Pre-surgical factors related to latent trajectories of 5-year weight loss for a diverse bariatric surgery population.

BACKGROUND: Analyzing trajectories of weight loss may address how particular groups of patients respond to metabolic and bariatric surgery. OBJECTIVES: The Bariatric Experience Long Term (BELONG) study was designed to use a theoretical model to examine determinants of weight loss and recurrence. SETTING: Large integrated health system in Southern California with 11 surgical practices and 23 surgeons. METHODS: A total of n = 1338 patients who had metabolic and bariatric surgery were surveyed before surgery to measure factors related to median percent total weight loss (%TWL) over 5 years. Longitudinal weight data were available for n = 1024 (76.5% of the sample). Data were analyzed using latent growth mixture models (GMM) to estimate trajectories of weight change separately for gastric sleeve and bypass operations. These trajectories were then described using relevant variables from the baseline survey. RESULTS: For both gastric sleeve (n = 733) and bypass (n = 291) operations, 3 latent trajectories of median %TWL were found corresponding to most, moderate, and least %TWL. Sleeve trajectories were distinguished by body mass index at surgery and geocoded environmental factors. Bypass trajectories varied by self-reported and geocoded environmental factors, comorbidity burden, race, experiential avoidance, and weight control strategies. CONCLUSIONS: Future research should examine the role of the built and perceived environment in surgical weight loss. Bariatric practices should focus less on the presurgical period for predictors of long-term weight loss and begin efforts to monitor real-time patient-reported outcomes to help tailor intervention strategies for patients who either do not lose an expected amount of weight or who begin to experience weight recurrence.

Markers of Natural Killer Cell Exhaustion in HIV/HCV Coinfection and Their Dynamics After HCV Clearance Mediated by Direct-Acting Antivirals.

Background: Liver fibrosis is a leading cause of morbimortality in people with HIV/hepatitis C virus (HCV). Natural killer (NK) cells are linked with amelioration of liver fibrosis; however, NK cells from individuals coinfected with HIV/HCV with cirrhosis display impaired functionality and high PD-1 expression. Here, we aimed to study PD-1, TIGIT, and Tim3 as potential exhaustion markers in NK cells from persons coinfected with HIV/HCV with mild and advanced liver fibrosis. We also evaluated the role of PD-1 expression on NK cells after HCV clearance by direct-acting antivirals (DAAs). Methods: Peripheral blood mononuclear cells were isolated from individuals coinfected with HIV/HCV (N = 54; METAVIR F0/F1, n = 27; F4, evaluated by transient elastography, n = 27). In 26 participants, samples were collected before, at the end of, and 12 months after successful DAA treatment. The frequency, immunophenotype (PD-1, TIGIT, and Tim3 expression), and degranulation capacity (CD107a assay) of NK cells were determined by flow cytometry. Results: Unlike PD-1, Tim3 and TIGIT were comparably expressed between persons with mild and advanced fibrosis. Degranulation capacity was diminished in NK/TIGIT+ cells in both fibrosis stages, while NK/PD-1+ cells showed a lower CD107a expression in cirrhotic cases. Twelve months after DAA treatment, those with advanced fibrosis showed an improved NK cell frequency and reduced NK/PD-1+ cell frequency but no changes in CD107a expression. In individuals with mild fibrosis, neither PD-1 nor NK cell frequency was modified, although the percentage of NK/CD107a+ cells was improved at 12 months posttreatment. Conclusions: Although DAA improved exhaustion and frequency of NK cells in cirrhotic cases, functionality was reverted only in mild liver fibrosis, remarking the importance of an early DAA treatment.

Baseline Psychosocial, Environmental, Health, and Behavioral Correlates of 1- and 3-Year Weight Loss After Bariatric Surgery.

