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Background Understanding the immune response to the SARS-CoV-2 virus is critical for efficient monitoring and control strategies. The ProHEpic-19 cohort provides a fine-grained description of the kinetics of antibodies after SARS-CoV-2 infection with an exceptional resolution over 17 months. Methods We established a cohort of 769 healthcare workers including healthy and infected with SARS-CoV-2 in northern Barcelona to determine the kinetics of the IgM against the nucleocapsid (N) and the IgG against the N and spike (S) of SARS-CoV-2 in infected healthcare workers. The study period was from 5 May 2020 to 11 November 2021.We used non-linear mixed models to investigate the kinetics of IgG and IgM measured at nine time points over 17 months from the date of diagnosis. The model included factors of time, gender, and disease severity (asymptomatic, mild-moderate, severe-critical) to assess their effects and their interactions. Findings 474 of the 769 participants (61.6%) became infected with SARS-CoV-2. Significant effects of gender and disease severity were found for the levels of all three antibodies. Median IgM(N) levels were already below the positivity threshold in patients with asymptomatic and mild-moderate disease at day 270 after the diagnosis, while IgG(N and S) levels remained positive at least until days 450 and 270, respectively. Kinetic modelling showed a general rise in both IgM(N) and IgG(N) levels up to day 30, followed by a decay with a rate depending on disease severity. IgG(S) levels remained relatively constant from day 15 over time. Interpretation IgM(N) and IgG(N, S) SARS-CoV-2 antibodies showed a heterogeneous kinetics over the 17 months. Only the IgG(S) showed a stable increase, and the levels and the kinetics of antibodies varied according to disease severity. The kinetics of IgM and IgG observed over a year also varied by clinical spectrum can be very useful for public health policies around vaccination criteria in adult population. Funding Regional Ministry of Health of the Generalitat de Catalunya (Call COVID19-PoC SLT16_04; NCT04885478).

The evolution of multimorbidity patterns during aging is still an under-researched area. We lack evidence concerning the time spent by older adults within one same multimorbidity pattern, and their transitional probability across different patterns when further chronic diseases arise. The aim of this study is to fill this gap by exploring multimorbidity patterns across decades of age in older adults, and longitudinal dynamics among these patterns.Longitudinal study based on the Swedish National study on Aging and Care in Kungsholmen (SNAC-K) on adults ≥60 years (N=3,363). Hidden Markov Models were applied to model the temporal evolution of both multimorbidity patterns and individuals' transitions over a 12-year follow-up.Within the study population (mean age 76.1 years, 66.6% female), 87.2% had ≥2 chronic conditions at baseline. Four longitudinal multimorbidity patterns were identified for each decade. Individuals in all decades showed the shortest permanence time in anOur findings highlight the dynamism and heterogeneity underlying multimorbidity by quantifying the varying permanence times and transition probabilities across patterns in different decades. With increasing age, older adults experience decreasing stability and progressively shorter permanence time within one same multimorbidity pattern.

Resumen Objetivo El objetivo de este estudio es analizar el uso, la efectividad, la seguridad y los costes de la prevencion de ictus en fibrilacion auricular (FA) no valvular en pacientes que inician tratamiento con dabigatran o antagonistas de la vitamina K (AVK). Emplazamiento Atencion Primaria (AP) del Instituto Catalan de la Salud (ICS), en Cataluna, durante el periodo 2011-2013. Participantes Todos los pacientes atendidos en los centros de AP del ICS con diagnostico de FA que inician dabigatran o AVK. Intervenciones No aplica (estudio observacional). Mediciones principales Numero de prescripciones y facturaciones de dabigatran y AVK, incidencia de ictus y eventos tromboembolicos, incidencia de hemorragias mayores, incidencia de muertes durante el seguimiento, numero de bajas laborales y medida de los costes asociados a estas variables. Resultados Se incluyo a 14.930 pacientes en el estudio; el 94,6% inicio AVK y el 5,4%, dabigatran. Estos ultimos eran pacientes mas jovenes y con menos comorbilidades asociadas. No hubo diferencias estadisticamente significativas entre AVK y dabigatran en el riesgo de ictus, hemorragias y mortalidad. Los costes asociados al manejo de la FA eran mayores para visitas de AP en el grupo de AVK y mayores para laboratorio, y farmacia en el grupo de dabigatran, aunque los costes totales no fueron estadisticamente diferentes. Conclusiones La mayoria de los pacientes iniciaron AVK. No hubo diferencias entre AVK y dabigatran en el riesgo de ictus, hemorragias y mortalidad.

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BackgroundUnderstanding the immune response to the SARS-CoV-2 virus is critical for efficient monitoring and defence strategies. The ProHEpic-19 cohort provides a fine-grained description of the kinetics of antibodies after SARS-CoV-2 infection with an exceptional resolution over 17 months.MethodsWe established a cohort of 769 health professionals including healthy and infected with SARS-CoV-2 in northern Barcelona to determine the kinetics of the IgM against the nucleocapsid (N) and the IgG against the N and spike (S) of SARS-CoV-2. We used non-linear mixed models to investigate the kinetics of IgG and IgM measured at nine time points over 17 months from the diagnosis. The model included factors of time, gender, and disease severity (asymptomatic, mild-moderate, severe-critical) to assess their effects and their interactions.Findings: 474 of the 769 participants (61.6%) became infected with SARS-CoV-2. Significant effects of gender and disease severity were found for the levels of all three antibodies. Median IgM(N) levels were already below the positivity threshold in patients with asymptomatic and mild-moderate disease at day 270 after the diagnosis, while IgG(N and S) levels remained positive at least until days 450 and 270, respectively. Kinetic modelling showed a general rise in both IgM(N) and IgG(N) levels up to day 30, followed by a decay with a rate depending on disease severity. IgG(S) levels remained relatively constant from day 15 over time.Interpretation: IgM(N) and IgG(N, S) SARS-CoV-2 antibodies showed a heterogeneous kinetics over the 13 months. Only the IgG(S) showed a stable increase, and the levels and the kinetics of antibodies varied according to disease severity. The kinetics of IgM and IgG observed over a year also varied by clinical spectrum can be very useful for public health policies around vaccination criteria in adult population.Funding: Regional Ministry of Health of the Generalitat de Catalunya (Call COVID19-PoC SLT16_04; NCT04885478)

