Immune-Related Adverse Events of Immune Checkpoint Inhibitors.

Immune-related adverse events (irAEs) are toxicities that arise after the administration of monoclonal antibodies targeting immune checkpoints (immune checkpoint inhibitors [ICIs]) in patients with cancer. They can occur at any time after initiation of ICI treatment, with a broad clinical phenotype that can be organ-specific or systemic. Although most irAEs manifest as mild to moderate signs and symptoms, severe forms of irAEs can lead to irreversible organ failure and have acute life-threatening presentations. Treatment should be tailored to the specific organ involved and the severity. Glucocorticoids are the first-line treatment for most irAEs, with immunosuppressants and biologics mainly used as second-line treatments.

A Practice-Proven Adaptive Case Management Approach for Innovative Health Care Services (Health Circuit): Cluster Randomized Clinical Pilot and Descriptive Observational Study.

BACKGROUND: Digital health tools may facilitate the continuity of care. Enhancement of digital aid is imperative to prevent information gaps or redundancies, as well as to facilitate support of flexible care plans. OBJECTIVE: The study presents Health Circuit, an adaptive case management approach that empowers health care professionals and patients to implement personalized evidence-based interventions, thanks to dynamic communication channels and patient-centered service workflows; analyze the health care impact; and determine its usability and acceptability among health care professionals and patients. METHODS: From September 2019 to March 2020, the health impact, usability (measured with the system usability scale; SUS), and acceptability (measured with the net promoter score; NPS) of an initial prototype of Health Circuit were tested in a cluster randomized clinical pilot (n=100) in patients with high risk for hospitalization (study 1). From July 2020 to July 2021, a premarket pilot study of usability (with the SUS) and acceptability (with the NPS) was conducted among 104 high-risk patients undergoing prehabilitation before major surgery (study 2). RESULTS: In study 1, Health Circuit resulted in a reduction of emergency room visits (4/7, 13% vs 7/16, 44%), enhanced patients' empowerment (P<.001) and showed good acceptability and usability scores (NPS: 31; SUS: 54/100). In study 2, the NPS was 40 and the SUS was 85/100. The acceptance rate was also high (mean score of 8.4/10). CONCLUSIONS: Health Circuit showed potential for health care value generation and good acceptability and usability despite being a prototype system, prompting the need for testing a completed system in real-world scenarios. TRIAL REGISTRATION: ClinicalTrials.gov NCT04056663; https://clinicaltrials.gov/ct2/show/NCT04056663.

Prevention of Unplanned Hospital Admissions in Multimorbid Patients Using Computational Modeling: Observational Retrospective Cohort Study.

BACKGROUND: Enhanced management of multimorbidity constitutes a major clinical challenge. Multimorbidity shows well-established causal relationships with the high use of health care resources and, specifically, with unplanned hospital admissions. Enhanced patient stratification is vital for achieving effectiveness through personalized postdischarge service selection. OBJECTIVE: The study has a 2-fold aim: (1) generation and assessment of predictive models of mortality and readmission at 90 days after discharge; and (2) characterization of patients' profiles for personalized service selection purposes. METHODS: Gradient boosting techniques were used to generate predictive models based on multisource data (registries, clinical/functional and social support) from 761 nonsurgical patients admitted in a tertiary hospital over 12 months (October 2017 to November 2018). K-means clustering was used to characterize patient profiles. RESULTS: Performance (area under the receiver operating characteristic curve, sensitivity, and specificity) of the predictive models was 0.82, 0.78, and 0.70 and 0.72, 0.70, and 0.63 for mortality and readmissions, respectively. A total of 4 patients' profiles were identified. In brief, the reference patients (cluster 1; 281/761, 36.9%), 53.7% (151/281) men and mean age of 71 (SD 16) years, showed 3.6% (10/281) mortality and 15.7% (44/281) readmissions at 90 days following discharge. The unhealthy lifestyle habit profile (cluster 2; 179/761, 23.5%) predominantly comprised males (137/179, 76.5%) with similar age, mean 70 (SD 13) years, but showed slightly higher mortality (10/179, 5.6%) and markedly higher readmission rate (49/179, 27.4%). Patients in the frailty profile (cluster 3; 152/761, 19.9%) were older (mean 81 years, SD 13 years) and predominantly female (63/152, 41.4%, males). They showed medical complexity with a high level of social vulnerability and the highest mortality rate (23/152, 15.1%), but with a similar hospitalization rate (39/152, 25.7%) compared with cluster 2. Finally, the medical complexity profile (cluster 4; 149/761, 19.6%), mean age 83 (SD 9) years, 55.7% (83/149) males, showed the highest clinical complexity resulting in 12.8% (19/149) mortality and the highest readmission rate (56/149, 37.6%). CONCLUSIONS: The results indicated the potential to predict mortality and morbidity-related adverse events leading to unplanned hospital readmissions. The resulting patient profiles fostered recommendations for personalized service selection with the capacity for value generation.

