack of effectiveness explained non-significance. From the NHS&PSS perspective, economic analysis showed that PFBA and eBI were not cost-effective compared with SA: PFBA yielded incremental cost-effectiveness ratio of £6213 (-£736 843, £812 884), with the intervention having 54% probability of being cost-effective compared with SA at the £20 000 WTP threshold. CONCLUSIONS: In emergency departments in England, neither personalized feedback and brief advice nor personalized feedback plus electronic brief intervention showed evidence of being effective or cost-effective when compared with screening alone in reducing alcohol consumption among adolescents.

Associations with Post-Consultation Health-Status in Primary Care Managed Acute Exacerbation of COPD.

BACKGROUND: It has been demonstrated that antibiotic prescribing for Acute Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) can be safely reduced in primary care when general practitioners have access to C-reactive protein (CRP) rapid testing. AIM: To investigate the factors associated with post-consultation COPD health status in patients presenting with AECOPD in this setting. DESIGN AND SETTING: A cohort study of patients enrolled in a randomised controlled trial. Patients aged 40+ years with a clinical diagnosis of COPD who presented in primary care across England and Wales with an AECOPD were included. METHODS: Participants were contacted for follow-up at one- and two-weeks by phone and attended the practice four weeks after the index consultation. The outcome of interest was the Clinical COPD Questionnaire (CCQ) score. Multivariable multilevel linear regression models fitted to examine the factors associated with COPD health status in the four-weeks following consultation for an AECOPD. RESULTS: A total of 649 patients were included, with 1947 CCQ total scores analysed. Post-consultation CCQ total scores were significantly higher (worse) in participants with diabetes (adjusted mean difference [AMD]=0.26; 95% confidence interval (CI) 0.08-0.45), obese patients compared to those with normal body mass index (AMD = 0.25, 95% CI 0.07-0.43), and those who were prescribed oral antibiotics in the prior 12 months (AMD = 0.26; 95% CI 0.11-0.41), but only the two latter associations remained after adjusting for other sociodemographic variables. CONCLUSION: COPD health status was worse in the four weeks following primary care consultation for AECOPD in patients with obesity and those prescribed oral antibiotics in the preceding year.

QCovSML: A reliable COVID-19 detection system using CBC biomarkers by a stacking machine learning model.

The reverse transcription-polymerase chain reaction (RT-PCR) test is considered the current gold standard for the detection of coronavirus disease (COVID-19), although it suffers from some shortcomings, namely comparatively longer turnaround time, higher false-negative rates around 20-25%, and higher cost equipment. Therefore, finding an efficient, robust, accurate, and widely available, and accessible alternative to RT-PCR for COVID-19 diagnosis is a matter of utmost importance. This study proposes a complete blood count (CBC) biomarkers-based COVID-19 detection system using a stacking machine learning (SML) model, which could be a fast and less expensive alternative. This study used seven different publicly available datasets, where the largest one consisting of fifteen CBC biomarkers collected from 1624 patients (52% COVID-19 positive) admitted at San Raphael Hospital, Italy from February to May 2020 was used to train and validate the proposed model. White blood cell count, monocytes (%), lymphocyte (%), and age parameters collected from the patients during hospital admission were found to be important biomarkers for COVID-19 disease prediction using five different feature selection techniques. Our stacking model produced the best performance with weighted precision, sensitivity, specificity, overall accuracy, and F1-score of 91.44%, 91.44%, 91.44%, 91.45%, and 91.45%, respectively. The stacking machine learning model improved the performance in comparison to other state-of-the-art machine learning classifiers. Finally, a nomogram-based scoring system (QCovSML) was constructed using this stacking approach to predict the COVID-19 patients. The cut-off value of the QCovSML system for classifying COVID-19 and Non-COVID patients was 4.8. Six datasets from three different countries were used to externally validate the proposed model to evaluate its generalizability and robustness. The nomogram demonstrated good calibration and discrimination with the area under the curve (AUC) of 0.961 for the internal cohort and average AUC of 0.967 for all external validation cohort, respectively. The external validation shows an average weighted precision, sensitivity, F1-score, specificity, and overall accuracy of 92.02%, 95.59%, 93.73%, 90.54%, and 93.34%, respectively.