Objective To create an electronic frailty index (eFRAGICAP) using electronic health records (EHR) in Catalunya (Spain) and assess its predictive validity with a two-year follow-up of the outcomes: homecare need, institutionalization and mortality in the elderly. Additionally, to assess its concurrent validity compared to other standardized measures: the Clinical Frailty Scale (CFS) and the Risk Instrument for Screening in the Community (RISC). Methods The eFRAGICAP was based on the electronic frailty index (eFI) developed in United Kingdom, and includes 36 deficits identified through clinical diagnoses, prescriptions, physical examinations, and questionnaires registered in the EHR of primary health care centres (PHC). All subjects > 65 assigned to a PHC in Barcelona on 1st January, 2016 were included. Subjects were classified according to their eFRAGICAP index as: fit, mild, moderate or severe frailty. Predictive validity was assessed comparing results with the following outcomes: institutionalization, homecare need, and mortality at 24 months. Concurrent validation of the eFRAGICAP was performed with a sample of subjects (n = 333) drawn from the global cohort and the CFS and RISC. Discrimination and calibration measures for the outcomes of institutionalization, homecare need, and mortality and frailty scales were calculated. Results 253,684 subjects had their eFRAGICAP index calculated. Mean age was 76.3 years (59.5% women). Of these, 41.1% were classified as fit, and 32.2% as presenting mild, 18.7% moderate, and 7.9% severe frailty. The mean age of the subjects included in the validation subsample (n = 333) was 79.9 years (57.7% women). Of these, 12.6% were classified as fit, and 31.5% presented mild, 39.6% moderate, and 16.2% severe frailty. Regarding the outcome analyses, the eFRAGICAP was good in the detection of subjects who were institutionalized, required homecare assistance, or died at 24 months (c-statistic of 0.841, 0.853, and 0.803, respectively). eFRAGICAP was also good in the detection of frail subjects compared to the CFS (AUC 0.821) and the RISC (AUC 0.848). Conclusion The eFRAGICAP has a good discriminative capacity to identify frail subjects compared to other frailty scales and predictive outcomes.

(1) Introduction: Cardiovascular disease is associated with high mortality, especially in older people. This study aimed to characterize the evolution of combined multimorbidity and polypharmacy patterns in older people with different cardiovascular disease profiles. (2) Material and methods: This longitudinal study drew data from the Information System for Research in Primary Care in people aged 65 to 99 years with profiles of cardiovascular multimorbidity. Combined patterns of multimorbidity and polypharmacy were analysed using fuzzy c-means clustering techniques and hidden Markov models. The prevalence, observed/expected ratio, and exclusivity of chronic diseases and/or groups of these with the corresponding medication were described. (3) Results: The study included 114,516 people, mostly men (59.6%) with a mean age of 78.8 years and a high prevalence of polypharmacy (83.5%). The following patterns were identified: Mental, behavioural, digestive and cerebrovascular; Neuropathy, autoimmune and musculoskeletal; Musculoskeletal, mental, behavioural, genitourinary, digestive and dermatological; Non-specific; Multisystemic; Respiratory, cardiovascular, behavioural and genitourinary; Diabetes and ischemic cardiopathy; and Cardiac. The prevalence of overrepresented health problems and drugs remained stable over the years, although by study end, cohort survivors had more polypharmacy and multimorbidity. Most people followed the same pattern over time; the most frequent transitions were from Non-specific to Mental, behavioural, digestive and cerebrovascular and from Musculoskeletal, mental, behavioural, genitourinary, digestive and dermatological to Non-specific. (4) Conclusions: Eight combined multimorbidity and polypharmacy patterns, differentiated by sex, remained stable over follow-up. Understanding the behaviour of different diseases and drugs can help design individualised interventions in populations with clinical complexity.

BackgroundUnderstanding humoral responses and seroprevalence in SARS-CoV-2 infection is essential for guiding vaccination strategies in both infected and uninfected individuals.MethodsWe determine the kinetics of IgM against the nucleocapsid (N) and IgG against the spike (S) and N proteins of SARS-CoV-2 in a cohort of 860 health professionals (healthy and infected) in northern Barcelona. We model the kinetics of IgG and IgM at nine time points over 13.5 months from infection, using non-linear mixed models by sex and clinical disease severity.ResultsOf the 781 participants who were followed up, 478 (61.2%) became infected with SARS-CoV-2. Significant differences were found for the three antibodies by disease severity and sex. At day 270 after diagnosis, median IgM(N) levels were already below the positivity threshold in patients with asymptomatic and mild-moderate disease, while IgG(N, S) levels remained positive to days 360 and 270, respectively. Kinetic modelling showed a general rise in both IgM(N) and IgG(N) levels up to day 30, followed by a decay whose rate depended on disease severity. IgG(S) levels increased at day 15 and remained relatively constant over time.ConclusionsWe describe kinetic models of IgM(N) and IgG(N, S) SARS-CoV-2 antibodies at 13.5 months from infection and disease spectrum. Our analyses delineate differences in the kinetics of IgM and IgG over a year and differences in the levels of IgM and IgG as early as 15 days from symptoms onset in severe cases. These results can inform public health policies around vaccination criteria.Funded by the regional Ministry of Health of the Generalitat de Catalunya (Call COVID19-PoC SLT16_04; NCT04885478)

Background/Objectives To assess the adherence to reporting confidence intervals (CI) for measures of association in multivariable regression models (MRM) in articles with observational design indexed in MEDLINE. Material and methods A literature search was conducted using the MEDLINE bibliographic database to obtain a representative sample of studies with observational design and applying MRM (logistic, linear, and Cox regression) (n = 428). Proportions and 95% CI of articles reporting CI for measures of association in MRM were calculated. Percentage ratios (PRs) were also calculated to describe the change in CI reporting before and after the publication of the STROBE statement. Results 188 of the 236 abstracts with measures of association (79.7%; 95% CI 74.5, 84.8) and 360 of the 428 main texts (84.1%; 80.6, 87.6) were provided with CI. A non-significant increase of 1% in the abstract, PR = 1.01 (0.77, 1.29), and 7% in the main text, PR = 1.07 (0.87, 1.28), occurred in the CI reporting after the publication of the STROBE guideline. Conclusions The STROBE guideline recommendation on reporting CI should be more thoroughly followed.

Ambulatory blood pressure (BP) is associated with mortality, but it is also interesting to expand its association with cardiovascular morbidity. This study sought to evaluate association with cardiovascular morbidity and cardiovascular mortality. Patients without cardiovascular disease who had a first 24-hour ambulatory BP monitoring were followed-up until the onset of the first event (a combined variable of cardiovascular mortality, coronary heart disease, cerebrovascular disease, peripheral arteriopathy, or hospital admission for heart failure). Changes in antihypertensive treatment couldn't be collected. Cox regression analysis was adjusted for risk factors and office BP. We included 3907 patients (mean age, 58.0, SD 13.8 years), of whom 85.5% were hypertensive. The follow up period was 6.6 (95% CI 5.0-8.5) years. A total of 496 (12.7%) events were recorded. The incidence rate was 19.3 (95% CI 17.7-21.1) cases per 1000 person-years. The patients with an event compared to the rest of patients were mostly men, older, with higher office and ambulatory systolic BP, higher prevalence of diabetes, chronic kidney disease, dyslipidemia, and non-dipper or riser circadian profile. In the fully adjusted model, office BP loses its significant association with the main variable. Ambulatory BP association remained significant with cardiovascular morbidity and mortality, HR 1.494 (1.326-1.685) and 0.767 (0.654-0.899) for 24-hour systolic and diastolic BP, respectively. Nighttime systolic BP also maintained this significant association, 1.270 (1.016-1.587). We conclude that nighttime systolic BP and 24-hour BP are significantly associated with cardiovascular events and cardiovascular mortality in patients without cardiovascular disease attended under conditions of routine clinical practice.

