Mapping the Evidence on the Impact of mHealth Interventions on Patient-Reported Outcomes in Patients With Breast Cancer: A Systematic Review.

PURPOSE: To comprehensively synthesize the existing evidence concerning mHealth interventions for patients with breast cancer (BC). DESIGN: On July 30, 2023, we searched PubMed, PsycINFO, and Google Scholar for articles using the following inclusion criteria: evaluation of mHealth interventions in patients with cancer, at least 30 participants with BC, randomized control trials or prospective pre-post studies, determinants of health (patient-reported outcomes [PROs] and quality of life [QoL]) as primary outcomes, interventions lasting at least 8 weeks, publication after January 2015. Publications were excluded if they evaluated telehealth or used web-based software for desktop devices only. The quality of the included studies was analyzed with the Cochrane Collaboration Risk of Bias Tool and the Methodological Index for Non-Randomized Studies. RESULTS: We included 30 studies (20 focused on BC), encompassing 5,691 patients with cancer (median 113, IQR, 135.5). Among these, 3,606 had BC (median 99, IQR, 75). All studies contained multiple interventions, including physical activity, tailored information for self-management of the disease, and symptom tracker. Interventions showed better results on self-efficacy (3/3), QoL (10/14), and physical activity (5/7). Lifestyle programs (3/3), expert consulting (4/4), and tailored information (10/11) yielded the best results. Apps with interactive support had a higher rate of positive findings, while interventions targeted to survivors showed worse results. mHealth tools were not available to the public in most of the studies (17/30). CONCLUSION: mHealth interventions yielded heterogeneous results on different outcomes. Identifying lack of evidence on clinical scenarios (eg, patients undergoing systemic therapy other than chemotherapy) could aid in refining strategic planning for forthcoming research endeavors within this field.

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.

A motivational interview program for cardiac rehabilitation after acute myocardial infarction: study protocol of a randomized controlled trial in primary healthcare.

BACKGROUND: Cardiac rehabilitation after acute myocardial infarction permits recovery of the heart function and enables secondary prevention programs in which changes in lifestyle habits are crucial. Cardiac rehabilitation often takes place in hospitals without coordination with primary healthcare and is not focused on individual patient preferences and goals, which is the core of the motivational interview. The objective of this study was to evaluate the efficacy of a cardiac rehabilitation program with a motivational interview in patients discharged from hospital after acute myocardial infarction. METHODS/DESIGN: A randomized, non-pharmacological clinical trial in six primary healthcare centers in Barcelona (Spain) will assess whether a tailored cardiac rehabilitation program consisting of four motivational interviews and visits with family physicians, primary healthcare nurses and a cardiologist, coordinated with the reference hospital, results in better cardiac rehabilitation than standard care. A minimum sample of 284 participants requiring cardiac rehabilitation after acute myocardial infarction will be randomized to a cardiac rehabilitation group with a motivational interview program or to standard primary healthcare. The main outcome will be physical function measured by the six-minute walk test, and the secondary outcome will be the effectiveness of secondary prevention: a composite outcome comprising control of blood pressure, cholesterol, diabetes mellitus, smoking and body weight. Results will be evaluated at 1,3 and 6 months. DISCUSSION: This is the first clinical trial to study the impact of a new primary healthcare cardiac rehabilitation program with motivational interviews for patients discharged from hospital after myocardial infarction. Changes in lifestyles and habits after myocardial infarction are a core element of secondary prevention and require patient-centered care strategies such as motivational interviews. Therefore, this study could clarify the impact of this approach on health indicators, such as functional capacity. TRIAL REGISTRATION: ClinicalTriasl.gov NCT05285969 registered on March 18, 2022.

Trends in the Prescription of Strong Opioids for Chronic Non-Cancer Pain in Primary Care in Catalonia: Opicat-Padris-Project.