Impact of the COVID-19 Pandemic on Primary Health Care Disease Incidence Rates: 2017 to 2020.

We assessed the impact of the COVID-19 pandemic in Spain on new cases of diseases and conditions commonly seen in primary care. In 2020, there were significant reductions from 2017-2019 in the annual incidences of hypertension (40% reduction), hypercholesterolemia (36%), type 2 diabetes (39%), chronic kidney disease (43%), ischemic heart disease (48%), benign prostatic hypertrophy (38%), osteoporosis (40%), hypothyroidism (46%), chronic obstructive pulmonary disease (50%), alcohol use disorder (46%), benign colon polyps and tumors (42%), and melanomas (45%). Prioritization of COVID-19 care changed the physician-patient relationship to the detriment of face-to-face scheduled visits for chronic disease detection and monitoring, which fell by almost 41%. To return to prepandemic levels of diagnosis and management of chronic diseases, primary health care services should reorganize and carry out specific actions for groups at higher risk.VISUAL ABSTRACTAnnals "Online First" article.

Practical diagnostic tips for the Sjögren Clinic: pearls, myths and mistakes.

More than 90 years have passed since Hendrik Sjögren began to consider that behind the dryness that several of his patients presented, there could be a systemic disease potentially linked to abnormal immune responses. For many years, the disease was mostly considered a minor syndrome compared with other systemic autoimmune diseases such as systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and vasculitis, and advances in its understanding were slow and little recognised. The irruption of new technologies at the end of the 20th century rapidly promoted the development of international projects with a wide impact and diffusion. In the last 20 years, a significant improvement has been achieved in epidemiological determinants, pathogenic mechanisms, diagnostic accuracy, and a standardised therapeutic approach for patients with Sjögren's syndrome (SS). These developments have provided the tools for an early diagnosis and personalised management for most patients. However, a significant number of early myths and ongoing controversies are still making the appropriate management of SS difficult in daily clinical practice. This review provides a selection of pearls, myths, and mistakes that may serve as practical diagnostic tips for the Sjögren Clinic in four specific scenarios: defining the appropriate epidemiological background, enabling the earliest diagnostic suspicion as possible, improving the systemic characterisation of the disease, and designing an optimal follow-up of patients.

Long-Term Effects on Preventing Frailty and Health Care Costs Associated with a Multifactorial Intervention in the Elderly: Three-Year Follow-Up Data from the Pre-Frail 80 Study.

INTRODUCTION: Preventing or delaying frailty has important benefits. Studies show the effectiveness of multifactorial interventions in the frail and pre-frail elderly, but few have evaluated their long-term effectiveness. Frailty and its consequences have been shown to increase the use of health resources. The main aim was to evaluate the long-term effect of a multifactorial primary healthcare intervention in pre-frail elderly people at 36 months and determine the health resources used and their cost. METHODS: A follow-up of a cohort study of patients who participated in a randomized clinical trial in an urban primary care centre in Barcelona was carried out. We included 200 non-institutionalized people aged ≥80 years who met the Fried pre-frailty criteria. The intervention group (IG) received a 6-month interdisciplinary intervention based on physical exercise, Mediterranean diet advice, assessment of inadequate prescribing in polypharmacy patients, and social assessment, while the control group (CG) received standard of care primary healthcare treatment. Sociodemographic variables were collected at baseline. The Fried criteria, comorbidities, and geriatric syndromes were collected at baseline and 12 and 36 months. For the analysis of health costs, data were collected on visits, complementary tests, hospital admissions, and surgical interventions in the last 36 months. Complexity, the rate of expected emergency admission, and the rate of expected mortality were collected at 36 months. Between-group characteristics were compared at baseline and 36 months using the χ2 test and the t test for independent samples. The post-intervention (12-month follow-up) versus longitudinal follow-up (36-month follow-up) comparison used McNemar's test for each group. The nonparametric Mann-Whitney test was used to compare health costs. RESULTS: Of the 200 patients initially included, we evaluated 135 (67.5%) patients who completed the 36-month follow-up. The mean age was 88.5 years and 64.4% were female. At 36 months, the transition to frailty was much lower in the IG than in the CG (22.1% vs. 32.8%, p = 0.013). The total mean health cost at 36 months was 3,110 EUR in the CG and 2,679 EUR in the IG. No significant between-group differences were observed according to Clinical Risk Groups. CONCLUSIONS: A multifactorial, interdisciplinary intervention carried out in primary care prevented frailty in pre-frail elderly people at 36-month follow-up. Although the IG was grouped into higher grade Clinical Risk Groups and therefore had greater morbidity, the cost was lower than that in the CG.

