Subcutaneous anti-COVID-19 hyperimmune immunoglobulin for prevention of disease in asymptomatic individuals with SARS-CoV-2 infection: a double-blind, placebo-controlled, randomised clinical trial.

Background: Anti-COVID-19 hyperimmune immunoglobulin (hIG) can provide standardized and controlled antibody content. Data from controlled clinical trials using hIG for the prevention or treatment of COVID-19 outpatients have not been reported. We assessed the safety and efficacy of subcutaneous anti-COVID-19 hyperimmune immunoglobulin 20% (C19-IG20%) compared to placebo in preventing development of symptomatic COVID-19 in asymptomatic individuals with SARS-CoV-2 infection. Methods: We did a multicentre, randomized, double-blind, placebo-controlled trial, in asymptomatic unvaccinated adults (≥18 years of age) with confirmed SARS-CoV-2 infection within 5 days between April 28 and December 27, 2021. Participants were randomly assigned (1:1:1) to receive a blinded subcutaneous infusion of 10 mL with 1 g or 2 g of C19-IG20%, or an equivalent volume of saline as placebo. The primary endpoint was the proportion of participants who remained asymptomatic through day 14 after infusion. Secondary endpoints included the proportion of individuals who required oxygen supplementation, any medically attended visit, hospitalisation, or ICU, and viral load reduction and viral clearance in nasopharyngeal swabs. Safety was assessed as the proportion of patients with adverse events. The trial was terminated early due to a lack of potential benefit in the target population in a planned interim analysis conducted in December 2021. ClinicalTrials.gov registry: NCT04847141. Findings: 461 individuals (mean age 39.6 years [SD 12.8]) were randomized and received the intervention within a mean of 3.1 (SD 1.27) days from a positive SARS-CoV-2 test. In the prespecified modified intention-to-treat analysis that included only participants who received a subcutaneous infusion, the primary outcome occurred in 59.9% (91/152) of participants receiving 1 g C19-IG20%, 64.7% (99/153) receiving 2 g, and 63.5% (99/156) receiving placebo (difference in proportions 1 g C19-IG20% vs. placebo, -3.6%; 95% CI -14.6% to 7.3%, p = 0.53; 2 g C19-IG20% vs placebo, 1.1%; -9.6% to 11.9%, p = 0.85). None of the secondary clinical efficacy endpoints or virological endpoints were significantly different between study groups. Adverse event rate was similar between groups, and no severe or life-threatening adverse events related to investigational product infusion were reported. Interpretation: Our findings suggested that administration of subcutaneous human hyperimmune immunoglobulin C19-IG20% to asymptomatic individuals with SARS-CoV-2 infection was safe but did not prevent development of symptomatic COVID-19. Funding: Grifols.

Higher Arm Versus Lower Arm Systolic Blood Pressure and Cardiovascular Outcomes: a Meta-Analysis of Individual Participant Data From the INTERPRESS-IPD Collaboration.

BACKGROUND: Guidelines recommend measuring blood pressure (BP) in both arms, adopting the higher arm readings for diagnosis and management. Data to support this recommendation are lacking. We evaluated associations of higher and lower arm systolic BPs with diagnostic and treatment thresholds, and prognosis in hypertension, using data from the Inter-arm Blood Pressure Difference-Individual Participant Data Collaboration. METHODS: One-stage multivariable Cox regression models, stratified by study, were used to examine associations of higher or lower reading arm BPs with cardiovascular mortality, all-cause mortality, and cardiovascular events, in individual participant data meta-analyses pooled from 23 cohorts. Cardiovascular events were modelled for Framingham and atherosclerotic cardiovascular disease risk scores. Model fit was compared throughout using Akaike information criteria. Proportions reclassified across guideline recommended intervention thresholds were also compared. RESULTS: We analyzed 53 172 participants: mean age 60 years; 48% female. Higher arm BP, compared with lower arm, reclassified 12% of participants at either 130 or 140 mm Hg systolic BP thresholds (both P<0.001). Higher arm BP models fitted better for all-cause mortality, cardiovascular mortality, and cardiovascular events (all P<0.001). Higher arm BP models better predicted cardiovascular events with Framingham and atherosclerotic cardiovascular disease risk scores (both P<0.001) and reclassified 4.6% and 3.5% of participants respectively to higher risk categories compared with lower arm BPs). CONCLUSIONS: Using BP from higher instead of lower reading arms reclassified 12% of people over thresholds used to diagnose hypertension. All prediction models performed better when using the higher arm BP. Both arms should be measured for accurate diagnosis and management of hypertension. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: CRD42015031227.

