Kinetics of humoral immune response over 17 months of COVID-19 pandemic in a large cohort of healthcare workers in Spain: the ProHEpiC-19 study.

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).

Long-term efficacy and effectiveness of a behavioural and community-based exercise intervention (Urban Training) to increase physical activity in patients with COPD: a randomised controlled trial.

There is a need to increase and maintain physical activity in patients with chronic obstructive pulmonary disease (COPD). We assessed 12-month efficacy and effectiveness of the Urban Training intervention on physical activity in COPD patients.This randomised controlled trial (NCT01897298) allocated 407 COPD patients from primary and hospital settings 1:1 to usual care (n=205) or Urban Training (n=202). Urban Training consisted of a baseline motivational interview, advice to walk on urban trails designed for COPD patients in outdoor public spaces and other optional components for feedback, motivation, information and support (pedometer, calendar, physical activity brochure, website, phone text messages, walking groups and a phone number). The primary outcome was 12-month change in steps·day-1 measured by accelerometer.Efficacy analysis (with per-protocol analysis set, n=233 classified as adherent to the assigned intervention) showed adjusted (95% CI) 12-month difference +957 (184-1731) steps·day-1 between Urban Training and usual care. Effectiveness analysis (with intention-to-treat analysis set, n=280 patients completing the study at 12 months including unwilling and self-reported non-adherent patients) showed no differences between groups. Leg muscle pain during walks was more frequently reported in Urban Training than usual care, without differences in any of the other adverse events.Urban Training, combining behavioural strategies with unsupervised outdoor walking, was efficacious in increasing physical activity after 12 months in COPD patients, with few safety concerns. However, it was ineffective in the full population including unwilling and self-reported non-adherent patients.

Socio-environmental correlates of physical activity in patients with chronic obstructive pulmonary disease (COPD).

BACKGROUND: Study of the causes of the reduced levels of physical activity in patients with COPD has been scarce and limited to biological factors. AIM: To assess the relationship between novel socio-environmental factors, namely dog walking, grandparenting, neighbourhood deprivation, residential surrounding greenness and residential proximity to green or blue spaces, and amount and intensity of physical activity in COPD patients. METHODS: This cross-sectional study recruited 410 COPD patients from five Catalan municipalities. Dog walking and grandparenting were assessed by questionnaire. Neighbourhood deprivation was assessed using the census Urban Vulnerability Index, residential surrounding greenness by the satellite-derived Normalized Difference Vegetation Index, and residential proximity to green or blue spaces as living within 300 m of such a space. Physical activity was measured during 1 week by accelerometer to assess time spent on moderate-to-vigorous physical activity (MVPA) and vector magnitude units (VMU) per minute. FINDINGS: Patients were 85% male, had a mean (SD) age of 69 (9) years, and post-bronchodilator FEV1 of 56 (17) %pred. After adjusting for age, sex, socio-economic status, dyspnoea, exercise capacity and anxiety in a linear regression model, both dog walking and grandparenting were significantly associated with an increase both in time in MVPA (18 min/day (p<0.01) and 9 min/day (p<0.05), respectively) and in physical activity intensity (76 VMU/min (p=0.05) and 59 VMUs/min (p<0.05), respectively). Neighbourhood deprivation, surrounding greenness and proximity to green or blue spaces were not associated with physical activity. CONCLUSIONS: Dog walking and grandparenting are associated with a higher amount and intensity of physical activity in COPD patients. TRIAL REGISTRATION NUMBER: Pre-results, NCT01897298.

Child and Adolescent Sexual Abuse in Women Seeking Help for Sexual and Reproductive Mental Health Problems: Prevalence, Characteristics, and Disclosure.

This is a multicentric, descriptive, cross-sectional study of child and adolescent sexual abuse in women over 18 years in 24 primary care sexual and reproductive health centers in Catalonia. A total of 1,013 women were recruited; 345 (37.6%, 95% CI: 34.6-40.9) reported exposure to child sexual abuse: 32.4% disclosed being touched in a sexual way, and 9.6% reported completed sexual intercourse. Abuse occured before the age of 13 in 63.4% of respondents. The perpetrator was a relative or an acquaintance in almost 80% of cases. The risk was higher among women of Central or South American origin (OR: 2.86; 95% CI: 1.33-6.12). Only 31.9% of women disclosed the abuse and 17.3% were blamed. Abuse that involved attempted or completed sexual intercourse was significantly associated with recurrence, physical violence, and revictimization in adulthood.

