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Purpose Multimorbidity impacts quality of life. We constructed hypothyroidism comorbidity networks to identify positive and negative associations with other prevalent diseases. Methods We analyzed data of 285 342 patients with hypothyroidism from 3 135 948 adults with multimorbidity in a population-based study in Catalonia, Spain, (period: 2006-2017). We constructed hypothyroidism comorbidity networks using logistic regression models, adjusted by age and sex, and for men and women separately. We considered relevant associations those with odds ratios (OR) >1.2 or Results The conditions associated included larynx cancer (adjusted OR: 2.48), congenital anomalies (2.26), thyroid cancer (2.13), hyperthyroidism (1.66), vitamin B12/folate deficiency anemia (1.57), and goiter (1.56). The network restricted to men had more connections (mental, cardiovascular, and neurological) and stronger associations with thyroid cancer (7.26 vs 2.55), congenital anomalies (5.11 vs 2.13), hyperthyroidism (4.46 vs 1.69), larynx cancer (3.55 vs 1.67), and goiter (3.94 vs 1.64). After adjustment for comorbidities, OR values were more similar in men and women. The strongest negative associations after adjusting for comorbidities were with HIV/AIDS (OR: 0.71) and tobacco abuse (0.77). Conclusions Networks show direct and indirect hypothyroidism multimorbidity associations. The strongest connections were thyroid and larynx cancer, congenital anomalies, hyperthyroidism, anemia, and goiter. Negative associations included HIV/AIDS and tobacco abuse. The network restricted to men had more and stronger associations, but not after adjusting for comorbidities, suggesting important indirect interactions.

Miguel Angel Luque-Fernandez is supported by a Miguel Servet I Investigator award (Grant CP17/00206) and a project grant EU-FEDER-FIS PI-18/01593 from the Instituto de Salud Carlos III, Madrid, Spain. Danilo Alvares is supported by the National Fund for Scientific and Technological Development (FONDECYT, Chile) grant number 11190018., Cancer survival represents one of the main indicators of interest in cancer epidemiology. However, the survival of cancer patients can be affected by several factors, such as comorbidities, that may interact with the cancer biology. Moreover, it is interesting to understand how different cancer sites and tumour stages are affected by different comorbidities. Identifying the comorbidities that affect cancer survival is thus of interest as it can be used to identify factors driving the survival of cancer patients. This information can also be used to identify vulnerable groups of patients with comorbidities that may lead to worst prognosis of cancer. We address these questions and propose a principled selection and evaluation of the effect of comorbidities on the overall survival of cancer patients. In the first step, we apply a Bayesian variable selection method that can be used to identify the comorbidities that predict overall survival. In the second step, we build a general Bayesian survival model that accounts for time-varying effects. In the third step, we derive several posterior predictive measures to quantify the effect of individual comorbidities on the population overall survival. We present applications to data on lung and colorectal cancers from two Spanish population-based cancer registries. The proposed methodology is implemented with a combination of the R-packages mombf and rstan. We provide the code for reproducibility at https://github.com/migariane/ BayesVarImpComorbiCancer., Miguel Servet I Investigator award CP17/00206 EU-FEDER-FIS PI-18/01593, Instituto de Salud Carlos III, Comision Nacional de Investigacion Cientifica y Tecnologica (CONICYT) CONICYT FONDECYT 11190018

Background Numerous studies have analysed the effect of comorbidity on cancer outcomes, but evidence on the association between multimorbidity and short-term mortality among colorectal cancer patients is limited. We aimed to assess this association and the most frequent patterns of multimorbidity associated with a higher short-term mortality risk among colorectal cancer patients in Spain. Methods Data were obtained from two Spanish population-based cancer registries and electronic health records. We estimated the unadjusted cumulative incidence of death by comorbidity status at 6 months and 1 year. We used a flexible parametric model to derive the excess mortality hazard ratios (HRs) for multimorbidity after adjusting for sex, age at diagnosis, cancer stage and treatment. We estimated the adjusted cumulative incidence of death by comorbidity status and identified multimorbidity patterns. Results Among the study participants, 1,048 cases were diagnosed with cancers of the colon and rectum, 2 cases with cancer of the anus with overlapping sites of the rectum and 11 cases with anal adenocarcinomas but treated as colorectal cancer patients. Among 1,061 colorectal cancer patients, 171 (16.2%) died before 6 months, 246 (23.3%) died before the 1-year follow-up, and 324 (30.5%) had multimorbidity. Patients with multimorbidity had two times higher mortality risk than those without comorbidities at 6 months (adjusted HR: 2.04; 95% confidence interval [CI]: 1.30–3.20, p = 0.002). The most frequent multimorbidity pattern was congestive heart failure + diabetes. However, patients with rheumatologic disease + diabetes had two times higher 1-year mortality risk than those without comorbidities (HR: 2.23; 95% CI: 1.23–4.07, p = 0.008). Conclusions Multimorbidity was a strong independent predictor of short-term mortality at 6 months and 1 year among the colorectal cancer patients in Spain. The identified multimorbidity pattern was consistent. Our findings might help identify patients at a higher risk for poor cancer and treatment outcomes M.A.L.F. received support from the Instituto de Salud Carlos III, Madrid, Spain (grant/award no. CP17/ 00206-EU-FEDER), and M.J.S. received support from the Andalusian Department of Health (grant no. PI0152/2017)

Severe COVID-19 disease requiring ICU admission is possible in the fully vaccinated population, especially in those with immunocompromised status and other comorbidities. Interventions to improve vaccine response might be necessary in this population. Peer Reviewed "Article signat per 23 autors/es: Anna Motos, Alexandre López-Gavín, Jordi Riera, Adrián Ceccato, Laia Fernández-Barat, Jesús F. Bermejo-Martin, Ricard Ferrer, David de Gonzalo-Calvo, Rosario Menéndez, Raquel Pérez-Arnal, Dario García-Gasulla, Alejandro Rodriguez, Oscar Peñuelas, José Ángel Lorente, Raquel Almansa, Albert Gabarrus, Judith Marin-Corral, Pilar Ricart, Ferran Roche-Campo, Susana Sancho Chinesta, Lorenzo Socias, Ferran Barbé, Antoni Torres on behalf of the CIBERESUCICOVID Project (COV20/00110, ISCIII)"

In the wake of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic, an increasing number of patients with neurological disorders, including Guillain-Barré syndrome (GBS), have been reported following this infection. It remains unclear, however, if these cases are coincidental or not, as most publications were case reports or small regional retrospective cohort studies. The International GBS Outcome Study is an ongoing prospective observational cohort study enrolling patients with GBS within 2 weeks from onset of weakness. Data from patients included in this study, between 30 January 2020 and 30 May 2020, were used to investigate clinical and laboratory signs of a preceding or concurrent SARS-CoV-2 infection and to describe the associated clinical phenotype and disease course. Patients were classified according to the SARS-CoV-2 case definitions of the European Centre for Disease Prevention and Control and laboratory recommendations of the World Health Organization. Forty-nine patients with GBS were included, of whom eight (16%) had a confirmed and three (6%) a probable SARS-CoV-2 infection. Nine of these 11 patients had no serological evidence of other recent preceding infections associated with GBS, whereas two had serological evidence of a recent Campylobacter jejuni infection. Patients with a confirmed or probable SARS-CoV-2 infection frequently had a sensorimotor variant 8/11 (73%) and facial palsy 7/11 (64%). The eight patients who underwent electrophysiological examination all had a demyelinating subtype, which was more prevalent than the other patients included in the same time window [14/30 (47%), P = 0.012] as well as historical region and age-matched control subjects included in the International GBS Outcome Study before the pandemic [23/44 (52%), P = 0.016]. The median time from the onset of infection to neurological symptoms was 16 days (interquartile range 12–22). Patients with SARS-CoV-2 infection shared uniform neurological features, similar to those previously described in other post-viral GBS patients. The frequency (22%) of a preceding SARS-CoV-2 infection in our study population was higher than estimates of the contemporaneous background prevalence of SARS-CoV-2, which may be a result of recruitment bias during the pandemic, but could also indicate that GBS may rarely follow a recent SARS-CoV-2 infection. Consistent with previous studies, we found no increase in patient recruitment during the pandemic for our ongoing International GBS Outcome Study compared to previous years, making a strong relationship of GBS with SARS-CoV-2 unlikely. A case-control study is required to determine if there is a causative link or not., Luijten et al. report that patients with Guillain-Barré syndrome (GBS) after SARS-CoV-2 infection share uniform neurological features, similar to those previously described in other cases of post-viral GBS. They conclude that SARS-CoV-2 infection may be an occasional trigger for GBS, but that a strong association is unlikely.

Background: The association between markers of inflammation (interleukin (IL)-6 and IL-10), monocyte activation (sCD163 and sCD14), and microbial translocation (lipopolysaccharide (LPS) and LPS binding protein) and liver fibrosis in patients with alcohol use disorder (AUD) and no overt liver disease is not well established. Methods: We studied patients admitted for treatment of AUD at two hospitals in Barcelona. Advanced liver fibrosis (ALF) was defined as FIB-4 &gt, 3.25. Results: A total of 353 participants (76.3% male) were included and 94 (26.5%) had ALF. In adjusted correlation analyses, sCD163, sCD14, IL-6, IL-10, and LPS binding protein levels directly correlated with FIB-4 values (adjusted correlation coefficients 0.214, 0.452, 0.317, 0.204, and 0.171, respectively). However, LPS levels were inversely associated with FIB-4 (−0.283). All plasma marker levels in the highest quartile, except LPS, were associated with ALF (sCD163, sCD14, IL-6, IL-10, and LPS binding protein: adjusted odds ratio (aOR) 11.49 (95% confidence interval 6.42–20.56), 1.87 (1.11–3.16), 2.99 (1.79–5.01), 1.84 (1.11–3.16), and 2.13 (1.30–3.50), respectively). Conversely, LPS levels in the lowest quartile were associated with ALF (aOR 2.58 (1.48–4.58), p &lt, 0.01). Conclusion: In AUD patients, plasma levels of the markers of inflammation, monocyte activation, and microbial translocation are associated with ALF.