Associations Between Systolic Interarm Differences in Blood Pressure and Cardiovascular Disease Outcomes and Mortality: Individual Participant Data Meta-Analysis, Development and Validation of a Prognostic Algorithm: The INTERPRESS-IPD Collaboration.

Systolic interarm differences in blood pressure have been associated with all-cause mortality and cardiovascular disease. We undertook individual participant data meta-analyses to (1) quantify independent associations of systolic interarm difference with mortality and cardiovascular events; (2) develop and validate prognostic models incorporating interarm difference, and (3) determine whether interarm difference remains associated with risk after adjustment for common cardiovascular risk scores. We searched for studies recording bilateral blood pressure and outcomes, established agreements with collaborating authors, and created a single international dataset: the Inter-arm Blood Pressure Difference - Individual Participant Data (INTERPRESS-IPD) Collaboration. Data were merged from 24 studies (53 827 participants). Systolic interarm difference was associated with all-cause and cardiovascular mortality: continuous hazard ratios 1.05 (95% CI, 1.02-1.08) and 1.06 (95% CI, 1.02-1.11), respectively, per 5 mm Hg systolic interarm difference. Hazard ratios for all-cause mortality increased with interarm difference magnitude from a ≥5 mm Hg threshold (hazard ratio, 1.07 [95% CI, 1.01-1.14]). Systolic interarm differences per 5 mm Hg were associated with cardiovascular events in people without preexisting disease, after adjustment for Atherosclerotic Cardiovascular Disease (hazard ratio, 1.04 [95% CI, 1.00-1.08]), Framingham (hazard ratio, 1.04 [95% CI, 1.01-1.08]), or QRISK cardiovascular disease risk algorithm version 2 (QRISK2) (hazard ratio, 1.12 [95% CI, 1.06-1.18]) cardiovascular risk scores. Our findings confirm that systolic interarm difference is associated with increased all-cause mortality, cardiovascular mortality, and cardiovascular events. Blood pressure should be measured in both arms during cardiovascular assessment. A systolic interarm difference of 10 mm Hg is proposed as the upper limit of normal. Registration: URL: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42015031227.

Vascular structure and function and their relationship with health-related quality of life in the MARK study.

BACKGROUND: There is limited evidence concerning the relationship between vascular disease and health-related quality of life (HRQL). We investigated the relationship between vascular structure and function with health-related quality of life in a population with intermediate cardiovascular risk. METHODS: This study analyzed 303 subjects with ankle-brachial index (ABI) values ranging from 0.9 to 1.4 who were included in the MARK study (age 35 to 74 years; mean:60.5 ± 8.5), of which 50.2 % were women. Measurements included: ABI, brachial-ankle pulse wave velocity (ba-PWV), and cardio-ankle vascular index (CAVI), all measured using the VaSera device. The central augmentation index was adjusted to 75 lpm (AIx_75) using the Mobil-O-Graph device. HRQL was assessed by the Spanish version of the SF-12, version2. The highest obtained CAVI and ba-PWV values and the lowest ABI values were considered for the study. RESULTS: The cohort was composed of21 % smokers, 76 % hypertensive patients, and 24 % diabetic patients. The ABI mean was 1.09 ± 0.07,the ba-PWV mean was 14.64 ± 2.55 m/s with a 12.9 % of subjects higher than 17.5 m/s, AIx_75 26.46 ± 14.05, and CAVI 8.61 ± 1.08 with a 36.6 % of subjects higher than 9. Men scored higher than women in the HRQL measurements for physical (PSC-12; 49.9 vs. 46.9, p = 0.004) and mental (MSC-12) domains (51.2 vs. 47.7, p = 0.003). Age was positively correlated with CAVI (r = 0.547), ba-PWV (r = 0.469), AIx_75 (r = 0.255, p < 0.01), and the MSC-12 (r = 0.147, p < 0.05), but not the PSC-12. In the adjusted multiple linear regression analysis, the positive association of ABI and CAVI with the PSC-12 was maintained. CONCLUSIONS: The ABI in the normal range has a positive association with the PSC-12 of HRQL evaluated with the SF-12. The CAVI also showed a positive association with the PSC-12 of HRQL. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01428934 .