Effectiveness of an intervention designed to optimize statins use: a primary prevention randomized clinical trial.

BACKGROUND: Although hypercholesterolemia is considered a cardiovascular risk factor, in isolation it is not necessarily sufficient cause for a cardiovascular event. To improve event prediction, cardiovascular risk calculators have been developed; the REGICOR calculator has been validated for use in our population. The objective of this project is to develop an intervention with general practitioners (GPs) and evaluate its impact on prescription adequacy of cholesterol-lowering drugs in primary prevention of cardiovascular disease and in controlling the costs associated with this disease. METHODS: This nonblinded, cluster-randomized clinical trial analyzes data from primary care electronic medical records (ECAP) and other databases. Inclusion criteria are patients aged 35 to 74 years with no known cardiovascular disease and a new prescription for cholesterol-lowering drugs during the 2-year study period. Dependent variables include the following: RETIRA, defined as new cholesterol-lowering drugs initiated during the year preceding the intervention, considered inadequate, and withdrawn during the study period; EVITA, defined as new cholesterol-lowering drugs initiated during the study period and considered inadequate; COST, defined as the total cost of inadequate new treatments prescribed; and REGISTER, defined as the recording of cardiovascular risk factors. Independent variables include the GP's quality-of-care indicators and randomly assigned study group (intervention vs control), patient demographics, and clinical variables. Aggregated descriptive analysis will be done at the GP level and multilevel analysis will be performed to estimate the intervention effect, adjusted for individual and GP variables. DISCUSSION: The study objective is to generate evidence about the effectiveness of implementing feedback information programs directed to GPs in the context of Primary Care. The goal is to improve the prescription adequacy of lipid-lowering therapies for primary prevention. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01997671. November 28, 2013.

Effect of health professional education on outcomes of chronic obstructive pulmonary disease in primary care: a non-randomized clinical trial.

BACKGROUND AND OBJECTIVE: The best strategy to achieve optimal integrated management to patients with chronic obstructive pulmonary disease (COPD) in primary care (PC) is not clear. We aimed to evaluate the effectiveness of an intervention in PC based on an integrated programme, which combines diverse strategies directed at health professionals to improve quality of life and clinical outcomes of their patients with COPD. We compared the outcome with results from standard practice. METHODS: A prospective, multicentre, quasi-experimental study and a 12-month follow up was performed. Intervention consisted of an integrated education programme in PC. The main outcome variable was the change in total score of the St. George's Respiratory Questionnaire (SGRQ) at the end of follow up between the control and intervention group. RESULTS: A total of 801 patients participated in the study with a mean age of 70.2 years and a mean FEV1 (% predicted) of 55%. At 1-year follow up, the SGRQ score did not significantly differ. Although the intervention group showed an improvement in dietary, exercise and smoking habits, there was an increase in reported exacerbations and hospital admissions (P < 0.001). CONCLUSIONS: Implementation of an integrated education programme in a PC setting, which combines diverse strategies directed at health professionals, did not achieve the expected changes in quality of life measured by SGRQ at 1-year follow up. Nonetheless, this study observed an improvement in patients' lifestyle choices, even though this did not result in a significant change in the clinical evolution or heath status over 12 months.

Primary health care research in COVID-19: analysis of the protocols reviewed by the ethics committee of IDIAPJGol, Catalonia.