PURPOSE: Weight loss surgery is an effective, long-term treatment for severe obesity but individual response to surgery varies widely. The purpose of this study was to test a comprehensive theoretical model of factors that may be correlated with the greatest surgical weight loss at 1-3 years following surgery. Such a model would help determine what predictive factors to measure when patients are preparing for surgery that may ensure the best weight outcomes. MATERIALS AND METHODS: The Bariatric Experience Long Term (BELONG) study collected self-reported and medical record-based baseline information as correlates of 1- and 3-year % total weight loss (TWL) in n = 1341 patients. Multiple linear regression was used to determine the associations between 120 baseline variables and %TWL. RESULTS: Participants were 43.4 ± 11.3 years old, Hispanic or Black (52%; n = 699), women (86%; n = 1149), and partnered (72%; n = 965) and had annual incomes of ≥ $51,000 (60%; n = 803). A total of 1006 (75%) had 3-year follow-up weight. Regression models accounted for 10.1% of the variance in %TWL at 1-year and 13.6% at 3 years. Only bariatric operation accounted for a clinically meaningful difference (~ 5%) in %TWL at 1-year. At 3 years after surgery, only bariatric operation, Black race, and BMI ≥ 50 kg/m2 were associated with clinically meaningful differences in %TWL. CONCLUSIONS: Our findings combined with many others support a move away from extensive screening and selection of patients at the time of surgery to a focus on improving access to this treatment.

Neighborhood deprivation and residential property values do not affect weight loss at 1 or 3 years after bariatric surgery.

OBJECTIVE: This study examined the association between individual- and neighborhood-level sociodemographic factors and surgical weight loss at 1 year (short term) and 3 years (long term). METHODS: Data were obtained from the baseline survey of the BELONG (Bariatric Experience Long Term) prospective longitudinal cohort study. Individual-level self-reported data on sex, race and ethnicity, education, and household income were obtained by survey. Data from the 2010 US Census were used to calculate area Neighborhood Deprivation Index score and median value of owner-occupied housing units at the census tract level. RESULTS: Patients (N = 1341) had a mean age of 43.4 (SD 11.3) years, were mostly female (86%), were mostly Black or Hispanic (52%), had some college education (83%), and had annual household incomes ≥$51,000 (55%). Percentage total weight loss was 25.8% (SD 9.0%) at year 1 and 22.2% (SD 10.5%) at year 3. Race and ethnicity and age were significant predictors of weight loss at 1 and 3 years with a small effect of self-reported household income at year 1. There were no significant associations between census tract-level Neighborhood Deprivation Index score or value of owner-occupied housing units and weight loss at either time point. CONCLUSIONS: Health systems could improve the chances of weight-loss maintenance after surgery by addressing factors related to racial and ethnic disparities and to income disparities.

Cost-Effectiveness of the CNIC-Polypill Strategy Compared With Separate Monocomponents in Secondary Prevention of Cardiovascular and Cerebrovascular Disease in Portugal: The MERCURY Study.

Background: Cardiovascular (CV) diseases remain a leading and costly cause of death globally. Patients with previous CV events are at high risk of recurrence. Secondary prevention therapies improve CV risk factor control and reduce disease costs. Objectives: To assess the cost-effectiveness of a CV polypill strategy (CNIC-Polypill) compared with the loose combination of monocomponents to improve the control of CV risk factors in patients with previous coronary heart disease or stroke. Methods: A Markov model cost-utility analysis was developed using 4 health states, SMART risk equation, and 3-month cycles for year 1 and annual cycles thereafter, over a lifetime horizon from the perspective of the National Health System in Portugal (base case). The NEPTUNO study, Portuguese registries, mortality tables, official reports, and the literature were consulted to define effectiveness, epidemiological costs, and utility data. Outcomes were costs (estimated in 2020 euros) per life-year (LY) and quality-adjusted LY (QALY) gained. A 4% discount rate was applied. Alternative scenarios and one-way and probabilistic sensitivity analyses tested the consistency and robustness of results. Results: The CNIC-Polypill strategy in secondary prevention provides more LY and QALY, at a higher cost, than monocomponents. The incremental cost-utility ratio is €1557/QALY gained. Assuming a willingness-to-pay threshold of €30 000/QALY gained, there is a 79.7% and a 44.4% probability of the CNIC-Polypill being cost-effective and cost-saving, respectively, compared with the loose combination of monocomponents. Results remain consistent in the alternative scenarios and robust in the sensitivity analyses. Discussion: The model reflects increments in the number of years patients would live and in quality of life with the CNIC-Polypill. The clinical effectiveness of the CNIC-Polypill strategy initially demonstrated in the NEPTUNO study has been recently corroborated in the SECURE trial. The incremental cost of the CNIC-Polypill strategy emerges slightly above the comparator, but willingness-to-pay estimates and sensitivity analyses indicate that the CNIC-Polypill strategy is consistently cost-effective compared with monocomponents and remains within acceptable affordability margins. Conclusion: The CNIC-Polypill is a cost-effective secondary prevention strategy. In patients with histories of coronary heart disease or stroke, the CNIC-Polypill more effectively controls CV risk factors compared with monocomponents.

