Patient and health professional views on risk-stratified monitoring of immune-suppressing treatment in adults with inflammatory diseases.

OBJECTIVE: To explore the acceptability of an individualised risk-stratified approach to monitoring for target-organ toxicity in adult patients with immune-mediated inflammatory diseases established on immune-suppressing treatment(s). METHODS: Adults (≥18 years) taking immune-suppressing treatment(s) for at-least six months, and healthcare professionals (HCPs) with experience of either prescribing and/or monitoring immune-suppressing drugs were invited to participate in a single, remote, one-to-one, semi-structured interview. Interviews were conducted by a trained qualitative researcher and explored their views and experiences of current monitoring and acceptability of a proposed risk-stratified monitoring plan. Interviews were transcribed verbatim and inductively analysed using thematic analysis in NVivo. RESULTS: Eighteen patients and 13 HCPs were interviewed. While participants found monitoring of immune-suppressing drugs with frequent blood-tests reassuring, the current frequency of these was considered burdensome by patients and HCPs alike, and to be a superfluous use of healthcare resources. Given abnormalities rarely arose during long-term treatment, most felt that monitoring blood-tests were not needed as often. Patients and HCPs found it acceptable to increase the interval between monitoring blood-tests from three-monthly to six-monthly or annually depending on the patients' risk profiles. Conditions of accepting such a change included: allowing for clinician and patient autonomy in determining an individuals' frequency of monitoring blood-tests, the flexibility to change monitoring frequency if someone's risk profile changed, and endorsement from specialist societies and healthcare providers such as the National Health Service. CONCLUSION: A risk-stratified approach to monitoring was acceptable to patients and HCPs. Guideline groups should consider these findings when recommending blood-test monitoring intervals.

Health Centers and Value-Based Payment: A Framework for Health Center Payment Reform and Early Experiences in Medicaid Value-Based Payment in Seven States.

Policy Points As essential access points to primary care for almost 29 million US patients, of whom 47% are Medicaid enrollees, health centers are positioned to implement the population health management necessary in value-based payment (VBP) contracts. Primary care payment reform requires multiple payment methodologies used together to provide flexibility to care providers, encourage investments in infrastructure and new services, and offer incentives for achieving better health outcomes. State policy and significant financial incentives from Medicaid agencies and Medicaid managed care plans will likely be required to increase health center participation in VBP, which is consistent with broader state efforts to expand investment in primary care. CONTEXT: Efforts are ongoing to advance value-based payment (VBP), and health centers serve as essential access points to comprehensive primary care services for almost 29 million people in the United States. Therefore, it is important to assess the levels of health center participation in VBP, types of VBP contracts, characteristics of health centers participating in VBP, and variations in state policy environments that influence VBP participation. METHODS: This mixed methods study combined qualitative research on state policy environments and health center participation in VBP with quantitative analysis of Uniform Data System and health center financial data in seven vanguard states: Oregon, Washington, California, Colorado, New York, Hawaii, and Kentucky. VBP contracts were classified into three layers: base payments being transformed from visit-based to population-based (Layer 1), infrastructure and care coordination payments (Layer 2), and performance incentive payments (Layer 3). FINDINGS: Health centers in all seven states participated in Layer 2 and Layer 3 VBP, with VBP participation growing from 35% to 58% of all health centers in these states from 2013 to 2017. Among participating health centers, the average percentage of Medicaid revenue received as Layer 2 and Layer 3 VBP rose from 6.4% in 2013 to 9.1% in 2017. Oregon and Washington health centers participating in Layer 1 payment reforms received most of their Medicaid revenue in VBP. In 2017, VBP participation was associated with larger health center size in four states (P <.05), and higher average number of days cash on hand (P <.05) in three states. CONCLUSIONS: A multilayer payment model is useful for implementing and monitoring VBP adoption among health centers. State policy, financial incentives from Medicaid agencies and Medicaid managed plans, and health center-Medicaid collaboration under strong primary care association and health center leadership will likely be required to increase health center participation in VBP.

