A Cluster-Randomized Trial of Hydroxychloroquine for Prevention of Covid-19.

BACKGROUND: Current strategies for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are limited to nonpharmacologic interventions. Hydroxychloroquine has been proposed as a postexposure therapy to prevent coronavirus disease 2019 (Covid-19), but definitive evidence is lacking. METHODS: We conducted an open-label, cluster-randomized trial involving asymptomatic contacts of patients with polymerase-chain-reaction (PCR)-confirmed Covid-19 in Catalonia, Spain. We randomly assigned clusters of contacts to the hydroxychloroquine group (which received the drug at a dose of 800 mg once, followed by 400 mg daily for 6 days) or to the usual-care group (which received no specific therapy). The primary outcome was PCR-confirmed, symptomatic Covid-19 within 14 days. The secondary outcome was SARS-CoV-2 infection, defined by symptoms compatible with Covid-19 or a positive PCR test regardless of symptoms. Adverse events were assessed for up to 28 days. RESULTS: The analysis included 2314 healthy contacts of 672 index case patients with Covid-19 who were identified between March 17 and April 28, 2020. A total of 1116 contacts were randomly assigned to receive hydroxychloroquine and 1198 to receive usual care. Results were similar in the hydroxychloroquine and usual-care groups with respect to the incidence of PCR-confirmed, symptomatic Covid-19 (5.7% and 6.2%, respectively; risk ratio, 0.86 [95% confidence interval, 0.52 to 1.42]). In addition, hydroxychloroquine was not associated with a lower incidence of SARS-CoV-2 transmission than usual care (18.7% and 17.8%, respectively). The incidence of adverse events was higher in the hydroxychloroquine group than in the usual-care group (56.1% vs. 5.9%), but no treatment-related serious adverse events were reported. CONCLUSIONS: Postexposure therapy with hydroxychloroquine did not prevent SARS-CoV-2 infection or symptomatic Covid-19 in healthy persons exposed to a PCR-positive case patient. (Funded by the crowdfunding campaign YoMeCorono and others; BCN-PEP-CoV2 ClinicalTrials.gov number, NCT04304053.).

Hydroxychloroquine for Early Treatment of Adults With Mild Coronavirus Disease 2019: A Randomized, Controlled Trial.

BACKGROUND: No effective treatments for coronavirus disease 2019 (COVID-19) exist. We aimed to determine whether early treatment with hydroxychloroquine (HCQ) would be efficacious for outpatients with COVID-19. METHODS: Multicenter open-label, randomized, controlled trial conducted in Catalonia, Spain, between 17 March and 26 May 2020. Patients recently diagnosed with <5-day of symptom onset were assigned to receive HCQ (800 mg on day 1 followed by 400 mg once daily for 6 days) or usual care. Outcomes were reduction of viral load in nasopharyngeal swabs up to 7 days after treatment start, disease progression up to 28 days, and time to complete resolution of symptoms. Adverse events were assessed up to 28 days. RESULTS: A total of 293 patients were eligible for intention-to-treat analysis: 157 in the control arm and 136 in the intervention arm. The mean age was 41.6 years (SD, 12.6), mean viral load at baseline was 7.90 log10 copies/mL (SD, 1.82), and median time from symptom onset to randomization was 3 days. No differences were found in the mean reduction of viral load at day 3 (-1.41 vs -1.41 log10 copies/mL in the control and intervention arm, respectively) or at day 7 (-3.37 vs -3.44). Treatment did not reduce risk of hospitalization (7.1% control vs 5.9% intervention) nor shorten the time to complete resolution of symptoms (12 days, control vs 10 days, intervention). No relevant adverse events were reported. CONCLUSIONS: In patients with mild COVID-19, no benefit was observed with HCQ beyond the usual care.

Divergences on expected pneumonia cases during the COVID-19 epidemic in Catalonia: a time-series analysis of primary care electronic health records covering about 6 million people.