BACKGROUND: Since March of 2020, the scientific community has been engaged a marathon to answer the different questions that COVID-19 pandemic has brought. During this time, Ethics Committees played an important role in reviewing the research protocols, COVID-19 or not, ensuring that the quality of scientific research is not relaxed by the hasty need for answers. METHODS: Descriptive study from January 2019 to December 2021, comparing COVID-19 protocols to those not COVID-19 related protocols and comparing the work overload. Variables related to the characteristics of the research protocols (i.e. study design, funding…), the principal investigators (gender, PhD degree, professional role…) and outcomes of the Ethics Committee process (requirements of modifications and time until approval) were analyze. RESULTS: The number of sessions increased during COVID-19 pandemics (12 in 2019, 25 in 2020 and 18 in 2021). In total 751 protocols were evaluated during the study period; 513 (68.3%) had an observational design and 434 (57.8%) had no funding. The principal investigator was a woman in 491 (65.4%) studies and a General Practitioner in 330 (43.9%). The mean of the days until the protocol approval was 42.09 days (SD 60.2) with a decrease of 20.1 days from 2019 to 2021. A total of 614 (81.7%) protocols were approved, 336 (54.7%) within the first month after their initial evaluation. Less than half of the protocols were COVID-19 related (208, 44.3%). The COVID-19 protocols main topics were impact on the population (71, 34.1%); and COVID-19 pharmacological treatments (including vaccines) showed a higher increase in 2021 (37, 30.3%). CONCLUSIONS: Despite the work overload during the pandemic due to the increase in the number of meetings and protocols, the IDIAPJGol EC reviewed all of them (COVID-19 or not) adapting to the new situation but according to its criteria of good practices to provide a quick response in the EC opinion. In Primary Health Care the most study designs have been observational studies, many of them with no funding and led by GPs. In 2021 there was an increase in the number of protocols focused on drugs, most likely related to COVID-19 vaccines studies.

Diagnostic and Therapeutic Management of Urinary Tract Infections in Catalonia, Spain: Protocol for an Observational Cohort Study.

BACKGROUND: Antibiotic resistance is an individual and public health problem; multidrug-resistant infections could cause an estimated 10 million deaths worldwide by 2050. Unnecessary use of antimicrobials is the most important cause of resistance generation in the community, and an estimated 80% of antimicrobials are prescribed in primary health care, frequently for urinary tract infections (UTIs). OBJECTIVE: This paper presents the protocol for the first phase of the Urinary Tract Infections in Catalonia (Infeccions del tracte urinari a Catalunya) project. We aim to examine the epidemiology of the different types of UTIs in Catalonia (an autonomous community in Spain) and their diagnostic and therapeutic management by health professionals. Furthermore, we aim to evaluate the correlation between types and total consumption of antibiotics for recurrent UTIs in 2 cohorts of women with the presence and severity of infectious complications of urological origin, especially pyelonephritis and sepsis, and 2 potentially serious infections: pneumonia and COVID-19. METHODS: The study is a population-based observational cohort study including adults with a diagnosis of UTI registered in the Information System for the Development of Research in Primary Care (in Catalan: Sistema d'informació per al desenvolupament de la investigació en atenció primària), the Minimum Basic Data Sets of Hospital Discharges and Emergency Departments (in Catalan: Conjunt mínim bàsic de dades a l'hospitalització d'aguts i d'atenció urgent), and data from the Hospital Dispensing Medicines Register (in Catalan: Medicació hospitalària de dispensació ambulatòria) of Catalonia from the period between 2012 and 2021. We will evaluate the variables obtained from the databases to analyze the proportion of different types of UTIs, the percentage of adequate antibiotic treatments prescribed or received for recurrent UTIs according to the national guidelines, and the proportion of UTIs with complications. RESULTS: We expect to describe the epidemiology of UTIs in Catalonia from 2012 to 2021, as well as describe the diagnostic and therapeutic management of UTIs by health professionals. CONCLUSIONS: We expect to find a high percentage of UTI cases with inadequate management according to the national guidelines, considering that on many occasions UTIs are treated with second- or third-line antibiotic therapies with a preference for the longest regimens. Furthermore, the use of antibiotic suppressive therapies, or prophylaxis, in recurrent UTIs will likely be highly variable. Moreover, we aim to determine whether women with recurrent UTIs treated with antibiotic suppressive therapies have a higher incidence and severity of potentially serious future infections, with special attention to acute pyelonephritis, urosepsis, COVID-19, and pneumonia, compared to women who receive antibiotic treatment after they present with a UTI. This is an observational study of data from administrative databases that will not allow causality analysis. The limitations of the study will be handled according to the appropriate statistical methods. TRIAL REGISTRATION: European Union Electronic Register of Post-Authorisation Studies EUPAS49724; https://www.encepp.eu/encepp/viewResource.htm?id=49725. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/44244.

Urinary Tract Infections in Men in Primary Care in Catalonia, Spain.