Direct healthcare resource utilisation, health-related quality of life, and work productivity in patients with moderate rheumatoid arthritis: an observational study.

BACKGROUND: The aim was to describe the population of patients with moderate rheumatoid arthritis (RA) in the United Kingdom and the burden of disease from the perspectives of the patient, caregiver, and health service. METHODS: In this descriptive study, retrospective patient-level data were extracted from hospital medical records to assess healthcare resource utilisation and validated outcome measures were administered via questionnaire to patients with moderate RA (Disease Activity Score [DAS28] between 3.2 and 5.1) from eight secondary care centres, and their caregivers. Patient-reported outcome instruments were scored according to licensed manuals. RESULTS: Outcome measures were completed by 102 patients and 38 caregivers. The mean EuroQoL-5 dimension-5 level crosswalk index value for patients was 0.62 (SD 0.24) compared to an England population norm of 0.82. Mean pain VAS score was 37.7 (SD 24.0) and mean Health Assessment Questionnaire Disability Index was 1.1 (SD 0.8). In employed patients who completed the Work Productivity and Activity Impairment questionnaire (n = 26), a mean 29% (SD 26%) reduction in work productivity was recorded. Patients experienced significant fatigue as a result of their RA (median Functional Assessment of Chronic Illness Therapy fatigue score 17.2 of a possible 52, interquartile range [IQR] 11.0-28.8). Over 50% of caregivers reported providing > 7 h of support care per week to the patient with RA, and 16 and 11% took paid/unpaid leave or reduced working hours, respectively. Mean Caregiver Reaction Assessment subscale scores were 1.9 (SD 0.9) for finance, 1.7 (SD 0.8) for health, 2.3 (SD 1.0) for schedule disruption, and 1.9 (SD 0.8) for family support. Patients had a mean 5.5 (SD 4.1) outpatient attendances and a median 9.0 (IQR 2.0-20.0) diagnostic and monitoring tests in the 12 months prior to enrolment. CONCLUSIONS: This study shows that moderate RA has a considerable impact on healthcare resources and on patients' and caregivers' lives. There is scope to improve the management of patients with moderate RA.

Memory and Markov Blankets.

In theoretical biology, we are often interested in random dynamical systems-like the brain-that appear to model their environments. This can be formalized by appealing to the existence of a (possibly non-equilibrium) steady state, whose density preserves a conditional independence between a biological entity and its surroundings. From this perspective, the conditioning set, or Markov blanket, induces a form of vicarious synchrony between creature and world-as if one were modelling the other. However, this results in an apparent paradox. If all conditional dependencies between a system and its surroundings depend upon the blanket, how do we account for the mnemonic capacity of living systems? It might appear that any shared dependence upon past blanket states violates the independence condition, as the variables on either side of the blanket now share information not available from the current blanket state. This paper aims to resolve this paradox, and to demonstrate that conditional independence does not preclude memory. Our argument rests upon drawing a distinction between the dependencies implied by a steady state density, and the density dynamics of the system conditioned upon its configuration at a previous time. The interesting question then becomes: What determines the length of time required for a stochastic system to 'forget' its initial conditions? We explore this question for an example system, whose steady state density possesses a Markov blanket, through simple numerical analyses. We conclude with a discussion of the relevance for memory in cognitive systems like us.

Primary Care: the New Frontier for Reducing Readmissions.

To date, efforts to reduce hospital readmissions have centered largely on hospitals. In a recently published environmental scan, we examined the literature focusing on primary care-based efforts to reduce readmissions. While rigorous studies on interventions arising from primary care are limited, we found that multi-component care transitions programs that are initiated early in the hospitalization and are part of broader primary care practice transformation appear most promising. However, policy changes are necessary to spur innovation and support effective primary care-led transitions interventions. Though more rigorous research is needed, our findings suggest that primary care can and should lead future efforts for reducing hospital readmissions.

Tinkering with cognitive gadgets: Cultural evolutionary psychology meets active inference.