BACKGROUND: Pneumonia is one of the complications of COVID-19. Primary care electronic health records (EHR) have shown the utility as a surveillance system. We therefore analyse the trends of pneumonia during two waves of COVID-19 pandemic in order to use it as a clinical surveillance system and an early indicator of severity. METHODS: Time series analysis of pneumonia cases, from January 2014 to December 2020. We collected pneumonia diagnoses from primary care EHR, a software system covering > 6 million people in Catalonia (Spain). We compared the trend of pneumonia in the season 2019-2020 with that in the previous years. We estimated the expected pneumonia cases with data from 2014 to 2018 using a time series regression adjusted by seasonality and influenza epidemics. RESULTS: Between 4 March and 5 May 2020, 11,704 excess pneumonia cases (95% CI: 9909 to 13,498) were identified. Previously, we identified an excess from January to March 2020 in the population older than 15 years of 20%. We observed another excess pneumonia period from 22 october to 15 november of 1377 excess cases (95% CI: 665 to 2089). In contrast, we observed two great periods with reductions of pneumonia cases in children, accounting for 131 days and 3534 less pneumonia cases (95% CI, 1005 to 6064) from March to July; and 54 days and 1960 less pneumonia cases (95% CI 917 to 3002) from October to December. CONCLUSIONS: Diagnoses of pneumonia from the EHR could be used as an early and low cost surveillance system to monitor the spread of COVID-19.

Identifying factors of activities of daily living important for cost and caregiver outcomes in Alzheimer's disease.

BACKGROUND: We aimed to obtain a better understanding of how different aspects of patient functioning affect key cost and caregiver outcomes in Alzheimer's disease (AD). METHODS: Baseline data from a prospective observational study of community-living AD patients (GERAS) were used. Functioning was assessed using the Alzheimer's Disease Cooperative Study-Activities of Daily Living Scale. Generalized linear models were conducted to analyze the relationship between scores for total activities of daily living (ADL), basic ADL (BADL), instrumental ADL (IADL), ADL subdomains (confirmed through factor analysis) and individual ADL questions, and total societal costs, patient healthcare and social care costs, total and supervision caregiver time, and caregiver burden. RESULTS: Four distinct ADL subdomains were confirmed: basic activities, domestic/household activities, communication, and outside activities. Higher total societal costs were associated with impairments in all aspects of ADL, including all subdomains; patient costs were associated with total ADL and BADL, and basic activities subdomain scores. Both total and supervision caregiver hours were associated with total ADL and IADL scores, and domestic/household and outside activities subdomain scores (greater hours associated with greater functional impairments). There was no association between caregiver burden and BADL or basic activities subdomain scores. The relationship between total ADL, IADL, and the outside activities subdomain and outcomes differed between patients with mild and moderate-to-severe AD. CONCLUSIONS: Identification of ADL subdomains may lead to a better understanding of the association between patient function and costs and caregiver outcomes at different stages of AD, in particular the outside activities subdomain within mild AD.

Determinants of societal costs in Alzheimer's disease: GERAS study baseline results.

BACKGROUND: To identify the main factors associated with societal costs of Alzheimer's disease (AD) in community-dwelling patients across three European countries. METHODS: Baseline cost data from a prospective, observational study were used. Assessments included patients' cognition, activities of daily living (ADLs) and behavioral symptoms, and caregiver burden. Cost calculations (2010) from the societal perspective were based on patient/caregiver resource use. Generalized linear models estimated factors associated with costs. RESULTS: Mean monthly costs per patient differed for France (€1881), Germany (€2349), and the UK (€2016), with informal care costs accounting for 50% to 61%. Independent factors associated with costs across all countries were ADL total score, patient living arrangements, caregiver working status, and caregiver burden (all P < .05). Additional factors were significant for the pooled cohort or individual countries. CONCLUSIONS: Several patient and caregiver factors, including factors associated with informal care, should be included when evaluating care options for patients with AD.

The development and successful implementation of the VINCat Program.