Introduction AIDS‐mortality remains unacceptably high in sub‐Saharan Africa, largely driven by advanced HIV disease (AHD). We nested a study in an existing tuberculosis (TB) contact‐tracing intervention (Xpatial‐TB). The aim was to assess the burden of AHD among high‐risk people living with HIV (PLHIV) identified and to evaluate the provision of the WHO‐recommended package of care to this population. Methods All PLHIV ≥14 years old identified between June and December 2018 in Manhiça District by Xpatial‐TB were offered to participate in the study if ART naïve or had suboptimal ART adherence. Consenting individuals were screened for AHD. Patients with AHD (CD4

Objective The aim of this study was to evaluate periodontal disease as a predictor of chronic kidney disease (CKD) stage in older adults. Methods A total of 1159 adults aged 65 to 80 years and diagnosed with periodontal disease and CKD (stages 1, 2, and 3) were randomly selected for a cross-sectional study. Periodontal status was assessed using the Community Periodontal Index of Treatment Needs (CPITN) and CKD was staged using the National Kidney Foundation Kidney Disease Outcomes Quality Initiative (NKF-KDOQI) guidelines. Results In patients with stage 1 CKD, the odds ratios (ORs) (95% confidence intervals [CIs]) for CPITN-1, CPITN-2, CPITN-3, and CPITN-4 were 1.13 (0.83–1.55), 1.47 (1.13–1.81), 1, and 1, respectively. In patients with stage 2 CKD, the ORs (95% CIs) for CPITN-1, CPITN-2, CPITN-3, and CPITN-4 were 1.49 (1.14–1.93), 1.37 (1.02–1.78), 3.07 (2.81–3.25), and 3.65 (3.49–3.71), respectively. In patients with stage 3 CKD, the ORs (95% CIs) for CPITN-1, CPITN-2, CPITN-3, and CPITN-4 were 1, 1, 4.61 (4.47–5.21), and 5.23 (5.14–5.47), respectively. Conclusion The highest CPITN values (CPITN-3 and CPITN-4) were associated with CKD stages 2 and 3. Thus, periodontal disease may be associated with progression of CKD.

Clinical and epidemiological research suggests that behavioral addictions (BA) are associated with a wide range of psychiatric disorders. However, the relationship between BA and bipolar disorders (BD) has not been thoroughly explored. The aim of this systematic review was to critically summarize and evaluate the current available evidence regarding a possible association between BA and BD. A systematic review of major electronic databases according to PRISMA guidelines was conducted from inception to 31st December 2017. We sought quantitative studies data concerning prevalence of comorbidity, features and treatment related to BA-BD comorbidity. Data were narratively synthesized. Of the 1250 studies returned from the search, a total of 28 articles were included in this review. BA may be overrepresented in BD samples, and the other way around. Pathological gambling and kleptomania were the most prevalent conditions followed by compulsive buying, compulsive sexual behavior and internet addiction. BA was also associated with other mood disorders, anxiety disorders and substance use disorder. BD-BA comorbidity was related with more severe course of illness. Studies on treatment strategies for BD–BA comorbidity are rather limited; only one randomized controlled trial that fulfilled inclusion criteria was identified. Methodological heterogeneity in terms of design and results among studies was found. BD-BA commonly co-occurs although there is a need for rigorous studies. Routine screening and adequate assessment may be helpful in BD patients to identify individuals at risk for BA and to effectively manage the complex consequences associated with BA-BD comorbidity.

This study aimed to examine the prevalence of comorbidities in patients diagnosed with chronic lymphocytic leukemia (CLL), and to assess its influence on survival and cause-specific mortality at a population-based level. Incident CLL cases diagnosed in the Girona province (Spain) during 2008&ndash, 2016 were extracted from the Girona Cancer Registry. Rai stage and presence of comorbidities at diagnosis, further categorized using the Charlson comorbidity index (CCI), were obtained from clinical records. Observed (OS) and relative survival (RS) were estimated and Cox&rsquo, s proportional hazard models were used to explore the impact of comorbidity on mortality. Among the 400 cases included in the study, 380 (99.5%) presented at least one comorbidity at CLL diagnosis, with diabetes without end organ damage (21%) being the most common disease. 5-year OS and RS were 68.8 (95% CI: 64.4&ndash, 73.6) and 99.5 (95% CI 3.13&ndash, 106.0), respectively, which decreased markedly with increasing CCI, particularly in patients with CCI &ge, 3. Multivariate analysis identified no statistically significant association between the CCI and overall CLL-related or CLL-unrelated mortality. In conclusion, a high CCI score negatively influenced the OS and RS of CLL patients, yet its effect on mortality was statistically non-significant when also considering age and the Rai stage.

The high comorbidity of Major Depressive Disorder (MDD), Anxiety Disorders (ANX), and Posttraumatic Stress Disorder (PTSD) has hindered the study of their structural neural correlates. The authors analyzed specific and common grey matter volume (GMV) characteristics by comparing them with healthy controls (HC). The meta-analysis of voxel-based morphometry (VBM) studies showed unique GMV diminutions for each disorder (p < 0.05, corrected) and less robust smaller GMV across diagnostics (p < 0.01, uncorrected). Pairwise comparison between the disorders showed GMV differences in MDD versus ANX and in ANX versus PTSD. These results endorse the hypothesis that unique clinical features characterizing MDD, ANX, and PTSD are also reflected by disorder specific GMV correlates.

Background Food biodiversity, encompassing the variety of plants, animals, and other organisms consumed as food and drink, has intrinsic potential to underpin diverse, nutritious diets and improve Earth system resilience. Dietary species richness (DSR), which is recommended as a crosscutting measure of food biodiversity, has been positively associated with the micronutrient adequacy of diets in women and young children in low- and middle-income countries (LMICs). However, the relationships between DSR and major health outcomes have yet to be assessed in any population. Methods and findings We examined the associations between DSR and subsequent total and cause-specific mortality among 451,390 adults enrolled in the European Prospective Investigation into Cancer and Nutrition (EPIC) study (1992 to 2014, median follow-up: 17 years), free of cancer, diabetes, heart attack, or stroke at baseline. Usual dietary intakes were assessed at recruitment with country-specific dietary questionnaires (DQs). DSR of an individual’s yearly diet was calculated based on the absolute number of unique biological species in each (composite) food and drink. Associations were assessed by fitting multivariable-adjusted Cox proportional hazards regression models. In the EPIC cohort, 2 crops (common wheat and potato) and 2 animal species (cow and pig) accounted for approximately 45% of self-reported total dietary energy intake [median (P10–P90): 68 (40 to 83) species consumed per year]. Overall, higher DSR was inversely associated with all-cause mortality rate. Hazard ratios (HRs) and 95% confidence intervals (CIs) comparing total mortality in the second, third, fourth, and fifth (highest) quintiles (Qs) of DSR to the first (lowest) Q indicate significant inverse associations, after stratification by sex, age, and study center and adjustment for smoking status, educational level, marital status, physical activity, alcohol intake, and total energy intake, Mediterranean diet score, red and processed meat intake, and fiber intake [HR (95% CI): 0.91 (0.88 to 0.94), 0.80 (0.76 to 0.83), 0.69 (0.66 to 0.72), and 0.63 (0.59 to 0.66), respectively; PWald < 0.001 for trend]. Absolute death rates among participants in the highest and lowest fifth of DSR were 65.4 and 69.3 cases/10,000 person-years, respectively. Significant inverse associations were also observed between DSR and deaths due to cancer, heart disease, digestive disease, and respiratory disease. An important study limitation is that our findings were based on an observational cohort using self-reported dietary data obtained through single baseline food frequency questionnaires (FFQs); thus, exposure misclassification and residual confounding cannot be ruled out. Conclusions In this large Pan-European cohort, higher DSR was inversely associated with total and cause-specific mortality, independent of sociodemographic, lifestyle, and other known dietary risk factors. Our findings support the potential of food (species) biodiversity as a guiding principle of sustainable dietary recommendations and food-based dietary guidelines., Dr. Giles T. Hanley-Cook and colleagues, analyzed data from a prospective cohort study to investigate the association between food biodiversity, and total and cause-specific mortality in nine European countries., Author summary Why was this study done? Facilitating populations to transition to diets that are both nutritious and sustainable is a key challenge for human and environmental health. Dietary (between food group) diversity is increasingly advocated within the framework of dietary recommendations and food-based dietary guidelines. Food biodiversity, defined as the variety of plants, animals, and other organisms that are consumed between and within food groups globally, is a potential lever for improved public and planetary health. Nevertheless, scientific evidence is a prerequisite to understand the associations between metrics of food biodiversity and major health outcomes. Thus far, evidence regarding the positive association between dietary species richness (DSR), i.e., the absolute number of unique species consumed by an individual, and micronutrient adequacy of diets is limited to low- and middle-income countries (LMICs). What did the researchers do and find? This study assessed the relationships between DSR and all-cause and cause-specific mortality in the large and diverse European population that constitutes the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, including 451,390 adults from 9 European countries with 46,627 recorded deaths between 1992 and 2014. In addition, this study provides a picture of the usual consumption of food and beverage species across 9 European countries. Higher DSR was inversely associated with total mortality rate and cause-specific deaths due to cancer, heart disease, respiratory disease, and digestive disease, independent of other established components of diet quality. Overall, self-reported total energy intake was derived from a narrow range of species. What do these findings mean? Our findings add to the evidence base on the relevance of food biodiversity, both between and within food groups, as a basis for public health strategies championing dietary (species) diversity in European countries. These findings will play a key role in communications about the merits of biodiversity stewardship, in the context of ongoing European/global debate on nutritious and sustainable diets for a stable Earth system.

