Rheumatoid arthritis (RA) is a chronic inflammatory joint disease. The introduction of a new class of disease-modifying anti-rheumatic drugs, which work by inhibiting the Janus kinase-signal transducer and activator of transcription (JAK/STAT) pathway, has led to new possibilities for achieving remission of RA. Tofacitinib and baricitinib are both JAK/STAT inhibitors, which have shown efficacy in line with anti-tumour necrosis factor treatment. The side effects seem manageable, and up to now only increased risk of herpes zoster has raised consideration. JAK/STAT inhibitors create new possibilities for reaching low disease activity or remission for patients with RA.

Sieben neue direkt antivirale Substanzen (DAA) sind zwischen Januar 2014 und Januar 2015 zur Therapie der chronischen Hepatitis C zugelassen worden. Effektivität und Sicherheit der neuen Therapien außerhalb kontrollierter klinischer Studien sind weitgehend unbekannt. Das Deutsche Hepatitis C-Register (DHCR) ist ein Projekt der Deutschen Leberstiftung in Kooperation mit dem bng und hat das Ziel, mind. 10.000 Patienten inkl. Langzeitnachbeobachtung von bis zu 5 Jahren zu dokumentieren.

Introduction Post-discharge pulmonary rehabilitation (PR) within 7–10 days after discharge from hospital admission for acute exacerbation of COPD (AECOPD) has been shown not only to result in the well-described benefits of PR (reduced breathlessness, improved exercise performance and health-related quality of life), but also to reduce emergency department attendances over a 3 month period. We report the outcomes of a locally-provided post-exacerbation PR (PEPR) pilot study for patients admitted to hospital with AECOPD, and compares outcomes and subsequent 90-day re-admission rates with published RCT data showing re-admission reduction from 33 to 7%1. Methods Patients were recruited during AECOPD admission to start PR within 10 days of discharge from hospital. Taxi transport was offered to all patients.Outcome measures chosen were change in: 6-Minute Walking Test (6MWT), Hospital Anxiety and Depression Score (HADS), Chronic Respiratory Disease Questionnaire (CRDQ), and 90-day re-admission rates. Results 43 patients were offered PEPR, 32 started and 21/32 (66% of starters, 49% of all referrals) completed the course (>11/16 sessions). Mean (range) age was 67(40–86) years and mean (SD) %predicted FEV1 32(15)%. Median time (range) between discharge from hospital and starting PEPR was 8(0–17) days. There were clinically significant improvements in 6MWT median (range) 27%(-40- + 233) and CRDQ dyspnoea domain 0.79(-0.60– + 3.00). There was no clear effect on 90-day re-admission rate: 45% patients who started PEPR were re-admitted v 58% who were offered but declined PEPR. Local 90-day re-admission rate for all 2012 AECOPD admissions was 39%. Conclusion This study failedto replicate published reductions in re-admission rates in a patient population that was more severe than the comparison study, mean%predicted FEV1 32% v 52%1. Value of PEPR programmes in reducing AECOPD re-admission rates needs further investigation across disease severity spectrum. An additional area that would benefit from further investigation is completion rate for PEPR2; completion rate from referral for PEPR at 49% compares to 43% for our standard PR programme. References Seymour et al. Outpatient pulmonary rehabilitation following acute exacerbations of COPD. Thorax 2010;65:423–428 National Institute of Health Research, HTA no 13/24 ‘does starting PR early following AECOPD improve adherence and outcomes compared to starting rehabilitation later?’