In 2006 the VINCat Program was established in order to develop and support a standardized surveillance system of hospital-acquired infections (HAI). All acute care hospitals included in the public health system network of Catalonia (Spain) were invited to participate. The aim was to provide risk-adjusted, procedure-specific rates for most relevant infections. Data are collected by the local multidisciplinary infection control teams and transmitted electronically to the Coordinating Centre, which acts as the core of a network of infection control committees and has the support of a Technical Advisory Committee. The program website provides updated information on program activities, training workshops, aggregated data on past infection rates and access to databases, manuals and protocols. During the period 2007-2011, 64 hospitals have joined the program: 9 tertiary, 16 district and 39 small hospitals, providing records on 4.044 episodes of catheter-related blood stream infections, 14.389 elective colorectal surgical interventions, 14.214 hip and 29.599 knee arthroplasties, among the most significant indicators. Nowadays, it appears that VINCat has been successfully implemented and is well established as the official HAI surveillance program in Catalonia. Determinants for success have been: the maintenance of a close contact between the hospitals and the coordinating center, the timely and regular data feedback to institutions, the program's contribution towards reducing HAIs, the ongoing efforts to improve performance and, a key factor, the perception among the infection control professionals of the value added by the program to their daily work in different ways. Adequate funding, commitment of infection control teams and the generous collaboration of experts from different specialties are essential for maintaining the success of the VINCat Program.

Evolving mortality and clinical outcomes of hospitalized subjects during successive COVID-19 waves in Catalonia, Spain.

BACKGROUND: The changes in shield strategies, treatments, emergence variants, and healthcare pathways might shift the profile and outcome of patients hospitalized with COVID-19 in successive waves of the outbreak. METHODS: We retrospectively analysed the characteristics and in-hospital outcomes of all patients admitted with COVID-19 in eight university hospitals of Catalonia (North-East Spain) between Feb 28, 2020 and Feb 28, 2021. Using a 7-joinpoint regression analysis, we split admissions into four waves. The main hospital outcomes included 30-day mortality and admission to intensive care unit (ICU). FINDINGS: The analysis included 17,027 subjects admitted during the first wave (6800; 39.9%), summer wave (1807; 10.6%), second wave (3804; 22.3%), and third wave (4616; 27.1%). The highest 30-day mortality rate was reported during the first wave (17%) and decreased afterwards, remaining stable at 13% in the second and third waves (overall 30% reduction); the lowest mortality was reported during the summer wave (8%, 50% reduction). ICU admission became progressively more frequent during successive waves. In Cox regression analysis, the main factors contributing to differences in 30-day mortality were the epidemic wave, followed by gender, age, diabetes, chronic kidney disease, and neoplasms. INTERPRETATION: Although in-hospital COVID-19 mortality remains high, it decreased substantially after the first wave and is highly dependent of patient's characteristics and ICU availability. Highest mortality reductions occurred during a wave characterized by younger individuals, an increasingly frequent scenario as vaccination campaigns progress. FUNDING: This work did not receive specific funding.

Evidence based practice in postgraduate healthcare education: a systematic review.