La enfermedad de Alzheimer y otras demencias en el Sistema de Información para el Desarrollo de la Investigación en Atención Primaria (SIDIAP) / Alzheimer's disease and other dementias in the InformationSystem for Primary Care Research Development (SIDIAP)

La informatización de la historia clínica en el ámbito de la Atención Primaria proporciona un gran potencial para la investigación, particularmente en estudios de prevalencia e incidencia, en estudios de evaluación de servicios de salud y en estudios de farmacoepidemiología. El Institut Català de la Salut y el IDIAP Jordi Gol crearon SIDIAP en el año 2010. Esta base de datos contiene la información clínica registrada por profesionales de atención primaria de la salud (médicos y enfermeras) y personal administrativo de los registros médicos electrónicos, incluyendo las características sociodemográficas, la morbilidad (Clasificación Inter - nacional de Enfermedades, CIE-10), variables clínicas y de estilos de vida, pruebas de laboratorio y tratamientos (prescripciones médicas, medicamentos dispensados en la farmacia), y también información de las altas hospitalarias. La base de datos contiene esta información de cerca de cinco millones de personas, lo que representa aproximadamente el 80 % de la población total mayor de 15 años de edad de Cataluña. Las bases de datos de atención primaria como SIDIAP presentan unas claras ventajas en relación con otras fuentes de información: contienen grandes muestras, permiten seguimientos de larga duración, tienen bajo coste, permiten relación con múltiples fuentes de información, no interfieren en la práctica clínica, y aportan representatividad de la práctica real. La demencia de Alzheimer (DA) es un claro ejemplo de patología para la que la información adicional que pueden proporcionar estudios realizados en la base de datos SIDIAP puede ser de gran utilidad. SIDIAP permite diseñar estudios transversales para el análisis de patrones de tratamientos o comorbilidades asociadas a las demencias; estudios de cohortes con largos períodos de seguimiento o estudios de caso y control para evaluar factores de riesgo asociados a la aparición de las distintas demencias y estudios de efectividad de los tratamientos y las intervenciones preventivas (AU)

Computerized databases of primary care clinical records are widely used for epidemiological research, particularly in studies of disease prevalence and incidence, studies of health services and in pharmacoepidemiological research. The Information System for the Development of Research in Primary Care (SIDIAP) was created in 2010 by the Catalan Institute of Health (ICS) and the Jordi Gol Primary Care Research Institute (IDIAP Jordi Gol). SIDIAP comprises clinical information recorded by primary care health professionals (GPs and nurses) and administrative staff in electronic medical records, including sociodemographic characteristics, morbidity (International Classification of Diseases, ICD-10), clinical and lifestyle variables, laboratory tests and treatments (drug prescriptions, drugs purchased at the community pharmacy) and also hospital discharge information. The database contains this information for almost five million people, representing approximately 80% of the total population aged over 15 years old in Catalonia (north-east Spain). The fact that these databases can provide large sample sizes at a comparatively low cost and that they permit long follow-up periods without directly requiring the participation of the subjects, whilst minimizing biases such as the Healthy Worker and the Hawthorne effects, has made them especially interesting for public health research. Alzheimer's dementia is a clear example of pathology in which the information provided by SIDIAP can be very useful for research purposes. SIDIAP allows cross-sectional studies for the analysis of treatment patterns or co-morbidities associated with dementia; cohort studies with long follow- up periods or case-control study to evaluate risk factors associated with the onset of various dementias and also permit studies of effectiveness of treatments and preventive interventions (AU)

Resultados finales de un estudio de intervención multifactorial y comunitario para la prevención de caídas en ancianos / Final results of a multifactorial and community intervention study for the prevention of falls in the elderly

Objetivo Evaluar la efectividad de un programa de intervención multifactorial y comunitario para disminuir el número de caídas y sus complicaciones en la población de 70 años o más de una comunidad. Diseño Estudio de intervención comunitaria, multicéntrico, con grupo control y sin asignación aleatorizada. Emplazamiento Dos zonas básicas de salud de la provincia de Girona (España). Participantes Muestra aleatorizada de personas 70 años o más, 2.515 en el grupo de intervención (GI) y 1.212 en el grupo control (GC). Participantes El GI recibió una intervención multifactorial con actividades comunitarias, individuales en la consulta o domicilio y sobre los profesionales durante 2 años. El GC recibió la atención sanitaria habitual. Mediciones y resultados principales Se valoró la situación basal de 2 muestras aleatorizadas representativas, GI (n=329) y GC (n=379), y la situación posintervención del GI (n=292) y el GC (n=310) mediante una encuesta. Personas con caídas GI basal, el 29% (intervalo de confianza [IC] del 95%: 25,8–31,9) y posintervención, el 31% (IC del 95%: 25,6–36,5); GC basal, el 32% (IC del 95%: 28,8–35,2) y posintervención, el 30% (IC del 95%: 24,9–35,4). Caídas con fracturas: GI basal, el 10,4% (IC del 95%: 6–16,3) y posintervención, el 5,3% (IC del 95%: 2–11,2); GC basal, el 7% (IC del 95%: 4–11,2) y posintervención, el 10,7% (IC del 95%: 5,8–17,7). Caídas con asistencia médica: GI basal, el 45,4% (IC del 95%: 37–54) y posintervención, el 43,8% (IC del 95%: 34,4–54,4); GC basal, el 30,3% (IC del 95%: 24,3–36,8) y posintervención, el 40,8% (IC del 95%: 31–51,2). Conclusiones n programa de intervención comunitario multifactorial en personas de 70 años o más no reduce el número de caídas a los 2 años, pero se observa una tendencia a la reducción de sus consecuencias y puede integrarse dentro de la actividad asistencial habitual (AU)