SARS-CoV-2 infection in patients with primary Sjögren syndrome: characterization and outcomes of 51 patients.

OBJECTIVE: To analyse the prognosis and outcomes of SARS-CoV-2 infection in patients with primary SS. METHODS: We searched for patients with primary SS presenting with SARS-CoV-2 infection (defined following and according to the European Centre for Disease Prevention and Control guidelines) among those included in the Big Data Sjögren Registry, an international, multicentre registry of patients diagnosed according to the 2002/2016 classification criteria. RESULTS: A total of 51 patients were included in the study (46 women, mean age at diagnosis of infection of 60 years). According to the number of patients with primary SS evaluated in the Registry (n = 8211), the estimated frequency of SARS-CoV-2 infection was 0.62% (95% CI 0.44, 0.80). All but two presented with symptoms suggestive of COVID-19, including fever (82%), cough (57%), dyspnoea (39%), fatigue/myalgias (27%) and diarrhoea (24%), and the most frequent abnormalities included raised lactate dehydrogenase (LDH) (88%), CRP (81%) and D-dimer (82%) values, and lymphopenia (70%). Infection was managed at home in 26 (51%) cases and 25 (49%) required hospitalization (five required admission to ICU, four died). Compared with patients managed at home, those requiring hospitalization had higher odds of having lymphopenia as laboratory abnormality (adjusted OR 21.22, 95% CI 2.39, 524.09). Patients with comorbidities had an older age (adjusted OR 1.05, 95% CI 1.00, 1.11) and showed a risk for hospital admission six times higher than those without (adjusted OR 6.01, 95% CI 1.72, 23.51) in the multivariate analysis. CONCLUSION: Baseline comorbidities were a key risk factor for a more complicated COVID-19 in patients with primary SS, with higher rates of hospitalization and poor outcomes in comparison with patients without comorbidities.

SARS-CoV-2 infection in patients with systemic autoimmune diseases.

Systemic autoimmune diseases (SAD) are a heterogeneous group of diseases with a common aetiopathogenic basis affecting all ages characterised by a systemic phenotypic expression with a wide range of severity and outcomes that often require immunosuppressive therapies, leaving patients at high risk of infection. Knowledge of the impact of COVID-19 in patients with SAD is limited because most are included in studies carried out in patients with autoimmune and rheumatic diseases (mainly inflammatory arthritis). Most studies supported an increased risk of SARS-Cov-2 infection in patients with AD and SAD. Although case-control studies reported no significant differences in the rate of poor outcomes between patients with and without AD, large population-based studies analysing baseline risk factors reported a 2-3 times higher rate of poor outcomes in patients with AD, especially in those with SAD. Individual risk factors associated with poor outcomes included gender male, older age, and underlying comorbidities and therapies (glucocorticoids, sulfasalazine, immunosuppressants and rituximab). Patients with SAD had less favourable COVID-19 outcomes than those with inflammatory arthritis, possibly due to a differentiated underlying therapeutic approach (glucocorticoids, immunosuppressants and B-cell depleting agents for most SAD, anti-cytokine therapies and JAK inhibitors for inflammatory arthritis). Despite the limited evidence, most studies suggest that patients with SAD have an increased risk of a worse evolution of SARS-CoV-2 infection, including a greater risk of hospitalisation/ICU admission and worse survival rates and, therefore, should be considered a high-risk group for COVID-19.

Practical guidelines for the early diagnosis of Sjögren's syndrome in primary healthcare.

Primary care physicians can play a crucial role by recognising Sjögren's syndrome (SS) in the early stages identifying those patients with the greatest probability of being diagnosed with SS. SS has a very specific epidemiological profile at presentation (female aged 30-50 years), which may aid an early diagnosis. Although the disease may be expressed in many guises, there are three predominant clinical presentations that should be considered as key clues to increased clinical suspicion (multiple symptoms of dryness, asthenia-polyalgia syndrome and systemic organ-specific manifestations). The physical examination may provide important clues to systemic involvement (parotid gland enlargement, skin lesions suggestive of purpura or annular erythema, respiratory crackles, arthritis, neurological sensory or motor deficits). Simple laboratory studies may be very useful in reinforcing the clinical suspicion of SS, and the triad of cytopenia, raised erythrocyte sedimentation rate and high serum gamma globulin levels is a very specific "biological" pattern suggesting SS. A solid clinical suspicion of SS requires both the patient reporting sicca symptoms and objective evidence that these symptoms are associated with dysfunction of the lachrymal and salivary glands. Ultrasonography of the parotid glands, a non-invasive method, may be a major advance in the diagnostic approach to SS in primary care. Primary care physicians must be considered essential members of the multidisciplinary team in charge of the follow-up of SS patients, due to their key role in the continuum of patient care and their cross-sectional knowledge of common diseases that frequently coexist in patients with SS.