Idiopathic Parkinson’s disease (iPD) and type 2 diabetes mellitus (T2DM) are chronic, multisystemic, and degenerative diseases associated with aging, with eventual epidemiological co-morbidity and overlap in molecular basis. This study aims to explore if metabolic and mitochondrial alterations underlie the previously reported epidemiologic and clinical co-morbidity from a molecular level. To evaluate the adaptation of iPD to a simulated pre-diabetogenic state, we exposed primary cultured fibroblasts from iPD patients and controls to standard (5 mM) and high (25 mM) glucose concentrations to further characterize metabolic and mitochondrial resilience. iPD fibroblasts showed increased organic and amino acid levels related to mitochondrial metabolism with respect to controls, and these differences were enhanced in high glucose conditions (citric, suberic, and sebacic acids levels increased, as well as alanine, glutamate, aspartate, arginine, and ornithine amino acids; p-values between 0.001 and 0.05). The accumulation of metabolites in iPD fibroblasts was associated with (and probably due to) the concomitant mitochondrial dysfunction observed at enzymatic, oxidative, respiratory, and morphologic level. Metabolic and mitochondrial plasticity of controls was not observed in iPD fibroblasts, which were unable to adapt to different glucose conditions. Impaired metabolism and mitochondrial activity in iPD may limit energy supply for cell survival. Moreover, reduced capacity to adapt to disrupted glucose balance characteristic of T2DM may underlay the co-morbidity between both diseases. Conclusions: Fibroblasts from iPD patients showed mitochondrial impairment, resulting in the accumulation of organic and amino acids related to mitochondrial metabolism, especially when exposed to high glucose. Mitochondrial and metabolic defects down warding cell plasticity to adapt to changing glucose bioavailability may explain the comorbidity between iPD and T2DM., This work was supported by funds from the Integrated Projects of Excellence PIE14/00061 and the Fondo de Investigaciones Sanitarias of the Instituto de Salud Carlos III (ISCIII) (grant numbers PI1800498 and PI1800451), the Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), all initiatives of ISCIII and FEDER (‘Una manera de hacer Europa’), as well as Fundació Privada Cellex and Suports a Grups de Recerca (grant code 2017 SGR 893) and CERCA programs from the Generalitat de Catalunya. Maria de Maeztu Unit of Excellence funded our institution (Institute of Neurosciences, University of Barcelona) as consolidated excellence centre (MDM-2017-0729, Ministry of Science, Innovation and Universities). Two grants from the Spanish government allowed facility maintenance (SAF2017-85877-R from CGR and both SAF2015-69944-R and PID2019-111669RB-I00 from JCFC)

BACKGROUND:Atrial fibrillation (AF) patients with diabetes (DM) are at increased risk of cardiovascular events and have higher related morbidity and mortality. PURPOSE:To compare clinical characteristics, cardiovascular adverse outcomes and quality of anticoagulation in AF patients with and without DM. METHODS:AF patients from the Spanish national, multicentric, prospective FANTASIIA registry were included. Patients received oral anticoagulation (vitamin K antagonists (VKA) or direct oral anticoagulants (DOAC)) for at least 6 months before inclusion. Baseline clinical characteristics and comorbidities were recorded. After 2-years follow-up, the association between adverse events and the presence of DM was evaluated. RESULTS:1956 individuals (mean age 73.8 ± 9.5 years, 56% male) were analysed; of these, 574 (29.3%) had DM. Diabetic patients had increased prevalence of other risk factors such as hypertension (90.6% vs 76.1%; p

Objectives: The aim of this study was to determine the effects of escalation of respiratory support and prolonged postoperative invasive ventilation on patient–centered outcomes, and identify perioperative factors associated with these two respiratory complications. Design: A retrospective cohort analysis of cardiac surgical patients admitted to cardiothoracic intensive care unit (ICU) between August 2015 and January 2018. Escalation of respiratory support was defined as ‘unplanned continuous positive airway pressure’, ‘non-invasive ventilation’ or ‘reintubation’ following surgery; prolonged invasive ventilation was defined as ‘invasive ventilation beyond the first 12 hours following surgery’. The primary endpoint was the composite of escalation of respiratory support and prolonged ventilation. Setting: Tertiary cardiothoracic ICU. Participants: A total of 2,098 patients were included and analyzed. Interventions: None. Measurements and Main Results: The composite of escalation of support or prolonged ventilation occurred in 509 patients (24.3%). Patients who met the composite had higher mortality (2.9% vs 0.1%; P, ACM is supported by a Clinical Research Career Development Fellowship from the Wellcome Trust (WT 2055214/Z/16/Z). VZ is supported by an Academic Clinical Fellowship from the National Institute for Health Research (ACF-2016-09-011).

Sporadic inclusion body myositis (sIBM) is an inflammatory myopathy associated, among others, with mitochondrial dysfunction. Similar molecular features are found in Alzheimer’s disease (AD) and Type 2 Diabetes Mellitus (T2DM), underlying potential comorbidity. This study aims to evaluate common clinical and molecular hallmarks among sIBM, AD, and T2DM. Comorbidity with AD was assessed in n = 14 sIBM patients by performing neuropsychological and cognitive tests, cranial magnetic resonance imaging, AD cerebrospinal fluid biomarkers (levels of amyloid beta, total tau, and phosphorylated tau at threonine-181), and genetic apolipoprotein E genotyping. In the same sIBM cohort, comorbidity with T2DM was assessed by collecting anthropometric measures and performing an oral glucose tolerance test and insulin determinations. Results were compared to the standard population and other myositis (n = 7 dermatomyositis and n = 7 polymyositis). Mitochondrial contribution into disease was tested by measurement of oxidative/anaerobic and oxidant/antioxidant balances, respiration fluxes, and enzymatic activities in sIBM fibroblasts subjected to different glucose levels. Comorbidity of sIBM with AD was not detected. Clinically, sIBM patients showed signs of misbalanced glucose homeostasis, similar to other myositis. Such misbalance was further confirmed at the molecular level by the metabolic inability of sIBM fibroblasts to adapt to different glucose conditions. Under the standard condition, sIBM fibroblasts showed decreased respiration (0.71 ± 0.08 vs. 1.06 ± 0.04 nmols O2/min; p = 0.024) and increased anaerobic metabolism (5.76 ± 0.52 vs. 3.79 ± 0.35 mM lactate; p = 0.052). Moreover, when glucose conditions were changed, sIBM fibroblasts presented decreased fold change in mitochondrial enzymatic activities (−12.13 ± 21.86 vs. 199.22 ± 62.52 cytochrome c oxidase/citrate synthase ratio; p = 0.017) and increased oxidative stress per mitochondrial activity (203.76 ± 82.77 vs. −69.55 ± 21.00; p = 0.047), underlying scarce metabolic plasticity. These findings do not demonstrate higher prevalence of AD in sIBM patients, but evidences of prediabetogenic conditions were found. Glucose deregulation in myositis suggests the contribution of lifestyle conditions, such as restricted mobility. Additionally, molecular evidences from sIBM fibroblasts confirm that mitochondrial dysfunction may play a role. Monitoring T2DM development and mitochondrial contribution to disease in myositis patients could set a path for novel therapeutic options.

Objective To determine mortality rates and to rank the causes and predictors of mortality using a wide range of sociodemographic and clinical variables. Materials and methods It is a prospective population-based cohort study of adults living in the community, 2013–15 N = 48,691, age ≥50; deceased = 1,944. Clinical and sociodemographic data were obtained from the Survey of Health, Ageing and Retirement in Europe SHARE: Age, Gender, Marital Status, Years of Schooling, Income, Loneliness, Cognition, Self-Rated Health, Diseases, Activities of daily living ADL, and Frailty. Mortality rates were calculated. A Cox proportional hazards model were used to determine risk-adjusted mortality ratios. Results The crude mortality rate was 18.39 (1000 person-years at risk), (99 % CI, 18.37–18.42). The factors most associated with an increased mortality risk were older age, lower self-rated health, lower cognition, male gender, ADL deficits, higher comorbidity, frailty and loneliness. The diseases with a higher mortality risk were: cancer (Hazard ratio, HR = 2.67), dementia (HR = 2.19), depressive symptoms (HR = 2.10), fractures (hip, femur) (HR = 1.57), stroke (HR = 1.55), chronic lung disease (HR = 1.52), diabetes (HR = 1.36) and heart attack (HR = 1.21). Conclusions The main mortality risk factors, associated independently in the eight diseases were: older age, poor self-rated health, ADL deficits, male gender, lower cognition, comorbidity and the presence of depressive symptoms, with a different influence in the European regions. The need to evaluate and treat the depressive symptoms that accompanies diseases with higher risk of mortality is stressed.