Funding: Swedish National study on Aging and Care; Ministry of Health and Social Affairs; Swedish Research Council, Grant/Award Number: 2016-00981; Swedish Research Council for Health,Working Life andWelfare, Grant/Award Number: 2017-01764; Italian Ministry of Health, Grant/Award Number: PE-2016-02364885 We investigate dementia risk in older adults with different disease patterns and explore the role of inflammation and apolipoprotein E (APOE) genotype. A total of 2,478 dementia-free participants with two or more chronic diseases (ie, multimorbidity) part of the Swedish National study on Aging and Care in Kungsholmen (SNAC-K) were grouped according to their multimorbidity patterns and followed to detect clinical dementia. The potential modifier effect of C-reactive protein (CRP) and apolipoprotein E (APOE) genotype was tested through stratified analyses. People with neuropsychiatric, cardiovascular, and sensory impairment/cancer multimorbidity had increased hazards for dementia compared to the unspecific (Hazard ration (HR) 1.66, 95% confidence interval [CI] 1.13-2.42; 1.61, 95% CI 1.17-2.29; 1.32, 95% CI 1.10-1.71, respectively). Despite the lack of statistically significant interaction, high CRP increased dementia risk within these patterns, and being APOE ε4 carriers heightened dementia risk for neuropsychiatric and cardiovascular multimorbidity. Individuals with neuropsychiatric, cardiovascular, and sensory impairment/cancer patterns are at increased risk for dementia and APOE ε4, and inflammation may further increase the risk. Identifying such high-risk groups might allow tailored interventions for dementia prevention.

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 mathematical model, we split admissions into four waves, one of them (summer wave) with little incidence. 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 (6,800; 39.9%), summer wave (1,807; 10.6%), second wave (3,804; 22.3%), and third wave (4,616; 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 independent predictors of 30-day mortality were the epidemic wave, followed by gender, age, diabetes, chronic kidney disease, and neoplasms. Interpretation: In-hospital COVID-19 mortality has decreased substantially after the first wave, but continues to be high 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 Information: This work was partially funded by the grant COVID19 6_17 (to Francesc Vidal), Direccio General de Recerca i Innovacio en Salut (Departament de Salut) and BIOCAT, Generalitat de Catalunya. Declaration of Interests: KK is a member of the UK Scientific Advisory Group for Emergencies. All other authors have nothing to declare. Ethics Approval Statement: The study protocol was approved by the independent ethics committee of the Hospital Germans Trias i Pujol (Badalona, Spain), which waived obtaining informed consent.

The presence of multiple chronic conditions (i.e., multimorbidity) increases the risk of hospitalisation in older adults. We aimed to examine the association between different multimorbidity patterns and unplanned hospitalisations over 5 years. To that end, 2,250 community-dwelling individuals aged 60 years and older from the Swedish National Study on Aging and Care in Kungsholmen (SNAC-K) were studied. Participants were grouped into six multimorbidity patterns using a fuzzy c-means cluster analysis. The associations between patterns and outcomes were tested using Cox models and negative binomial models. After 5 years, 937 (41.6%) participants experienced at least one unplanned hospitalisation. Compared to participants in the unspecific multimorbidity pattern, those in the cardiovascular diseases, anaemia and dementia pattern, the psychiatric disorders pattern and the metabolic and sleep disorders pattern presented with a higher hazard of first unplanned hospitalisation (hazard ratio range: 1.49&ndash, 2.05, p &lt, 0.05 for all), number of unplanned hospitalisations (incidence rate ratio (IRR) range: 1.89&ndash, 2.44, 0.05 for all), in-hospital days (IRR range: 1.91&ndash, 3.61, 0.05 for all), and 30-day unplanned readmissions (IRR range: 2.94&ndash, 3.65, 0.05 for all). Different multimorbidity patterns displayed a differential association with unplanned hospital care utilisation. These findings call for a careful primary care follow-up of older adults with complex multimorbidity patterns.

Objectives The aim was to evaluate patterns of multimorbidity that increase the risk of institutionalization in older persons, also exploring the potential buffering effect of formal and informal care. Design Prospective cohort study. Setting and Participants The population-based Swedish National study on Aging and Care in Kungsholmen, Stockholm, Sweden. Measures In total, 2571 community-dwelling older adults were grouped at baseline according to their underlying multimorbidity patterns, using a fuzzy c-means cluster algorithm, and followed up for 6 years to test the association between multimorbidity patterns and institutionalization. Results Six patterns of multimorbidity were identified: psychiatric diseases; cardiovascular diseases, anemia, and dementia; metabolic and sleep disorders; sensory impairments and cancer; musculoskeletal, respiratory, and gastrointestinal diseases; and an unspecific pattern including diseases of which none were overrepresented. In total, 110 (4.3%) participants were institutionalized during the follow-up, ranging from 1.7% in the metabolic and sleep disorders pattern to 8.4% in the cardiovascular diseases, anemia, and dementia pattern. Compared with the unspecific pattern, only the cardiovascular diseases, anemia, dementia pattern was significantly associated with institutionalization [relative risk ratio (RRR) = 2.23; 95% confidence interval (CI) 1.07‒4.65)], after adjusting for demographic characteristics and disability status at baseline. In stratified analyses, those not receiving formal care in the psychiatric diseases pattern (RRR 3.34; 95% CI 1.20‒9.32) and those not receiving formal or informal care in the ‘cardiovascular diseases, anemia, dementia’ pattern (RRR 2.99; 95% CI 1.20‒7.46; RRR 2.79; 95% CI 1.16‒6.71, respectively) had increased risks of institutionalization. Conclusions and Implications Older persons suffering from specific multimorbidity patterns have a higher risk of institutionalization, especially if they lack formal or informal care. Interventions aimed at preventing the clustering of diseases could reduce the associated burden on residential long-term care. Formal and informal care provision may be effective strategies in reducing the risk of institutionalization.