Post-COVID-19 syndrome in patients with primary Sjögren's syndrome after acute SARS-CoV-2 infection.

OBJECTIVES: To analyse the frequency and characteristics of post-COVID-19 syndrome in patients with primary Sjögren's syndrome (pSS) affected by acute SARS-CoV-2 infection. METHODS: By the first week of April 2021, all centres included in the Big Data Sjögren Consortium were contacted asking for patients included in the Registry diagnosed with SARSCoV-2 infection according to the ECDC guidelines. According to the NICE definitions, symptoms related to COVID-19 were classified as acute COVID-19 (signs and symptoms for up to 4 weeks), ongoing symptomatic COVID-19 (presence of signs and symptoms from 4 to 12 weeks) and post-COVID-19 syndrome (signs and symptoms that continue for > 12 weeks not explained by an alternative diagnosis after a protocolized study). RESULTS: We identified 132 patients who were followed a mean follow-up of 137.8 days (ranging from 5 days to 388 days) after being diagnosed with COVID-19. In the last visit, 75 (57%) patients remained symptomatic: 68 (52%) remained symptomatic for more than 4 weeks fulfilling the NICE definition for ongoing symptomatic post-COVID-19, and 38 (29%) remained symptomatic for more than 12 weeks fulfilling the definition of post-COVID-19 syndrome. More than 40% of pSS patients reported the persistence of four symptoms or more, including anxiety/depression (59%), arthralgias (56%), sleep disorder (44%), fatigue (40%), anosmia (34%) and myalgias (32%). Age-sex adjusted multivariate analysis identified raised LDH levels (OR 10.36), raised CRP levels (OR 7.33), use of hydroxychloroquine (OR 3.51) and antiviral agents (OR 3.38), hospital admission (OR 8.29), mean length of hospital admission (OR 1.1) and requirement of supplemental oxygen (OR 6.94) as factors associated with a higher risk of developing post-COVID-19 syndrome. A sensitivity analysis including hospital admission in the adjusted model confirmed raised CRP levels (OR 8.6, 95% CI 1.33-104.44) and use of hydroxychloroquine (OR 2.52, 95% CI 1.00-6.47) as the key independent factors associated with an enhanced risk of developing post-COVID-19 syndrome. CONCLUSIONS: This is the first study that analyses the frequency and characteristics of post-COVID-19 syndrome in patients affected by a systemic autoimmune disease. We found that 57% of patients with pSS affected by COVID-19 remain symptomatic after a mean follow-up of 5 months. The risk of developing post-COVID-19 syndrome in patients who required hospitalisation was 8-times higher than in non-hospitalised patients, with baseline raised CRP levels and the use of hydroxychloroquine being independent risk factors for post-COVID-19.

Influence of the age at diagnosis in the disease expression of primary Sjögren syndrome. Analysis of 12,753 patients from the Sjögren Big Data Consortium.