Introduction: Older people with complex, chronic conditions often receive insufficient or inefficient care provision, and few instruments are able to measure their perception of care provision. The &ldquo, User Reported Measure of Care Coordination&rdquo, instrument has been satisfactorily used to evaluate chronic care provision and integration. The aim of this study is to validate this instrument in Spanish. Methods: The questionnaire was adapted and validated in two phases: translation and cultural adaptation of the questionnaire and psychometric property measurement. Study population were chronic care conditions patients. Results: A total of 332 participants completed test re-test as part of the questionnaire validation process. The final version of the questionnaire had 6 domains: Health and Well-being (D1), Health day to day (D2), Social Services (D3), Planned Care (D4), Urgent Care (D5), and Hospital Care (D6). Cronbach&rsquo, s alpha for the overall questionnaire was 0.86, indicating good internal consistency. When analyzing each domain, only Planned Care (D4) and Urgent Care (D5) had Cronbach&rsquo, s Alphas slightly lower than 0.7, although this could be related to the low number of items in each domain. A good temporal stability was observed for the distinct subscales and items, with intraclass correlation coefficients varying from 0.412 to 0.929 (p &lt, 0.05). Conclusion: The adapted version of the &ldquo, into Spanish proved to be a practical tool for use in our daily practice and an efficient instrument for assessment of care coordination in chronic, complex conditions in older people across services and levels of care.

With more people living with HIV (PLHIV) ageing into their 50s and beyond in settings where antiretroviral therapy is widely available, non-AIDS comorbidities and health-related quality of life (HRQoL) are becoming major challenges. Information is needed about whether national HIV monitoring programmes have evolved to reflect the changing focus of HIV care. " - " We created a 56-item English-language survey to assess whether health systems report on common health-related issues for people with HIV including physical and mental health comorbidities, HRQoL, psychosocial needs, and fertility desires. One expert was identified via purposive sampling in each of six countries (Estonia, Italy, the Netherlands, Slovenia, Sweden, and Turkey) and was asked to participate in the survey. " - " Three respondents reported that the current monitoring systems in their countries do not monitor any of four specified aspects of 10 comorbidities including bone loss, cardiovascular disease, and neurocognitive disorders. Two respondents stated that their countries potentially can report on leading causes of hospital admission among PLHIV, and five on leading cases of death. In three countries, respondents reported that there was the ability to report on the HRQoL of PLHIV. In two countries, respondents provided data on the percentage of PLHIV denied health services because of HIV status in the past 12 months. " - " This study identified areas for potential HIV monitoring improvements in six European countries in relation to comorbidities, HRQoL, discrimination within health systems, and other issues associated with the changing nature of the HIV epidemic. It also indicated that some countries either currently monitor or have the ability to monitor some of these issues. There are opportunities for health information systems in European countries to expand the scope of their HIV monitoring in order to support decision-making about how the long-term health-related needs of PLHIV can best be met.

Introduction and objective: Anemia is a common comorbidity in patients with acute coronary syndromes (ACS), and is associated with higher risk for both bleeding and ischemic complications. We aimed to assess the predictive ability of bleeding risk scores (Can Rapid risk stratification of Unstable angina patients Suppress ADverse outcomes with Early implementation of the ACC/AHA guidelines [CRUSADE], Mehran and Acute Coronary Treatment and Intervention Outcomes Network [ACTION]) in ACS patients with anemia. Methods: All consecutive ACS patients were prospectively included. The primary outcome was in-hospital major bleeding according to the CRUSADE, Mehran and ACTION definitions. Anemia was defined as hemoglobin

Introduction.Bipolar disorder (BD) and obsessive compulsive disorder (OCD) are prevalent, comorbid, and disabling conditions, often characterized by early onset and chronic course. When comorbid, OCD and BD can determine a more pernicious course of illness, posing therapeutic challenges for clinicians. Available reports on prevalence and clinical characteristics of comorbidity between BD and OCD showed mixed results, likely depending on the primary diagnosis of analyzed samples.Methods.We assessed prevalence and clinical characteristics of BD comorbidity in a large international sample of patients with primary OCD (n = 401), through the International College of Obsessive–Compulsive Spectrum Disorders (ICOCS) snapshot database, by comparing OCD subjects with vs without BD comorbidity.Results.Among primary OCD patients, 6.2% showed comorbidity with BD. OCD patients with vs without BD comorbidity more frequently had a previous hospitalization (p < 0.001) and current augmentation therapies (p < 0.001). They also showed greater severity of OCD (p < 0.001), as measured by the Yale–Brown Obsessive Compulsive Scale (Y-BOCS).Conclusion.These findings from a large international sample indicate that approximately 1 out of 16 patients with primary OCD may additionally have BD comorbidity along with other specific clinical characteristics, including more frequent previous hospitalizations, more complex therapeutic regimens, and a greater severity of OCD. Prospective international studies are needed to confirm our findings.

ObjectivesYoung people are a critical target group for sexually transmitted infections (STI) surveillance due to their particular behavioural and social related vulnerability. The aim of this study was to describe the epidemiological characteristics and trends in the incidence of gonorrhoea, syphilis, HIV and venereal lymphogranuloma (LGV) among 15–24-year-olds in Barcelona, and to determine factors associated with HIV coinfection.DesignWe performed a population-based incidence study covering the 2007–2015 period.ParticipantsAll new cases of STI—HIV, gonorrhoea, infectious syphilis and LGV—notified to the epidemiological surveillance system in Barcelona between 2007 and 2015. 1218 cases were studied: 84.6% were men, 19.3% were 15–19 years old and 50.6% were born in Spain. Among men, 73.7% were men who have sex with men (MSM); among women, 85.6% were women that have sex with men.Primary and secondary outcomesIncidence of HIV, gonorrhoea, infectious syphilis and LGV. HIV coinfection.ResultsThere was an increase in the incidence of gonorrhoea, from 1.9 cases per 10 000 people in 2007 to 7.6/10 000 in 2015 (p10 sexual partners (ORa=4.11, 95% CI 1.53 to 11.01) or STI diagnosis during the previous 12 months (ORa=2.06; 95% CI 1.13 to 3.77).ConclusionsThe incidence of gonorrhoea and syphilis among 15–24-year-olds increased, while HIV infection remained stable but with a high incidence among MSM. Being MSM, having sex with multiple partners and having a diagnosis of an STI in the previous 12 months were factors associated with HIV coinfection.

Background: Immunodeficiencies (ID), in particular primary immunodeficiencies (PID), are often associated with haematological manifestations, such as peripheral cytopenias or lymphoproliferative syndromes. Early diagnosis and management have significant prognostic implications. Secondary immunodeficiencies (SID) may also be induced by oncohaematological diseases and their treatments. Haematologists and oncologists must therefore be aware of the association between blood disorders and cancer and ID, and be prepared to offer their patients appropriate treatment without delay. Our aim was to define the warning signs of primary and secondary IDs in paediatric and adult patients with oncohaematological manifestations. Methods: A multidisciplinary group of six experts (2 haematologists, 2 immunologists, and 2 paediatricians specializing in ID) conducted a literature review and prepared a document based on agreements reached an in-person meeting. An external group of 44 IDs specialists from all over Spain assessed the document and were consulted regarding their level of agreement. Results: This document identifies the haematological and extra-haematological diseases that should prompt a suspicion of PIDs in adults and children, in both primary care and haematology and oncology departments. Cytopenia and certain lymphoproliferative disorders are key diagnostic pointers. The diagnosis must be based on a detailed clinical history, physical exploration, complete blood count and standard laboratory tests. The immunological and haematological tests included in the diagnostic process will depend on the care level. Patients who are candidates for immunoglobulin replacement therapy must be carefully selected, and treatment should be offered as soon as possible to avoid the development of complications. Finally, this document recommends procedures for monitoring these patients. Conclusions: This document combines scientific evidence with the opinion of a broad panel of experts, and emphasizes the importance of an early diagnosis and treatment to avoid complications. The resulting document is a useful tool for primary care physicians and specialists who see both adult and paediatric patients with oncohaematological diseases., This article received funding fee from CSL Behring.

Altres ajuts: FLMTV3/2010/062930 Psychosis and/or aggression are common problems in dementia, and when severe or persistent, cause considerable patient distress and disability, caregiver stress, and early institutionalization. In 2005, the Food and Drug Administration (FDA) determined that atypical antipsychotics were associated with a significantly greater mortality risk compared to placebo, which prompted the addition of an FDA black-box warning. The American College of Neuropsychopharmacology (ACNP) White Paper, 2008, reviewed this issue and made clinical and research recommendations regarding the use of antipsychotics in dementia patients with psychosis and/or agitation. Increased mortality risk has also been described in cerebrovascular adverse events in elderly users of antipsychotics. In the present work, at the translational level, we used male 3xTg-AD mice (PS1M146V, APPSwe, tauP301L) at advanced stages of the disease reported to have worse survival than females, to study the behavioral effects of a low chronic dose of risperidone (0.1 mg/ kg, s.c., 90 days, from 13 to 16 months of age) and its impact on long-term survival, as compared to mice with normal aging. Animals were behaviorally assessed for cognitive and BPSD (behavioral and psychological symptoms of dementia)-like symptoms in naturalistic and experimental conditions (open-field test, T-maze, social interaction, Morris water maze, and marble test) before and after treatment. Weight, basal glucose levels, and IPGTT (i.p. glucose tolerance test) were also recorded. Neophobia in the corner test was used for behavioral monitoring. Survival curves were recorded throughout the experiment until natural death. The benefits of risperidone were limited, both at cognitive and BPSD-like level, and mostly restricted to burying, agitation/vibrating tail, and other social behaviors. However, the work warns about a clear early mortality risk window during the treatment and long-lasting impact on survival. Reduced life expectancy and life span were observed in the 3xTg-AD mice, but total lifespan (36 months) recorded in C57BL/6 × 129Sv counterparts with normal aging was also truncated to 28 months in those with treatment. Sarcopenia at time of death was found in all groups, but was more severe in wild-type animals treated with risperidone. Therefore, the 3xTg-AD mice and their non-transgenic counterparts can be useful to delimitate critical time windows and for studying the physio-pathogenic factors and underlying causal events involved in this topic of considerable public health significance.