The association of 1-year weight loss from bariatric surgery and self-reported sleep: a prospective cohort.

OBJECTIVE: This study examined the association of weight loss following bariatric surgery with self-reported sleep quality after accounting for other sleep-related factors. METHODS: Participants were from the Bariatric Experience Long Term (BELONG) study. Participants completed a survey up to 6 months before surgery and approximately 1 year after surgery. The Pittsburgh Sleep Quality Index (PSQI) was used to measure sleep quality. One-year percentage total weight loss (%TWL) was determined from electronic medical records. Covariates included demographics, Charlson Comorbidity Index, geocoded variables to assess neighborhood quality, and physical activity. The authors assessed the association between %TWL at 1 year and PSQI component scores with separate cumulative logit models. RESULTS: There were 997 participants in the analytic cohort. Participants were 86.2% women, 37.0% Hispanic, and 13.7% Black adults. Mean one-year %TWL was 26.3 (SD 8.7). Each 1% increase in %TWL was associated with a 3% better daytime dysfunction score (odds ratio = 1.03; 95% CI: 1.02-1.05) and a 2% better sleep quality score (odds ratio = 1.02; 95% CI: 1.00-1.03). No significant differences were found for the other PSQI components. CONCLUSIONS: Weight loss from bariatric surgery was associated with better self-reported sleep at 1 year. For people undergoing bariatric surgery, there may be an added benefit of better sleep.

Cohort profile: The Bariatric Experience Long Term (BELONG): a long-term prospective study to understand the psychosocial, environmental, health and behavioural predictors of weight loss and regain in patients who have bariatric surgery.

PURPOSE: The Bariatric Experience Long Term (BELONG) prospective study cohort was created to address limitations in the literature regarding the relationship between surgical weight loss and psychosocial, health, behaviour and environmental factors. The BELONG cohort is unique because it contains 70% gastric sleeve and 64% patients with non-white race/ethnicity and was developed with strong stakeholder engagement including patients and providers. PARTICIPANTS: The BELONG cohort study included 1975 patients preparing to have bariatric surgery who completed a baseline survey in a large integrated health system in Southern California. Patients were primarily women (84%), either black or Hispanic (59%), with a body mass index (BMI) of 45.1±7.4 kg/m2, age 43.3±11.5 years old, and 32% had at least one comorbidity. FINDINGS TO DATE: A total of 5552 patients were approached before surgery between February 2016 and May 2017, and 1975 (42%) completed a baseline survey. A total of 1203 (73%) patients completed the year 1 and 1033 (74%) patients completed the year 3 postoperative survey. Of these survey respondents, 1341 at baseline, 999 at year 1, and 951 at year 3 were included in the analyses of all survey and weight outcome data. A total of 803 (60% of eligible patients) had survey data for all time points. Data collected were self-reported constructs to support the proposed theoretical model. Height, weight and BMI were abstracted from the electronic medical record to obtain the main outcomes of the study: weight loss and regain. FUTURE PLANS: We will collect self-reported constructs and obtain height, weight and BMI from the electronic medical record 5 years after bariatric surgery between April 2022 and January 2023. We will also collect patient experiences using focus groups of 8-12 patients each throughout 2022.