Introduction PR is associated with functional, emotional and resource benefits for breathless COPD patients which decline over 12–18 months. Patients who complete PR express the desire to continue exercising regularly with other breathless patients but there is currently no evidence for efficacy. This study evaluated regular community-based LTEfor these patients. Methods Patients completing PR were recruited to once weekly LTE held in accessible venues by 2 exercise instructors (Loughborough trained for exercising patients with chronic respiratory disease). Baseline demographics and disease severity were collected and outcomes: 6 minute walk test (6MWT), Hospital Anxiety & Depression (HAD) score, COPD Assessment Test (CAT), Chronic Respiratory Questionnaire (CRQ) and patient satisfaction measured at baseline, 6 and 12 months. Patients who accepted referral for LTE but never attended or dropped-out were recalled for outcomes at 12 months. Hospital admissions were audited for 12 months after PR-completion. Results Between June-2010 and January-2012 75 patients mean(SD) age 69.3(9.7)yrs, FEV1 1.26(0.54)L, MRC 3.16(0.81) 63% female, 19.2% current smokers and 3 on LTOT accepted referral to LTE. 35% (26/75) never attended and 27%(20/75) dropped out after starting; 39% (29/75) continued to exercise for at least 6 months and 25% (19/75) exercised to 1 yr. For patients who exercised for 12 months there was no significant decline in exercise capacity (6MWT), a significant improvement in CAT over 6/12 (p=0.002) maintained to 12/12 (p=0.02) and no increase in anxiety levels, which remained below clinical relevance for the 12 months post PR. In comparison, patients who did not continue LTE had a significant (p=0.001) decline in 6MWT, no change in CAT score and a significant(p=0.04) increase in anxiety to a clinically important range (table 1). Self reported hospital admissions in the year following PR were higher for patients who did not exercise (mean 0.61 (SD 1.47)) compared to those who did, 0.16 (0.50). Conclusions This pilot demonstrates that community-based LTE with trained instructors is safe and realistic for breathless patients after completing PR and, for the first time, demonstrates significant prolongation of functional and emotional benefits. This offers acheaper, more durable alternative to repeating PR.

Einleitung: Insulinresistenz (IR)+metabolisches Syndrom wurden bei Patienten mit chronischer Hepatitis C Virus Infektion (HCV) berichtet, die Assoziation mit Genotypen wird kontrovers diskutiert. Es wird angenommen, dass IR einen negativen Einfluss auf den Erfolg einer antiviralen Therapie haben kann.

Einleitung: Insulinresistenz (IR) ist mit einer chronischen Hepatitis C Virus (HCV) Infektion assoziiert. Daneben können IR & Präsenz des metabolischen Syndroms einen negativen Einfluss auf den Erfolg einer antiviralen Therapie haben.

Background: Insulin resistance (IR) has been documented in patients chronically infected with hepatitis C virus (HCV), but the association with specific genotypes is still controversial.Yet it has been observed that IR or presence of the metabolic syndrome might have a negative influence on antiviral treatment responses.Methods: The German gastroenterologists in private practice are conducting a Germany-wide, non-interventional study in cooperation with Roche.Within this observational study markers of insulin resistance and cardiovascular risk parameters are investigated.Results: In this Interim-analysis of 2513 patients that completed therapy with PEG-interferon alfa-2a 180 mg and Ribavirin as well as week 24 of follow-up were evaluated for cardiovascular and metabolic risk markers.63% of patients were male.60.6% were infected with GT1/4/5/6, 39.4% with GT2/3.At baseline GT1/4/5/6 patients more often presented signs of metabolic syndrome: BMI > 27 kg/m 2 (29.2% vs. 23.8%),glucose >100 mg/dl (23% vs. 20.5%),diabetes (4.7% vs. 3.2%), treated hypertension (8.9% vs. 5.5%) and elevated triglyceride levels >150 mg/dl (31.3% vs. 21.9%).Sustained virological response (SVR) was observed in 44.3%.Markers of metabolic syndrome like treated hypertension [Odds ratio for nonSVR (OR) 1.47], glucose >100 mg/dl (OR 1.35), diabetes (OR 3.12), insulin treatment (OR 2.81) were predictive of non-SVR in addition to viral genotype, viral load, duration of infection and age.Presence of diabetes had especially a negative effect on SVR in patients with GT1/4/5/6 (OR3.33), but had no effect on SVR in GT2/3 patients.In contrast a total cholesterol >190 mg/dl was predictive of an increased SVR (OR 1.35) independent of genotype.Conclusions: Patients infected with GT1,4,5,6 have more often signs of metabolic syndrome.More important elevated hypertension, elevated fasting glucose or diabetes were negative prognostic parameters for SVR besides viral genotype and viral load.In contrast elevated cholesterol levels predicted a better SVR.IR therefore identifies difficult to treat patients who might need further treatment options.