In chronic non-cancer pain (CNCP), evidence of the effectiveness of strong opioids (SO) is very limited. Despite this, their use is increasingly common. To examine SO prescriptions, we designed a descriptive, longitudinal, retrospective population-based study, including patients aged ≥15 years prescribed SO for ≥3 months continuously in 2013-2017 for CNCP in primary care in Catalonia. Of the 22,691 patients included, 17,509 (77.2%) were women, 10,585 (46.6%) were aged >80 years, and most had incomes of <€18,000 per year. The most common diagnoses were musculoskeletal diseases and psychiatric disorders. There was a predominance of transdermal fentanyl in the defined daily dose (DDD) per thousand inhabitants/day, with the greatest increase for tapentadol (312% increase). There was an increase of 66.89% in total DDD per thousand inhabitants/day for SO between 2013 (0.737) and 2017 (1.230). The mean daily oral morphine equivalent dose/day dispensed for all drugs was 83.09 mg. Transdermal fentanyl and immediate transmucosal release were the largest cost components. In conclusion, there was a sustained increase in the prescription of SO for CNCP, at high doses, and in mainly elderly patients, predominantly low-income women. The new SO are displacing other drugs.

Risk Prescriptions of Strong Opioids in the Treatment of Chronic Non-Cancer Pain by Primary Care Physicians in Catalonia: Opicat Padris Project.

The prescription of strong opioids (SO) for chronic non-cancer pain (CNCP) is steadily increasing. This entails a high risk of adverse effects, a risk that increases with the concomitant prescription of SO with central nervous system depressant drugs and with the use of SO for non-recommended indications. In order to examine this concomitant risk prescription, we designed a descriptive, longitudinal, retrospective population-based study. Patients aged ≥15 years with a continued SO prescription for ≥3 months during 2013-2017 for CNCP were included. Of these, patients who had received concomitant prescriptions of SO and risk drugs (gabapentinoids, benzodiazepines and antidepressants) and those who had received immediate-release fentanyl (IRF) were selected. The study included 22,691 patients; 20,354 (89.7%) patients received concomitant risk prescriptions. Men and subjects with a higher socioeconomic status received fewer concomitant risk prescriptions. Benzodiazepines or Z-drugs were prescribed concomitantly with SO in 15,883 (70%) patients, antidepressants in 14,932 (65%) and gabapentinoids in 11,267 (49%), while 483 (21.32%) patients received IRF (2266 prescriptions in total) without a baseline SO. In conclusion, our study shows that a high percentage of patients prescribed SO for CNCP received concomitant prescriptions with known risks, as well as IRF for unauthorized indications.

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.

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.

[Primary Healthcare management models in Catalonia: May the best win?] / Modelos de gestión de la Atención Primaria en Cataluña: ¿Que gane el mejor?

OBJECTIVE: In Catalonia, the variety of the provision of Primary Healthcare has sparked intense debates over the last 20 years regarding the efficiency of the various management models. Our study analyzed the differences in the three existing management models of primary healthcare in Catalonia (the Catalan Health Institute, public consortiums and associative base entities). METHODS: The primary data were obtained from the reports of the Results Center of The Observatory of the Health System of Catalonia. Representative indicators were selected and compared with the Kruskall-Wallis test. They were later adjusted for confounding factors. RESULTS: There were differences in the average number of visits per population attended, the percentage of the population attended in the subgroup of population over 75 years of age, the percentage of patients over 74 years with more than twelve appointments, the rate of potentially avoidable hospitalizations (total and in the subgroup of patients with chronic obstructive pulmonary disease (COPD)), polypharmacy, the use of lipid-lowering drugs and the detection of prostate-specific antigen (PSA). When adjusting for confounding variables, the differences disappeared in all of them except for the indicator on the detection of PSA. CONCLUSIONS: The differences favoured mainly the associative base entities disappear when they are corrected for confounding variables. The legal status of each provider does not significantly influence the health outcomes.