Bariatric Surgical Alterations in Tolerability, Enjoyment and Cravings in the Diet (BSATED) instrument: A new scale to measure food preferences following bariatric surgery.

Bariatric surgery is associated with changing food preferences, but it is not known whether these changes differ by type of operation or are associated with weight loss. The current study presents validation results for a new 27-item scale, Bariatric Surgical Alterations in Tolerability, Enjoyment and Cravings in the Diet (BSATED). This scale measured enjoyment, craving, and intolerance changes for nine food and beverage categories common to dietary habits in the Southern California region of the U.S. one year following bariatric surgery in the Bariatric Experience Long Term (BELONG) study. Validation of BSATED was done using exploratory factor analyses, construct validity with other conceptually related survey instruments, and criterion validity using hypothesized differences for operation type and percent total weight loss (%TWL) at 12-18 months after surgery. Participants (n = 999) were 86% female, 41% non-Hispanic White, with a mean age of 43.1 ± 11.3 years and a body mass index (BMI) of 43.4 ± 6.8 kg/m2 at the time of surgery. Participants reported less enjoyment and craving for high-fat meats (62%), grains (54%), candy and other desserts (e.g. candy bars, chocolate, ice cream) (52%), and sweet baked goods (48%) 12 months after surgery. These changes were more common among participants undergoing Roux-en-Y gastric bypass (RYGB) compared to those receiving sleeve gastrectomy (SG). Participants who reported decreased enjoyment and craving for foods and beverages that post-bariatric patients are counseled to reduce or avoid had greater %TWL at 12-18 months following surgery (p < .001 and p = .003 respectively). The foods and beverages in BSATED that post-bariatric patients are counseled to reduce or avoid could be used to understand how changes in enjoyment, craving and tolerability of these foods/beverages contribute to weight loss following surgery.

The Bariatric Experience Long Term (BELONG): Factors Related to Having Bariatric Surgery in a Large Integrated Healthcare System.

PURPOSE: Bariatric surgery is the most effective treatment for severe obesity, but currently, only 1-2% of all eligible patients undergo surgery each year. This study examined which factors were associated with a patient receiving bariatric surgery after referral in a real-world healthcare setting. MATERIALS AND METHODS: The current study used the baseline survey and electronic medical record (EMR) data from the Bariatric Experience Long Term (BELONG) study (n = 1975). Predictors of who did (n = 1680) and who did not (n = 295) have surgery were analyzed using multivariate logistic regression. RESULTS: Participants (n = 1975; 42.4% response rate) were primarily women (84%) and either non-Hispanic Black or Hispanic (60%). In the fully adjusted multivariate model, the strongest predictors of having surgery were being a woman (OR = 3.17; 95% CI = 2.15, 4.68; p < .001) and losing at least 5% of their body weight in the year before surgery (OR = 3.16; 95% CI = 2.28, 4.38; p < .001). The strongest predictors of not having surgery were a ≥ BMI 50 kg/m2 (OR = .39; 95% CI = .27, .56; p < .001) and having a higher physical comorbidity burden (OR = .84; 95% CI = .75, .94; p = .004). CONCLUSIONS: Practices such as 5-10% total weight loss before surgery and selection of patients with safer operative risk profiles (younger with lower comorbidity burden) may inadvertently contribute to under-utilization of bariatric surgery among some demographic subpopulations who could most benefit from this intervention.

Prevalence and incidence of systemic lupus erythematosus in Tucumán, Argentina.

