Erythrocyte deformability in naïve HIV-infected patients

HIV-infected patients are at increased cardiovascular risk. Although several studies have analyzed the hemorheological profile in these patients, studies dealing with erythrocyte deformability are scarce. Moreover, studies have been performed in HIV patients on antiretroviral treatment which may influence this rheological parameter. We analyzed erythrocyte deformability (Elongation Index) at 12, 30 and 60 Pa by means of the Rheodyn SSD in 34 na?ve HIV-infected patients (22 males and 12 females) and 34 HIV negative control subjects (24 males and 10 females). Erythrocyte indices (MCV, MCH, MCHC), reticulocytes, plasma lipids, iron, folic acid, vitamin B12 and hepatic enzymes were also determined. When compared with controls, na?ve HIV-infected patients showed lower total cholesterol, iron, bilirubin and folic acid (p = 0.009, p = 0.003, p = 0.004, p = 0.004, respectively) and higher triglycerides (TG), aspartate aminotransferase (AST) and gamma glutamyl transferase (γGt) levels (p = 0.017, p = 0.042, p = 0.004, respectively). In the multivariate regression analysis, MCV, γGt and triglycerides were independent predictors of EI60. Neither erythrocyte indices nor reticulocyte count showed differences (p > 0.05). No differences in the Elongation Index at any of the shear stresses tested (12, 30, 60 Pa) were found (p > 0.05). The results of the present study indicate that na?ve HIV-infected patients not on antiretroviral treatment do not present decreased erythrocyte deformability when compared with HIV negative control subjects.     

Metabolic syndrome in drug naïve schizophrenic patients

Introduction

Research in the last decade tried to focus on natural and unnatural causes of death in schizophrenic patients, but recent few years has focussed on emerging cardio-metabolic risk factors, as a cause of mortality in such patients.

Metabolomics study of fatigue in patients with rheumatoid arthritis naïve to biological treatment

Fatigue occurs in all chronic inflammatory diseases, in cancer, and in some neurological conditions. Patients often regard fatigue as one of their most debilitating problems, but currently there is no established treatment and the mechanisms that lead to and regulate fatigue are incompletely understood. Our objective was to more completely understand the physiology of this phenomenon. Twenty-four patients with rheumatoid arthritis (RA) naïve to treatment with biological drugs were enrolled for the study. Fatigue was measured with a fatigue visual analogue scale (fVAS). Ethylenediaminetetraacetic acid (EDTA) plasma samples were subjected to gas chromatography–time-of-flight mass spectrometry (GC/MS-TOF)-based metabolite profiling. Obtained metabolite data were evaluated by multivariate data analysis with orthogonal projections to latent structures (OPLS) method to pinpoint metabolic changes related to fatigue severity. A significant multivariate OPLS model was obtained between the fVAS scores and the measured metabolic levels. Increasing fatigue scores were associated with a metabolic pattern characterized by down-regulation of metabolites from the urea cycle, fatty acids, tocopherols, aromatic amino acids, and hypoxanthine. Uric acid levels were increased. Apart from fatigue, we found no other disease-related variables that might be responsible for these changes. Our MS-based metabolomic approach demonstrated strong associations between fatigue and several biochemical patterns related to oxidative stress.     

Fast and sharp decrease in calprotectin predicts remission by infliximab in anti-TNF naïve patients with ulcerative colitis

AimTo evaluate the effect of infliximab induction therapy on calprotectin levels in patients with ulcerative colitis (UC).Patients and MethodsIn this prospective study 53 patients with active UC from 17 centers were treated with infliximab therapy (5 mg/kg) at baseline, week 2, and week 6. Faecal calprotectin was measured every week. Sigmoidoscopies were performed at baseline, week 6 and week 10.ResultsMedian calprotectin levels decreased from 1260 (IQR 278.5- 3418 ) at baseline to 72.5 (IQR 18.5 - 463) at week 10 (p < 0.001). After 10 weeks, infliximab therapy induced endoscopic remission and a decrease in calprotectin to < 50 mg/kg or at least a 80% decrease from baseline level in 58% of patients.A significant and steep decrease of calprotectin levels was seen at week 2 for patients with an endoscopic remission at week 10 as compared to patients who did not show a remission. (p < 0.001).At week 10 an excellent correlation was found between endoscopic remission and clinical Mayo score reflected by an AUC of ROC analyses of 0.94 (0.87-1) and with calprotectin measurements (AUC 0.91 (0.81-1)) : all patients with calprotectin levels < 50 mg/kg, and a normal clinical Mayo score (= 0) were in endoscopic remission.ConclusionsInfliximab induces a fast and significant decrease of faecal calprotectin levels in anti-TNF naïve patients with ulcerative colitis predictive for remission of disease     