OBJECTIVE To develop a model for the prediction of type 2 diabetes mellitus (T2DM) risk on the basis of a multivariate logistic model and 1-h plasma glucose concentration (1-h PG). RESEARCH DESIGN AND METHODS The model was developed in a cohort of 1,562 nondiabetic subjects from the San Antonio Heart Study (SAHS) and validated in 2,395 nondiabetic subjects in the Botnia Study. A risk score on the basis of anthropometric parameters, plasma glucose and lipid profile, and blood pressure was computed for each subject. Subjects with a risk score above a certain cut point were considered to represent high-risk individuals, and their 1-h PG concentration during the oral glucose tolerance test was used to further refine their future T2DM risk. RESULTS We used the San Antonio Diabetes Prediction Model (SADPM) to generate the initial risk score. A risk-score value of 0.065 was found to be an optimal cut point for initial screening and selection of high-risk individuals. A 1-h PG concentration >140 mg/dL in high-risk individuals (whose risk score was >0.065) was the optimal cut point for identification of subjects at increased risk. The two cut points had 77.8, 77.4, and 44.8% (for the SAHS) and 75.8, 71.6, and 11.9% (for the Botnia Study) sensitivity, specificity, and positive predictive value, respectively, in the SAHS and Botnia Study. CONCLUSIONS A two-step model, based on the combination of the SADPM and 1-h PG, is a useful tool for the identification of high-risk Mexican-American and Caucasian individuals.

Introduction and Objectives COPD is a major cause of mortality/morbidity in high smoking prevalence Primary Care Trusts (PCTs). Our PCT expected COPD prevalence (3.7%) is therefore high but recorded prevalence (2009/2010) was 1.4%, suggesting large numbers of undiagnosed patients. COPD, as the 2nd commonest cause of emergency admission locally, is one of the most costly diseases for secondary care. Local research (Bastin et al, 20101) shows that, while most patients admitted for the first time with acute exacerbations of COPD have severe disease, there is no prior diagnosis in ∼1/3 cases. A COPD Local Enhanced Service (LES) was developed, to incentivise practices to proactively identify, diagnose and manage COPD patients using evidence-based interventions. Methods All GP practices in were invited to participate in the COPD LES. Key elements included number of case finding spirometries performed in smokers/ex-smokers =35 y, and provision of interventions (pulmonary rehabilitation (PR) referral, self-management, oxygen auditing) with regular reviews/assessments. Primary outcomes were the number of new COPD diagnoses, a change in the gap between recorded and estimated COPD prevalence and number of non-elective hospital admissions. Data were extracted from the PCT GP dataset, QMAS (diagnosed prevalence), APHO COPD-prevalence model (expected prevalence) and Secondary Users Services (hospital admission data). Results 37/38 (97%) GP practices signed up to provide the LES. Between April 2010 and May 2011, 1807 case finding spirometries were performed resulting in an estimated 477 new COPD diagnoses, significantly reducing the undiagnosed COPD prevalence by 0.2% (p<0.05). Compared to the same period in 2009, referrals to PR increased from 78 to 119 (52%) in the first 6/12. Audits of oxygen therapy identified ongoing unnecessary payment in 52 patients (47 died/moved, five patients no longer required oxygen). Twenty-nine patients on LTOT had not been reviewed and were subsequently referred. The LES impact on the rate of emergency admissions for COPD remains unclear. Conclusions One year evaluation demonstrates the COPD-LES is an effective strategy to improve case finding and diagnosis of COPD, improve PR referrals and rationalise oxygen prescribing. Ongoing audit of COPD emergency admissions will determine whether the LES achieves its objective.Abstract P223a Table 1 Changes between recorded and expected prevalence of COPD, persons aged 16+, 2009–2011 (QOF) Time period Recorded prevalence Expected prevalence Undiagnosed prevalence Number % Number % 2010/2011 2966 1.6% 3.7% 3750 2.1% 2009/2010 2651 1.4% 4240 2.3% 2008/2009 2579 1.4% 4160 2.3%