Cryptococcosis is a major opportunistic infection and is one of the leading causes of death in adults living with HIV in sub-Saharan Africa. Recent estimates indicate that more than 130,000 people may die annually of cryptococcal meningitis in this region. Although complete diagnostic autopsy (CDA) is considered the gold standard for determining the cause of death, it is seldom performed in low income settings. In this study, a CDA was performed in 284 deceased patients from Mozambique (n = 223) and Brazil (n = 61). In depth histopathological and microbiological analyses were carried out in all cases dying of cryptococcosis. We determined the cryptococcal species, the molecular and sero-mating types and antifungal susceptibility. We also described the organs affected and reviewed the clinical presentation and patient management. Among the 284 cases included, 17 fatal cryptococcal infections were diagnosed. Cryptococcus was responsible for 16 deaths among the 163 HIV-positive patients (10%; 95%CI: 6–15%), including four maternal deaths. One third of the cases corresponded to C. gattii (VGI and VGIV molecular types, Bα and Cα strains) and the remaining infections typed were caused by C. neoformans var. Grubii (all VNI and Aα strains). The level of pre-mortem clinical suspicion was low (7/17, 41%), and 7/17 patients (41%) died within the first 72 hours of admission. Cryptococcosis was responsible for a significant proportion of AIDS-related mortality. The clinical diagnosis and patient management were inadequate, supporting the need for cryptococcal screening for early detection of the disease. This is the first report of the presence of C. gattii infection in Mozambique.

Background: Among patients with substance use disorder (SUD), major depressive disorder (MDD) is highly prevalent. Even though, personality plays an important role in treatment outcomes for individuals with SUD and SUD + MDD, few studies have explored personality characteristics in these samples. This study aims to describe personality for patients with SUD taking into account the comorbid MDD, using the Alternative Five Factor Model (AFFM). We also aim to compare SUD + MDD patients with population norms and to elucidate possible personality clinical correlates. Methods: For our study, 116 male patients undergoing for SUD treatment were divided in two groups: SUD only (N = 58) and SUD + MDD (N = 58). To examine personality, we used the Zuckerman-Kuhlman Personality Questionnaire and multiple analyses of covariance were performed to identify differences. In a first analysis, age was introduced as a covariate whereas in a second analysis the continuous variables that showed to have a discriminant value for the groups were added as covariates. Variables predicting the presence of dual diagnosis and personality clinical correlates were analyzed by logistic and linear regression models, respectively. We observed that patients with SUD + MDD show distinctive personality characteristics compared with patients with SUD only and population norms. Results: According to the AFFM, SUD + MDD patients are characterized by higher Neuroticism-Anxiety (positively associated to depressive symptoms) and Impulsivity; and by lower Parties and Friends. Moreover, the probability of having a dual depressive disorder was represented by the amount of medications and substances used. The preference for hard work and the energy self-reported levels (Work Activity trait) are linked to these clinical variables rather than to the presence/absence of a dual depressive disorder. Conclusions: Even when controlling clinical variables related to a higher probability of having a dual depressive disorder, the Neuroticism-Anxiety is a personality trait that strongly differentiates between SUD only and SUD + MDD patients. Further investigation is needed to explore the role of this personality trait as endophenotype in dual depressive men. Our results underline the importance of a dimensional understanding of personality and its clinical correlates among patients with SUD + MDD; this approach could provide us information on specific treatment strategies to improve the prognosis of patients.

According to the DSM-5, 'reduction in the need for sleep' is the only sleep-related criteria for mixed features in depressive episodes. We aimed at studying the prevalence, clinical correlates and the role of hypersomnia in a sample of acutely depressed patients. Secondarily, we factors significantly increasing the odds of hypersomnia were studied. We conducted a post-hoc analysis of the BRIDGE-II-Mix study. Variables were compared between patients with hypersomnia (SLEEP+) and with insomnia (SLEEP-) with standard bivariate tests. A stepwise backward logistic regression model was performed with SLEEP+ as dependent variable. A total of 2514 subjects were dichotomized into SLEEP+ (n = 423, 16.8%) and SLEEP- (n = 2091, 83.2%). SLEEP+ had significant higher rates of obese BMI (p < 0.001), BD diagnosis (p = 0.027), severe BD (p < 0.001), lifetime suicide attempts (p < 0.001), lower age at first depression (p = 0.004) than SLEEP-. Also, SLEEP+ had significantly poorer response to antidepressants (AD) such as (hypo)manic switches, AD resistance, affective lability, or irritability (all 0

The purpose of this review is to describe how quality of life (QoL) is impaired in patients with hypercortisolism due to Cushing's syndrome of any aetiology, including pituitary-dependent Cushing's disease. It is worse in active disease, but improvement after successful therapy is often incomplete, due to persistent physical and psychological co-morbidities, even years after endocrine "cure". Physical symptoms like extreme fatigability, central obesity with limb atrophy, hypertension, fractures, and different skin abnormalities severely impair the affected patients' everyday life. Psychological and cognitive problems like bad memory, difficulties to concentrate and emotional distress, often associated with anxiety and depression, make it difficult for many patients to overcome the aftermath of treated Cushing's syndrome. Recent studies have shown diffuse structural abnormalities in the central nervous system during active hyper-cortisolism, thought to be related to the wide distribution of glucocorticoid receptors throughout the brain. Even though they improve after treatment, normalization is often not complete. Shortening the exposure to active Cushing's syndrome by reducing the often long delay to diagnosis and promptly receiving effective treatment is highly desirable, together with preparing the patient for the difficult periods, especially after surgery. In this way they are prepared for the impairments they perceive in every day life, and live with the hope of later improvement, which can be therapeutic in many instances.

Background Depression in tuberculosis increases the risk for adverse health outcomes. However, little is known about comorbid depression and tuberculosis in the general population. Thus, we assessed the association between depression and tuberculosis, and the decrements in health status associated with this comorbidity in 48 low- and middle-income countries. Methods Cross-sectional, community-based data from the World Health Survey on 242,952 individuals aged ≥ 18 years were analyzed. Based on the World Mental Health Survey version of the Composite International Diagnostic Interview, past 12-month depression was categorized into depressive episode, brief depressive episode, subsyndromal depression, and no depression. Health status across six domains (cognition, interpersonal activities, sleep/energy, self-care, mobility, pain/discomfort) was assessed. Multivariable logistic and linear regression analyses were performed to assess the associations. Results The prevalence of depressive episode among those with and without tuberculosis was 23.7% and 6.8%, respectively (P

Obesity comorbidities are closely associated with chronic low-grade adipose tissue inflammation. A number of SNPs associated with inflammation has been identified, underscoring the impact of genetic determinants on this process. Here, we screened SNPs in genes with pro-inflammatory (IL-1β, IL-6, STAT3 and JAK2), anti-inflammatory (IL-10 and SOCS3) and pro-resolving (ERV1/ChemR23) properties in 101 obese and 99 non-obese individuals. Among the SNPs analyzed, we identified that individuals carrying a C allele in the rs1878022 polymorphism of the ERV1/ChemR23 gene, which encodes for the receptor of the pro-resolving mediator RvE1, had increased ERV1/ChemR23 protein expression and reduced levels of the inflammatory cytokine IL-6 in adipose tissue. Moreover, patients carrying the C allele in homozygosity had lower plasma levels of IL-6, IFN-α2, IL-15, IL-1ra, IL-10, GM-CSF, G-CSF and VEGF and enhanced leukocyte responsiveness to RvE1. C-carriers also exhibited decreased TAG to HDL ratio, a surrogate marker of insulin resistance and a predictor of incident fatty liver. Finally, we confirmed in vivo that the ERV1/ChemR23 receptor regulates systemic and tissue inflammation since mice lacking ERV1/ChemR23 expression showed increased IL-6 levels in adipose tissue and peritoneal macrophages. Together, our study identified an ERV1/ChemR23 variant that protects patients with obesity from excessive inflammatory burden.

The aim of this study was to describe the clinical characteristics of ANCA-associated vasculitides (AAV) at presentation, in a wide cohort of Spanish patients, and to analyze the impact of the vasculitis type, ANCA specificity, prognostic factors, and treatments administered at diagnosis, in the outcome. A total of 450 patients diagnosed between January 1990 and January 2014 in 20 Hospitals from Spain were included. Altogether, 40.9% had granulomatosis with polyangiitis (GPA), 37.1% microscopic polyangiitis (MPA), and 22% eosinophilic granulomatosis with polyangiitis (EGPA). The mean age at diagnosis was 55.6 +/- 17.3 years, patients with MPA being significantly older (P < 0.001). Fever, arthralgia, weight loss, respiratory, and ear-nose-throat (ENT) symptoms, were the most common at disease onset. ANCAs tested positive in 86.4% of cases: 36.2% C-ANCA-PR3 and 50.2% P-ANCA-MPO. P-ANCA-MPO was significantly associated with an increased risk for renal disease (OR 2.6, P < 0.001) and alveolar hemorrhage (OR 2, P = 0.010), while C-ANCA-PR3 was significantly associated with an increased risk for ENT (OR 3.4, P < 0.001) and ocular involvement (OR 2.3, P = 0.002). All patients received corticosteroids (CS) and 74.9% cyclophosphamide (CYC). The median follow-up was 82 months (IQR 100.4). Over this period 39.9% of patients suffered bacterial infections and 14.6% opportunistic infections, both being most prevalent in patients with high-cumulated doses of CYC and CS (P < 0.001). Relapses were recorded in 36.4% of cases with a mean rate of 2.5 +/- 2.3, and were more frequent in patients with C-ANCA-PR3 (P = 0.012). The initial disease severity was significantly associated with mortality but not with the occurrence of relapses. One hundred twenty-nine (28.7%) patients (74 MPA, 41 GPA, 14 EGPA) died. The mean survival was 58 months (IQR 105) and was significantly lower for patients with MPA (P < 0.001). Factors independently related to death were renal involvement (P = 0.010), cardiac failure (P = 0.029) and age over 65 years old (P < 0.001) at disease onset, and bacterial infections (P < 0.001). An improved outcome with significant decrease in mortality and treatment-related morbidity was observed in patients diagnosed after 2000, and was related to the implementation of less toxic regimens adapted to the disease activity and stage, and a drastic reduction in the cumulated CYC and CS dose.