Objective To evaluate the effectiveness of a multifactorial and community intervention programme to decrease the number of falls and their complications in the >=70 years population in a community. Design Multicentre, community intervention study, with no random assignment and with controls. Setting Two basic health areas in the province of Girona (Spain). Participants Random sample of people >=70 years, 2515 in the intervention group (IG) and 1212 in the control group (CG). Participants The IG received multifactorial intervention with community activities, individual in the clinic or at home and by the professionals, for 2 years. The CG received routine health care. Measurements and primary outcomes The baseline situation of two representative random samples, IG (n=329) and CG (n=379) and post-intervention IG (n=292) and CG (n=310), usinn a survey. Results (People with falls): IG baseline 29% (95% confidence interval [CI]: 25.8–31.9) and post-intervention 31% (95% CI: 25.6–36.5). CG baseline 32% (95% CI: 28.8–35.2) and post-intervention 30% (95% CI: 24.9–35.4). Falls with fractures: IG baseline 10.4% (95% CI:6–16.3) and post-intervention 5.3% (95% CI:2–11,2); CG baseline 7% (95% CI:4–11.2) and post-intervention 10.7% (95% CI:5.8–17.7). Falls with medical care: IG baseline 45.4% (95% CI: 37–54) and post-intervention 43.8% (95% CI: 34.4–54.4). GC baseline 30.3% (95% CI: 24.3–36.8) and post-intervention 40.8% (95% CI: 31–51.2). Conclusions A multifactorial community intervention programme in people >=70 years did not reduce the number of falls at 2 years, but a tendency to reduce their consequences was observed, and could be integrated within routine care activities(AU)

[Prevalence of occult chronic kidney disease and associated variables in a population of patients with type 2 diabetes]. / Prevalencia de insuficiencia renal oculta y variables asociadas en una población de pacientes con diabetes tipo 2.

BACKGROUND AND OBJECTIVE: To determine the prevalence of occult chronic kidney disease (CKD) and the associated clinical variables in patients with type 2 diabetes mellitus (DM-2). PATIENTS AND METHOD: Observational, laboratory and cross-sectional study of patients with DM-2 from primary care settings. Demographic and anthropometric data, previous illnesses and measures of cardiovascular risk and kidney function were collected from electronic medical records. We determined the prevalence of occult CKD defined as patients with normal values of plasma creatinine (Cr) and reduced glomerular filtration rate (GFr) (< 60 ml/min/1,73 m(2)). The GFr was determined by the Modification of Diet in Renal Disease (MDRD) equation. RESULTS: The sample consisted of 3,197 patients, the mean age was 67.7 years (SD = 11.7) and 53.9% were men. The prevalence of CKD according to the MDMR values was 16.6% (n = 532), of which 60.3% (n = 321) corresponded to occult CKD. 6.6% (n = 211) of the participants had CKD with high Cr values. Multivariate analysis showed an association of occult CKD with female sex (OR = 2.7; CI 95% = 1,83-3,99). Occult CKD was associated with age, blood pressure higher than 150/100 mm/Hg and with a history of ischemic heart disease, heart failure, peripheral arterial disease and dyslipemia. CONCLUSIONS: The prevalence of CKD is 16.6%, of which 60.3% (n = 321) corresponds to occult CKD. Female sex is associated with the presence of occult CKD.

[Final results of a multifactorial and community intervention study for the prevention of falls in the elderly]. / Resultados finales de un estudio de intervención multifactorial y comunitario para la prevención de caídas en ancianos.