A challenge to solve when analyzing multimorbidity patterns in elderly people is the management of a high number of characteristics associated with each patient. The main variables to study multimorbidity are diseases, however other variables should be considered to better classify the people included in each pattern. Age, sex, social class and medication are frequently used in the typing of each multimorbidity pattern. Subsequently the cardinality of the set of features that characterize a patient is very high and normally, the set is compressed to obtain a patient vector of new variables whose dimension is noticeably smaller than that of the initial set. To minimize the loss of information by compression, traditionally Principal Component Analysis (PCA) based projection techniques have been used, which although they are generally a good option, the projection is linear, which somehow reduces its flexibility and limits the performance. As an alternative to the PCA based techniques, in this paper, it is proposed to use autoencoders, and it is shown the improvement in the obtained multimorbidity patterns from the compressed database, when the registered data on about a million patients (5 years' follow-up) are processed. This work demonstrates that autoencoders retain a larger amount of information in each pattern and results are more consistent with clinical experience than other approaches frequently found in the literature.Clinical relevance- From an epidemiological perspective, the contribution is relevant, since it allows for a more precise analysis of multimorbidity patterns, leading to better approaches to patient health strategies. Work supported by Carlos III Institute of Health, Spanish Ministry of Economy and Competitiveness and ERDF (UE) funds under Grant PI16/00639, and in part by Catalan Government funds under Grants 2017 SGR 578 AGAUR and Strategic Plan for Research in Health PERIS grant number SLT002/16/00058

Background: The implementation of individual clinical practice guidelines in patients with multimorbidity often results in polypharmacy. Our aim was to analyse medication use according to longitudinal multimorbidity patterns (MP) and determine during a 5-year period (2012-16) which MP are associated with abnormal liver and kidney function in primary care patients over 65 years of age living in Catalonia.Methods: Design: Longitudinal study (years 2012 to 2016) based on the electronic health records contained in Information System for Research in Primary Care database of the Catalan Institute of Health (SIDIAP). Variables: age, sex, MP, medication and polypharmacy (drug exposure obtained from the Pharmacy Invoice Registry). Medicines were classified in accordance with the Anatomical Therapeutic Chemical Classification System (ATC). Glomerular filtration rate was used to determine abnormal kidney function, and serum levels of alkaline phosphatase, alanine transaminase and gamma-glutamyl transpeptidase were used to diagnose abnormal liver function. Statistics: For medication use in MP, we calculated annual mean packages of each drug in each MP, and observed/expected ratios were obtained by dividing mean packages in the cluster by mean packages of the same drug in the overall population. Logistic regression models were fitted to estimate the association between MP at baseline and abnormal kidney and liver function tests during follow up.Results: 916,619 patients were included, and 743,827 completed the follow up. We identified one polypharmacy profile per MP, and concluded that the most prescribed drugs in each pattern corresponded to the diseases overrepresented in that specific MP. The median of drugs ranged from 3 (Cluster 1 - Non-Specific) to 8 (Cluster 10 - Multisystem Pattern). Abnormal kidney function was most commonly observed in the Cluster 4 - Cardio-Circulatory and Renal (Odds Ratio [OR] 2.19; Confidence interval [CI] 95% 2.15-2.23) and Cluster 3 - Minority Metabolic Autoimmune-Inflammatory (OR 2.16; CI 95% 2.12-2.20) MP. A higher risk of abnormal liver function was observed in the Cluster 8 - Digestive (OR 3.39; CI 95% 3.30-3.49), and Cluster 4 - Cardio-Circulatory and Renal (OR 1.96; CI 95% 1.91-2.02) MP.Conclusions: A higher risk of abnormal kidney and liver function was observed in specific MP. The long-term characterisation of MP and polypharmacy illustrates the burden of chronic multimorbidity and polypharmacy in the elderly population.

Background: Different multimorbidity patterns present with different prognoses, but it is unknown to what extent they may influence the effectiveness of an individualized multicomponent exercise program offered to hospitalized older adults. Methods: This study is a secondary analysis of a randomized controlled trial conducted in the Department of Geriatric Medicine of a tertiary hospital. In addition to the standard care, an exercise-training multicomponent program was delivered to the intervention group during the acute hospitalization period. Multimorbidity patterns were determined through fuzzy c-means cluster analysis, over 38 chronic diseases. Functional, cognitive and affective outcomes were considered. Results: Three hundred and six patients were included in the analyses (154 control; 152 intervention), with a mean age of 87.2 years, and 58.5% being female. Four patterns of multimorbidity were identified: heart valves and prostate diseases (26.8%); metabolic diseases and colitis (20.6%); psychiatric, cardiovascular and autoimmune diseases (16%); and an unspecific pattern (36.6%). The Short Physical Performance Battery (SPPB) test improved across all patterns, but the intervention was most effective for patients in the metabolic/colitis pattern (2.48-point difference between intervention/control groups, 95% CI 1.60-3.35). Regarding the Barthel Index and the Mini Mental State Examination (MMSE), the differences were significant for all multimorbidity patterns, except for the psychiatric/cardio/autoimmune pattern. Differences concerning quality of life were especially high for the psychiatric/cardio/autoimmune pattern (16.9-point difference between intervention/control groups, 95% CI 4.04, 29.7). Conclusions: Patients in all the analyzed multimorbidity patterns improved with this tailored program, but the improvement was highest for those in the metabolic pattern. Understanding how different chronic disease combinations are associated with specific functional and cognitive responses to a multicomponent exercise intervention may allow further tailoring such interventions to older patients’ clinical profile. The author(s) disclosed receipt of the following financial support for the research, authorship, and/or publication of this article. This work was supported by the Gobierno de Navarra project grant 2186/2014 and acknowledged with the “Beca Ortiz de Landázuri” as the best research clinical project in 2014, as well as by a research grant PI17/01814 of the Ministerio de Economía, Industria y Competitividad (ISCIII, FEDER). Additional contributions: NM-V received funding from “la Caixa” Foundation (ID 100010434), under agreement LCF/PR/PR15/51100006.

Altres ajuts: Department of Health of the Catalan Government/SLT002/16/00058 The aim of this study was to determine medication-related problems (MRPs) in primary care patients over 65 years of age. Cross-sectional study based on the electronic health records of patients (65-99 years of age) visited in 284 primary health care centers during 2012 in Catalonia. Variables: age, sex, sociodemographic variables, number of drugs, kidney and liver function and MRPs (duplicate therapy, drug-drug interactions, potentially inappropriate medications [PIMs] and drugs contraindicated in chronic kidney disease and in liver diseases). Unconditional logistic regression models were used to identify the factors associated with MRPs in patients with multimorbidity. 916 619 older people were included and 853 085 of them met the criteria for multimorbidity. Median age was 75 years and 57.7% of them were women. High percentages of MRPs were observed: PIMs (62.8%), contraindicated drugs in chronic kidney disease (12.1%), duplicate therapy (11.1%), contraindicated drugs in liver diseases (4.2%), and drug-drug interactions (1.0%). These numbers were higher in the subgroup of patients with ≥10 diseases. The most common PIMs were connected to drugs that increase the risk of fall (66.8%), antiulcer agents without criteria for gastroprotection (40.6%), and the combination of drugs with anticholinergic effects (39.7%). In the multivariate analysis, the variables associated with all MRPs among the patients with multimorbidity were the number of drugs and the number of visits. The coexistence of multimorbidity and polypharmacy is associated with an elevated risk of MRPs in older people. Medication safety for older patients constitutes a pressing concern for health services.