The aim of this study was to determine the prevalence and incidence of Systemic Lupus Erythematosus (SLE) in Tucumán, Argentina. METHODS: The study included inpatient and outpatient charts from four public hospitals and private practice rheumatology clinics, all of them members of the Tucumán Rheumatology Society. Patients older than 16 years with diagnosis of SLE between January 2005 and December 2012 were included. Prevalence and annual incidence were calculated as the number of cases per 100.000 inhabitants during the period 2005 to 2012. RESULTS: Three hundred fifty-three patients were identified. The mean age at diagnosis was 30.5 ± 11.7 years, 93.5% women, 83% mestizos. Prevalence was 24.3 cases/100.000 inhabitants (CI 95% 22.6-28.8) and age-adjusted (≥16 years) of 34.9 cases/100.000 inhabitants (CI 95% 32.8-41.1). The annual incidence in 2005 was 1.8 cases/100.000 inhabitants (95% CI 1-2.9) and 2012 of 4.2 cases/100.000 inhabitants (95% CI 2.9-5.8). Mortality was 9.1%, with infections being the most frequent cause (14/32). CONCLUSION: The prevalence of SLE in the province of Tucumán was 34.9 cases/100.000 inhabitants.

The capacity of schizophrenia and bipolar disorder individuals to make autonomous decisions about pharmacological treatments for their illness in real life: A scoping review.

BACKGROUND AND AIM: Having decision making capacity is central to the exercise of autonomy in mental health care. The objective of this scoping review is to summarize the evidence on the capacity of people with schizophrenia or bipolar disorder to make decisions about their treatment in real life to support medical practice. METHODS: Systematic search of observational studies on the assessment of capacity of patients with schizophrenia, psychosis, or bipolar disorder to make healthcare and treatment-related decisions, conducted in any clinical setting published up to January 31, 2020 was performed. Free text searches and medical subject headings in English were combined in PubMed, Scopus, CINAHL, and PsycInfo. Publications were selected as per inclusion and exclusion criteria. The Newcastle-Ottawa Scale for observational studies was used to assess the quality of publications. RESULTS: Thirty publications were reviewed. According to the Newcastle-Ottawa Scale criteria, the publications reviewed were good quality. Findings showed that more than 70% of schizophrenia and schizoaffective disorder outpatients understood treatment options at the point of making decisions about their illness and healthcare. Patients treated voluntarily had considerably better scores for decisional capacity than those treated involuntarily. The burden of psychiatric symptoms could compromise decisional capacity temporarily. Decision-making capacity improved over time from admission to discharge from hospital, and with treatment among psychiatry inpatients. Schizophrenia and bipolar disorder patients could be as competent as nonpsychiatric individuals in making decisions about their treatments in everyday life. CONCLUSIONS: This scoping review provides a body of evidence for healthcare professionals in need of assessing the capacity of schizophrenia and bipolar disorder patients for autonomously decide about their treatments. Decisional capacity judgements should consider variations in capacity over time and be based on the type of decision to be made, the severity of symptoms, and the specific phase of the mental disorder.

Telephone-based motivational interviewing versus usual care in primary care to increase physical activity: a randomized pilot study.

BACKGROUND: Diabetes and prediabetes are chronic conditions that affect over 40% of the US adult population combined. Regular physical activity can benefit people with diabetes through improved glucose control and can reduce the conversion of prediabetes to diabetes. Studies are needed in settings where people with these conditions can be identified and provided the skills and support to increase physical activity. The primary care setting meets this need, but there are insufficient high-quality trials to recommend this approach be broadly implemented. METHODS: We conducted a randomized, 24-week pilot study in Southern California to assess the feasibility of using information technology systems available in primary care for identifying potential participants, test methods for obtaining physical activity clearance, conducting mail-based assessments, and delivering telephone-based motivational interviewing to increase physical activity. Eligibility criteria included age between 18 and 74 years, diabetes or prediabetes, and physically inactive based on a clinical assessment tool. At baseline and follow-up, physical activity was assessed by a 7-day accelerometry, cardiometabolic risk factors were collected from electronic medical records, and psychosocial factors were assessed from validated questionnaires administered through a mail survey. Participants were block randomized into intervention or usual care. Staff collecting outcome data were blinded to group assignment. Analysis of covariance was used to assess the difference at follow-up between the intervention and usual care, adjusting for baseline. RESULTS: A total of 67 participants were randomized. Follow-up mail assessments were completed by 53 participants. Of 224 potential intervention calls, 194 were completed (87%). Psychosocial measures significantly improved in four of the five factors for physical activity motivation relative to participants in the usual care arm. The more internally focused factors for exercise self-regulation and outcome expectancies scores were significantly greater for participants in intervention compared with usual care. Moderate to vigorous physical activity improved in intervention participants relative to usual care, but the difference was not statistically significant. No adverse events were noted. CONCLUSIONS: The objectives of this pilot study were met. If a fully powered trial is successful, primary care settings with "behind-the-scenes" information technology support may be appropriate to increase physical activity among patients with prediabetes and diabetes. TRIAL REGISTRATION: Exercise Promotion in Primary Care (EPPC), NCT03429088, registered on February 5, 2018.