Background Deep mining of healthcare data has provided maps of comorbidity relationships between diseases. In parallel, integrative multi-omics investigations have generated high-resolution molecular maps of putative relevance for understanding disease initiation and progression. Yet, it is unclear how to advance an observation of comorbidity relations (one disease to others) to a molecular understanding of the driver processes and associated biomarkers. Results Since Chronic Obstructive Pulmonary disease (COPD) has emerged as a central hub in temporal comorbidity networks, we developed a systematic integrative data-driven framework to identify shared disease-associated genes and pathways, as a proxy for the underlying generative mechanisms inducing comorbidity. We integrated records from approximately 13 M patients from the Medicare database with disease-gene maps that we derived from several resources including a semantic-derived knowledge-base. Using rank-based statistics we not only recovered known comorbidities but also discovered a novel association between COPD and digestive diseases. Furthermore, our analysis provides the first set of COPD co-morbidity candidate biomarkers, including IL15, TNF and JUP, and characterizes their association to aging and life-style conditions, such as smoking and physical activity. Conclusions The developed framework provides novel insights in COPD and especially COPD co-morbidity associated mechanisms. The methodology could be used to discover and decipher the molecular underpinning of other comorbidity relationships and furthermore, allow the identification of candidate co-morbidity biomarkers. Electronic supplementary material The online version of this article (doi:10.1186/s12859-016-1291-3) contains supplementary material, which is available to authorized users.

Infection with human papillomavirus (HPV) is recognized as one of the major causes of infection-related cancer worldwide, as well as the causal factor in other diseases. Strong evidence for a causal etiology with HPV has been stated by the International Agency for Research on Cancer for cancers of the cervix uteri, penis, vulva, vagina, anus and oropharynx (including base of the tongue and tonsils). Of the estimated 12.7 million new cancers occurring in 2008 worldwide, 4.8% were attributable to HPV infection, with substantially higher incidence and mortality rates seen in developing versus developed countries. In recent years, we have gained tremendous knowledge about HPVs and their interactions with host cells, tissues and the immune system; have validated and implemented strategies for safe and efficacious prophylactic vaccination against HPV infections; have developed increasingly sensitive and specific molecular diagnostic tools for HPV detection for use in cervical cancer screening; and have substantially increased global awareness of HPV and its many associated diseases in women, men, and children. While these achievements exemplify the success of biomedical research in generating important public health interventions, they also generate new and daunting challenges: costs of HPV prevention and medical care, the implementation of what is technically possible, socio-political resistance to prevention opportunities, and the very wide ranges of national economic capabilities and health care systems. Gains and challenges faced in the quest for comprehensive control of HPV infection and HPV-related cancers and other disease are summarized in this review. The information presented may be viewed in terms of a reframed paradigm of prevention of cervical cancer and other HPV-related diseases that will include strategic combinations of at least four major components: 1) routine introduction of HPV vaccines to women in all countries, 2) extension and simplification of existing screening programs using HPV-based technology, 3) extension of adapted screening programs to developing populations, and 4) consideration of the broader spectrum of cancers and other diseases preventable by HPV vaccination in women, as well as in men. Despite the huge advances already achieved, there must be ongoing efforts including international advocacy to achieve widespread-optimally universal-implementation of HPV prevention strategies in both developed and developing countries. This article summarizes information from the chapters presented in a special ICO Monograph 'Comprehensive Control of HPV Infections and Related Diseases' Vaccine Volume 30, Supplement 5, 2012. Additional details on each subtopic and full information regarding the supporting literature references may be found in the original chapters. (C) 2013 Elsevier Ltd. All rights reserved.

Background: decisive information on the parameters involved in cognitive impairment in patients with chronic heart failure is as yet lacking. Our aim was to determine the functional and psychosocial variables related with cognitive impairment using the mini-mental-state examination (MMSE) with age-and education-corrected scores. Methods: a cohort study of chronic heart failure patients included in an integrated multidisciplinary hospital/primary care program. The MMSE (corrected for age and education in the Spanish population) was administered at enrolment in the program. Analyses were performed in 525 patients. Demographic and clinical variables were collected. Comprehensive assessment included depression (Yesavage), family function (family APGAR), social network (Duke), dependence (Barthel Index), frailty (Barber), and comorbidities. Univariate and multivariate logistic regression were performed to determine the predictors of cognitive impairment. Results: cognitive impairment affected 145 patients (27.6 %). Explanatory factors were gender (OR: 2.77 (1.75-4.39) p 3.5 (OR: 0.59 (0.35-0.99) p = 0.048), and beta-blocker treatment (OR: 0.36 (0.17 to 0.76, p = 0.007)). No association was found between cognitive impairment and social support or family function. Conclusion: the observed prevalence of cognitive impairment using MMSE corrected scores was 27.6 %. A global approach in the management of these patients is needed, especially focusing on women and patients with frailty, low albumin levels, and ischemic aetiology heart failure.

High rates of comorbidity are found among eating disorder (ED) patients, which may negatively affect treatment outcome and prognosis. However, there is a shortage of studies in Spain using clinician administered interviews to assess rates of comorbidity among these patients, particularly in adolescents. This study aimed to evaluate Axis I psychiatric diagnoses in adolescent patients with an ED and to compare them with patients with a distinct disorder with adolescent onset, substance use disorder (SUD) patients. Considering that maternal psychological distress is another factor involved in ED prognosis, a secondary aim was to examine the relationship between patient's psychological variables and maternal distress (depression and anxiety). The cross-sectional study included 50 ED patients, 48 SUD patients, and their mothers. More than half of the patients received a diagnosis for a comorbid disorder. Internalizing problems were more common among EDs and externalizing disorders were the most common comorbidities among SUDs, similar to findings from other countries. Maternal distress was associated with higher levels of depression and symptom severity in patients. No differences in distress were found between mothers of patients with a comorbid diagnosis and those without. Elevated anxiety or depression in mothers did not increase the likelihood of patients having a particular primary diagnosis. In short, while both ED and SUD patients presented high rates of comorbidity, the types of comorbid diagnoses were specific to each group. Assessing for the presence of comorbid disorders and targeting maternal psychological distress may guide treatment interventions and improve patient prognosis, Dr. Sepulveda has a postdoctoral Ramon and Cajal scholarship from the Spanish Ministry of Science and Innovation (RYC-2009-05092) as well as a project funded from the same Ministry (PSI2011-23127). Dr. Anastasiadou was awarded with a Research Fellowship for students of PhD Programmes distinguished with Mention of Excellence. Dr. Graell is a member of the Spanish Psychiatric Research Network (CIBERSAM)

PubMed ID: 27701416, Background Clinical presentation phenotypes of obstructive sleep apnoea (OSA) and their association with comorbidity as well as impact on adherence to continuous positive airway pressure (CPAP) treatment have not been established. Methods A prospective follow-up cohort of adult patients with OSA (apnoea-hypopnoea index (AHI) of ?5/h) from 17 European countries and Israel (n = 6,555) was divided into four clinical presentation phenotypes based on daytime symptoms labelled as excessive daytime sleepiness ("EDS") and nocturnal sleep problems other than OSA (labelled as "insomnia"): 1) EDS (daytime+/nighttime-), 2) EDS/insomnia (daytime+/nighttime+), 3) non-EDS/noninsomnia (daytime-/nighttime-), 4) and insomnia (daytime-/nighttime+) phenotype. Results The EDS phenotype comprised 20.7%, the non-EDS/non-insomnia type 25.8%, the EDS/ insomnia type 23.7%, and the insomnia phenotype 29.8% of the entire cohort. Thus, clinical presentation phenotypes with insomnia symptoms were dominant with 53.5%, but only 5.6% had physician diagnosed insomnia. Cardiovascular comorbidity was less prevalent in the EDS and most common in the insomnia phenotype (48.9% vs. 56.8%, p

INTRODUCTION: Data specific to late-life bipolar disorder (BD) are limited. Current research is sparse and present guidelines are not adapted to this group of patients. OBJECTIVES: We present a literature review on clinical characteristics, comorbidities, and cognitive impairment in patients with late-life BD. This review discusses common comorbidities that affect BD elders and how aging might affect cognition and treatment. METHODS: Eligible studies were identified in MedLine by the Medical Subject Headings terms 'bipolar disorder' and 'aged'. We only included original research reports published in English between 2012 and 2015. RESULTS: From 414 articles extracted, 16 studies were included in the review. Cardiovascular and respiratory conditions, type II diabetes, and endocrinological abnormalities were observed as highly prevalent. BD is associated with a high suicide risk. Bipolar elderly had an increased risk of dementia and performed worse on cognitive screening tests compared to age-matched controls across different levels of cognition. Despite high rates of medical comorbidity among bipolar elderly, a systematic under-recognition and undertreatment of cardiovascular disease have been suggested. CONCLUSION: There was a high burden of physical comorbidities and cognitive impairment in late-life BD. Bipolar elderly might be under-recorded and undertreated in primary medical care, indicating that this group needs an adapted clinical assessment and specific clinical guidelines need to be established.