Introduction There is evidence that regular exercise profoundly affects both the course and outcome of COPD. While PR is well established for COPD patients limited by breathlessness, there is currently no evidence-base for follow-on LTE, which takes into account expressed desires of patients to continue exercise regularly. This pilot study aimed to evaluate an easily accessible, disease appropriate, regular LTE for COPD patients who complete PR, to confirm that it is realistic and assess whether PR benefits can be sustained. Methods Three suitable venues, geographically distributed to maximise access, and two exercise instructors (completed Loughborough Training for Chronic Respiratory Patients) were identified. Patients completing PR were recruited into 1×weekly LTE groups. Outcomes (demographic, disease severity, functional capacity (6 min walk test (6MWT), emotional (Hospital Anxiety and Depression HAD score, CAT and Chronic Respiratory Questionnaire CRQ)) were collected at baseline, 6 and 12 months. Patient and carer satisfaction was recorded at 6 and 12 months. Attendance data were monitored throughout. Hospital admissions for 12/12 before and after LTE commenced, continues to be audited. Results 60 COPD patients (Mean (SD) age 68.75 (10.31) yrs, FEV1 1.27 (0.56) l, 43% male, 22% current smokers, three on LTOT) were referred for LTE June 2010–May 2011. 20/60 (33%) never attended, 14/60 (23%) dropped out within 2 (1–7) months (median (range). 26/60 (43%) continue to exercise, median (range) since starting 5 (1–12) months with 50 (28)%. (Mean (SD) classes attendance. CAT, CRQ, HADS and 6MWT findings are given in the Abstract P149 table 1. Satisfaction surveys indicate high levels of satisfaction with venue, instructor and content. No adverse events occurred during the classes. Direct cost per class (hall hire and instructor) £63.Abstract P149 Table 1 Health related quality of life and exercise capacity at end-PR, 6 months and 12 months of long-term exercise Baseline, n=60, mean (SD) 6 Months, n=11, mean (SD) 12 Months, n=3, mean (SD) MRC 3.2 (0.8) CAT score 22.2 (6.8) 12.4 (7.4) 17.0 (14.1) CRQ Dyspnoea 3.3 (1.4) 4.2 (1.6) 4.9 (1.9) CRQ fatigue 4.1 (1.5) 4.9 (1.2) 4.7 (2.5) CRQ emotional function 4.8 (1.6) 5.3 (1.3) 4.8 (2.9) CRQ mastery 4.9 (1.7) 5.8 (1.4) 4.1 (1.9) HADS anxiety 7.4 (5.1) 4.3 (3.3) 6.0 (6.0) HADS depression 5.2 (4.2) 3.6 (2.5) 4.7 (4.7) 6 MWT (metres) 353 (116) 338 (83) 330 (122) Conclusions This pilot demonstrates feasibility of providing community-based LTE groups using instructors trained to exercise people with COPD. Patients who choose to attend LTE have moderate COPD, but high CAT scores indicating important disease impact on daily functioning. Attendance rate was high for a patient group susceptible to exacerbations, possibly reflecting high patient satisfaction. Preliminary findings suggest LTE in group settings promotes maintenance of benefits acquired from PR with further improvement in health-related quality of life (CRQ and CAT).

Diabetes, primarily type 2 diabetes, has increased in prevalence throughout the world and current projections suggest a continued rise worldwide for at least the next quarter century. Insulin resistance, which frequently accompanies obesity, is known to be a key factor in the pathogenic development of type 2 diabetes (1–6). Type 2 diabetes occurs when insulin secretion is no longer sufficient to compensate for the resistance to the actions of insulin. Measurements of insulin sensitivity and secretion are currently done only for research purposes and are only comparable in individual studies. There are no clinical applications for these measures. In fact, there are no criteria by which an individual could be classified as being insulin sensitive or resistant or as having mild, moderate, or severe impairment of insulin secretion. In theory, one could envision that knowledge of an individual's response to insulin or the ability to secrete insulin might be useful for selecting patients for intensified prevention efforts, in the choice of initial therapy upon onset of overt hyperglycemia, or in evaluating the response to therapy beyond glycemia. For example, if a person newly diagnosed with diabetes could be determined to be very insulin resistant, the choice of initial therapy could be a drug that primarily improves insulin sensitivity. On the other hand, if the person was only moderately insulin resistant but had more of a defect in insulin secretion, a drug that improves insulin secretion might …