OBJECTIVES: To analyse how the main components of the disease phenotype (sicca symptoms, diagnostic tests, immunological markers and systemic disease) can be driven by the age at diagnosis of primary Sjögren's syndrome (pSS). METHODS: By January 2021, the participant centres had included 12,753 patients from 25 countries that fulfilled the 2002/2016 classification criteria for pSS. The age at diagnosis was defined as the time when the attending physician confirmed fulfilment of the criteria. Patients were clustered according to age at diagnosis. 50 clusters with more than 100 observations (from 27 to 76 years) were used to study the influence of the age at diagnosis in the disease expression. RESULTS: There was a consistent increase in the frequency of oral dryness according to the age at diagnosis, with a frequency of <90% in patients diagnosed at the youngest ages and >95% in those diagnosed at the oldest ages. The smooth curves that best fitted a linear model were the frequency of dry mouth (adjusted R2 0.87) and the frequency of abnormal oral tests (adjusted R2 0.72). Therefore, for each 1-year increase in the age at diagnosis, the frequency of dry mouth increased by 0.13%, and the frequency of abnormal oral diagnostic tests by 0.11%. There was a consistent year-by-year decrease in the frequency of all autoantibodies and immunological markers except for cryoglobulins. According to the linear models, for each 1-year increase in the age at diagnosis, the frequency of a positive result decreased by 0.57% (for anti-Ro antibodies), 0.47% (for RF) and 0.42% (for anti-La antibodies). The ESSDAI domains which showed a more consistent decrease were glandular and lymph node involvement (for each 1-year increase in the age at diagnosis, the frequency of activity decreased by 0.18%), and constitutional, cutaneous, and haematological involvements (the frequency decreased by 0.09% for each 1-year increase). In contrast, other domains showed an ascending pattern, especially pulmonary involvement (for each 1-year increase in the age at diagnosis, the frequency of activity increased by 0.22%), and peripheral nerve involvement (the frequency increased by 0.09% for each 1-year increase). CONCLUSIONS: The influence of the age at diagnosis on the key phenotypic features of pSS is strong, and should be considered critical not only for designing a personalised diagnostic approach, but also to be carefully considered when analysing the results of diagnostic tests and immunological parameters, and when internal organ involvement is suspected at diagnosis.

Intervention to reduce perceived loneliness in community-dwelling older people.

AIM: We evaluated the reduction in perceived loneliness and depression and the increase in social support and quality of life in community-dwelling lonely people aged >65 years included in a community intervention compared with nonlonely controls from the same urban area. DESIGN: Randomised clinical trial without blind evaluation. LOCATION: Urban area of Barcelona. PARTICIPANTS: Community dwellers aged >65 years with loneliness identified by the primary care team. INTERVENTIONS: The primary care team together with community agents (municipal social services, community civil and religious associations) carried out 18 sessions developing activities including educational workshops, mindfulness, yoga, walking and visits to urban gardens. RESULTS: We included 55 patients (87% female, mean age 80.6 ± 6.86 years) of whom 82% had moderate and 18% severe loneliness. Six months postintervention, 48.3% of the intervention group did not feel lonely compared with 26.9% of controls (p = 0.001). Social support (DUKE-UNC-11) increased from 33.5 ± 9.3 to 41.4 ± 6.6, and mental health (SF-12) from 36 ± 610.4 to 48 ± 11.1 and depressive symptoms (Yesavage test) decreased from 9.2 ± 3.6 to 5.2 ± 5.0 in the intervention but not the control group. CONCLUSIONS: The intervention mainly reached people with moderate loneliness and significantly improved the perception of loneliness, depressive symptoms, social support and the mental health component of the quality of life. The intervention may be more suitable for people with moderate loneliness, but these types of activities may be difficult to accept by people with severe loneliness not related to the barriers to socialisation generated by ageing.

EULAR recommendations for the management of Sjögren's syndrome with topical and systemic therapies.

The therapeutic management of Sjögren syndrome (SjS) has not changed substantially in recent decades: treatment decisions remain challenging in clinical practice, without a specific therapeutic target beyond the relief of symptoms as the most important goal. In view of this scenario, the European League Against Rheumatism (EULAR) promoted and supported an international collaborative study (EULAR SS Task Force) aimed at developing the first EULAR evidence and consensus-based recommendations for the management of patients with SjS with topical and systemic medications. The aim was to develop a rational therapeutic approach to SjS patients useful for healthcare professionals, physicians undergoing specialist training, medical students, the pharmaceutical industry and drug regulatory organisations following the 2014 EULAR standardised operating procedures. The Task Force (TF) included specialists in rheumatology, internal medicine, oral health, ophthalmology, gynaecology, dermatology and epidemiology, statisticians, general practitioners, nurses and patient representatives from 30 countries of the 5 continents. Evidence was collected from studies including primary SjS patients fulfilling the 2002/2016 criteria; when no evidence was available, evidence from studies including associated SjS or patients fulfilling previous sets of criteria was considered and extrapolated. The TF endorsed the presentation of general principles for the management of patients with SjS as three overarching, general consensus-based recommendations and 12 specific recommendations that form a logical sequence, starting with the management of the central triplet of symptoms (dryness, fatigue and pain) followed by the management of systemic disease. The recommendations address the use of topical oral (saliva substitutes) and ocular (artificial tear drops, topical non-steroidal anti-inflammatory drugs, topical corticosteroids, topical CyA, serum tear drops) therapies, oral muscarinic agonists (pilocarpine, cevimeline), hydroxychloroquine, oral glucocorticoids, synthetic immunosuppressive agents (cyclophosphamide, azathioprine, methotrexate, leflunomide and mycophenolate), and biological therapies (rituximab, abatacept and belimumab). For each recommendation, levels of evidence (mostly modest) and TF agreement (mostly very high) are provided. The 2019 EULAR recommendations are based on the evidence collected in the last 16 years in the management of primary 2002 SjS patients and on discussions between a large and broadly international TF. The recommendations synthesise current thinking on SjS treatment in a set of overarching principles and recommendations. We hope that the current recommendations will be broadly applied in clinical practice and/or serve as a template for national societies to develop local recommendations.