Purpose To describe the characteristics of new users of cilostazol in Europe with the aim to support the evaluation of its benefit/risk as used in regular clinical practice before the implementation of labeling changes recommended by the European Medicines Agency. Methods New users of cilostazol were identified in populations enrolled in five European health automated databases in the UK (The Health Improvement Network [THIN]), Spain (EpiChron cohort and Information System for the Improvement of Research in Primary Care [SIDIAP]), Sweden (National Registers), and Germany (German Pharmacoepidemiological Research Database [GePaRD]) between 2002 and 2012. New users were characterized according to the prevalence of cardiovascular disease and other comorbidities, concurrent use of interacting medications, new contraindications, duration of use, and potential off-label prescribing. Results We identified 22 593 new users of cilostazol. The median age was between 68.0 (THIN) and 73.7 (Sweden) years. More than 78% of users had concomitant cardiovascular disease, and between 78.8% (GePaRD) and 91.6% (THIN) were treated with interacting medications. Prevalence of new cardiovascular contraindications ranged from 1.5% (THIN) to 11.6% (GePaRD), and concurrent use of two or more antiplatelet drugs ranged from 6.3% (SIDIAP) to 13.5% (EpiChron cohort). Between 39.4% (Sweden) and 52.9% (THIN) of users discontinued cilostazol in the first 3 months. Between 41.0% (SIDIAP) and 93.4% (THIN) were considered to have received cilostazol according to the European Medicines Agency labeling. Conclusions In this collaborative European study, most cilostazol users were elderly patients with a high prevalence of cardiovascular diseases and other comorbidity and concurrent use of interacting drugs, indicating that this is a vulnerable population at high risk of complications, especially cardiovascular events. © 2017 The Authors. Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd.

Purpose The aim of this study was to assess effectiveness and safety of antithrombotics for stroke prevention in non-valvular atrial fibrillation in real-use conditions. Methods We used a population-based retrospective cohort study. Information emerges from SIDIAP, a database containing anonymized information from electronic health records from 274 primary healthcare centres of the Catalan Health Institute, Catalonia (Spain), with a reference population of 5 835 000 people. Population includes all adults with a new diagnosis of non-valvular atrial fibrillation registered in SIDIAP from 2007 to 2012. The main outcome of antithrombotics' effectiveness was stroke. The main outcomes of safety were cerebral and gastrointestinal haemorrhages. We also estimated all-cause mortality. We used multivariable Cox proportional hazard models to examine association between antithrombotic treatment and main outcomes. Results We included 22 205 subjects with non-valvular atrial fibrillation; 40.8% initiated on vitamin K antagonists (VKA), 33.4% on antiplatelets and 25.8% untreated. We found stroke-risk reduction with VKA, hazard ratio (HR) 0.72 (95% confidence interval (CI), 0.58–0.91), also seen in patients with CHADS2 ≥ 2, HR 0.65 (95%CI, 0.49–0.86), and CHA2DS2-VASc ≥ 2, HR 0.66 (95%CI, 0.52–0.84). We observed a higher risk of digestive bleeding with antiplatelets, HR 1.32 (95%CI, 1.01–1.73). Both VKA and antiplatelets were associated with reduction of all-cause mortality risk; HR 0.55 (95%CI, 0.49–0.62) and HR 0.89 (95%CI, 0.80–0.97), respectively. Conclusions This study found a stroke-risk reduction associated with VKA and an increased risk of gastrointestinal bleeding associated with platelet-aggregation inhibitors in comparison with untreated patients. Both antithrombotic groups showed a reduction in all-cause mortality. Copyright © 2016 John Wiley & Sons, Ltd.

Resumen Fundamentos En el ambito de la investigacion medica los modelos de regresion logistica, lineal, Cox y Poisson son tecnicas estadisticas ampliamente conocidas. El objetivo de este trabajo es describir la evolucion de estas tecnicas de regresion en los articulos observacionales indexados en PubMed (1970-2013) y revisar los requerimientos de las normas de autor de revistas espanolas para conocer si requieren el cumplimiento de la guia STROBE. Metodos Se realizo una busqueda dirigida en PubMed para identificar los articulos que utilizaron modelos de regresion logistica, lineal, Cox y Poisson. Ademas, se revisaron las normas de autor de las revistas editadas en Espana indexadas en PubMed e incluidas en Web Of Science. Resultados El 6,1% de los articulos de estudios observacionales contenian algun termino relativo a los modelos seleccionados, pasando del 0,14% en 1980 hasta un 12,3% en 2013. Este ultimo ano, un 6,7% de los articulos contenian algun termino referido a regresion logistica, un 2,5% a lineal, un 3,5% a Cox y un 0,31% a Poisson. Por otro lado, el 12,8% de las normas de autor de las revistas revisadas recomendaban explicitamente seguir la guia STROBE, y el 35,9%, la guia CONSORT. Conclusiones Los modelos de regresion multivariantes en estudios observacionales publicados, tales como la regresion logistica, lineal, Cox y Poisson, son cada vez mas utilizados tanto a nivel global como en revistas publicadas en lengua espanola. Ademas, un porcentaje bajo de las revistas cientificas espanolas indexadas en PubMed incluyen en las normas de autoria el requerimiento de la guia STROBE.

Purpose The purpose of this study is to describe the pharmacologic management of rate and rhythm and assess which factors are associated with the prescription of these drugs in patients with nonvalvular atrial fibrillation (AF) from the Effectiveness, Safety, and Costs in Atrial Fibrillation study. Methods This retrospective, cross-sectional study describes the pharmacologic rate and rhythm control management strategies adopted during 2012 in all patients diagnosed as having nonvalvular AF in 2007 to 2011. The data source is the Information System for the Improvement of Research in Primary Care database, which is based on primary care electronic health records. To answer the study objectives, 3 multivariate regression models to assess the independent factors associated with the prescription of these drugs were conducted for 2012. The rate and rhythm control drugs assessed were β-blockers, nondihydropyridine calcium channel blockers, antiarrhythmic agents, and digoxin. Findings A total of 21,304 patients were diagnosed as having nonvalvular AF; 11,638 (54.6%) had at least one heart rate measure during 2012. Of them, 7777 (66.8%) received one or more rate and/or rhythm control drugs during 2012. Most patients (5751 [73.9%] of 7777) received only one drug for rate and/or rhythm control. Rate control agents were the most frequently used in 2012, with β-blockers the most prescribed group (4091 patients [52.6%]). A variety of different variables were associated with the prescription of rate and/or rhythm control drugs in the multivariate regression models. Implications The most used pharmacologic treatment of rate and rhythm control in our AF population is β-blockers, indicating that a rate control strategy is preferred in our setting, as widely recommended.