A randomized trial to assess the efficacy of interferon-alpha daily in combination with ribavirin in the treatment of naïve patients with chronic hepatitis C

Summary. A randomized trial was conducted to assess the efficacy of interferon-alpha (IFN) daily in combination with ribavirin in 301 naïve patients with chronic hepatitis C (CHC). Patients were randomized to receive ribavirin 1.2 g daily (QD) for 48 weeks with either IFN 5 MU (thrice weekly) TIW for 8 weeks followed by IFN 3 MU TIW for 40 weeks (IFN TIW, n  = 154) or IFN 5 MU QD for 8 weeks followed by IFN 3 MU QD for 16 weeks followed by IFN 3 MU TIW for 24 weeks (IFN QD, n  = 147). Treatment discontinuation rates, because of adverse events, were similar in the two arms (14.9% in IFN TIW and 14.3% in IFN QD, P  = 0.87). The proportion of patients with sustained virological response (SVR) was 27.9% for patients treated TIW and 38.8% for those treated QD ( P  = 0.046). According to logistic regression analysis, patients in the IFN QD arm had 1.7 times higher probability of achieving SVR, than those receiving IFN TIW ( P  = 0.038). Low baseline viral load ( P  = 0.017) and genotype non-1 ( P  = 0.036) were associated with higher SVR rates. Combination of IFN/ribavirin for 48 weeks is more effective when IFN is administered daily for the first 24 weeks in naïve patients with CHC.     

Biochemical efficacy of long-acting lanreotide depot/Autogel in patients with acromegaly naïve to somatostatin-receptor ligands: analysis of three multicenter clinical trials

Purpose

In clinical research involving acromegalic patients naïve to somatostatin-receptor ligands (SRLs), 19 and 31% of those receiving the SRLs octreotide LAR and pasireotide LAR, respectively, achieved GH?<?2.5 ng/mL?+?normalized IGF-1 concentrations. The proportions achieving control appeared higher in the post-surgery compared with the de-novo setting with pasireotide, but more similar with octreotide. Using pooled data from multicenter clinical trials, we examined the biochemical efficacy of lanreotide depot/Autogel in similar settings.

Methods

Inclusion criteria: Ipsen-sponsored, 48–52-week trials in SRL-naïve acromegalic populations receiving lanreotide depot (60–120 mg); patients were included if de novo (no prior acromegaly treatment) or post-surgery (no medical treatment; radiotherapy allowed unless within previous 3 years). Efficacy endpoints included normalized IGF-1 levels and GH?<?2.5 ng/mL?+?normalized IGF-1 at study end/last value available. Analyses: all patients (analysis #1) and subset with baseline GH?>?5 ng/mL (analysis #2).

Results

Three studies were included. Analysis #1: normalized IGF-1 was achieved by 42% (71/171) of patients overall (post-surgery, 46% [21/46]; de-novo, 40% [50/125]); GH?<?2.5 ng/mL?+?normalized IGF-1 was achieved by 35% (59/171) (39% [18/46] and 33% [41/125], respectively). Analysis #2: normalized IGF-1 levels, 39% (46/118) (post-surgery, 40% [10/25]; de-novo, 39% [36/93]); GH?<?2.5 ng/mL?+?normalized IGF-1, 31% (36/118) (28% [7/25] and 31% [29/93], respectively).

Conclusion

In these pooled analyses of SRL-naïve patients receiving lanreotide depot, 39–42% achieved IGF-1 control and 31–35% achieved GH and IGF-1 control. Control rates within post-surgery cohorts did not differ markedly from those in corresponding de-novo cohorts.