Overweight/Obesity and Time Preference: Evidence from a Survey among Adults in the UK.

INTRODUCTION: Overweight and obesity is a global problem incurring substantial health and economic implications. This has also been highlighted by the ongoing COVID-19 pandemic which has disproportionately affected overweight and obese individuals. Most of the interventions have concentrated on promotion of physical activities and healthy eating which may involve current sacrifices for future health gains. The purpose of this study was to explore the relationship between bodyweight and how individuals state they would trade-off immediate income for higher amounts in the future (time preference). METHODS: An online survey was conducted targeting adults aged >16 years in the UK (England, Northern Ireland, Scotland, and Wales) from January 1, 2016 to July 31, 2016. Using paid online adverts, as well as personal and professional networks for distribution of links to the online survey, the questionnaire asked respondents to report socio-economic and demographic information, height, and weight and to complete a time preference exercise. Data were analysed using descriptive statistics; associations were explored between BMI and respondents' characteristics and time preference using Spearman rank-order correlation and χ2 tests as appropriate. We adopted STROBE guidelines for the reporting of the study. RESULTS: A total of 561 responses were analysed (female = 293, males = 268). The relationship between time preference and overweight/obesity, using BMI as the measure is highly significant (χ2 = 95.92: p < 0.001). Individuals of normal weight have low time preferences and are more likely to invest in activities in a bid to reap future health benefits. There are also significant relationships between BMI and employment status (χ2 = 37.03; p < 0.001), physical activities (p < 0.0001), income levels (χ2 = 6.68; p < 0.035), family orientation, i.e., with or without children (χ2 = 12.88; p < 0.012), and ethnicity (χ2 = 18.31; p < 0.001). These imply that individuals in employment and with children in their families are less likely to be overweight or obese compared to those who do not. People from black backgrounds are also more likely to be overweight or obese and have higher time preferences compared to people from white backgrounds. DISCUSSIONS/CONCLUSIONS: People's preventive behaviours today can be predicted by their time preference and this understanding could be vital in improving population's uptake and maintenance of overweight and obesity prevention actions. People who have low time preference are more likely to invest time and resources in physical activities and healthy lifestyles to reap future health benefits hence value utilities-in-anticipation. Public health programmes should therefore use the knowledge of the association between time preference and overweight/obesity to inform designs of intervention programmes.

Cost-Effectiveness and Cost-Utility of Palbociclib versus Ribociclib in Women with Stage IV Breast Cancer: A Real-World Data Evaluation.

Palbociclib and ribociclib are indicated in the first-line treatment of hormonal-receptor-positive HER-2 negative (HR+/HER-2 negative) advanced breast cancer. Despite their clinical benefit, they can increase healthcare expenditure. Yet, there are no comparative pharmacoeconomic evaluations for them in developing countries, the Middle East, or Gulf countries. This study compared the cost-effectiveness of palbociclib and ribociclib in Qatar. A 10-year within-cycle-corrected Markov's model was developed using TreeAge Pro® software. The model consisted of three main health states: progression-free (PFS), progressed-disease (PD), and death. Costs were obtained from the actual hospital settings, transition probabilities were calculated from individual-patient data, and utilities were summarized from the published literature. The incremental cost-effectiveness ratio (ICER) and the incremental cost-utility ratio (ICUR) were calculated and compared to three gross-domestic-products per capita. Deterministic and probabilistic sensitivity analyses were performed. Ribociclib dominated palbociclib in terms of costs, life-years gained, and quality-adjusted life-years gained. The conclusions remained robust in the different cases of the deterministic sensitivity analyses. Taking all combined uncertainties into account, the confidence in the base-case conclusion was approximately 60%. Therefore, in HR+/HER-2 negative stage IV breast cancer patients, the use of ribociclib is considered cost-saving compared to palbociclib.