Background The axillary lymph nodes (ALNs) in breast cancer patients are the body regions to where tumoral cells most often first disseminate. The tumour immune response is important for breast cancer patient outcome, and some studies have evaluated its involvement in ALN metastasis development. Most studies have focused on the intratumoral immune response, but very few have evaluated the peritumoral immune response. The aim of the present article is to evaluate the immune infiltrates of the peritumoral area and their association with the presence of ALN metastases. Methods The concentration of 11 immune markers in the peritumoral areas was studied in 149 patients diagnosed with invasive breast carcinoma of no special type (half of whom had ALN metastasis at diagnosis) using tissue microarrays, immunohistochemistry and digital image analysis procedures. The differences in the concentration of the immune response of peritumoral areas between patients diagnosed with and without metastasis in their ALNs were evaluated. A multivariate logistic regression model was developed to identify the clinical-pathological variables and the peritumoral immune markers independently associated with having or not having ALN metastases at diagnosis. Results No statistically significant differences were found in the concentrations of the 11 immune markers between patients diagnosed with or without ALN metastases. Patients with metastases in their ALNs had a higher histological grade, more lymphovascular and perineural invasion and larger-diameter tumours. The multivariate analysis, after validation by bootstrap simulation, revealed that only tumour diameter (OR = 1.04; 95% CI [1.00–1.07]; p = 0.026), lymphovascular invasion (OR = 25.42; 95% CI [9.57–67.55]; p p = 0.033) and 3 (OR = 5.18; 95% CI [1.40–19.17]; p = 0.014) were associated with the presence of ALN metastases at diagnosis. This study is one of the first to study the association of the peritumoral immune response with ALN metastasis. We did not find any association of peritumoral immune infiltrates with the presence of ALN metastasis. Nevertheless, this does not rule out the possibility that other peritumoral immune populations are associated with ALN metastasis. This matter needs to be examined in greater depth, broadening the types of peritumoral immune cells studied, and including new peritumoral areas, such as the germinal centres of the peritumoral tertiary lymphoid structures found in extensively infiltrated neoplastic lesions.

Multimorbidity is an emerging topic in public health policy because of its increasing prevalence and socio-economic impact. However, the age- and gender-dependent trends of disease associations at fine resolution, and the underlying genetic factors, remain incompletely understood. Here, by analyzing disease networks from electronic medical records of primary health care, we identify key conditions and shared genetic factors influencing multimorbidity. Three types of diseases are outlined: “central”, which include chronic and non-chronic conditions, have higher cumulative risks of disease associations; “community roots” have lower cumulative risks, but inform on continuing clustered disease associations with age; and “seeds of bursts”, which most are chronic, reveal outbreaks of disease associations leading to multimorbidity. The diseases with a major impact on multimorbidity are caused by genes that occupy central positions in the network of human disease genes. Alteration of lipid metabolism connects breast cancer, diabetic neuropathy and nutritional anemia. Evaluation of key disease associations by a genome-wide association study identifies shared genetic factors and further supports causal commonalities between nervous system diseases and nutritional anemias. This study also reveals many shared genetic signals with other diseases. Collectively, our results depict novel population-based multimorbidity patterns, identify key diseases within them, and highlight pleiotropy influencing multimorbidity.

Atrial fibrillation (AF) is the most common chronic arrhythmia, with increasing healthcare and economic burden and a prevalence which increases with progressive ageing. This study aims to describe overall annual costs per patient for management of non-valvular AF in a primary healthcare (PHC) setting and compare these costs between the groups of patients treated with vitamin K antagonists, antiplatelets or non-treated through a population-based study conducted with electronic health records. We analysed annual costs per person of 19,787 patients in 2012; PHC visits, hospital admissions, AF-related events requiring hospital admission, referrals to secondary specialists, sick leave, diagnostic tests and laboratory tests at PHC level, including INR determinations performed in PHC, and drug therapy. Higher costs of AF management were associated with increasing age, male sex, stroke and bleeding risks, comorbidities and occurrence of events associated to AF. The sensitivity analyses conducted showed that PHC visits and hospitalizations represented the most important part of overall costs for all patients.

Introduction and objectives: Atrial fibrillation constitutes a serious public health problem because it can lead to complications. Thus, the management of this arrhythmia must include not only its treatment, but antithrombotic therapy as well. The main goal is to determine the proportion of cases of undiagnosed atrial fibrillation and the proportion of patients not being treated with oral anticoagulants. Methods: A multicenter, population-based, retrospective, cross-sectional, observational study. In all, 1043 participants over 60 years of age were randomly selected to undergo an electrocardiogram in a prearranged appointment. Demographic data, CHA2DS2-VASc and HAS-BLED scores, international normalized ratio results, and reasons for not receiving oral anticoagulant therapy were recorded. Results: The overall prevalence of atrial fibrillation was 10.9% (95% confidence interval, 9.1%-12.8%), 20.1% of which had not been diagnosed previously. In the group with known atrial fibrillation, 23.5% of those with CHA2DS2-VASc≥2 were not receiving oral anticoagulant therapy, and 47.9% had a HAS-BLED score≥3. The odds ratio for not being treated with oral anticoagulation was 2.04 (95% confidence interval, 1.11-3.77) for women, 1.10 (95% confidence interval, 1.05-1.15) for more advanced age at diagnosis, and 8.61 (95% confidence interval 2.38-31.0) for a CHA2DS2-VASc score

Resumen Introduccion y objetivos La fibrilacion auricular significa un grave problema de salud publica por sus complicaciones, por lo que su manejo deberia incluir no solo su tratamiento, sino tambien la prevencion de las complicaciones tromboembolicas. El objetivo principal es conocer las proporciones de la fibrilacion auricular desconocida y la no tratada con anticoagulantes. Metodos Estudio observacional, transversal, retrospectivo, de base poblacional y multicentrico. Se selecciono aleatoriamente a 1.043 sujetos mayores de 60 anos para realizarles un electrocardiograma en visita concertada. Se registraron variables sociodemograficas, valores en las escalas CHA2DS2-VASc y HAS-BLED, razon internacional normalizada y motivos de no recibir tratamiento anticoagulante oral. Resultados La prevalencia total de fibrilacion auricular fue del 10,9% (intervalo de confianza del 95%, 9,1-12,8%), de la que el 20,1% era desconocida. De la fibrilacion auricular conocida, el 23,5% con un valor de CHA2DS2-VASc ≥ 2 no recibia tratamiento anticoagulante y el 47,9% tenia un valor HAS-BLED ≥ 3. La odds ratio de no recibir tratamiento anticoagulante fue 2,04 (intervalo de confianza del 95%, 1,11-3,77) para las mujeres, 1,10 (intervalo de confianza del 95%, 1,05-1,15) para la mayor edad de diagnostico y 8,61 (intervalo de confianza del 95%, 2,38-31,0) si el valor de CHA2DS2-VASc es Conclusiones El 20,1% de las fibrilaciones auriculares de pacientes mayores de 60 anos son desconocidas previamente y no se trata con anticoagulantes al 23,5% del total.