OBJETIVO: En Cataluña, la diversificación de la provisión de la Atención Primaria ha suscitado en los últimos 20 años intensos debates en torno a la eficiencia de los diversos modelos de gestión. El objetivo de este trabajo fue analizar las diferencias existentes en resultados de salud entre los modelos clásicos de gestión de la Atención Primaria existentes en Cataluña (Institut Català de la Salut, consorcios públicos y entidades de base asociativa). METODOS: Los datos primarios se obtuvieron de los informes de la Central de resultados del Observatori del Sistema de Salut de Catalunya de la Generalitat de Cataluña. Se seleccionaron indicadores representativos y se compararon con la prueba de Kruskall-Wallis. Posteriormente, se ajustaron por factores de confusión. RESULTADOS: Se observaron diferencias en los indicadores sobre la media de visitas por población atendida, el porcentaje de población asignada atendida en el subgrupo de mayores de 75 años, el porcentaje de pacientes mayores de 74 años con más de doce visitas, la tasa de hospitalizaciones potencialmente evitables, tanto total como en el subgrupo de pacientes con enfermedad pulmonar obstructiva crónica (EPOC), la polimedicación, el uso de hipolipemiantes y la detección del antígeno prostático específico (PSA). Al ajustar por variables confusoras, las diferencias desaparecieron en todos ellos excepto en el indicador sobre la detección del PSA. CONCLUSIONES: Las diferencias favorables a las entidades de base asociativas desaparecen cuando se corrigen por variables confusoras. La fórmula jurídica o de provisión de servicios no parece influir de forma significativa en los resultados de salud poblacionales.

Therapeutic Recommendations for the Management of Older Adult Patients with Sjögren's Syndrome.

Primary Sjögren's syndrome (SjS) is a systemic autoimmune disease most commonly diagnosed in middle-aged women. Although the disease can occur at all ages, it is diagnosed between 30 and 60 years of age in two-thirds of patients. In more than 20% of cases, the people are older than 65 years. In this review, we focus on the therapeutic management of primary SjS in older patients, following the recently published 2020 European League Against Rheumatism (EULAR) recommendations for the management of the disease with topical and systemic therapies. These recommendations are applicable to all patients with primary SjS regardless of age at diagnosis, although the therapeutic management in older patients requires additional considerations. Older patients are more likely to have pulmonary, liver, kidney, or heart-related comorbidities (even cognitive disturbances); caution is required when most drugs are used, including muscarinic agents, systemic corticosteroids and synthetic immunosuppressants. It is also important to monitor the use of eye drops containing steroids due to the increased risk of developing cataracts, a frequent ocular complication in the older population. In contrast, the majority of drugs that can be used topically (pilocarpine rinses, eye drops containing topical non-steroidal anti-inflammatory drugs (NSAIDs) or cyclosporine A, topical dermal formulations of NSAIDs) have shown an acceptable safety profile in older patients, as well as rituximab. A rigorous evaluation of the medical history of older patients is essential when drugs included in the EULAR guidelines are prescribed, with special attention to factors frequently related to ageing, such as polypharmacy, the existence of organ-specific comorbidities, or the enhanced susceptibility to infections.

Haemophagocytic syndrome and COVID-19.

Primary and secondary haemophagocytic lymphohistiocytosis (HLH) are hyperferritinaemic hyperinflammatory syndromes with a common terminal pathway triggered by different etiopathogenetic factors. HLH is characterised by a decreased capacity of interferon gamma production with an activated NK phenotype profile similar to other hyperinflammatory syndromes. Viruses are closely linked to the development of HLH as infectious triggers, and the break of tolerance to self-antigens is considered a critical mechanism involved in the development of immune-mediated conditions triggered by viral infections. Emerging studies in patients with COVID-19 are suggesting a key role of monocytes/macrophages in the pathogenesis of this viral infection, and there is a significant overlap between several features reported in severe COVID-19 and the features included in the HLH-2004 diagnostic criteria. Therefore, SARS-Cov-2, as other respiratory viruses, may also be considered a potential etiological trigger of HLH. The frequency of HLH in adult patients with severe COVID-19 is lower than 5%, although this figure could be underestimated considering that most reported cases lacked information about some specific criteria (mainly the histopathological criteria and the measurement of NK cell function and sCD25 levels). Because HLH is a multi-organ syndrome, the diagnostic approach in a patient with severe COVID-19 in whom HLH is suspected must be carried out in a syndromic and holistic way, and not in the light of isolated clinical or laboratory features. In COVID-19 patients presenting with persistent high fever, progressive pancytopenia, and hepatosplenic involvement, together with the characteristic triad of laboratory abnormalities (hyperferritinaemia, hypertriglyceridaemia, and hypofibrinogenaemia), the suspicion of HLH is high, and the diagnostic workup must be completed with specific immunological and histopathological studies.