Cognitive Gadgets offers a new, convincing perspective on the origins of our distinctive cognitive faculties, coupled with a clear, innovative research program. Although we broadly endorse Heyes' ideas, we raise some concerns about her characterisation of evolutionary psychology and the relationship between biology and culture, before discussing the potential fruits of examining cognitive gadgets through the lens of active inference.

Understanding Patient, Provider, and System Factors Related to Medicaid Readmissions.

BACKGROUND: Efforts on reducing hospital readmissions, which are intended to improve quality and reduce costs, tend to focus on elderly Medicare beneficiaries without recognition of another high-risk population--adult nonmaternal Medicaid patients. This study was undertaken to understand the complexity of Medicaid readmission issues at the patient, provider, and system levels. METHODS: Multiple qualitative methods, including site visits to nine safety-net hospitals, patient/family/caregiver inter views, and semistructured interviews with health plans and state Medicaid agencies, were used in 2012 and 2013 to obtain information on patient, provider, and system issues related to Medicaid readmissions; strategies considered or currently used to address those issues; and any perceived financial, regulatory or, other policy factors inhibiting or facilitating readmission reduction efforts. RESULTS: Significant risk factors for Medicaid readmissions included financial stress, high prevalence of mental health and substance abuse disorders, medication nonadherence, and housing instability. Lacking awareness on Medicaid patients' high risk, a sufficient business case, and proven strategies for reducing readmissions were primary barriers for providers. Major hurdles at the system level included shortage of primary care and mental health providers, lack of coordination among providers, lack of partnerships between health plans and providers, and limited data capacity for realtime monitoring of readmissions. CONCLUSIONS: The intertwining of behavioral, socioeconomic, and health factors; the difficulty of accessing appropriate care in the outpatient setting; the lack of clear financial incentives for health care providers to reduce readmissions; and the fragmentation of the current health care system warrant greater attention and more concerted efforts from all stakeholders to reduce Medicaid readmissions.

PERI-operative biologic DMARD management: Stoppage or COntinuation during orthoPaEdic operations (the PERISCOPE trial) - a study protocol for a pragmatic, UK multicentre, superiority randomised controlled trial with an internal pilot, economic evaluation and nested qualitative study.

INTRODUCTION: Biological disease-modifying antirheumatic drugs (bDMARDs) have revolutionised the treatment of inflammatory arthritis (IA). However, many people with IA still require planned orthopaedic surgery to reduce pain and improve function. Currently, bDMARDs are withheld during the perioperative period due to potential infection risk. However, this predisposes patients to IA flares and loss of disease control. The question of whether to stop or continue bDMARDs in the perioperative period has not been adequately addressed in a randomised controlled trial (RCT). METHODS AND ANALYSIS: PERISCOPE is a multicentre, superiority, pragmatic RCT investigating the stoppage or continuation of bDMARDs. Participants will be assigned 1:1 to either stop or continue their bDMARDs during the perioperative period. We aim to recruit 394 adult participants with IA. Potential participants will be identified in secondary care hospitals in the UK, screened by a delegated clinician. If eligible and consenting, baseline data will be collected and randomisation completed. The primary outcome will be the self-reported PROMIS-29 (Patient Reported Outcome Measurement Information System) over the first 12 weeks postsurgery. Secondary outcome measures are as follows: PROMIS - Health Assessment Questionnaire (PROMIS-HAQ), EQ-5D-5L, Disease activity: generic global Numeric Rating Scale (patient and clinician), Self-Administered Patient Satisfaction scale, Health care resource use and costs, Medication use, Surgical site infection, delayed wound healing, Adverse events (including systemic infections) and disease-specific outcomes (according to IA diagnosis). The costs associated with stopping and continuing bDMARDs will be assessed. A qualitative study will explore the patients' and clinicians' acceptability and experience of continuation/stoppage of bDMARDs in the perioperative period and the impact postoperatively. ETHICS AND DISSEMINATION: Ethical approval for this study was received from the West of Scotland Research Ethics Committee on 25 April 2023 (REC Ref: 23/WS/0049). The findings from PERISCOPE will be submitted to peer-reviewed journals and feed directly into practice guidelines for the use of bDMARDs in the perioperative period. TRIAL REGISTRATION NUMBER: ISRCTN17691638.