Autoimmune congenital heart block and primary Sjögren's syndrome: characterisation and outcomes of 49 cases.

OBJECTIVES: To characterise autoimmune congenital heart block (CHB) associated with a maternal diagnosis of primary Sjögren's syndrome (pSS) confirmed either before, concomitant or after the first pregnancy complicated with CHB. METHODS: The following inclusion criteria were applied: (i) Mothers with positive Ro/La autoantibodies detected previously or at the time of diagnosis of the first case of CHB; (ii) diagnosis of CHB confirmed by fetal echocardiography; (iii) AV block diagnosed in uterus, at birth or within the neonatal period (0-27 days after birth) (8); (iv) absence of anatomical cardiac abnormalities which might be causal of AV block; and (v) maternal fulfillment of the 2002 SS criteria before, during or after having a pregnancy complicated with CHB. RESULTS: We identified 49 cases of autoimmune CHB in children born from 44 mothers who had a mean age at the time of pregnancy of 30.3 years (range 18 to 41). At the time of diagnosis of autoimmune CHB, all mothers had positive anti-Ro antibodies and 28/44 (64%) were positive for anti-La antibodies. Only 10 (22%) mothers with affected pregnancies had a diagnosis of primary SS at the time of diagnosis of the first pregnancy complicated by CHB (a mean of 4 years before, ranging from 1 to 10 years). In 6 (14%) mothers, primary SS was diagnosed during pregnancy or less than 12 months after the delivery/termination. In the remaining 28 (64%) mothers, pSS was confirmed 1-5 years after CHB diagnosis (n=19, 68%), 6-10 years after (n=2, 7%), or more than 10 years after the first case of CHB was diagnosed (n=7, 25%). CHB was diagnosed in uterus in all cases but two. AV block was initially incomplete in 11 fetuses and complete in 36 (no available data in 2 cases). Among the 35 (71%) surviving children with CHB, 5 (14%) developed other features of neonatal lupus. After the index pregnancy, 12 women had 20 subsequent pregnancies: five were complicated by a CHB (recurrence rate of CHB of 25%). The 4 women who had recurrent CHB were double-positive for anti-Ro and anti-La antibodies, and all had a confirmed pSS before having the first index case of CHB. CONCLUSIONS: In pSS, autoimmune CHB could be one of the first "indirect" signs of the disease in women of childbearing-age, in whom the diagnosis is confirmed several years later. Some maternal characteristics could be related with recurrent CHB, such as having an already-confirmed diagnosis of pSS and carrying the two Ro/La autoantibodies.

Indicator condition-guided HIV testing with an electronic prompt in primary healthcare: a before and after evaluation of an intervention.

OBJECTIVE: Indicator condition (IC)-guided HIV testing is a strategy for the diagnosis of patients with HIV. The aim of this study was to assess the impact on the proportion of HIV tests requested after the introduction of an electronic prompt instructing primary healthcare (PHC) physicians to request an HIV test when diagnosing predefined IC. METHODS: A prospective interventional study was conducted in 2015 in three PHC centres in Barcelona to assess the number of HIV test requests made during the implementation of an electronic prompt. Patients aged 18-65 years without HIV infection and with a new diagnosis of predefined IC were included. The results were compared with preprompt (2013) and postprompt data (2016). RESULTS: During the prompt period, 832 patients presented an IC (median age 41.6 years [IQR 30-54], 48.2% female). HIV tests were requested in 296 individuals (35, 6%) and blood tests made in 238. Four HIV infections were diagnosed (positivity rate 1.7%, 95% CI 0.5% to 4.4%). The number of HIV tests requested based on IC increased from 12.6% in 2013 to 35.6% in 2015 (p<0.001) and fell to 17.9% after removal of the prompt in 2016 (p<0.001). Younger patient age (OR 0.97, 95% CI 0.96 to 0.98), birth outside Spain (OR 1.53, 95% CI 1.06 to 2.21) and younger physician age (OR 0.97, 95% CI 0.96 to 0.99) were independent predictive factors for an HIV test request during the prompt period. The electronic prompt (OR 3.36, 95% CI 2.70 to 4.18) was the factor most closely associated with HIV test requests. It was estimated that 10 (95% CI 3.0 to 26.2) additional new cases would have been diagnosed if an HIV test had been performed in all patients presenting an IC. CONCLUSIONS: A significant increase in HIV test requests was observed during the implementation of the electronic prompt. The results suggest that this strategy could be useful in increasing IC-guided HIV testing in PHC centres.