Availability of Spanish-Language Medical Apps in Google Play and the App Store: Retrospective Descriptive Analysis Using Google Tools.

BACKGROUND: The number of medical and health apps in the App Store and Google Play repositories has been increasing in the recent years, and most of these apps are in English. However, little is known about the domain of Spanish health apps and their evolution. OBJECTIVE: The aim of this study was to perform a retrospective descriptive analysis of medical apps for patients in the Spanish language by using Google search tools over a 5-year period and to compare the results by using a reproducible methodology to obtain a better knowledge of the medical apps available in the Spanish Language. METHODS: Over a 5-year period, medical apps were catalogued using a Google-based methodology. Keywords of the first 14 categories of the International Classification of Diseases, Tenth Revision, were selected, and in December of each year, searches of the URLs of Google Play and the App Store were conducted using Google Advanced Search. The first 10 results were taken, and apps meeting the inclusion criteria were selected and rated with the iSYScore method. RESULTS: Out of a sample of 1358 apps, 136 met the inclusion criteria. The 3 main categories of the medical apps were in the fields of endocrinology (diabetes), respiratory (chronic obstructive pulmonary disease, asthma, and allergies), and neurology (multiple sclerosis, Parkinson disease, and Alzheimer disease). Few apps were maintained over the 5 years. Only 10 of the 136 apps were maintained for 3 years or more. There was a large number of original apps in other languages that were translated into Spanish (56/136, 41.2%). In the last year of the study, the main reason (73/280, 26.1%) for discarding an app was the date of the last update. CONCLUSIONS: The market of Spanish apps is poor; only few apps have appeared repeatedly over 5 years. Differences were found with the international market in terms of apps related to mental health, heart and circulatory system, and cancer, and coincidences were found in the relevance of apps for diabetes control.

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).

Clinically-useful serum biomarkers for diagnosis and prognosis of sarcoidosis.

INTRODUCTION: Sarcoidosis is a complex systemic disease with a silent, long-term evolution, and a heterogeneous clinical presentation. The diagnostic approach is complex with no single diagnostic test that may confirm the disease. Areas covered: A large list of serum biomarkers has been tested during the last 40 years. In this review, we analyse the potential usefulness in the diagnosis and prognosis of sarcoidosis of serum biomarkers classified according to their corresponding cellular source. Expert commentary: Diagnosis of sarcoidosis must always be approached as a multistep process based on a case-by-case integration of clinical, radiological, histological and serological data, none of which being pathognomonic. We found sIL-2R, CRP, SAA and chitotriosidase to be the best markers to confirm sarcoidosis (highest sensitivity), while ACE, gammaglobulins and lysozyme may be more useful for discarding sarcoidosis (highest specificity), taking into account that with the use of a higher cut-off we can increase specificity and with a lower cut-off we can increase sensitivity. Other biomarkers (TNF-a and CCL18) could help to identify patients with an enhanced risk of developing pulmonary fibrosis or progressive disease. The future scenario of the serological diagnostic approach of sarcoidosis will be the use of multi-assays including biomarkers from different cellular sources.

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.

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.

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.

Google-driven search for big data in autoimmune geoepidemiology: analysis of 394,827 patients with systemic autoimmune diseases.

Systemic autoimmune diseases (SADs) are a significant cause of morbidity and mortality worldwide, although their epidemiological profile varies significantly country by country. We explored the potential of the Google search engine to collect and merge large series (>1000 patients) of SADs reported in the Pubmed library, with the aim of obtaining a high-definition geoepidemiological picture of each disease. We collected data from 394,827 patients with SADs. Analysis showed a predominance of medical vs. administrative databases (74% vs. 26%), public health system vs. health insurance resources (88% vs. 12%) and patient-based vs. population-based designs (82% vs. 18%). The most unbalanced gender ratio was found in primary Sjögren syndrome (pSS), with nearly 10 females affected per 1 male, followed by systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and antiphospholipid syndrome (APS) (ratio of nearly 5:1). Each disease predominantly affects a specific age group: children (Kawasaki disease, primary immunodeficiencies and Schonlein-Henoch disease), young people (SLE Behçet disease and sarcoidosis), middle-aged people (SSc, vasculitis and pSS) and the elderly (amyloidosis, polymyalgia rheumatica, and giant cell arteritis). We found significant differences in the geographical distribution of studies for each disease, and a higher frequency of the three SADs with available data (SLE, inflammatory myopathies and Kawasaki disease) in African-American patients. Using a "big data" approach enabled hitherto unseen connections in SADs to emerge.