The role of community pharmacists in depression management: a survey of attitudes, practices and perceived barriers.

Background Community pharmacists play a significant role in depression care. Depression is a health priority in national health strategies around the world, including in Qatar. Objective To describe current practices, attitudes and perceived barriers of community pharmacists towards depression care, and to investigate factors associated with these practices. Setting Community pharmacies in Qatar. Method A cross-sectional online survey using an adapted survey instrument. Scores were measured on a five-point Likert scale. Descriptive univariate and bivariate analyses of study outcomes, followed by multivariate regression examining the association between pharmacists' practices and their attitudes, socio-demographic and professional characteristics. Main outcome measure Pharmacists' scores on self-reported attitudes towards depression and depression care practices and the number of perceived barriers for depression care. Result: 358 pharmacists (response rate 39%) completed the questionnaire. Pharmacists' attitudes to depression were moderately positive (mean score = 3.41, SD = 0.26) but involvement in depression care was very low (mean score = 2.64, SD = 0.94). Three major barriers were lack of access to patients' medical records (83.21%), lack of patients' insight on depression and the importance of treatment (81.85%), and lack of knowledge and training on mental health (79.63%). Female pharmacists and those graduated more than 10 years prior were significantly less involved in depression care compared to their counterparts (practice scores (95% CI) -4.36 (-7.46 to -1.26) and -7.51 (-15.10 to -1.35), respectively), while those who had access to private counselling area were more involved (practice score 3.39 (0.20 to 6.59). Pharmacists' depression practice score was positively associated with attitudes (p = 0.001). Conclusion Pharmacists' moderately positive attitudes were not reflected in their suboptimal depression-care practices. Action from policymakers is needed to improve pharmacists' practices and attitudes to depression.

The Effect of Ivabradine on Hospitalization of Heart Failure Patients: A Retrospective Cohort Study.

BACKGROUND: Ivabradine is recommended in heart failure (HF) patients to reduce cardiovascular death and hospitalization due to worsening of HF symptoms. AIMS AND OBJECTIVES: To study the effect of Ivabradine in addition to guideline-directed medical therapy (GDMT) in a group of HF patients with HR more than 70 bpm, HF with reduced ejection fraction (HFrEF) left ventricular ejection fraction (LVEF ≤ 40%), and New York Heart Association class II-IV. METHODS: The study was conducted at Heart Hospital, Hamad Medical Corporation, Qatar. HF patients with age > 18 years, LVEF ≤40%, on GDMT, and HR of ≥70 bpm were included. The study population was divided into two groups: ivabradine group and non-ivabradine group. The primary outcomes were risk, number and length of hospitalizations due to worsening HF, and cardiovascular mortality. The secondary outcome was all-cause mortality. Baseline characteristics were collected at enrollment. Study outcomes were compared in the two groups by applying Chi-square and Fisher's exact tests. Logistic regression model was applied to assess both hospitalizations and cardiovascular mortality. RESULTS: A total of 111 patients were studied, 37 (33.94%) ivabradine group and 74 (66.67%) non-ivabradine group. Risk of hospitalization was lower in Ivabradine group compared to non-Ivabradine group (odds ratio: 0.43, 95% confidence interval [CI]: 0.16-1.015, P = 0.094). Average length of hospitalization in ivabradine and non-ivabradine groups was 12.54 and 8.91 days, respectively (incidence rate ratio [IRR]: 1.63, 95% CI: 0.79-3.38, P = 0.187). Compared to non-ivabradine, ivabradine patients had lower number of hospitalizations (IRR: 1.13, 95% CI: 0.61-2.11, P = 0.694). Death rate in both ivabradine and non-ivabradine groups was 3. CONCLUSIONS: Ivabradine along with GDMT reduces the risk of hospitalization due to worsening HF symptoms. Ivabradine had no significant effect on cardiovascular mortality and all-cause mortality. HFrEF non-Arabs patients have lower risk, number and length of hospitalization, and mortality compared to Arabs.