Bipolar disorder (BD) and alcohol use disorders (AUDs) are usually comorbid, and both have been associated with significant neurocognitive impairment. Patients with the BD-AUD comorbidity (dual diagnosis) may have more severe neurocognitive deficits than those with a single diagnosis, but there is paucity of research in this area. To explore this hypothesis more thoroughly, we carried out a systematic literature review through January 2015. Eight studies have examined the effect of AUDs on the neurocognitive functioning of BD patients. Most studies found that BD patients with current or past history of comorbid AUDs show more severe impairments, especially in verbal memory and executive cognition, than their non-dual counterparts. Greater neurocognitive dysfunction is another facet of this severe comorbid presentation. Implications for clinical practice and research are discussed. Specifically, the application of holistic approaches, such as clinical staging and systems biology, may open new avenues of discoveries related to the BD-AUD comorbidity. The authors of this report would like to acknowledge the support of the Spanish Ministry of Economy and Competitiveness, Instituto de Salud Carlos III (ISCIII), CIBERSAM. This work was sponsored by a national grant PI14/00894 which belongs to the Spanish “Plan Nacional de I+D+I 2013-2016” and is co-funded by the “ISCIII-Subdirección General de Evaluación y el Fondo Europeo de Desarrollo Regional (FEDER).”

BACKGROUND The European AIDS Clinical Society (EACS) guidelines are intended for all clinicians involved in the care of HIV-positive persons, and are available in print, online, and as a free App for download for iPhone and Android. GUIDELINE HIGHLIGHTS The 2015 version of the EACS guidelines contains major revisions in all sections; antiretroviral treatment (ART), comorbidities, coinfections and opportunistic diseases. Among the key revisions is the recommendation of ART for all HIV-positive persons, irrespectively of CD4 count, based on the Strategic Timing of AntiRetroviral Treatment (START) study results. The recommendations for the preferred and the alternative ART options have also been revised, and a new section on the use of pre-exposure prophylaxis (PrEP) has been added. A number of new antiretroviral drugs/drug combinations have been added to the updated tables on drug-drug interactions, adverse drug effects, dose adjustment for renal/liver insufficiency and for ART administration in persons with swallowing difficulties. The revisions of the coinfection section reflect the major advances in anti-hepatitis C virus (HCV) treatment with direct-acting antivirals with earlier start of treatment in individuals at increased risk of liver disease progression, and a phasing out of interferon-containing treatment regimens. The section on opportunistic diseases has been restructured according to individual pathogens/diseases and a new overview table has been added on CD4 count thresholds for different primary prophylaxes. CONCLUSIONS The diagnosis and management of HIV infection and related coinfections, opportunistic diseases and comorbidities continue to require a multidisciplinary effort for which the 2015 version of the EACS guidelines provides an easily accessable and updated overview.

Cryptococcal antigenemia was prevalent and an independent predictor of mortality/loss-to-follow-up in this Tanzanian cohort of ART-naïve HIV-infected individuals with CD4, Background. Cryptococcal meningitis is a leading cause of death in people living with human immunodeficiency virus (HIV)/acquired immune deficiency syndrome. The World Health Organizations recommends pre-antiretroviral treatment (ART) cryptococcal antigen (CRAG) screening in persons with CD4 below 100 cells/µL. We assessed the prevalence and outcome of cryptococcal antigenemia in rural southern Tanzania. Methods. We conducted a retrospective study including all ART-naive adults with CD4 1:160 was associated with meningitis development (odds ratio, 4.83; 95% CI, 1.24–8.41; P = .008). Fluconazole receipt decreased death or LFU in CRAG-positive patients (HR, 0.18; 95% CI, .04–.78; P = .022). Conclusions. Cryptococcal antigenemia predicted mortality or LFU among ART-naive HIV-infected persons with CD4

Background: With the advent of the fifth edition of Diagnostic and Statistical Manual of Mental Disorders, body dysmorphic disorder (BDD) has been subsumed into the obsessive-compulsive disorders and related disorders (OCDRD) category. Objective: We aimed to determine the empirical evidence regarding the potential relationship between BDD and obsessive-compulsive disorder (OCD) based on the prevalence data, etiopathogenic pathways, and clinical characterization of patients with both disorders. Method: A comprehensive search of databases (PubMed and PsycINFO) was performed. Published manuscripts between 1985 and May 2015 were identified. Overall, 53 studies fulfilled inclusion criteria. Results: Lifetime comorbidity rates of BDD–OCD are almost three times higher in samples with a primary diagnosis of BDD than those with primary OCD (27.5% vs 10.4%). However, other mental disorders, such as social phobia or major mood depression, are more likely among both types of psychiatric samples. Empirical evidence regarding the etiopathogenic pathways for BDD–OCD comorbidity is still inconclusive, whether concerning common shared features or one disorder as a risk factor for the other. Specifically, current findings concerning third variables show more divergences than similarities when comparing both disorders. Preliminary data on the clinical characterization of the patients with BDD and OCD indicate that the deleterious clinical impact of BDD in OCD patients is greater than vice versa. Conclusion: Despite the recent inclusion of BDD within the OCDRD, data from comparative studies between BDD and OCD need further evidence for supporting this nosological approach. To better define this issue, comparative studies between BDD, OCD, and social phobia should be carried out. Keywords: obsessive-compulsive disorder, body dysmorphic disorder, comorbidity

There are sex differences in the progression of drug addiction, relapse, and response to therapies. Because biological factors participate in these differences, they should be considered when using biomarkers for addiction. In the current study, we evaluated the sex differences in psychiatric comorbidity and the concentrations of plasma mediators that have been reported to be affected by cocaine. Fifty-five abstinent cocaine-addicted subjects diagnosed with lifetime cocaine use disorders (40 men and 15 women) and 73 healthy controls (48 men and 25 women) were clinically assessed with the diagnostic interview “Psychiatric Research Interview for Substance and Mental Disorders.” Plasma concentrations of chemokines, cytokines, N-acyl-ethanolamines, and 2-acyl-glycerols were analyzed according to history of cocaine addiction and sex, controlling for covariates age and body mass index (BMI). Relationships between these concentrations and variables related to cocaine addiction were also analyzed in addicted subjects. The results showed that the concentrations of chemokine (C-C motif) ligand 2/monocyte chemotactic protein-1 (CCL2/MCP-1) and chemokine (C-X-C motif) ligand 12/stromal cell-derived factor-1 (CXCL12/SDF-1) were only affected by history of cocaine addiction. The plasma concentrations of interleukin 1-beta (IL-1b), IL-6, IL-10, and tumor necrosis factor-alpha (TNFa)were affected by history of cocaine addiction and sex. In fact, whereas cytokine concentrations were higher in control women relative to men, these concentrations were reduced in cocaine-addicted women without changes in addicted men. Regarding fatty acid derivatives, history of cocaine addiction had a main effect on the concentration of each acyl derivative, whereas N-acyl-ethanolamines were increased overall in the cocaine group, 2-acyl-glycerolswere decreased. Interestingly, N-palmitoleoyl-ethanolamine (POEA) was only increased in cocaine-addicted women. The covariate BMI had a significant effect on POEA and N-arachidonoyl-ethanolamine concentrations. Regarding psychiatric comorbidity in the cocaine group, women had lower incidence rates of comorbid substance use disorders than did men. For example, alcohol use disorders were found in 80% of men and 40% of women. In contrast, the addicted women had increased prevalences of comorbid psychiatric disorders (i.e., mood, anxiety, and psychosis disorders). Additionally, cocaine-addicted subjects showed a relationship between the concentrations of N-stearoyl-ethanolamine and 2-linoleoyl-glycerol and diagnosis of psychiatric comorbidity.These results demonstrate the existence of a sex influence on plasma biomarkers for cocaine addiction and on the presence of comorbid psychopathologies for clinical purposes, The present study has been supported by Instituto de Salud Carlos III (ISC-III), Red de Trastornos Adictivos UE-FEDER 2012 (RD 12/0028); Ministerio de Economía y Competitividad PI13/02261); Plan Nacional sobre Drogas 049/2009 and 049/2013; Consejería de Economía, Innovación y Ciencia, Junta de Andalucía UE-FEDER (CTS-433); Consejería de Salud y Bienestar Social, Junta Andalucía (PI0228-2013 and PI0823- 2012); Departament d’Innovació, Universitats i Empresa, Generalitat de Catalunya (2014-SGR-680). JS, AS,and FJP hold a “Miguel Servet” research contract from ISC-III(CP12/03109, CP14/00173, and CP14/00212, respectively). PRS holds a “Río Hortega” research contract from ISC-III (CM13/0115). ECO holds a “Sara Borrell” research contract from ISC-III (CD12/00455).