Racial Differences in Perceptions of Genetic Wellness Programs.

PURPOSE: Genetic wellness programs (GWPs) are a highly innovative workforce wellness product. Recently marketed to U.S. employers by at least 16 vendors, GWPs take advantage of low-cost DNA sequencing to detect genetic risk factors for an increasing array of diseases. The purpose of this research is to understand perceptions, concerns, and barriers related to GWPs, among employees from Black, White, and Asian backgrounds and different income levels. APPROACH: Qualitative study with 3 focus groups (FGs). SETTING: Employees of large high-technology companies (deemed likely early GWP adopters). RESPONDENTS: 21 individuals recruited online through User Interviews. METHOD: FG guide developed via literature review and landscape analysis, and pre-tested. FGs led by a trained moderator and audio-recorded. Transcripts content analyzed for key themes. RESULTS: Nearly all respondents saw potential benefits to GWP participation for themselves or their families. However, there were profound differences in perceptions of risks to GWP participation between Black and White/Asian respondents. These differences surfaced in three broad areas: privacy and discrimination risks; family impact risks; and feelings about the employer. Willingness to participate in a GWP also varied between Black employee respondents and White and Asian employee respondents (including low-income White employees). Only 27% of Black employees would participate in GWP, compared to 90% of the other employees. CONCLUSION: Most employees appear likely to support employer adoption of GWPs. However, Black employees report significant concerns regarding participation. Addressing these concerns through program design would benefit all employees, and could increase trust and uptake of GWPs.

An examination of the diagnostic efficiency of post-deployment mental health screens.

OBJECTIVE: To conduct a blinded study to examine the diagnostic efficiency of the Department of Defense (DoD) Post-Deployment Health Reassessment (PDHRA) screens for major depressive disorder (MDD), posttraumatic stress disorder (PTSD), and alcohol abuse. METHOD: Participants were 148 post-deployed soldiers who were completing the PDHRA protocol. Soldiers' mean age was 27.7 (standard deviation = 6.6) years, and 89.0% were male. Mental health professionals blinded to the PDHRA screening results administered the Structured Clinical Interview for the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition directly after the PDHRA assessment protocol. RESULTS: All screens exhibited excellent negative predictive power. Sensitivity metrics were lower, consistent with the relatively low base rates observed for MDD (10.1%), PTSD (8.8%), and alcohol abuse (5.4%). Metrics obtained for the PTSD screen were consistent with previous research with a similar base rate. A two-item screen containing PTSD reexperiencing and hyperarousal symptom items revealed excellent psychometric properties (sensitivity = .92; specificity = .79). The alcohol abuse screen yielded high sensitivity (.86), but very poor precision; these metrics were somewhat improved when the screen was reduced to a single item. CONCLUSIONS: The PDHRA MDD, PTSD, and alcohol abuse screens appear to be functioning well in accurately ruling out these diagnoses, consistent with a population-level screening program. Cross validation of the current results is indicated. Additional refinement may yield more sensitive screening measures within constraints imposed by the low base rates in a typically healthy population.

Improving Quality and Safety for Patients After Hospital Discharge: Primary Care as the Lead Integrator in Postdischarge Care Transitions.

To understand current and idealized primary care-based care transition workflow processes for hospitalized patients, we conducted 133 interviews with staff at 9 primary care sites; community agency staff (n = 18); recently discharged patients (n = 33); and primary care thought leaders (n = 9). Current postdischarge workflows in primary care vary widely across settings, are often implemented inconsistently, and rarely involve communications with the patient or inpatient team during hospitalization. Based on these findings, we propose 5 principles for primary care practices to facilitate active involvement in postdischarge care, beginning during the hospital admission and extending until after the initial postdischarge primary care visit.