Differential methylation of TCF7L2 promoter in peripheral blood DNA in newly diagnosed, drug-naïve patients with type 2 diabetes.

TCF7L2 is the susceptibility gene for Type 2 diabetes (T2D) with the largest effect on disease risk that has been discovered to date. However, the mechanisms by which TCF7L2 contributes to the disease remain largely elusive. In addition, epigenetic mechanisms, such as changes in DNA methylation patterns, might have a role in the pathophysiology of T2D. This study aimed to investigate the differences in terms of DNA methylation profile of TCF7L2 promoter gene between type 2 diabetic patients and age- and Body Mass Index (BMI)- matched controls. We included 93 type 2 diabetic patients that were recently diagnosed for T2D and exclusively on diet (without any pharmacological treatment). DNA was extracted from whole blood and DNA methylation was assessed using the Sequenom EpiTYPER system. Type 2 diabetic patients were more insulin resistant than their matched controls (mean HOMA IR 2.6 vs 1.8 in controls, P<0.001) and had a poorer beta-cell function (mean HOMA B 75.7 vs. 113.6 in controls, P<0.001). Results showed that 59% of the CpGs analyzed in TCF7L2 promoter had significant differences between type 2 diabetic patients and matched controls. In addition, fasting glucose, HOMA-B, HOMA-IR, total cholesterol and LDL-cholesterol correlated with methylation in specific CpG sites of TCF7L2 promoter. After adjustment by age, BMI, gender, physical inactivity, waist circumference, smoking status and diabetes status uniquely fasting glucose, total cholesterol and LDL-cholesterol remained significant. Taken together, newly diagnosed, drug-naïve type 2 diabetic patients display specific epigenetic changes at the TCF7L2 promoter as compared to age- and BMI-matched controls. Methylation in TCF7L2 promoter is further correlated with fasting glucose in peripheral blood DNA, which sheds new light on the role of epigenetic regulation of TCF7L2 in T2D.

Specificity and sensitivity of objective tests to detect possible malingering in fibromyalgia: a case-control study in 211 Spanish patients.

OBJECTIVES: To characterise patients diagnosed with fibromyalgia (FM) who present a clinical profile suggestive of simulation. METHODS: Observational case-control study of 218 patients who met the classification criteria for FM. The profile supporting simulation was based on the proposed criteria for evaluating disability related to the simulation of pain. RESULTS: Compared with controls (n=105), patients with suspected simulation of FM (n=106) had a higher mean age (52.5 vs. 49.2 years, p=0.003), a higher frequency of primary education (88.7% vs. 58.1%; p<0.001), a higher percentage of separated/widowed persons (33.9% vs. 8.6%, p<0.001), a higher frequency of psychiatric disorders (100% vs. 67.6%, p<0.001), a higher mean number of positive 'control' tender points (4.5 vs. 1.3, p<0.001), a higher mean FIQ questionnaire score (89.8 vs. 68.8, p<0.001) and a lower mean LHS questionnaire score (41.0 vs. 59.9, p<0.001). Patients with suspected simulation were able to walk a shorter distance in the 6-minute walk test than controls (231.0 vs. 356.3 metres, p<0.001), while the appearance of allodynia was achieved with a significantly lower mmHg pressure (159.8 vs. 229.9 mm Hg, p<0.001). CONCLUSIONS: Some physical/functional tests, together with the administration of specific questionnaires, may identify a subgroup of patients with FM with a profile consistent with simulation or malingering; these patients have a differentiated demographic and psychiatric profile in comparison with FM patients without a profile of simulation.