BACKGROUND: Integrated Management of Childhood Illness (IMCI) guidelines were developed to decrease morbidity and mortality, yet implementation varies across settings. Factors associated with poor adherence are not well understood. METHODS: We used data from Manhica District Hospital outpatient department and five peripheral health centers to examine pneumonia management for children

We investigated the clinico-biological features, outcomes, and prognosis of 949 patients with chronic lymphocytic leukemia according to age. No biological differences (cytogenetics by fluorescent in situ hybridization, IGHV, ZAP-70, CD38, NOTCH1, SF3B1) were found across age groups. Elderly patients (>70 years; n=367) presented more frequently with advanced disease (Binet C/Rai III-IV: 10/12% versus 5/5%; P4; hazard ratio 2.2, P

Francesc Formiga,1,2 Assumpta Ferrer,3 Gloria Padros,4 Abelardo Montero,1,2 Carme Gimenez-Argente,1 Xavier Corbella1,2,5 On behalf of the Octabaix study members 1Internal Medicine Department, Geriatric Unit, Hospital Universitari de Bellvitge, Institut Català de la Salut, 2Bellvitge Biomedical Research Institute, IDIBELL, L’Hospitalet de Llobregat, 3Primary Care Centre “ElPlà”, Direcció d’Atenció Primària Costa de Ponent, Institut Català de la Salut, Sant Feliu de Llobregat, 4South Metropolitan Clinical Laboratory, Direcció d’Atenció Primària Costa de Ponent, Institut Català de la Salut, L’Hospitalet de Llobregat, 5Albert J Jovell Institute of Public Health and Patients, Faculty of Medicine and Health Sciences, Universitat Internacional de Catalunya, Barcelona,Spain Objective: To investigate the predictive value of functional impairment, chronic conditions, and laboratory biomarkers of aging for predicting 5-year mortality in the elderly aged 85 years.Methods: Predictive value for mortality of different geriatric assessments carried out during the OCTABAIX study was evaluated after 5 years of follow-up in 328 subjects aged 85 years. Measurements included assessment of functional status comorbidity, along with laboratory tests on vitamin D, cholesterol, CD4/CD8 ratio, hemoglobin, and serum thyrotropin.Results: Overall, the mortality rate after 5 years of follow-up was 42.07%. Bivariate analysis showed that patients who survived were predominantly female (P=0.02), and they showed a significantly better baseline functional status for both basic (P

The population is aging throughout the world. Preserving physical and cognitive functions is crucial to successful aging. The aim of this study was to determine the proportion of 85-year-old community-dwelling subjects aging successfully, applying a quantitative approach, and assessing the association of successful aging with sociodemographic data, global geriatric assessment, and co-morbidity. This was a community-based survey of inhabitants aged 85 years, with 328 out of 487 subjects born in 1924 assigned to seven primary health-care teams, representing a participation rate of 67.5%. Sociodemographic variables, Barthel index (BI), the Spanish version of the Mini-Mental State Examination (MEC), Mini Nutritional Assessment (MNA), Charlson Index, Gait Rating Scale, social risk, quality of life (QoL), and prevalent chronic diseases were assessed. Subjects scoring higher than 90 on the BI and higher than 24 on the MEC were compared with the rest. Multiple regression analysis was performed. Using these criteria, successful aging status was defined in 162 (49.3%) subjects. Using multiple logistic regression analysis, successful agers had significantly lower co-morbidity scores (p < 0.02, odds ratio [OR] = 0.791, 95% confidence interval [CI] 0.657-0.952), higher scores on the Gait Rating Scale identifying lower risk of falls (p < 0.0001, OR = 1.753, 95% CI 1.501-2.046), and higher scores on the MNA, indicating lower risk of malnutrition (p < 0.0001, OR = 1.190, 95% CI 1.090-01.299). Regarding QoL, successful agers had significantly higher values than their unsuccessful aging counterparts (p > 0.0001). Almost half of the individuals presented successful aging. Successful agers had less co-morbidity and a lower risk of falls or malnutrition, and they had higher scores on the QoL scale.

Background: Comorbid psychiatric disorders among opioid-dependent patients are associated with several negative outcome factors. However, outcomes of maintenance treatment have not been sufficiently established, and no evidence is available with respect to heroin-assisted treatment (HAT). Methods: For patients in the German heroin trial outcome measures were analyzed for HAT versus methadone maintenance treatment (MMT) both for patients with and without a comorbid diagnosis according to CIDI. Results: 47.2% of the sample had at least one comorbid psychiatric diagnosis, mainly neurotic, stress-related or somatoform (F4) or affective (F3) disorders. HAT had a better outcome than MMT concerning improvement of health and reduction of illicit drug use in both comorbid and non-comorbid patients, but weaker effects were found in the comorbid group. Conclusions:The better outcome of HAT also in comorbid patients suggests that psychiatric comorbidity should be an inclusion criterion for HAT. The weaker advantage of HAT may be due to pharmacological or methodological reasons.

Antidepressants; Comorbidity; Drug utilization study; Europe Antidepresivos; Comorbilidad; Estudio de utilización de medicamentos; Europa Antidepressius; Comorbiditat; Estudi d'utilització de medicaments; Europa Background We aimed to describe patterns of use and characteristics of 10 commonly used antidepressants for the period 2009–2014 in Denmark, Germany, Spain, and Sweden. Methods Adult initiators from 2009 to 2014 of each study antidepressant were identified in four countries using five data sources: the Danish National registers, GePaRD (Germany), EpiChron (Aragon, Spain), SIDIAP (Catalonia, Spain), and the Swedish National Registers. The study included 10 study antidepressants: citalopram, escitalopram, fluoxetine, paroxetine, sertraline, duloxetine, venlafaxine, amitriptyline, mirtazapine, and agomelatine. Results Citalopram was the most prescribed study antidepressant, followed by mirtazapine. Paroxetine and agomelatine were the least prescribed antidepressants. Mirtazapine was widely used among older antidepressant initiators with higher percentages of comorbidities at baseline, and fluoxetine was used among young patients. Citalopram and amitriptyline had the lowest percentage of multiple antidepressant use in the 12 months prior to the current treatment episode, while agomelatine, duloxetine, and venlafaxine had the highest percentage of multiple antidepressant use in the year prior to the current treatment episode. Limitations The most important limitations are exposure information based on filled prescriptions, focus on antidepressant initiators only, lack of information on the indication, and heterogeneity of the type of data across data sources. Conclusions Results of this study including 4.8 million study antidepressant initiators of study antidepressants suggest that citalopram and mirtazapine are the most commonly prescribed antidepressants. Agomelatine and paroxetine were the least used antidepressants in the participating populations. Mirtazapine was the antidepressant most commonly prescribed among older antidepressant initiators with high percentage of comorbidities at baseline, whereas fluoxetine was commonly used among young patients.

Streptococcus pneumoniae is an infrequent cause of severe infectious endocarditis (IE). The aim of our study was to describe the epidemiology, clinical and microbiological characteristics, and outcome of a series of cases of S. pneumoniae IE diagnosed in Spain and in a series of cases published since 2000 in the medical literature. We prospectively collected all cases of IE diagnosed in a multicenter cohort of patients from 27 Spanish hospitals (n = 2539). We also performed a systematic review of the literature since 2000 and retrieved all cases with complete clinical data using a pre-established protocol. Predictors of mortality were identified using a logistic regression model. We collected 111 cases of pneumococcal IE: 24 patients from the Spanish cohort and 87 cases from the literature review. Median age was 51 years, and 23 patients (20.7%) were under 15 years. Men accounted for 64% of patients, and infection was community-acquired in 96.4% of cases. The most important underlying conditions were liver disease (27.9%) and immunosuppression (10.8%). A predisposing heart condition was present in only 18 patients (16.2%). Pneumococcal IE affected a native valve in 93.7% of patients. Left-sided endocarditis predominated (aortic valve 53.2% and mitral valve 40.5%). The microbiological diagnosis was obtained from blood cultures in 84.7% of cases. In the Spanish cohort, nonsusceptibility to penicillin was detected in 4.2%. The most common clinical manifestations included fever (71.2%), a new heart murmur (55%), pneumonia (45.9%), meningitis (40.5%), and Austrian syndrome (26.1%). Cardiac surgery was performed in 47.7% of patients. The in-hospital mortality rate was 20.7%. The multivariate analysis revealed the independent risk factors for mortality to be meningitis (OR, 4.3; 95% CI, 1.4–12.9; P

BACKGROUND AND HYPOTHESIS: Chronic Obstructive Pulmonary Disease (COPD) patients are characterized by heterogeneous clinical manifestations and patterns of disease progression. Two major factors that can be used to identify COPD subtypes are muscle dysfunction/wasting and co-morbidity patterns. We hypothesized that COPD heterogeneity is in part the result of complex interactions between several genes and pathways. We explored the possibility of using a Systems Medicine approach to identify such pathways, as well as to generate predictive computational models that may be used in clinic practice. OBJECTIVE AND METHOD: Our overarching goal is to generate clinically applicable predictive models that characterize COPD heterogeneity through a Systems Medicine approach. To this end we have developed a general framework, consisting of three steps/objectives: (1) feature identification, (2) model generation and statistical validation, and (3) application and validation of the predictive models in the clinical scenario. We used muscle dysfunction and co-morbidity as test cases for this framework. RESULTS: In the study of muscle wasting we identified relevant features (genes) by a network analysis and generated predictive models that integrate mechanistic and probabilistic models. This allowed us to characterize muscle wasting as a general de-regulation of pathway interactions. In the co-morbidity analysis we identified relevant features (genes/pathways) by the integration of gene-disease and disease-disease associations. We further present a detailed characterization of co-morbidities in COPD patients that was implemented into a predictive model. In both use cases we were able to achieve predictive modeling but we also identified several key challenges, the most pressing being the validation and implementation into actual clinical practice. CONCLUSIONS: The results confirm the potential of the Systems Medicine approach to study complex diseases and generate clinically relevant predictive models. Our study also highlights important obstacles and bottlenecks for such approaches (e.g. data availability and normalization of frameworks among others) and suggests specific proposals to overcome them.