Antimicrobial resistance is a major global problem that is primarily driven by the excessive and inappropriate utilization of antibiotics. Urinary tract infections (UTIs) are frequent in primary health care (PHC) and are typically treated with antibiotics. There is ample evidence on the management of this condition in women but not in men. The aim of this study was to describe the epidemiology of UTIs in men in Catalonia, Spain. We conducted a population-based observational cohort study that included male patients diagnosed with UTI within our SIDIAP and CMBD database during the period from 2012 to 2021. UTI diagnoses were grouped into five main groups (cystitis, prostatitis, orchitis and epididymitis, urethritis, and pyelonephritis). Of the 316,762 men with at least one recorded UTI episode, the majority were registered with a diagnosis of cystitis in PHC (212,958 patients). Quinolones were the most commonly recorded treatment for UTIs (between 18.3% and 38.6%, depending on the group), except for urethritis in which a combination of antibiotics (36.7%) was most frequently used. The treatment duration period was between 9 days and 18 days, except for the prostatitis group, in which treatment was extended to 21 days. Urine cultures were documented in up to 30% in the cystitis group. Pyelonephritis was the category linked to most septicemia cases (3.0%). Conclusions: This is the first study to assess UTIs in men using a large PHC database in Spain. The sociodemographic characteristics of our sample are similar to other studies in the literature. In our setting, the use of quinolones for the treatment of UTIs is the most registered, and its duration was between 9 days and 18 days, despite the fact that resistance to quinolones exceeds 20% of the strains in our area.

Effectiveness of Treatment With Dual Bronchodilation (LABA/LAMA) Compared With Combination Therapy (LABA/ICS) for Patients With COPD: A Population-Based Study.

BACKGROUND: Initiation of treatment of COPD with a combination of a long-acting beta-agonist (LABA) and an inhaled corticosteroid (ICS) is frequent irrespective of the risk of exacerbations. METHOD: We performed a retrospective, population-based, observational study aimed at comparing the effectiveness of a LABA/long-acting antimuscarinic agent (LAMA) and LABA/ICS in patients with COPD over a one-year follow-up. Data were obtained from an administrative healthcare claims database. The primary outcome was the risk of first exacerbation. A sensitivity analysis was conducted in a propensity-score matched population. RESULTS: The population consisted of 14,046 COPD patients; 11,329 (80.6%) initiated LABA/ICS and 2717 (19.4%) LABA/LAMA. The matched population included 1650 patients in each arm. During follow-up, 69.6% patients in the LABA/ICS group and 64.4% in the LABA/LAMA group presented an exacerbation. The mean time to the first exacerbation was 6.03 months (95% confidence interval (CI): 5.94-6.12) for LABA/ICS and 6.4 months (95%CI: 6.21-6.59) for LABA/LAMA; p<0.001. The time to scalation to triple therapy was also significantly prolonged in LABA/LAMA. Similar results were obtained in the matched population. LABA/LAMA was associated with a significantly lower risk of exacerbations and escalation to triple therapy compared to LABA/ICS, except in patients with frequent exacerbations and high blood eosinophils in which no differences were observed in the time to first exacerbation. CONCLUSION: Initiation of treatment with LABA/LAMA was associated with a lower risk of exacerbation and escalation to triple therapy compared to LABA/ICS in the majority of patients with COPD in primary care.

Characteristics and treatment patterns of patients with asthma on multiple-inhaler triple therapy in Spain.

The aim of this observational, retrospective study was to describe characteristics, treatment patterns, and adherence among patients with asthma who initiated multiple-inhaler triple therapy (MITT) in Catalonia, Spain. This study used data of patients initiating MITT in 2016 from the SIDIAP (Information System for Research in Primary Care) database, which covers ~80% of the Catalonian population (5.8 million). Of 1,204 patients initiating MITT, 361 (30.0%) stepped down (discontinued ≥ 1 and continued ≥1 MITT component) and 89 (7.4%) stopped all three components of MITT for a period of 60 days during the following 12 months. In the follow-up period, 196 (16.3%) patients were considered adherent to MITT (>0.8 proportion of days covered [PDC]), with a mean (standard deviation) PDC of 0.52 (0.51) days. Given the low adherence and substantial rates of step down/discontinuation among patients initiating MITT, there is an urgent need to implement strategies to improve treatment adherence/persistence.

Outcomes of COVID-19 Infection in People Previously Vaccinated Against Influenza: Population-Based Cohort Study Using Primary Health Care Electronic Records.