     

Adalimumab versus infliximab for the treatment of moderate to severe ulcerative colitis in adult patients naïve to anti-TNF therapy: An indirect treatment comparison meta-analysis

ObjectiveTo compare the efficacy of adalimumab and infliximab for the treatment of moderate to severe ulcerative colitis using indirect treatment comparison meta-analysis.MethodsA systematic review and Bayesian indirect treatment comparison meta-analyses were performed for seven patient-important clinical outcomes at 8 weeks and 52 weeks. Odds ratio (OR) estimates and associated 95% credible intervals (CrIs) were produced.ResultsFive eligible RCTs informed clinical remission, response, mucosal healing, quality of life, colectomy, serious adverse events, and discontinuation due to adverse events at 8 weeks and 52 weeks. At 8 weeks of induction therapy, clinical remission (OR = 0.42, 95% CrI 0.17–0.97), clinical response (OR = 0.45, 95% CrI 0.23–0.89) and mucosal healing (OR = 0.46, 95% CrI 0.25–0.86) statistically favored infliximab. However, after 52 weeks of maintenance therapy OR estimates showed no significant difference between infliximab and adalimumab. For serious adverse events and discontinuations due to adverse events, adalimumab and infliximab were similar to placebo. Further, the indirect treatment comparison of adalimumab and infliximab yielded odds ratios close to 1.00 with wide credible intervals.ConclusionThe findings of this indirect treatment comparison meta-analysis suggest that both infliximab and adalimumab are superior to placebo in the treatment of moderate to moderately severe ulcerative colitis. While infliximab is statistically more effective than adalimumab in the induction of remission, response and mucosal healing at 8 weeks, infliximab and adalimumab are comparable in efficacy at 52 weeks of maintenance treatment.     

Motivation to pursue anti-TNFα treatment in patients with Crohn's disease – the SPACE motivation study

BackgroundCrohn's disease (CD) is a chronic disorder requiring long-term treatment. However, up to 20% of patients interrupt temporarily or permanently anti-TNFα. Primary aim was to identify internal and external factors influencing patient's motivation to pursue anti-TNFα in active CD.MethodsThis was a French, multicentre, prospective study enrolling CD patients on anti-TNFα therapy since more than 3 months. Patients completed the Satisfaction of Patients with Crohn's Disease questionnaire (SPACE-Q) and other patient-reported-outcome tools at inclusion visit, and after 6 and 12 months.ResultsA total of 274 patients were included: 146 (53.3%) received adalimumab, while 128 (46.7%) infliximab. Most patients (78%) were still treated with anti-TNFα 12 months after enrolment. Patients’ perception of necessity (p = 0.01) and concerns (p<0.0001) regarding medication, evaluated through the Belief about Medicines Questionnaire (BMQ), and expectation confirmation towards treatment convenience (p = 0.02), towards efficacy (p = 0.04), and treatment satisfaction (p = 0.03) according to SPACE-Q, correlated with motivation to pursue treatment. Patients with higher treatment satisfaction (p = 0.0004), stronger belief in treatment necessity (p<0.0001) and fewer concerns (p = 0.0002) were more likely to be very motivated.ConclusionTreatment satisfaction, treatment necessity, and concerns are correlated to motivation to pursue anti-TNFα. Specific questions focused on these patients’ perceptions could help physicians to identify patients at risk of non-adherence and prevent therapy interruption.     