BACKGROUND: Training in Evidence-Based Practice (EBP) has been widely implemented throughout medical school and residency curricula. The aim of this study is to systematically review studies that assessed the effectiveness of EBP teaching to improve knowledge, skills, attitudes and behavior of postgraduate healthcare workers, and to describe instruments available to evaluate EBP teaching. METHODS: The design is a systematic review of randomized, non-randomized, and before-after studies. The data sources were MEDLINE, Cochrane Library, EMBASE, CINAHL and ERIC between 1966 and 2006. Main outcomes were knowledge, skills, attitudes and behavior towards EBP. Standardized effect sizes (E-S) were calculated. The E-S was categorized as small (E-S < 0.2), small to moderate (E-S between 0.2 and 0.5), moderate to large (E-S between 0.51 and 0.79), large (E-S > 0.79). Reliability and validity of instruments for evaluating education were assessed. Studies excluded were those that were not original, performed in medical students, focused on prescribing practices, specific health problems, theoretical reviews of different components of EBP, continuing medical education, and testing the effectiveness of implementing guidelines. RESULTS: Twenty-four studies met our inclusion criteria. There were 15 outcomes within the 10 studies for which E-S could be calculated. The E-S ranged from 0.27 (95%CI: -0.05 to 0.59) to 1.32 (95%CI: 1.11 to 1.53). Studies assessing skills, behavior and/or attitudes had a "small to moderate" E-S. Only 1 of the 2 studies assessing knowledge had E-S of 0.57 (95 CI: 0.32 to 0.82) and 2 of the 4 studies that assessed total test score outcomes had "large" E-S. There were 22 instruments used, but only 10 had 2 or more types of validity or reliability evidence. CONCLUSION: Small improvements in knowledge, skills, attitudes or behavior are noted when measured alone. A large improvement in skills and knowledge in EBP is noted when measured together in a total test score. Very few studies used validated measures tests.

Disease Progression in Mild Dementia due to Alzheimer Disease in an 18-Month Observational Study (GERAS): The Impact on Costs and Caregiver Outcomes.

BACKGROUND/AIMS: We assessed whether cognitive and functional decline in community-dwelling patients with mild Alzheimer disease (AD) dementia were associated with increased societal costs and caregiver burden and time outcomes. METHODS: Cognitive decline was defined as a ≥3-point reduction in the Mini-Mental State Examination and functional decline as a decrease in the ability to perform one or more basic items of the Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory (ADCS-ADL) or ≥20% of instrumental ADL items. Total societal costs were estimated from resource use and caregiver hours using 2010 costs. Caregiver burden was assessed using the Zarit Burden Interview (ZBI); caregiver supervision and total hours were collected. RESULTS: Of 566 patients with mild AD enrolled in the GERAS study, 494 were suitable for the current analysis. Mean monthly total societal costs were greater for patients showing functional (+61%) or cognitive decline (+27%) compared with those without decline. In relation to a typical mean monthly cost of approximately EUR 1,400 at baseline, this translated into increases over 18 months to EUR 2,254 and 1,778 for patients with functional and cognitive decline, respectively. The number of patients requiring supervision doubled among patients showing functional or cognitive decline compared with those not showing decline, while caregiver total time increased by 70 and 33%, respectively and ZBI total score by 5.3 and 3.4 points, respectively. CONCLUSION: Cognitive and, more notably, functional decline were associated with increases in costs and caregiver outcomes in patients with mild AD dementia.

[Transparency in public health decision-making]. / La transparencia en la toma de decisiones de salud pública.

Improving the quality and transparency of governmental healthcare decision-making has an impact on the health of the population through policies, organisational management and clinical practice. Moreover, the comparison between healthcare centres and the transparent feedback of results to professionals and to the wider public contribute directly to improved results. The "Results Centre" of the Catalan healthcare system measures and disseminates the results achieved by the different healthcare centres in order to facilitate a shared decision-making process, thereby enhancing the quality of healthcare provided to the population of Catalonia (Spain). This is a pioneering initiative in Spain and is aligned with the most advanced countries in terms of policies of transparency and accountability.

The GERAS Study: a prospective observational study of costs and resource use in community dwellers with Alzheimer's disease in three European countries--study design and baseline findings.