Factors associated with federally qualified health center financial performance.

OBJECTIVES: To understand factors associated with federally qualified health center (FQHC) financial performance. STUDY DESIGN: We used multivariate linear regression to identify correlates of health center financial performance. We examined six measures of health center financial performance across four domains: margin (operating margin), liquidity (days cash on hand [DCOH], current ratio), solvency (debt-to-equity ratio), and others (net patient accounts receivable days, personnel-related expenses). We examined potential correlates of financial performance, including characteristics of the patient population, health center organization, and location/geography. DATA SOURCES: We use 2012-2017 Uniform Data System (UDS) files, financial audit data from Capital link, and publicly available data. DATA COLLECTION/EXTRACTION METHODS: We focused on health centers in the 50 US states and District of Columbia, which reported information to UDS for at least 1 year between 2012 and 2017 and had Capital link financial audit data. PRINCIPAL FINDINGS: FQHC financial performance generally improved over the study period, especially from 2015 to 2017. In multivariate regression models, a higher percentage of Medicaid patients was associated with better margins (operating margin: 0.06, p < 0.001), liquidity (DCOH: 0.67, p < 0.001; current ratio: 0.28, p = 0.001), and solvency (debt-to equity ratio: -0.08, p = 0.004). Moreover, a staffing mix comprised of more nonphysician providers was associated with better margin (operating margin: 0.21, p = 0.001) and liquidity (current ratio: 1.12, p < 0.001) measures. Patient-centered medical home (PCMH) recognition was also associated with better liquidity (DCOH: 19.01, p < 0.001; current ratio: 4.68, p = 0.014) and solvency (debt-to-equity ratio: -2.03, p < 0.001). CONCLUSIONS: The financial health of FQHCs improved with provisions of the Affordable Care Act, which included significant Medicaid expansion and direct funding support for health centers. FQHC financial health was also associated with key staffing and operating characteristics of health centers. Maintaining the financial health of FQHCs is critical to their ability to continuously provide affordable and high-quality care in medically underserved areas.

Acceptability, safety and tolerability of antidepressant repetitive transcranial magnetic stimulation for adolescents: A mixed-methods investigation.

OBJECTIVE: Major depressive disorder (MDD) is relatively common in adolescence, with far-reaching impacts. Current treatments frequently fail to alleviate depression severity for a substantial portion of adolescents. Repetitive transcranial magnetic stimulation (rTMS) may assist with this unmet clinical need. However, little is known about adverse events (AEs) experienced by adolescents receiving rTMS, subjective treatment experiences of adolescents and their parents, or treatment acceptability. METHODS: Fourteen adolescents (16.5 years ± 1.2; 71.4% female) with MDD received 20 sessions of either high-frequency (10 Hz; n = 7) left dorsolateral prefrontal cortex (DLPFC) or low-frequency (1 Hz; n = 7) right DLPFC rTMS. AEs were monitored at baseline and at weekly intervals via New York State Psychiatric Institute Side Effects Form for Children and Adolescents. Eight adolescents and nine parents participated in interviews regarding subjective treatment experience, analysed via content analysis. RESULTS: Drowsiness and lethargy were common AEs, reported by 92.3% of participants in week one. Number of AEs decreased throughout treatment course (after 5 treatments: M = 11.23, SD = 5.00; after 20 treatments: M = 8.92, SD = 5.95). Thirty-five AEs emerged during treatment, most commonly transient dizziness. Frequency, severity, and number of AEs reported were equivalent between treatment groups. Treatment adherence and satisfaction were high. Qualitative findings identified three themes relating to rTMS experience: Preparation and connection; Physical experience of treatment; and Perceived role of treatment. LIMITATIONS: Sample size was small, therefore findings are preliminary. CONCLUSIONS: rTMS was an acceptable treatment for adolescent MDD, from both adolescents' and parents' perspectives, and was safe and well-tolerated, as AE frequency and type did not differ from rTMS treatment courses in adults.