BACKGROUND: A possible link between influenza immunization and susceptibility to the complications of COVID-19 infection has been previously suggested owing to a boost in the immunity against SARS-CoV-2. OBJECTIVE: This study aimed to investigate whether individuals with COVID-19 could have benefited from vaccination against influenza. We hypothesized that the immunity resulting from the previous influenza vaccination would boost part of the immunity against SARS-CoV-2. METHODS: We performed a population-based cohort study including all patients with COVID-19 with registered entries in the primary health care (PHC) electronic records during the first wave of the COVID-19 pandemic (March 1 to June 30, 2020) in Catalonia, Spain. We compared individuals who took an influenza vaccine before being infected with COVID-19, with those who had not taken one. Data were obtained from Information System for Research in Primary Care, capturing PHC information of 5.8 million people from Catalonia. The main outcomes assessed during follow-up were a diagnosis of pneumonia, hospital admission, and mortality. RESULTS: We included 309,039 individuals with COVID-19 and compared them on the basis of their influenza immunization status, with 114,181 (36.9%) having been vaccinated at least once and 194,858 (63.1%) having never been vaccinated. In total, 21,721 (19%) vaccinated individuals and 11,000 (5.7%) unvaccinated individuals had at least one of their outcomes assessed. Those vaccinated against influenza at any time (odds ratio [OR] 1.14, 95% CI 1.10-1.19), recently (OR 1.13, 95% CI 1.10-1.18), or recurrently (OR 1.10, 95% CI 1.05-1.15) before being infected with COVID-19 had a higher risk of presenting at least one of the outcomes than did unvaccinated individuals. When we excluded people living in long-term care facilities, the results were similar. CONCLUSIONS: We could not establish a protective role of the immunity conferred by the influenza vaccine on the outcomes of COVID-19 infection, as the risk of COVID-19 complications was higher in vaccinated than in unvaccinated individuals. Our results correspond to the first wave of the COVID-19 pandemic, where more complications and mortalities due to COVID-19 had occurred. Despite that, our study adds more evidence for the analysis of a possible link between the quality of immunity and COVID-19 outcomes, particularly in the PHC setting.

Polypharmacy Patterns in Multimorbid Older People with Cardiovascular Disease: Longitudinal Study.

(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.

Blood Eosinophil Counts and Their Variability and Risk of Exacerbations in COPD: A Population-Based Study.

BACKGROUND: There is controversy regarding the role of blood eosinophil levels as a biomarker of exacerbation risk in chronic obstructive pulmonary disease (COPD). Our aim was to quantify blood eosinophil levels and determine the risk of exacerbations associated with these levels and their variability. METHODS: Observational, retrospective, population-based study with longitudinal follow-up in patients with COPD identified in a primary care electronic medical record database in Catalonia, Spain, covering 80% of the general population. Patients were classified into 4 groups using the following cut-offs: (a) <150cells/µl; (b) ≥150 and <300cells/µl; (c) ≥300 and <500cells/µl; (d) ≥500cells/µl. RESULTS: A total of 57,209 patients were identified with a mean age of 70.2 years, a mean FEV1(% predicted) of 64.1% and 51.6% had at least one exacerbation the previous year. The number of exacerbations in the previous year was higher in patients with the lowest and the highest eosinophil levels compared with the intermediate groups. During follow-up the number of exacerbations was slightly higher in the group with the lowest blood eosinophil levels and in those with higher variability in eosinophil counts, but ROC curves did not identify a reliable threshold of blood eosinophilia to discriminate an increased risk of exacerbations. CONCLUSIONS: Our results do not support the use of blood eosinophil count as a reliable biomarker of the risk of exacerbation in COPD in a predominantly non-exacerbating population. Of note was that the small group of patients with the highest variability in blood eosinophils more frequently presented exacerbations.

Combined Multimorbidity and Polypharmacy Patterns in the Elderly: A Cross-Sectional Study in Primary Health Care.