The Clinical Features of Patients with Chronic Hepatitis C Virus Infections Are Associated with Killer Cell Immunoglobulin-Like Receptor Genes and Their Expression on the Surface of Natural Killer Cells.

Killer cell immunoglobulin-like receptor (KIR) genes are known to play a role in the acute phase of hepatitis C virus (HCV) infection. The present study investigated their roles in chronic HCV (CHCV) infection by analyzing the phenotypes and function of natural killer (NK) and T cells that express KIRs. T cells from CHCV patients showed a more differentiated phenotype, and NK cells exhibited an activated profile. These observations are consistent with the increased expression of the degranulation marker CD107a observed after PMA stimulation. We explored the correlations between the expression of KIR genes and lectin type-C receptors with clinical factors that predict progression to fibrosis and cirrhosis. The expression levels of KIR2DS3 and the functional alleles of KIR2DS4-FL were increased in patients with intermediate and high viral loads. Homozygous KIR2DS4 was also associated with the presence of cirrhosis. In the group of individuals with a shorter infection time who developed cirrhosis, we detected decreased expression of KIR3DL1 in CD56dim NK cells in the presence of its ligand. Similarly, in the group of patients with late CHCV infections complicated with cirrhosis, we detected lower expression of the strong inhibitory receptor NKG2A in CD56bright NK cells. We also detected an increase in NKG2C expression in CD56dim NK cells in CHCV patients who displayed high necroinflammatory activity. Decreased KIR3DL2 expression in CD56dim and CD56bright NK cells was associated with a high body mass index, and KIR3DL2 expression may be one factor associated with the more rapid progression of CHCV to fibrosis in patients.

Do new cancer drugs offer good value for money? The perspectives of oncologists, health care policy makers, patients, and the general population.

BACKGROUND: In oncology, establishing the value of new cancer treatments is challenging. A clear definition of the different perspectives regarding the drivers of innovation in oncology is required to enable new cancer treatments to be properly rewarded for the value they create. The aim of this study was to analyze the views of oncologists, health care policy makers, patients, and the general population regarding the value of new cancer treatments. METHODS: An exploratory and qualitative study was conducted through structured interviews to assess participants' attitudes toward cost and outcomes of cancer drugs. First, the participants were asked to indicate the minimum survival benefit that a new treatment should have to be funded by the Spanish National Health System (NHS). Second, the participants were requested to state the highest cost that the NHS could afford for a medication that increases a patient's quality of life (QoL) by twofold with no changes in survival. The responses were used to calculate incremental cost-effectiveness ratios (ICERs). RESULTS: The minimum improvement in patient survival means that justified inclusions into the NHS were 5.7, 8.2, 9.1, and 10.4 months, which implied different ICERs for oncologists (€106,000/quality-adjusted life year [QALY]), patients (€73,520/QALY), the general population (€66,074/QALY), and health care policy makers (€57,471/QALY), respectively. The costs stated in the QoL-enhancing scenario were €33,167, €30,200, €26,000, and €17,040, which resulted in ICERs of €82,917/QALY for patients, €75,500/QALY for the general population, €65,000/QALY for oncologists, and €42,600/QALY for health care policy makers, respectively. CONCLUSION: All estimated ICER values were higher than the thresholds previously described in the literature. Oncologists most valued gains in survival, whereas patients assigned a higher monetary value to treatments that enhanced QoL. Health care policy makers were less likely to pay more for therapeutic improvements compared to the remaining participants.