How the Frequency and Phenotype of Sarcoidosis is Driven by Environmental Determinants.

BACKGROUND: Sarcoidosis is a systemic disease in which the personal environment seems to drive a differentiated disease frequency and clinical expression. The main epidemiological studies suggest a key influence of potential environmentally linked exposures related to the type of occupation, the household, life style, socioeconomic status, and region of residence. OBJECTIVE: To provide an update on how sarcoidosis may be modulated by environmental factors. DATA SOURCES: We searched PubMed for epidemiological studies. SYNTHESIS: The risk of sarcoidosis is enhanced in people working in jobs related to agriculture, water, construction, metal machining, education, and health, and reduced in those working in jobs mainly centered on personal care. Studies have confirmed seasonal-related peaks of sarcoidosis incidence that follow geographical North-South and West-East gradients. Other personal factors include smoking, personal household exposures, and leisure activities. The evidence pointing to the crucial role of the environment in the etiopathogenesis of sarcoidosis is mounting rapidly. Few diseases so strongly combine geography, environment, gender, and ethnicity as key etiopathogenic factors, with susceptibility to any putative agent being modulated by the individual exposome and genome. CONCLUSION: Geoepidemiological research should focus on evaluating the combined effects of environmental and genetic factors, the identification of clusters of geographically driven exposures, and more precise measurement of all personal exposures (degree of combination, length, and level of exposure).

The Burden of Comorbidity and Complexity in Sarcoidosis: Impact of Associated Chronic Diseases.

PURPOSE: To evaluate comorbidity, complexity and poor outcomes in patients with sarcoidosis and to compare those scores with a control group. METHODS: 218 consecutive patients were diagnosed with sarcoidosis according to the ATS/ERS/WASOG criteria; extrathoracic involvement was evaluated using the 2014 WASOG organ assessment instrument. Sarcoidosis patients were compared with an age- and gender-matched control group of primary care outpatients without sarcoidosis. Comorbidities were assessed retrospectively using the Charlson Comorbidity Index (CCI); complexity was evaluated according to the classification into Clinical Risk Groups (CRG) and severity levels. RESULTS: The cohort included 142 women and 76 men; the mean age was 47.1 years at diagnosis of sarcoidosis and 55.9 years at the last visit. Patients with a CCI > 1 had a higher frequency of calcium/vitamin D abnormalities (p < 0.001), kidney involvement (p = 0.005) and a higher mortality rate (p < 0.001) compared with patients with a CCI ≤ 1. Patients with a CRG ≥ 6 had a higher frequency of extrathoracic involvement (p = 0.039), calcium/vitamin D abnormalities (p = 0.019) and treatment with glucocorticoids (p = 0.032) compared with patients with a CRG < 6. 11% patients died after a mean follow-up of 102.3 months. Country of birth, kidney involvement and extrathoracic disease were significantly associated with death. Patients with sarcoidosis had a higher frequency of liver (p < 0.001), pulmonary (p = 0.002) and autoimmune disease (p = 0.011) and cancer (p = 0.007) compared with the control group. CONCLUSION: We found higher rates of comorbidity and complexity in patients with sarcoidosis compared with a control group. Liver, pulmonary, autoimmune and neoplastic diseases were the main comorbidities found in patients with sarcoidosis.

[Effectiveness of an educational program for respiratory rehabilitation of Chronic Obstructive Pulmonary Disease patients in Primary Care in improving the quality of life, symptoms, and clinical risk]. / Efectividad de un programa educativo de rehabilitación respiratoria en atención primaria para mejorar la calidad de vida, la sintomatología y el riesgo clínico de los pacientes con enfermedad pulmonar obstructiva crónica.