A Variational Approach to Scripts.

This paper proposes a formal reconstruction of the script construct by leveraging the active inference framework, a behavioral modeling framework that casts action, perception, emotions, and attention as processes of (Bayesian or variational) inference. We propose a first principles account of the script construct that integrates its different uses in the behavioral and social sciences. We begin by reviewing the recent literature that uses the script construct. We then examine the main mathematical and computational features of active inference. Finally, we leverage the resources of active inference to offer a formal model of scripts. Our integrative model accounts for the dual nature of scripts (as internal, psychological schema used by agents to make sense of event types and as constitutive behavioral categories that make up the social order) and also for the stronger and weaker conceptions of the construct (which do and do not relate to explicit action sequences, respectively).

Outcomes in rheumatoid arthritis patients treated with abatacept: a UK multi-centre observational study.

BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory autoimmune disease that causes chronic synovitis, resulting in progressive joint destruction and functional disability and affects approximately 400,000 people in the UK. This real-world study aimed to describe the characteristics, treatment patterns and clinical outcomes of patients who received abatacept in UK clinical practice. METHODS: This was a multi-centre, retrospective, observational study of patients with RA treated with abatacept at four UK centres between 01 January 2013 and 31 December 2017. Data were collected from medical records of each patient from the index date (date of first bDMARD initiation) until the most recent visit, death or end of study (31 December 2017). RESULTS: In total, 213 patients were included in the study. Patients received up to eight lines of therapy (LOTs). Treatment with abatacept, or any other bDMARD, was associated with reductions in DAS28-ESR and DAS28-CRP scores at 6 and 12 months. The distribution of EULAR responses (good/moderate/no response) tended to be more favourable for patients when receiving abatacept than when receiving other bDMARDs (22.8%/41.3%/35.9% versus 16.6%/41.4%/42.1% at 6 months, and 27.9%/36.1%/36.1% versus 21.2%/34.5%/44.2% at 12 months). Patients receiving abatacept at LOT1 (n = 68) spent significantly longer on treatment compared with patients receiving other bDMARDs (53.4 vs. 17.4 months; p< 0.01); a similar trend was observed for LOT2. Among patients who discontinued after 6 months, a greater proportion experienced infection requiring antibiotics when receiving other bDMARDs compared to those receiving abatacept. CONCLUSIONS: RA patients who received bDMARDs, including abatacept, experienced reduced disease activity. When receiving abatacept as first or second line of therapy, patients persisted with treatment significantly longer than those receiving other bDMARDs.

Association of the tumour necrosis factor-308 variant with differential response to anti-TNF agents in the treatment of rheumatoid arthritis.

Anti-tumour necrosis factor (TNF) agents have revolutionized the treatment of patients with rheumatoid arthritis (RA). These therapies are, however, expensive and 30% of patients fail to respond. In a large cohort of Caucasian RA patients treated with anti-TNF medications (total n = 1050, etanercept n = 455, infliximab n = 450), we investigated whether genotypes of eight single nucleotide polymorphisms in the region containing the TNF gene were associated with response to anti-TNF therapy. Linear regression analyses adjusted for baseline 28 joint disease activity score (DAS28), baseline health assessment questionnaire score, gender and concurrent disease modifying anti-rheumatic drug treatment were used to assess association of these polymorphisms with treatment response, defined by change in DAS28 after 6 months. Analyses were performed in the entire cohort, and also stratified by anti-TNF agent. Association between DAS28 response and TNF-308 (rs1800629) genotype (P = 0.001) was detected across the whole cohort. After stratification by anti-TNF agent, the rare TNF-308AA genotype was associated with a significantly poorer response compared with TNF-308GG in etanercept (P = 0.001, n = 7) but not infliximab (P = 0.8, n = 17) treated patients. Conversely, the GA genotype at TNF-238 (rs361525) was associated with a poorer response to infliximab (P = 0.028, n = 40), but not etanercept (P = 0.6, n = 33). Owing to the small numbers of patients in some of the genotype groups examined, our data must be regarded as preliminary and will require replication in further large cohorts of anti-TNF-treated patients. If confirmed, our findings suggest the potential for genotype at these markers to aid selection of anti-TNF agent in patients with RA.