Associations with antibiotic prescribing for acute exacerbation of COPD in primary care: secondary analysis of a randomised controlled trial.

BACKGROUND: C-reactive protein (CRP) point-of-care testing can reduce antibiotic use in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in primary care, without compromising patient care. Further safe reductions may be possible. AIM: To investigate the associations between presenting features and antibiotic prescribing in patients with AECOPD in primary care. DESIGN AND SETTING: Secondary analysis of a randomised controlled trial of participants presenting with AECOPD in primary care (the PACE trial). METHOD: Clinicians collected participants' demographic features, comorbid illnesses, clinical signs, and symptoms. Antibiotic prescribing decisions were made after participants were randomised to receive a point-of-care CRP measurement or usual care. Multivariable regression models were fitted to explore the association between patient and clinical features and antibiotic prescribing, and extended to further explore any interactions with CRP measurement category (CRP not measured, CRP <20 mg/l, or CRP ≥20 mg/l). RESULTS: A total of 649 participants from 86 general practices across England and Wales were included. Odds of antibiotic prescribing were higher in the presence of clinician-recorded crackles (adjusted odds ratio [AOR] = 5.22, 95% confidence interval [CI] = 3.24 to 8.41), wheeze (AOR = 1.64, 95% CI = 1.07 to 2.52), diminished vesicular breathing (AOR = 2.95, 95% CI = 1.70 to 5.10), or clinician-reported evidence of consolidation (AOR = 34.40, 95% CI = 2.84 to 417.27). Increased age was associated with lower odds of antibiotic prescribing (AOR per additional year increase = 0.98, 95% CI = 0.95 to 1.00), as was the presence of heart failure (AOR = 0.32, 95% CI = 0.12 to 0.85). CONCLUSION: Several demographic features and clinical signs and symptoms are associated with antibiotic prescribing in AECOPD. Diagnostic and prognostic value of these features may help identify further safe reductions.

Brief interventions to prevent excessive alcohol use in adolescents at low-risk presenting to Emergency Departments: Three-arm, randomised trial of effectiveness and cost-effectiveness.

BACKGROUND: Alcohol consumption and related harm increase rapidly from the age of 12 years. We evaluated whether alcohol screening and brief intervention is effective and cost-effective in delaying hazardous or harmful drinking amongst low-risk or abstaining adolescents attending Emergency Departments (EDs). METHODS: This ten-centre, three-arm, parallel-group, single-blind, pragmatic, individually randomised trial screened ED attenders aged between 14 and 17 years for alcohol consumption. We sampled at random one third of those scoring at most 2 on AUDIT-C who had access to the internet and, if aged under 16, were Gillick competent or had informed consent from parent or guardian. We randomised them between: screening only (control intervention); one session of face-to-face Personalised Feedback and Brief Advice (PFBA); and PFBA plus an electronic brief intervention (eBI) on smartphone or web. We conducted follow-up after six and 12 months. The principal outcomes were alcohol consumed over the 3 months before 12-month follow up, measured by AUDIT-C; and quality-adjusted life-years. FINDINGS: Between October 2014 and May 2015, we approached 5,016 eligible patients of whom 3,326 consented to be screened and participate in the trial; 2,571 of these were low-risk drinkers or abstainers, consuming an average 0.14 units per week. We randomised: 304 to screening only; 285 to PFBA; and 294 to PFBA and eBI. We found no significant difference between groups, notably in weekly alcohol consumption: those receiving screening only drank 0.10 units (95% confidence interval 0.05 to 0.18); PFBA 0.12 (0.06 to 0.21); PFBA and eBI 0.10 (0.05 to 0.19). INTERPRETATION: While drinking levels remained low in this population, this trial found no evidence that PFBA with or without eBI was more effective than screening alone in reducing or delaying alcohol consumption.