To address socioeconomic challenges associated with its increasing prevalence, data are needed on country-level resource use and costs associated with Alzheimer's disease (AD). GERAS is an 18-month observational study being conducted in France, Germany, and the U.K. (with an 18-month extension in France and Germany), aimed at determining resource use and total costs associated with AD, stratified by AD severity at baseline. Resource use information and time spent on informal care by non-professional caregivers was obtained using the Resource Utilization in Dementia instrument. Total baseline societal costs were based on four cost components: patient health care costs, patient social care costs, caregiver health care costs, and caregiver informal care costs. Overall, 1,497 community-dwelling patients with AD were analyzed at baseline. Estimated mean monthly total societal costs per patient at baseline differed significantly between groups with mild, moderate, and moderately severe/severe AD (p < 0.001 in each country): euro $1,418, euro 1,737, and euro 2,453 in France; euro 1,312, euro $2,412, and euro 3,722 in Germany; and euro 1,621, euro 1,836, andeuro 2,784 in the U.K., respectively. All cost components except caregiver health care costs increased with AD severity. Informal caregiver costs were the largest cost component accounting for about half to just over 60% of total societal costs, depending on country and AD severity group. In conclusion, GERAS study baseline results showed that country-specific costs increase with AD severity. Informal care costs formed the greatest proportion of total societal costs, increasing with AD severity independent of costing method. Longitudinal data will provide information on cost trends with disease progression.

Narrowing the equity gap: the impact of organized versus opportunistic cancer screening in Catalonia (Spain).

OBJECTIVES: To assess the impact on equity of access of an organized breast cancer screening programme, compared with opportunistic breast and cervical cancer screening activities. METHODS: Two cross-sectional health interview surveys conducted in 1994 and 2006 in Catalonia (Spain), with 6382 and 7653 women participating in both surveys. The main outcome measures were having undergone regular mammography, and regular cytology. Age-standardized prevalence rates for both screening tests were computed using the direct method. The relative inequality index was computed to measure changes over time in inequality on screening utilization. RESULTS: Participation among women aged 50-69 has increased after the introduction of the organized breast screening programme; the greatest impact has been observed among those women with lower educational levels (from 17% in 1994 to 79% in 2006). Equity of access by education was particularly increased in the target group for breast cancer screening. CONCLUSION: This study indicates that an organized screening programme could improve participation and equity of access.

Health-related quality-of-life of care-givers as a predictor of nursing-home placement of patients with dementia.

Care-giver health-related quality-of-life (QoL) as a predictor of nursing-home placement of family-member patients with dementia was evaluated (using the SF-36 questionnaire) in 181 care providers (78% females; mean age 63 years) at the start and at the end of 12 months of follow-up. The patients and their carers were evaluated at home or at the local Primary Health-care Centers (n = 37) in the area of Barcelona (Catalunya, Spain). Data were evaluated using logistic regression analysis with nursing-home placement of patients as the main outcome measure, and the care-givers' QoL, demographic, medical, social and cognitive variables as covariates. The incidence rate of nursing-home placement was 10.5% (95%CI: 6.4-15.9). Carers of patients who had not been placed in a nursing home had better QoL scores, even after controlling for potential confounding factors. The adjusted odds ratio of being admitted to a nursing home was 6.4 (95%CI: 2.1-19.0) for patients cared-for by relatives who rated their health as being much worse compared with the previous year. The care-giver's poor health-related QoL significantly influenced rates of nursing-home admission of patients in their care.

Health-related quality of life in carers of patients with dementia.

BACKGROUND: Carers of patients with dementia experience high levels of stress that can adversely affect their health and well-being. OBJECTIVE: Our aim was to assess the health-related quality of life of carers of patients with dementia compared with an age- and gender-matched sample from the general population. METHODS: A cross-sectional study was conducted in 37 primary health care centres in Catalonia, Spain. Carers (n = 181; 78% females, mean age 63 years) of patients with dementia together with a random sample of 543 individuals from the general population, matched for age and gender, were assessed with the SF-36 questionnaire, which is a generic measure of health status. RESULTS: With the exception of physical function category, seven of the scales showed lower scores for females in the carer group. The most important differences were observed in the emotional role [95% confidence interval (CI) -37.7 to -3.6], mental health (95% CI -21.0 to -1.6) and bodily pain (95% CI -37.7 to -8.6) categories. In contrast, male carers had higher scores in the physical function category (95% CI 2.2-19.4), and no differences were observed on the other scales. CONCLUSION: Female carers of patients with dementia experienced a seriously decreased quality of life level compared with their contemporaries in the general population.