PADI4 genotype is not associated with rheumatoid arthritis in a large UK Caucasian population.

BACKGROUND: Polymorphisms of the peptidylarginine deiminase type 4 (PADI4) gene confer susceptibility to rheumatoid arthritis (RA) in East Asian people. However, studies in European populations have produced conflicting results. This study explored the association of the PADI4 genotype with RA in a large UK Caucasian population. METHODS: The PADI4_94 (rs2240340) single nucleotide polymorphism (SNP) was directly genotyped in a cohort of unrelated UK Caucasian patients with RA (n=3732) and population controls (n=3039). Imputed data from the Wellcome Trust Case Control Consortium (WTCCC) was used to investigate the association of PADI4_94 with RA in an independent group of RA cases (n=1859) and controls (n=10 599). A further 56 SNPs spanning the PADI4 gene were investigated for association with RA using data from the WTCCC study. RESULTS: The PADI4_94 genotype was not associated with RA in either the present cohort or the WTCCC cohort. Combined analysis of all the cases of RA (n=5591) and controls (n=13 638) gave an overall OR of 1.01 (95% CI 0.96 to 1.05, p=0.72). No association with anti-CCP antibodies and no interaction with either shared epitope or PTPN22 was detected. No evidence for association with RA was identified for any of the PADI4 SNPs investigated. Meta-analysis of previously published studies and our data confirmed no significant association between the PADI4_94 genotype and RA in people of European descent (OR 1.06, 95% CI 0.99 to 1.13, p=0.12). CONCLUSION: In the largest study performed to date, the PADI4 genotype was not a significant risk factor for RA in people of European ancestry, in contrast to Asian populations.

Alcohol consumption is inversely associated with risk and severity of rheumatoid arthritis.

OBJECTIVE: To investigate the association between frequency of alcohol consumption and the risk and severity of RA. METHODS: Frequency of alcohol consumption was recorded by patients and controls in a self-completed questionnaire. Odds ratios (ORs) for RA risk were calculated according to alcohol consumption, adjusted for age, gender and smoking status. Median values of all RA severity measures were then calculated according to the frequency of alcohol consumption, and the non-parametric trend test was used to assess association. A negative binomial regression model was used to adjust for potential confounding. RESULTS: Eight hundred and seventy-three patients with erosive RA, and 1004 healthy controls were included in the study. Risk of RA decreased according to frequency of alcohol consumption, such that non-drinkers had an OR for RA of 4.17 (3.01-5.77) compared with subjects consuming alcohol on >10 days per month (P for trend <0.0001). All measures of RA severity including CRP, 28-joint DAS, pain visual analogue scale, modified HAQ (mHAQ) and modified Larsen score were inversely associated with increasing frequency of alcohol consumption (P for trend, each <0.0001). After adjustment for potential confounding in a multivariate regression model, frequency of alcohol consumption remained significantly and inversely associated with X-ray damage and mHAQ. CONCLUSION: Although there are some limitations to this study, our data suggest that alcohol consumption has an inverse and dose-related association with both risk and severity of RA.

Genotype at the sIL-6R A358C polymorphism does not influence response to anti-TNF therapy in patients with rheumatoid arthritis.