Immune dysfunction in cirrhosis: Distinct cytokines phenotypes according to cirrhosis severity.

BACKGROUND/OBJECTIVES: Cirrhosis associated immune dysfunction has been proposed to switch from a pro-inflammatory phenotype in stable cirrhosis to an immunodeficient one in patients with decompensated cirrhosis and acute-on-chronic liver failure. The aim of the present study was to compare serum cytokine levels between healthy patients, stable cirrhosis, and decompensated cirrhotic patients with and without development of acute-on-chronic liver failure (ACLF); and to explore whether any of the measured cytokines is associated with cirrhosis severity and prognosis in ACLF patients. METHODS: Patients were enrolled from October 2013 to May 2014 in two hospitals located in Buenos Aires. Cirrhotic patients with an acute decompensating event were enrolled accordingly to the development of ACLF defined by the CANONIC study group. There were two control groups: healthy subjects (n=14) and stable cirrhotic patients (n=14). Demographic, clinical and biochemical data were obtained. Seventeen cytokines were measured using Bio-Plex Pro Human Cytokine 17-plex Assay. RESULTS: Of the 49 decompensated cirrhotic patients enrolled, 18 (36.7%) developed ACLF. Leukocyte count, MELD score at admission, Clif-SOFA at admission and day 7 were significantly higher in the ACLF group (p=0.046, p<0.001, p<0.001, p<0.001 respectively) as well as short-term mortality (p<0.001) compared to stable and decompensated cirrhotic patients. In comparison with healthy controls, stable cirrhotic and decompensated cirrhotic patients showed increased levels of pro-inflammatory and anti-inflammatory cytokines: IL-6, IL-7, IL-8, IL-10, IL 12, and TNF-α. Decompensated cirrhotic patients with the development of ACLF showed a significant decrease of IL-7, IL-10, IL-12, TNF-α, MCP-1 and IFN-γ, but a sustained response of IL-6 and IL-8. When evaluating cirrhosis severity, IL-6 and IL-8 correlated positively with MELD score, whereas only IL-6 correlated positively with Clif-SOFA score at day 7; IL-2 correlated negatively with Clif-SOFA at admission. In comparison with all scores, leukocyte count showed positive correlation and IFN-γ negative correlation with disease severity. When evaluating survival, only MELD and Clif-SOFA scores had a significant association with mortality. CONCLUSIONS: Pro-inflammatory cytokines and chemo-attractant elements are increased in cirrhosis in comparison with healthy subjects, and display higher values concomitantly with cirrhosis progression. However, in acute-on-chronic liver failure an opposite cytokine pattern that can be resumed as a combination of immune paresis and excessive inflammatory response was observed. Several pro-inflammatory cytokines (IL-2, IL-6, IL-8 and IFN-γ) showed correlation with disease severity; their utility as prognostic biomarkers needs to be further studied.

Parkinson Symptoms and Health Related Quality of Life as Predictors of Costs: A Longitudinal Observational Study with Linear Mixed Model Analysis.

OBJECTIVE: To estimate the magnitude in which Parkinson's disease (PD) symptoms and health- related quality of life (HRQoL) determined PD costs over a 4-year period. MATERIALS AND METHODS: Data collected during 3-month, each year, for 4 years, from the ELEP study, included sociodemographic, clinical and use of resources information. Costs were calculated yearly, as mean 3-month costs/patient and updated to Spanish €, 2012. Mixed linear models were performed to analyze total, direct and indirect costs based on symptoms and HRQoL. RESULTS: One-hundred and seventy four patients were included. Mean (SD) age: 63 (11) years, mean (SD) disease duration: 8 (6) years. Ninety-three percent were HY I, II or III (mild or moderate disease). Forty-nine percent remained in the same stage during the study period. Clinical evaluation and HRQoL scales showed relatively slight changes over time, demonstrating a stable group overall. Mean (SD) PD total costs augmented 92.5%, from € 2,082.17 (€ 2,889.86) in year 1 to € 4,008.6 (€ 7,757.35) in year 4. Total, direct and indirect cost incremented 45.96%, 35.63%, and 69.69% for mild disease, respectively, whereas increased 166.52% for total, 55.68% for direct and 347.85% for indirect cost in patients with moderate PD. For severe patients, cost remained almost the same throughout the study. For each additional point in the SCOPA-Motor scale total costs increased € 75.72 (p = 0.0174); for each additional point on SCOPA-Motor and the SCOPA-COG, direct costs incremented € 49.21 (p = 0.0094) and € 44.81 (p = 0.0404), respectively; and for each extra point on the pain scale, indirect costs increased € 16.31 (p = 0.0228). CONCLUSIONS: PD is an expensive disease in Spain. Disease progression and severity as well as motor and cognitive dysfunctions are major drivers of costs increments. Therapeutic measures aimed at controlling progression and symptoms could help contain disease expenses.