C-reactive protein point-of-care testing for safely reducing antibiotics for acute exacerbations of chronic obstructive pulmonary disease: the PACE RCT.

BACKGROUND: Most patients presenting with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in primary care are prescribed antibiotics, but these may not be beneficial, and they can cause side effects and increase the risk of subsequent resistant infections. Point-of-care tests (POCTs) could safely reduce inappropriate antibiotic prescribing and antimicrobial resistance. OBJECTIVE: To determine whether or not the use of a C-reactive protein (CRP) POCT to guide prescribing decisions for AECOPD reduces antibiotic consumption without having a negative impact on chronic obstructive pulmonary disease (COPD) health status and is cost-effective. DESIGN: A multicentre, parallel-arm, randomised controlled open trial with an embedded process, and a health economic evaluation. SETTING: General practices in Wales and England. A UK NHS perspective was used for the economic analysis. PARTICIPANTS: Adults (aged ≥ 40 years) with a primary care diagnosis of COPD, presenting with an AECOPD (with at least one of increased dyspnoea, increased sputum volume and increased sputum purulence) of between 24 hours' and 21 days' duration. INTERVENTION: CRP POCTs to guide antibiotic prescribing decisions for AECOPD, compared with usual care (no CRP POCT), using remote online randomisation. MAIN OUTCOME MEASURES: Patient-reported antibiotic consumption for AECOPD within 4 weeks post randomisation and COPD health status as measured with the Clinical COPD Questionnaire (CCQ) at 2 weeks. For the economic evaluation, patient-reported resource use and the EuroQol-5 Dimensions were included. RESULTS: In total, 653 participants were randomised from 86 general practices. Three withdrew consent and one was randomised in error, leaving 324 participants in the usual-care arm and 325 participants in the CRP POCT arm. Antibiotics were consumed for AECOPD by 212 out of 274 participants (77.4%) and 150 out of 263 participants (57.0%) in the usual-care and CRP POCT arm, respectively [adjusted odds ratio 0.31, 95% confidence interval (CI) 0.20 to 0.47]. The CCQ analysis comprised 282 and 281 participants in the usual-care and CRP POCT arms, respectively, and the adjusted mean CCQ score difference at 2 weeks was 0.19 points (two-sided 90% CI -0.33 to -0.05 points). The upper limit of the CI did not contain the prespecified non-inferiority margin of 0.3. The total cost from a NHS perspective at 4 weeks was £17.59 per patient higher in the CRP POCT arm (95% CI -£34.80 to £69.98; p = 0.408). The mean incremental cost-effectiveness ratios were £222 per 1% reduction in antibiotic consumption compared with usual care at 4 weeks and £15,251 per quality-adjusted life-year gained at 6 months with no significant changes in sensitivity analyses. Patients and clinicians were generally supportive of including CRP POCT in the assessment of AECOPD. CONCLUSIONS: A CRP POCT diagnostic strategy achieved meaningful reductions in patient-reported antibiotic consumption without impairing COPD health status or increasing costs. There were no associated harms and both patients and clinicians valued the diagnostic strategy. FUTURE WORK: Implementation studies that also build on our qualitative findings could help determine the effect of this intervention over the longer term. TRIAL REGISTRATION: Current Controlled Trials ISRCTN24346473. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 15. See the NIHR Journals Library website for further project information.