OBJECTIVE: To evaluate the effectiveness of a multifactorial and community intervention programme to decrease the number of falls and their complications in the >or=70 years population in a community. DESIGN: Multicentre, community intervention study, with no random assignment and with controls. SETTING: Two basic health areas in the province of Girona (Spain). PARTICIPANTS: Random sample of people >or=70 years, 2515 in the intervention group (IG) and 1212 in the control group (CG). The IG received multifactorial intervention with community activities, individual in the clinic or at home and by the professionals, for 2 years. The CG received routine health care. MEASUREMENTS AND PRIMARY OUTCOMES: The baseline situation of two representative random samples, IG (n=329) and CG (n=379) and post-intervention IG (n=292) and CG (n=310), usinn a survey. RESULTS: (People with falls): IG baseline 29% (95% confidence interval [CI]: 25.8-31.9) and post-intervention 31% (95% CI: 25.6-36.5). CG baseline 32% (95% CI: 28.8-35.2) and post-intervention 30% (95% CI: 24.9-35.4). Falls with fractures: IG baseline 10.4% (95% CI:6-16.3) and post-intervention 5.3% (95% CI:2-11,2); CG baseline 7% (95% CI:4-11.2) and post-intervention 10.7% (95% CI:5.8-17.7). Falls with medical care: IG baseline 45.4% (95% CI: 37-54) and post-intervention 43.8% (95% CI: 34.4-54.4). GC baseline 30.3% (95% CI: 24.3-36.8) and post-intervention 40.8% (95% CI: 31-51.2). CONCLUSIONS: A multifactorial community intervention programme in people >or=70 years did not reduce the number of falls at 2 years, but a tendency to reduce their consequences was observed, and could be integrated within routine care activities.

[Multidisciplinary intervention program for caregivers of patients in a home care program]. / Programa de intervención multidisciplinaria para cuidadores de pacientes en atención domiciliaria.

OBJECTIVES: To improve quality of life, anxiety and depression in caregivers of patients in home care. METHODS: We performed a randomized clinical trial in 79 main caregivers (39 control group and 40 intervention group) of patients in the home care program of a primary care health center between 2000 and 2001. Quality of life, anxiety and depression were measured by the COOP/WONCA and Goldberg questionnaires, respectively, at the beginning and at the end of the study. Interventions consisted of two medical visits to take a bio-psychosocial history of the caregiver and a nurse visit for health education. Two letters, adapted to each carer's needs, were sent and two telephone calls were made. RESULTS: The intervention group scored significantly better than the control group in relation to WONCA-feelings (p=0.03), WONCA-social activities (p=0.05), and WONCA-quality of life (p=0.02). CONCLUSIONS: A short multidisciplinary intervention program adapted to routine consultations could prevent deterioration in caregivers' quality of life.

Programa de intervención multidisciplinaria para cuidadores de pacientes en atención domiciliaria / Multidisciplinary intervention program for caregivers of patients in a home care program

Objetivos: Mejorar la calidad de vida, la ansiedad y la depresiónde los cuidadores de pacientes en atención domiciliaria.Métodos: Ensayo clínico aleatorizado; 79 cuidadores principales(39 grupo control y 40 grupo intervención) de pacientesen atención domiciliaria de un centro de salud entre 2000 y2001. La calidad de vida, la ansiedad y la depresión se midieronmediante los cuestionarios COOP/WONCA y la escalade Goldberg, respectivamente, al inicio y al final del estudio.Las intervenciones consistieron en 2 visitas médicas pararealizar la anamnesis biopsicosocial del cuidador y una visitade enfermería sobre educación sanitaria. Se enviaron doscartas adaptadas a cada cuidador y se realizaron dos llamadastelefónicas de apoyo.Resultados: Se observó una mejora significativa del grupointervención respecto al grupo control en relación conWONCA-sentimientos (p = 0,03), WONCA-actividades sociales(p = 0,05) y WONCA-calidad de vida (p = 0,02).Conclusiones: Una intervención multidisciplinaria y adaptadaa la consulta habitual podría reducir el deterioro de la calidadde vida de los cuidadores(AU)

Objectives: To improve quality of life, anxiety and depressionin caregivers of patients in home care.Methods: We performed a randomized clinical trial in 79 maincaregivers (39 control group and 40 intervention group) of patientsin the home care program of a primary care health centerbetween 2000 and 2001. Quality of life, anxiety and depressionwere measured by the COOP/WONCA and Goldbergquestionnaires, respectively, at the beginning and at the endof the study. Interventions consisted of two medical visits totake a bio-psychosocial history of the caregiver and a nursevisit for health education. Two letters, adapted to each carer’sneeds, were sent and two telephone calls were made.Results: The intervention group scored significantly betterthan the control group in relation to WONCA-feelings (p = 0.03),WONCA-social activities (p = 0.05), and WONCA-quality oflife (p = 0.02).Conclusions: A short multidisciplinary intervention programadapted to routine consultations could prevent deteriorationin caregivers’ quality of life(AU)