Patients' and physicians' preferences for type 2 diabetes mellitus treatments in Spain and Portugal: a discrete choice experiment.

OBJECTIVE: To assess Spanish and Portuguese patients' and physicians' preferences regarding type 2 diabetes mellitus (T2DM) treatments and the monthly willingness to pay (WTP) to gain benefits or avoid side effects. METHODS: An observational, multicenter, exploratory study focused on routine clinical practice in Spain and Portugal. Physicians were recruited from multiple hospitals and outpatient clinics, while patients were recruited from eleven centers operating in the public health care system in different autonomous communities in Spain and Portugal. Preferences were measured via a discrete choice experiment by rating multiple T2DM medication attributes. Data were analyzed using the conditional logit model. RESULTS: Three-hundred and thirty (n=330) patients (49.7% female; mean age 62.4 [SD: 10.3] years, mean T2DM duration 13.9 [8.2] years, mean body mass index 32.5 [6.8] kg/m(2), 41.8% received oral + injected medication, 40.3% received oral, and 17.6% injected treatments) and 221 physicians from Spain and Portugal (62% female; mean age 41.9 [SD: 10.5] years, 33.5% endocrinologists, 66.5% primary-care doctors) participated. Patients valued avoiding a gain in bodyweight of 3 kg/6 months (WTP: €68.14 [95% confidence interval: 54.55-85.08]) the most, followed by avoiding one hypoglycemic event/month (WTP: €54.80 [23.29-82.26]). Physicians valued avoiding one hypoglycemia/week (WTP: €287.18 [95% confidence interval: 160.31-1,387.21]) the most, followed by avoiding a 3 kg/6 months gain in bodyweight and decreasing cardiovascular risk (WTP: €166.87 [88.63-843.09] and €154.30 [98.13-434.19], respectively). Physicians and patients were willing to pay €125.92 (73.30-622.75) and €24.28 (18.41-30.31), respectively, to avoid a 1% increase in glycated hemoglobin, and €143.30 (73.39-543.62) and €42.74 (23.89-61.77) to avoid nausea. CONCLUSION: Both patients and physicians in Spain and Portugal are willing to pay for the health benefits associated with improved diabetes treatment, the most important being to avoid hypoglycemia and gaining weight. Decreased cardiovascular risk and weight reduction became the third most valued attributes for physicians and patients, respectively.

Estimating the direct and indirect costs associated with Parkinson's disease.

Parkinson's disease (PD) is a progressive, neurodegenerative disorder whose symptoms and manifestations greatly deteriorate the health, functional status and quality of life of patients, has severe consequences on their families and caregivers and supposes a challenge for the healthcare system and society. The aim of this paper is to comprehensively and descriptively review studies on the economic impact of the disease and interventions, analyzing major contributing factors to direct and indirect costs in PD. Cost-of-illness studies have shown that costs of PD are high, mainly due to drug, hospitalization and productivity loss, and tend to increase as the disease progresses. Studies on PD treatment have suggested that therapies for advanced PD (levodopa/carbidopa intestinal gel and apomorphine) and surgical procedures are cost-effective and cost saving, despite their high expenditures; however, further research such as on the economic impact of non-motor manifestations or on the cost-effectiveness of non-medical interventions is still needed.