(1) Background: The acquisition of multiple chronic diseases, known as multimorbidity, is common in the elderly population, and it is often treated with the simultaneous consumption of several prescription drugs, known as polypharmacy. These two concepts are inherently related and cause an undue burden on the individual. The aim of this study was to identify combined multimorbidity and polypharmacy patterns for the elderly population in Catalonia. (2) Methods: A cross-sectional study using electronic health records from 2012 was conducted. A mapping process was performed linking chronic disease categories to the drug categories indicated for their treatment. A soft clustering technique was then carried out on the final mapped categories. (3) Results: 916,619 individuals were included, with 93.1% meeting the authors' criteria for multimorbidity and 49.9% for polypharmacy. A seven-cluster solution was identified: one non-specific (Cluster 1) and six specific, corresponding to diabetes (Cluster 2), neurological and musculoskeletal, female dominant (Clusters 3 and 4) and cardiovascular, cerebrovascular and renal diseases (Clusters 5 and 6), and multi-system diseases (Cluster 7). (4) Conclusions: This study utilized a mapping process combined with a soft clustering technique to determine combined patterns of multimorbidity and polypharmacy in the elderly population, identifying overrepresentation in six of the seven clusters with chronic disease and chronic disease-drug categories. These results could be applied to clinical practice guidelines in order to better attend to patient needs. This study can serve as the foundation for future longitudinal regarding relationships between multimorbidity and polypharmacy.

Systematic review on long-term adverse effects of inhaled corticosteroids in the treatment of COPD.

Inhaled corticosteroids (ICSs) are indicated for the prevention of exacerbations in COPD; however, a significant proportion of patients at low risk of exacerbations are treated with ICSs. We conducted a systematic review including a diversity of types of study designs and safety outcomes with the objective of describing the risk of adverse effects associated with the long-term use of ICSs in patients with COPD.A total of 90 references corresponding to 83 studies were included, including 26 randomised clinical trials (RCTs), 33 cohort studies, and 24 nested case-control (NCC) studies. Analysis of 19 RCTs showed that exposure to ICSs for ≥1 year increased the risk of pneumonia by 41% (risk ratio 1.41, 95% CI 1.23-1.61). Additionally, cohort and NCC studies showed an association between ICSs and risk of tuberculosis and mycobacterial disease. There was a strong association between ICS use and local disorders such as oral candidiasis and dysphonia. The association between ICSs and the risk of diabetes and fractures was less clear and appeared significant only at high doses of ICSs.Since most patients with COPD are elderly and with frequent comorbidities, an adequate risk-benefit balance is crucial for the indication of ICSs.

Clinical characteristics and factors associated with triple therapy use in newly diagnosed patients with COPD.

There is limited information about the initiation of triple therapy (TT) in patients with chronic obstructive pulmonary disease (COPD) in primary care. This was an observational, population-based study in patients identified from a primary care electronic medical records database in Catalonia from 2011 to 2015 aimed to identify the use of TT in patients with newly diagnosed COPD. A total of 69,668 newly diagnosed patients were identified of whom 11,524 (16.5%) initiated TT, of whom 8626 initiated TT at or immediately after COPD diagnosis. Among them, 72.3% were GOLD A/B, 14.6% were frequent exacerbators, and 7.1% had asthma-COPD overlap (ACO). Variables associated with TT initiation were: male sex, older age, previous exacerbations, ACO, a previous treatment regimen containing an inhaled corticosteroid, previous pneumonia, and history of lung cancer. A significant number of COPD patients in Primary Care initiated TT shortly after or even before an established COPD diagnosis.

Treatment Pathways Before and After Triple Therapy in COPD: A Population-based Study in Primary Care in Spain.

BACKGROUND: Recent data from real world clinical practices on the use of Triple Therapy (TT) in patients with COPD are scarce. METHODS: Observational population-based study with longitudinal follow-up in patients with COPD identified in a primary care electronic medical records database in Catalonia, covering 80% of the general population. The aims were to characterize COPD patients who initiated TT and to describe treatment pathways before and after TT initiation. Time to and probability of step down or complete discontinuation of TT was described using restricted mean survival time and Kaplan-Meier analysis. RESULTS: A total of 34,018 COPD patients initiated TT during the study period. Of them, 23,867 (70.1%) were GOLD A/B. 18,453 (54.2%) were non-exacerbators, 9931 (29.2%) infrequent exacerbators, 5634 (16.5%) frequent exacerbators and 1923 (5.6%) had asthma-COPD overlap. Drugs most frequently used prior to initiation of TT were long-acting antimuscarinics (22.5%) and combination of long-acting beta2 agonists/inhaled corticosteroids (15.2%). A total of 11,666 (34.3%) stepped down and 1091 (3.2%) discontinued TT during follow-up. Step down following TT was more likely in patients with severe COPD, especially during the first year; however, discontinuation was more common among patients with mild COPD. CONCLUSION: Most patients initiating treatment with TT were non exacerbators and continued on the same treatment over time regardless severity of disease. Stepping down was more frequent in severe patients, while discontinuation was more common among mild patients. Overall, it appears that TT is extensively used in primary care for treatment of patients with COPD.