People with chronic obstructive pulmonary disease (COPD) often experience flare-ups known as acute exacerbations of chronic obstructive pulmonary disease. Antibiotics are prescribed for most flare-ups, but they do not always benefit patients and may cause harm, such as side effects or subsequent infections that are resistant. Rapid point-of-care tests (POCTs) can be used to help determine when antibiotics are more likely to be needed. C-reactive protein (CRP) is a marker of inflammation that can be measured with a POCT. Patients with flare-ups and a low CRP value are less likely to benefit from antibiotics. The PACE trial asked whether or not measuring CRP with a POCT could lead to fewer antibiotics being consumed for flare-ups, without having negative effects for patients. We aimed to recruit 650 patients with a COPD flare-up from primary care. Patients were randomly assigned to either (1) usual care with the addition of a CRP POCT, or (2) usual care without the addition of the test. Antibiotic use over the first 4 weeks and patients' self-assessment of their health 2 weeks after enrolment were measured in both groups. Patients in the CRP test group used fewer antibiotics than those managed as usual, and had improved patient-reported outcomes. Costs were a little higher in the CRP POCT group. Interviews with patients and clinicians found that they appreciated the CRP test being included in the decision-making process.

Adolescent perspectives about their participation in alcohol intervention research in emergency care: A qualitative exploration using ethical principles as an analytical framework.

AIMS: To explore adolescents' experiences of consenting to, and participating in, alcohol intervention trials when attending for emergency care. METHODS: In-depth semi-structured interviews with 27 adolescents (16 males; aged 14-17 years (Mage = 15.7)) who had taken part in one of two linked brief alcohol intervention trials based in 10 accident and emergency departments in England. Interviews were transcribed verbatim and subject to thematic analysis. RESULTS: Research and intervention methods were generally found to be acceptable though confidentiality was important and parental presence could hinder truthful disclosures regarding alcohol use. Participants discussed the importance of being involved in research that was relevant to them and recognised alcohol consumption as a normative part of adolescence, highlighting the importance of having access to appropriate health information. Beyond this, they recognised the benefits and risks of trial participation for themselves and others with the majority showing a degree of altruism in considering longer term implications for others as well as themselves. CONCLUSIONS: Alcohol screening and intervention in emergency care is both acceptable and relevant to adolescents but acceptability is reliant on confidentiality being assured and may be inhibited by parental presence. TRIAL REGISTRATION: ISRCTN Number: 45300218.

General practitioner use of a C-reactive protein point-of-care test to help target antibiotic prescribing in patients with acute exacerbations of chronic obstructive pulmonary disease (the PACE study): study protocol for a randomised controlled trial.

BACKGROUND: Most patients presenting with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in primary care are prescribed an antibiotic, which may not always be appropriate and may cause harm. C-reactive protein (CRP) is an acute-phase biomarker that can be rapidly measured at the point of care and may predict benefit from antibiotic treatment in AECOPD. It is not clear whether the addition of a CRP point-of-care test (POCT) to clinical assessment leads to a reduction in antibiotic consumption without having a negative impact on COPD health status. METHODS/DESIGN: This is a multicentre, individually randomised controlled trial (RCT) aiming to include 650 participants with a diagnosis of AECOPD in primary care. Participants will be randomised to be managed according to usual care (control) or with the addition of a CRP POCT to guide antibiotic prescribing. Antibiotic consumption for AECOPD within 4 weeks post randomisation and COPD health status (total score) measured by the Clinical COPD Questionnaire (CCQ) at 2 weeks post randomisation will be co-primary outcomes. Primary analysis (by intention-to-treat) will determine differences in antibiotic consumption for superiority and COPD health status for non-inferiority. Secondary outcomes include: COPD health status, CCQ domain scores, use of other COPD treatments (weeks 1, 2 and 4), EQ-5D utility scores (weeks 1, 2 and 4 and month 6), disease-specific, health-related quality of life (HRQoL) at 6 months, all-cause antibiotic consumption (antibiotic use for any condition) during first 4 weeks post randomisation, total antibiotic consumption (number of days during first 4 weeks of antibiotic consumed for AECOPD/any reason), antibiotic prescribing at the index consultation and during following 4 weeks, adverse effects over the first 4 weeks, incidence of pneumonia (weeks 4 and 6 months), health care resource use and cost comparison over the 6 months following randomisation. Prevalence and resistance profiles of bacteria will be assessed using throat and sputum samples collected at baseline and 4-week follow-up. A health economic evaluation and qualitative process evaluation will be carried out. DISCUSSION: If shown to be effective (i.e. leads to a reduction in antibiotic use with no worse COPD health status), the use of the CRP POCT could lead to better outcomes for patients with AECOPD and help reduce selective pressures driving the development of antimicrobial resistance. PACE will be one of the first studies to evaluate the cost-effectiveness of a POCT biomarker to guide clinical decision-making in primary care on patient-reported outcomes, antibiotic prescribing and antibiotic resistance for AECOPD. TRIAL REGISTRATION: ISRCTN registry, ID: ISRCTN24346473 . Registered on 20 August 2014.