AIM: To determine the impact of an educational program to improve the management of chronic obstructive pulmonary disease (COPD) that contributes to an increase of the quality of life, exercise capacity, level of dyspnoea, and clinical risk. DESIGN: Intervention study without controls. LOCATION: Primary Healthcare Centre. PARTICIPANTS: 193 patients with COPD were invited, 73 accepted and 55 participated in the educational program. INTERVENTIONS: Respiratory rehabilitation educational program with basic concepts of pulmonary and respiratory pathophysiology, respiratory physiotherapy exercises, practical workshop on the use of the most frequent inhalation devices, understanding of chronic disease and self-care measures in case of exacerbation. MAIN MEASUREMENTS: The quality of life (the COPD assessment test), exercise tolerance (the Six-Minute Walk Test), rating of perceived exertion (Borg Dyspnoea Score) and clinical risk (BODE index) were assessed by means of validated questionnaires in Spanish. RESULTS: A total of 43 (78.2%) participants completed the program. An improvement in the quality of life by a mean of 3.3 points was observed (95%CI; 1.76-4.84). Just over half (53.5%) of the participants obtained a clinically relevant improvement. Participants also improved their physical exercise capacity at post-intervention by increasing the distance that they walked in 6min by a mean of 20.76m (95%CI; 2.57-38.95). Improvements in the level of dyspnoea and clinical risk were also observed. CONCLUSIONS: The educational program shows a statistically significant and clinically relevant improvement in the quality of life, fatigue, symptomatology, exercise capacity, level of dyspnoea, and clinical risk. The program is adaptable to the health care routine of healthcare centres.

[Health literacy in patients with heart failure treated in primary care]. / Alfabetización en salud en pacientes con insuficiencia cardiaca atendidos en atención primaria.

OBJECTIVES: The level of health literacy is examined, as well as its conditioning factors in patients with heart failure who are seen routinely in a Primary Health Care Area. DESIGN: A multicentre cross-sectional study. SETTING: 10 Primary care centres from the metropolitan area of Barcelona. PARTICIPANTS: Patients diagnosed with heart failure. INCLUSION CRITERIA: to have visited the Primary Health Care centre in the last year, being able to arrive at the primary care setting independently, and voluntarily participation. MAIN MEASUREMENTS: Health Literacy Survey-European Union - Questionnaire (HLS-EU-Q) and Spanish version of the European Heart Failure Self-care Behaviour Scale. An analysis was made of the relationships between health literacy, self-care practices, sociodemographic, and clinical variables using ANOVA test and a multiple linear regression model. RESULTS: The study included 318 patients (51.2% women) with a mean age of 77.9±8.7 years. The index of health literacy of 79.6% (n=253) of the participants indicated problems in understanding healthcare information. Health literacy level was explained by academic level (P<.001), the extent of heart failure (P=.032), self-care, and age (P<.04).The academic level explained 61.6% of the health of literacy (95% bootstrap: 44.58%; 46.75%). CONCLUSIONS: In patients with stable heart failure, it is important to consider all factors that help patients to understand the healthcare information. Health literacy explains patient self-care attitude in heart failure.

Cryoglobulinaemic vasculitis at diagnosis predicts mortality in primary Sjögren syndrome: analysis of 515 patients.

OBJECTIVE: To evaluate the fulfilment of classification criteria for cryoglobulinaemic vasculitis (CV) at diagnosis in a large cohort of patients with primary SS and their correlation with poor outcomes. METHODS: We included 515 consecutive patients tested for serum cryoglobulins who fulfilled the 2002 classification criteria for primary SS. CV classification criteria and serum cryoglobulins at diagnosis were assessed as predictors of death and lymphoma using Cox proportional-hazards regression analysis adjusted for age and gender. RESULTS: Positive serum cryoglobulins were detected in 65 (12%) patients, of whom 21 (32%) fulfilled CV classification criteria. Compared with patients positive for cryoglobulins who did not fulfil CV criteria, patients with CV had a higher frequency of type II cryoglobulinaemia (86% vs 43%, P = 0.04), a higher mean cryocrit level (6.58% vs 1.25%, P < 0.001) and a higher cumulated mean EULAR-SS disease activity index score (35.3 vs 16.2, P < 0.001). After a mean follow-up of 110 months, 45 (9%) patients developed B-cell lymphoma and 33 (6%) died. Compared with patients without cryoglobulins, patients with cryoglobulins who fulfilled [hazard ratio (HR) = 7.47, 95% CI: 3.38, 16.53] and did not fulfil (HR = 2.56, 95% CI: 1.03, 6.35) CV criteria both showed a higher risk of B-cell lymphoma in the univariate analysis, but not in the multivariate models. Compared with patients without cryoglobulins, patients with CV had a higher risk of death in both the univariate (HR = 11.68, 95% CI: 4.44, 30.74) and multivariate (HR = 4.36, 95% CI: 1.32, 14.47) models. CONCLUSION: Patients with primary SS who fulfilled criteria for cryoglobulinaemic vasculitis at diagnosis are at higher risk of death.