Evaluation of a combined strategy directed towards health-care professionals and patients with chronic obstructive pulmonary disease (COPD): information and health education feedback for improving clinical monitoring and quality-of-life.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a health problem that is becoming increasingly attended-to in Primary Care (PC). However, there is a scarcity of health-care programs and studies exploring the implementation of Clinical Practice Guidelines (CPG). The principal objective of the present study is to evaluate the effectiveness of a combined strategy directed towards health-care professionals and patients to improve the grade of clinical control and the quality-of-life (QoL) of the patients via a feedback on their state-of-health. A training plan for the health-care professionals is based on CPG and health education. METHOD/DESIGN: Multi-centred, before-after, quasi experimental, prospective study involving an intervention group and a control group of individuals followed-up for 12 months. The patients receive attention from urban and semi-urban Primary Care Centres (PCC) within the administrative area of the Costa de Ponent (near Barcelona). All the pacients corresponding to the PCC of one sub-area were assigned to the intervention group and patients from the rest of sub-areas to the group control. The intervention includes providing data to the health-care professionals (clinician/nurse) derived from a clinical history and an interview. A course of training focused on aspects of CPG, motivational interview and health education (tobacco, inhalers, diet, physical exercise, physiotherapy). The sample random includes a total of 801 patients (> or = 40 years of age), recorded as having COPD, receiving attention in the PCC or at home, who have had at least one clinical visit, and who provided written informed consent to participation in the study. Data collected include socio-demographic characteristics, drug treatment, exacerbations and hospital admissions, evaluation of inhaler use, tobacco consumption and life-style and health-care resources consumed. The main endpoints are dyspnoea, according to the modified scale of the Medical Research Council (MRC) and the QoL, evaluated with the St George's Respiratory Questionnaire (SGRQ). The variables are obtained at the start and the end of the intervention. Information from follow-up visits focuses on the changes in life-style activities of the patient. DISCUSSION: This study is conducted with the objective of generating evidence that shows that implementation of awareness programs directed towards health-care professionals as well as patients in the context of PC can produce an increase in the QoL and a decrease in the disease exacerbation, compared to standard clinical practice. TRIAL REGISTRATION: Clinical Trials.gov Identifier: NCT00922545;

Incidence and risk factors of exacerbations among COPD patients in primary health care: APMPOC study.

BACKGROUND: Worldwide, chronic obstructive pulmonary disease (COPD) is the fourth cause of death. Exacerbations have a negative impact on the prognosis of COPD and the frequency and severity of these episodes are associated with a higher patient mortality. Exacerbations are the first cause of decompensation, hospital admission and death in COPD. The incidence of exacerbations has mainly been estimated in populations of patients with moderate-severe COPD requiring hospital care. However, little is known regarding the epidemiology of exacerbations in patients with less severe COPD forms. It is therefore possible that a high number of these less severe forms of exacerbations are underdiagnosed and may, in the long-term, have certain prognostic importance for the COPD evolution. The aim of this study was to know the incidence and risk factors associated with exacerbations in patients with COPD in primary care. METHODS AND DESIGN: A prospective, observational, 3-phase, multicentre study will be performed involving: baseline evaluation, follow up and final evaluation. A total of 685 smokers or ex-smokers from 40 to 80 years of age with COPD, without acute respiratory disease or any other long-term respiratory disease will be randomly selected among the population assigned to 21 primary care centres. The diagnosis of COPD and its severity will be confirmed by spirometry. Information regarding the baseline situation, quality of life and exposure to contaminants or other factors potentially related to exacerbations will be collected. A group of 354 patients with confirmed COPD of varying severity will be followed for one year through monthly telephone calls and daily reporting of symptoms with the aim of detecting all the exacerbations which occur. These patients will be evaluated again at the end of the study and the incidence of exacerbations and associated relative risks will be estimated by negative binomial regression. DISCUSSION: The results will be relevant to provide knowledge about natural history of the initial phases of the COPD and the impact and incidence of the exacerbations on the patients with mild-moderate forms of the disease. These data may be important to know the milder forms of exacerbation which are often silent or very little expressed clinically.