OBJECTIVES: To investigate the association between genotype at the soluble interleukin 6 receptor (sIL-6R) A358C single nucleotide polymorphism (SNP, rs8192284), previously reported to correlate with soluble receptor levels, and response to anti-TNF therapy in subjects with RA. METHODS: In a large cohort of Caucasian RA patients treated with anti-TNF medications (total, n = 1050; etanercept, n = 455; infliximab, n = 450; and adalimumab, n = 142), the sIL-6R A358C polymorphism was genotyped using a Taqman 5'-allelic discrimination assay. Linear regression analysis adjusted for baseline 28 joint disease activity score (DAS28), baseline HAQ score, gender and use of concurrent DMARDs was used to assess the association of genotype at this polymorphism with response to anti-TNF therapy, defined by change in DAS28 after 6 months of treatment. Analyses were performed in the entire cohort, and also stratified by an anti-TNF agent. Additional analysis according to the EULAR response criteria was also performed, with the chi-squared test used to compare genotype groups. RESULTS: No association between genotype at sIL-6R A358C and response to anti-TNF treatment was detected either in the cohort as a whole or after stratification by anti-TNF agent, in either the linear regression analysis or with response segregated according to EULAR criteria. CONCLUSIONS: This study shows that genotype at the functional sIL-6R A358C SNP is not associated with response to anti-TNF treatment in patients with RA.

Cost-effectiveness of integrated care for elderly depressed patients in the PRISM-E study.

BACKGROUND: One proposed strategy to improve outcomes associated with depression and other behavioral health disorders in primary care settings is to strengthen collaboration between primary care and specialty mental health care through integrated care (IC). AIMS: We compare the cost-effectiveness of IC in primary care to enhanced specialty referral (ESR) for elders with behavioral health disorders from the Primary Care Research in Substance Abuse and Mental Health study, which was a randomized trial conducted between 2000 and 2002, using a societal perspective. METHODS: The IC model had a behavioral health professional co-located in the primary care setting, and the primary care provider continued involvement in the mental health/substance abuse care of the patient. The comparison model, enhanced specialty referral (ESR), required referral to a behavioral health provider outside the primary care setting, and the behavioral health provider had primary responsibility for the mental health/substance abuse needs of the patient. Costs and clinical outcomes for 840 elders with depression were analyzed using incremental cost-effectiveness ratios, the net benefits framework, cost-effectiveness planes, and acceptability curves. Outcomes were measured by the Center for Epidemiologic Studies Depression Scale (CES-D) and converted to depression-free days and Quality Adjusted Life Years (QALY). A variation on depression free days was proposed as an improvement on current methods. Separate analyses were conducted for Veteran's Affairs (n=365; n=175 in IC and n=190 in ESR) and non-Veteran's Affairs (n=475; n=242 in IC and n=233 in ESR) settings. RESULTS: ESR participants in the non-VA sample exhibited lower average CES-D scores (i.e., an improvement in depressive symptoms) than did IC participants (beta = 2.8, p < 0.01), no such difference was noted in the VA sample (p > 0.05). Mean costs were $D6,338 for VA IC participants; $7,007 for VA ESR participants; $3,657 for non-VA IC participants; and $3,673 for non-VA ESR participants. Although the cost-effectiveness planes suggest some uncertainty about the cost-effectiveness of the intervention, more than 75% of the bootstrap draws were considered cost-effective due to a decrease in total costs for IC in the full Veteran's Affairs sample. DISCUSSION: The findings indicate that IC is likely to be a cost-effective intervention in contrast with ESR in the Veteran's Affairs setting. In the non-Veteran's Affairs settings, IC is not a more cost-effective intervention in comparison with ESR. In the VA setting, the greater clinical improvement associated with IC coupled with the variation in costs and outcomes were such that IC was determined to be more cost-effective than ESR with a probability of 73-80%. Among non-VA participants, the lower clinical outcomes combined with no discernable differences in costs translated with a low probability that IC was more cost-effective than ESR, at any of the estimated values of clinical improvements. This suggests the importance of clinical setting in determining the clinical and cost effectiveness of IC for mental health. LIMITATIONS: Our analyses were restricted to a six-month period, based on self-report, and did not include societal costs related to lost productivity and future costs. IMPLICATIONS: These results suggest that general integration has its advantages and, when such integration exists, further integrating behavioral health care into primary care might be considered as one way to improve depression in elders. The finding that ESR may be cost effective in some settings is also policy relevant. Further research is needed to analyze the components of the costs of ESR in non-VA settings and the effectiveness of IC in VA settings.