The purpose of this study was to characterize the profile of patients with non-valvular atrial fibrillation who start an anticoagulant treatment after diagnosis with dabigatran and compare it with those who start with vitamin K antagonists (VKAs). We analysed primary health care-based electronic health records data from 15,075 people with new diagnosis of atrial fibrillation who initiated treatment with dabigatran or VKA spanning 2011–2013. Logistic regression analysis for determination of factors associated with initiation of dabigatran was performed. We identified 14,266 (94.6%) people who initiated VKA and 809 (5.4%) who initiated dabigatran. Mean age of people treated with dabigatran was lower than in VKA patients (73.7 vs 75.5 years, p

The aim of this study was to assess effectiveness and safety of antithrombotics for stroke prevention in non-valvular atrial fibrillation in real-use conditions.We used a population-based retrospective cohort study. Information emerges from SIDIAP, a database containing anonymized information from electronic health records from 274 primary healthcare centres of the Catalan Health Institute, Catalonia (Spain), with a reference population of 5 835 000 people. Population includes all adults with a new diagnosis of non-valvular atrial fibrillation registered in SIDIAP from 2007 to 2012. The main outcome of antithrombotics' effectiveness was stroke. The main outcomes of safety were cerebral and gastrointestinal haemorrhages. We also estimated all-cause mortality. We used multivariable Cox proportional hazard models to examine association between antithrombotic treatment and main outcomes.We included 22 205 subjects with non-valvular atrial fibrillation; 40.8% initiated on vitamin K antagonists (VKA), 33.4% on antiplatelets and 25.8% untreated. We found stroke-risk reduction with VKA, hazard ratio (HR) 0.72 (95% confidence interval (CI), 0.58-0.91), also seen in patients with CHADSThis study found a stroke-risk reduction associated with VKA and an increased risk of gastrointestinal bleeding associated with platelet-aggregation inhibitors in comparison with untreated patients. Both antithrombotic groups showed a reduction in all-cause mortality. Copyright © 2016 John WileySons, Ltd.

Purpose To describe the characteristics of new users of cilostazol in Europe with the aim to support the evaluation of its benefit/risk as used in regular clinical practice before the implementation of labeling changes recommended by the European Medicines Agency. Methods New users of cilostazol were identified in populations enrolled in five European health automated databases in the UK (The Health Improvement Network [THIN]), Spain (EpiChron cohort and Information System for the Improvement of Research in Primary Care [SIDIAP]), Sweden (National Registers), and Germany (German Pharmacoepidemiological Research Database [GePaRD]) between 2002 and 2012. New users were characterized according to the prevalence of cardiovascular disease and other comorbidities, concurrent use of interacting medications, new contraindications, duration of use, and potential off‐label prescribing. Results We identified 22 593 new users of cilostazol. The median age was between 68.0 (THIN) and 73.7 (Sweden) years. More than 78% of users had concomitant cardiovascular disease, and between 78.8% (GePaRD) and 91.6% (THIN) were treated with interacting medications. Prevalence of new cardiovascular contraindications ranged from 1.5% (THIN) to 11.6% (GePaRD), and concurrent use of two or more antiplatelet drugs ranged from 6.3% (SIDIAP) to 13.5% (EpiChron cohort). Between 39.4% (Sweden) and 52.9% (THIN) of users discontinued cilostazol in the first 3 months. Between 41.0% (SIDIAP) and 93.4% (THIN) were considered to have received cilostazol according to the European Medicines Agency labeling. Conclusions In this collaborative European study, most cilostazol users were elderly patients with a high prevalence of cardiovascular diseases and other comorbidity and concurrent use of interacting drugs, indicating that this is a vulnerable population at high risk of complications, especially cardiovascular events. © 2017 The Authors. Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd.

ObjectiveThe aim was to compare multimorbidity patterns identified with the two most commonly used methods: hierarchical cluster analysis (HCA) and exploratory factor analysis (EFA) in a large primary care database. Specific objectives were: (1) to determine whether choice of method affects the composition of these patterns and (2) to consider the potential application of each method in the clinical setting.DesignCross-sectional study. Diagnoses were based on the 263 corresponding blocks of the International Classification of Diseases version 10. Multimorbidity patterns were identified using HCA and EFA. Analysis was stratified by sex, and results compared for each method.Setting and participantsElectronic health records for 408 994 patients with multimorbidity aged 45–64 years in 274 primary health care teams from 2010 in Catalonia, Spain.ResultsHCA identified 53 clusters for women, with just 12 clusters including at least 2 diagnoses, and 15 clusters for men, all of them including at least two diagnoses. EFA showed 9 factors for women and 10 factors for men. We observed differences by sex and method of analysis, although some patterns were consistent. Three combinations of diseases were observed consistently across sex groups and across both methods: hypertension and obesity, spondylopathies and deforming dorsopathies, and dermatitis eczema and mycosis.ConclusionsThis study showed that multimorbidity patterns vary depending on the method of analysis used (HCA vs EFA) and provided new evidence about the known limitations of attempts to compare multimorbidity patterns in real-world data studies. We found that EFA was useful in describing comorbidity relationships and HCA could be useful for in-depth study of multimorbidity. Our results suggest possible applications for each of these methods in clinical and research settings, and add information about some aspects that must be considered in standardisation of future studies: spectrum of diseases, data usage and methods of analysis.

Resumen Objetivo Identificar los patrones de multimorbilidad en pacientes de 19-44 años atendidos en atención primaria en Cataluña en el año 2010. Diseño Estudio descriptivo transversal. Emplazamiento Doscientos cincuenta y un centros de salud. Participantes Fueron 530.798 personas con multimorbilidad de 19-44 años. Mediciones principales La multimorbilidad fue definida como la coexistencia de ≥2 diagnósticos de la Clasificación Internacional de Enfermedades registrados en la historia clínica informatizada. Los patrones de multimorbilidad fueron identificados a través de un análisis jerárquico de clústeres y descritos por sexo y grupos de edad (19-24 y 25-44 años). Resultados De las 882.708 personas de la población inicial, 530.798 (60,1%) presentaron multimorbilidad. La media de edad fue de 33,0 años (DT: 7,0) y el 53,3% fueron mujeres. La multimorbilidad fue más alta en el grupo de 25-44 años respecto al grupo más joven (60,5 vs. 58,1%, p