Background: Insulin resistance (IR) has been documented in patients chronically infected with hepatitis C virus (HCV), but the association with specific genotypes is still controversial.Yet it has been observed that IR or presence of the metabolic syndrome might have a negative influence on antiviral treatment responses.Methods: The German gastroenterologists in private practice are conducting a Germany-wide, non-interventional study in cooperation with Roche.Within this observational study markers of insulin resistance and cardiovascular risk parameters are investigated.Results: In this Interim-analysis of 2501 patients receiving therapy with PEG-interferon alfa-2a 180 mg and ribavirin were evaluated for cardiovascular and metabolic risk markers and prospectively followed.62.9% of patients were male.61.8% were infected with GT1, 6.2% with GT2, 28.1% with GT3, 3.6% with GT4 and 0.2% with GT5/6.Patients infected with GT1, 4, 5 more often had high viral load (>400.000IU/ml) and longer duration of infection (12.8 vs. 10.8 years) compared with GT2, 3 infected patients.At baseline GT1, 4, 5 patients more often presented signs of metabolic syndrome: BMI >27 kg/m 2 (31% vs. 24) and elevated triglyceride levels (30% vs. 23%).Early virological response at week 12 (>2 log decline of viral load or HCV-RNA undetectable) (EVR) was observed in 89.8%.Markers of metabolic syndrome (obesity, hypertension, elevated triglycerides and blood sugar) and diabetes were predictive of initial non-response (NR).Multivariate regression analysis identified GT1, 4, 5 (OR 7.98), BMI >27 (OR 2.70), triglycerides >150 mg/dl (OR1.82) and fasting glucose >110 mg/dl (OR1.82) as independent parameters for NR, while surprisingly a total cholesterol >190 mg/dl was associated with improved EVR (OR0.45).1811 patients completed week 24 with a virological response of 80.3%.Although parameters of metabolic syndrome were negative predictive parameters for a virological response at week 24, multivariate analysis just revealed GT1, 4, 5 to be predictive of virological response at week 24 once EVR had been achieved.Conclusions: Patients infected with GT1, 4, 5 have more often signs of metabolic syndrome.More importantly elevated BMI, triglycerides and glucose were negative, independent prognostic parameters for EVR besides viral genotype, while elevated cholesterol levels predicted a better response at week 12. IR therefore identifies difficult to treat patients who might warrant further treatment options.

Einleitung: Insulinresistenz (IR) wurde bei Patienten mit chronischer Hepatitis C (HCV) nachgewiesen. Die Assoziation mit speziellen Genotypen ist noch umstritten. Es wurde beobachtet, dass IR & Präsenz des metabolischen Syndroms negativen Einfluss auf die antivirale Therapie haben können.

Aims: Treatment options for chronic hepatitis C have been continuously improved during the last decade. However subpopulations difficult to treat remain a particular challenge. Coinfection with HIV or HBV have been shown to adversely affect treatment outcome of cHC. In a large German multicenter surveillance study we assessed the effect of HIV- and HBV-coinfection on therapy compared to monoinfected pts. Methods: A total of 4061 HCV pts were treated with a combination of weight-adapted PEG-IFNα-2b and RBV. Of these, 92 (2.3%) and 73 (1.8%) had a coinfection with HBV and HIV respectively. Cirrhosis of liver was diagnosed in 238 pts (5.9%), in 2 HCV-HBV-coinfected (2.2%) and 5 HCV-HIV-coinfected pts (6.8%). 89.8% of all pts (n=3647) were treatment naïve, with 90.2% in pts with HCV-HBV coinfection and 89% in HCV-HIV coinfected persons. Pts past the planned treatment duration and the follow-up period of 6 months (n=3437) were analyzed. Results: SVR-rates (HCV-RNA-negativity 24 weeks after end of treatment) were 45.9% (34/74) for HCV-HBV and 35.7% (20/56) for HCV-HIV, respectively. In HCV-monoinfected pts 53.0% (1723/3250) achieved SVR. Relapse rates were 18.1% (382/2105) for HCV-monoinfected pts and 17.1% for HBV-HCV- (7/41) and 25.9% (7/27) for HCV-HIV-coinfected pts. Non-response to therapy was recorded for 22.5% of HCV-monoinfected pts (730/3250) compared to 28.4% (21/74) of HCV-HBV- and 30.4% (17/56) of HCV-HIV-coinfected pts. There were significant differences in SVR between HCV-monoinfection and coinfection with HIV but not HBV. Conclusions: SVR rates are encouraging in particular in HBV-coinfected HCV pts. For HIV-coinfection a trend to lower SVR-rates is observed, which may be partially explained by the historic use of lower RBV doses and comedication with abacavir. Less chance for SVR seems not to be due to higher relapse rates, but more probably due to higher risk for non-response on standard therapy within the two groups of coinfected pts.

In their recent commentary, Staten et al. (1) describe their very valuable attempt to standardize insulin assays. Their aim is to allow quantitative comparison of the results obtained in one lab with those measured by a different assay in another lab. I'd like to highlight an issue when it comes to reporting the results. The insulin concentration must be stated in SI units nowadays, i.e., in pmol/l instead of μU/ml. The latter unit refers to the biologic action of this hormone (i.e., its blood glucose–lowering activity) and the former to the number of insulin molecules in a given volume. A fixed conversion factor is used to convert the microunits …