Alcohol Consumption, Early-Onset Drinking, and Health-Related Consequences in Adolescents Presenting at Emergency Departments in England.

PURPOSE: Globally, alcohol use is the leading cause of ill health and life years lost in adolescents, although its clinical impact is often overlooked, particularly in England where most research is based in schools. This study aims to examine the prevalence of alcohol consumption and the association between alcohol consumption and age of onset with health and social consequences among adolescents presenting to emergency departments (EDs). METHODS: Consecutive attenders (n = 5,576) aged 10-17 years at 10 EDs were included. Information was collected on general health and functioning, quality of life, alcohol use, and alcohol-related health and social consequences. RESULTS: Nearly 40% of adolescents reported the consumption of alcohol that was more than a sip in their lifetime. Age of the first alcohol consumption before the age of 15 years was associated with tobacco use (p < .001), lower quality of life (p = .003), and evidence of an alcohol use disorder (p = .002). It was also associated with general social functioning (problems with conduct p = .001 and hyperactivity p = .001) and alcohol-related health and social consequences (accident p = .046, problems with a parent p = .017, school p = .0117, or police p = .012). CONCLUSIONS: Rates of alcohol consumption in adolescents presenting to the ED were similar to those reported in schools in England and globally. Associations of alcohol consumption and earlier onset of drinking with poorer health and social functioning were observed. The ED can offer an opportunity for the identification of hazardous alcohol use in adolescents.

All-Wales licensed premises intervention (AWLPI): a randomised controlled trial to reduce alcohol-related violence.

BACKGROUND: Alcohol-related violence in and in the vicinity of licensed premises continues to place a considerable burden on the United Kingdom's (UK) health services. Robust interventions targeted at licensed premises are therefore required to reduce the costs of alcohol-related harm. Previous evaluations of interventions in licensed premises have a number of methodological limitations and none have been conducted in the UK. The aim of the trial was to determine the effectiveness of the Safety Management in Licensed Environments intervention designed to reduce alcohol-related violence in licensed premises, delivered by Environmental Health Officers, under their statutory authority to intervene in cases of violence in the workplace. METHODS/DESIGN: A national randomised controlled trial, with licensed premises as the unit of allocation. Premises were identified from all 22 Local Authorities in Wales. Eligible premises were those with identifiable violent incidents on premises, using police recorded violence data. Premises were allocated to intervention or control by optimally balancing by Environmental Health Officer capacity in each Local Authority, number of violent incidents in the 12 months leading up to the start of the project and opening hours. The primary outcome measure is the difference in frequency of violence between intervention and control premises over a 12 month follow-up period, based on a recurrent event model. The trial incorporates an embedded process evaluation to assess intervention implementation, fidelity, reach and reception, and to interpret outcome effects, as well as investigate its economic impact. DISCUSSION: The results of the trial will be applicable to all statutory authorities directly involved with managing violence in the night time economy and will provide the first formal test of Health and Safety policy in this environment. If successful, opportunities for replication and generalisation will be considered. TRIAL REGISTRATION: UKCRN 14077; ISRCTN78924818.