BACKGROUND: Concurrent diseases, multiple pathologies and multimorbidity patterns are topics of increased interest as the world's population ages. To explore the impact of multimorbidity on affected patients and the consequences for health services, we designed a study to describe multimorbidity by sex and life-stage in a large population sample and to assess the association with acute morbidity, area of residency and use of health services. METHODS: A cross-sectional study was conducted in Catalonia (Spain). Participants were 1,749,710 patients aged 19+ years (251 primary care teams). PRIMARY OUTCOME: Multimorbidity (≥2 chronic diseases). Secondary outcome: Number of new events of each acute disease. Other variables: number of acute diseases per patient, sex, age group (19-24, 25-44, 45-64, 65-79, and 80+ years), urban/rural residence, and number of visits during 2010. RESULTS: Multimorbidity was present in 46.8% (95% CI, 46.7%-46.8%) of the sample, and increased as age increased, being higher in women and in rural areas. The most prevalent pair of chronic diseases was hypertension and lipid disorders in patients older than 45 years. Infections (mainly upper respiratory infection) were the most common acute diagnoses. In women, the highest significant RR of multimorbidity vs. non-multimorbidity was found for teeth/gum disease (aged 19-24) and acute upper respiratory infection. In men, this RR was only positive and significant for teeth/gum disease (aged 65-79). The adjusted analysis showed a strongly positive association with multimorbidity for the oldest women (80+ years) with acute diseases and women aged 65-79 with 3 or more acute diseases, compared to patients with no acute diseases (OR ranged from 1.16 to 1.99, p < 0.001). Living in a rural area was significantly associated with lower probability of having multimorbidity. The odds of multimorbidity increased sharply as the number of visits increased, reaching the highest probability in those aged 65-79 years. CONCLUSIONS: Multimorbidity is related to greater use of health care services and higher incidence of acute diseases, increasing the burden on primary care services. The differences related to sex and life-stage observed for multimorbidity and acute diseases suggest that further research on multimorbidity should be stratified according to these factors.

Background The burden of chronic conditions and multimorbidity is a growing health problem in developed countries. The study aimed to determine the estimated prevalence and patterns of multimorbidity in urban areas of Catalonia, stratified by sex and adult age groups, and to assess whether socioeconomic status and use of primary health care services were associated with multimorbidity. Methods A cross-sectional study was conducted in Catalonia. Participants were adults (19+ years) living in urban areas, assigned to 251 primary care teams. Main outcome: multimorbidity (≥2 chronic conditions). Other variables: sex (male/female), age (19–24; 25–44; 45–64; 65–79; 80+ years), socioeconomic status (quintiles), number of health care visits during the study. Results We included 1,356,761 patients; mean age, 47.4 years (SD: 17.8), 51.0% women. Multimorbidity was present in 47.6% (95% CI 47.5-47.7) of the sample, increasing with age in both sexes but significantly higher in women (53.3%) than in men (41.7%). Prevalence of multimorbidity in each quintile of the deprivation index was higher in women than in men (except oldest group). In women, multimorbidity prevalence increased with quintile of the deprivation index. Overall, the median (interquartile range) number of primary care visits was 8 (4–14) in multimorbidity vs 1 (0–4) in non-multimorbidity patients. The most prevalent multimorbidity pattern beyond 45 years of age was uncomplicated hypertension and lipid disorder. Compared with the least deprived group, women in other quintiles of the deprivation index were more likely to have multimorbidity than men until 65 years of age. The odds of multimorbidity increased with number of visits in all strata. Conclusions When all chronic conditions were included in the analysis, almost 50% of the adult urban population had multimorbidity. The prevalence of multimorbidity differed by sex, age group and socioeconomic status. Multimorbidity patterns varied by life-stage and sex; however, circulatory-endocrine-metabolic patterns were the most prevalent multimorbidity pattern after 45 years of age. Women younger than 80 years had greater prevalence of multimorbidity than men, and women’s multimorbidity prevalence increased as socioeconomic status declined in all age groups. Identifying multimorbidity patterns associated with specific age-related life-stages allows health systems to prioritize and to adapt clinical management efforts by age group.

Controlling for confounders is a crucial step in analytical observational studies, and multivariable models are widely used as statistical adjustment techniques. However, the validation of the assumptions of the multivariable regression models (MRMs) should be made clear in scientific reporting. The objective of this study is to review the quality of statistical reporting of the most commonly used MRMs (logistic, linear, and Cox regression) that were applied in analytical observational studies published between 2003 and 2014 by journals indexed in MEDLINE. Review of a representative sample of articles indexed in MEDLINE (n¼428) with observational design and use ofMRMs (logistic, linear, and Cox regression).We assessedthe quality of reporting about:model assumptions and goodness-of-fit, interactions, sensitivity analysis, crude and adjusted effect estimate, and specification of more than 1 adjusted model. The tests of underlying assumptions or goodness-of-fit of the MRMs used were described in 26.2% (95% CI: 22.0–30.3) of the articles and 18.5%(95% CI: 14.8–22.1) reported the interaction analysis. Reporting of all items assessedwas higher in articles published in journalswith a higher impact factor. A low percentage of articles indexed in MEDLINE that used multivariable techniques provided information demonstrating rigorous application of the model selected as an adjustment method. Given the importance of these methods to the final results and conclusions of observational studies, greater rigor is required in reporting the use of MRMs in the scientific literature.

Objective The purpose of this study was to identify clusters of diagnoses in elderly patients with multimorbidity, attended in primary care. Design Cross-sectional study. Setting 251 primary care centres in Catalonia, Spain. Participants Individuals older than 64 years registered with participating practices. Main outcome measures Multimorbidity, defined as the coexistence of 2 or more ICD-10 disease categories in the electronic health record. Using hierarchical cluster analysis, multimorbidity clusters were identified by sex and age group (65–79 and ≥80 years). Results 322,328 patients with multimorbidity were included in the analysis (mean age, 75.4 years [Standard deviation, SD: 7.4], 57.4% women; mean of 7.9 diagnoses [SD: 3.9]). For both men and women, the first cluster in both age groups included the same two diagnoses: Hypertensive diseases and Metabolic disorders. The second cluster contained three diagnoses of the musculoskeletal system in the 65- to 79-year-old group, and five diseases coincided in the ≥80 age group: varicose veins of the lower limbs, senile cataract, dorsalgia, functional intestinal disorders and shoulder lesions. The greatest overlap (54.5%) between the three most common diagnoses was observed in women aged 65–79 years. Conclusion This cluster analysis of elderly primary care patients with multimorbidity, revealed a single cluster of circulatory-metabolic diseases that were the most prevalent in both age groups and sex, and a cluster of second-most prevalent diagnoses that included musculoskeletal diseases. Clusters unknown to date have been identified. The clusters identified should be considered when developing clinical guidance for this population.

Background: Undiagnosed atrial fibrillation usually is only detected with the first complication. We estimated undiagnosed Atrial Fibrillation prevalence, overall AF and associated factors in a public