High sustained response to daily dosing of interferon with ribavirin in chronic hepatitis C patients naïve to therapy

Background : Viral kinetics suggests that daily administration of α‐interferon (IFN) will clear hepatitis C virus (HCV) RNA earlier and more frequently compared with standard t.i.w. To reduce the likelihood of viral replication, mutation and subsequent development of resistance, daily dosing with IFN may be appropriate. To determine the safety and efficacy of daily IFN with ribavirin in chronic HCV infection we performed a prospective study. Methods : Thirty‐five naïve adult HCV‐positive patients (25 male/10 female) were treated with IFN‐α2b; 5 MU daily for 2 weeks followed by 3 MU daily for 22 weeks and ribavirin 800–1200 mg/day depending on weight. Liver biopsy, performed in 25 patients, showed mild to moderate activity in 19 patients (76%) and severe activity in six patients (24%). Two patients showed staged IV fibrosis. Serotyping was performed in 29 patients by an enzyme immunoassay‐based Murex assay. Type 3 was the predominant serotype, present in 14 cases. Hepatitis C virus RNA was measured by the Chiron bDNA assay. Results : Mean baseline HCV‐RNA level was 14.2 ± 18.7 MEq/mL (median 6.09; range 0.2–92.5), which became undetectable in all but three patients at week 4. Normalization of alanine aminotransferase (ALT) at week 4 was seen in 27 patients. Three patients withdrew due to non‐compliance. Thirty‐two patients completed 24 weeks of therapy as per the protocol. At the end of treatment, the HCV‐RNA level was negative in 29 of 32 patients (90.6%) and ALT was normal in 31 of 32 patients (97%). Sustained viral response at 6 months follow up was seen in 28 of 32 patients (88%). The ALT level was normal in 28 of 32 patients (88%). Conclusion : Daily administration of IFN with ribavirin is well tolerated in the majority of patients. There is rapid elimination of virus with normalization of ALT and a significantly high sustained viral response. © 2002 Blackwell Publishing Asia Pty Ltd     

Erratum to: Effectiveness of adalimumab for the treatment of ulcerative colitis in clinical practice: comparison between anti-tumour necrosis factor-naïve and non-naïve patients

Journal of Gastroenterology -     

Bowel contrast-enhanced ultrasound perfusion imaging in the evaluation of Crohn's disease patients undergoing anti-TNFα therapy

AimTo evaluate whether changes in bowel perfusion parameters measured by dynamic-CEUS (D-CEUS) can be used for monitoring response to therapy in active Crohn disease (CD).MethodsFifty-four CD patients were evaluated with d-CEUS before (T0) and after 2 (T1), 6 (T2) and 12 weeks (T3) of anti-TNFα therapy. Variations from baseline were calculated for: peak intensity, PI; area under the curve, AUC; slope of wash in, P_w; time to peak, TP; mean transit time, MTT (median percentage values) and were correlated with combined endoscopic/clinical response after 12 weeks and clinical relapse within 6 months.Results70% of patients achieved combined endoscopic/clinical response (responders). The reduction in PI, AUC, P_w and MTT between T1 and T0 was higher in responders. Relapsers (21%) showed significantly lower reduction in delta PI and P_w at T1 and T2. At T3 they showed a new increase in PI and lower reduction in delta P_w. In relapsers, AUC showed a significantly lower decrease at T2 and T3, TP showed a significant reduction at T3 and MTT showed a progressive increase at the different time-points, reaching the statistical significance at T3.Conclusionsd-CEUS might become a reliable predictor of combined endoscopic/clinical response and clinical relapse in CD.     

Effectiveness of adalimumab for the treatment of ulcerative colitis in clinical practice: comparison between anti-tumour necrosis factor-naïve and non-naïve patients

Background

Ulcerative colitis (UC) treatment is focused to achieve mucosal healing, avoiding disease progression. The study aimed to evaluate the real-world effectiveness of adalimumab (ADA) in UC and to identify predictors of remission to ADA.

Methods

This cohort study used data from the ENEIDA registry. Clinical response, clinical remission, endoscopic remission, adverse events (AE), colectomy, and hospitalisations were evaluated; baseline characteristics and biological parameters were compared to determine predictors of response.

Results

We included 263 patients (87 naïve and 176 previously exposed to anti-tumour necrosis factor alpha, TNF). After 12 weeks, clinical response, clinical remission, and endoscopic remission rates were 51, 26, and 14 %, respectively. The naïve group demonstrated better response to treatment than the anti-TNF-exposed group at short-term. Clinical and endoscopic remission within 1 year of treatment was better in the naïve group (65 vs. 49 and 50 vs. 35 %, respectively). The rates of AE, dose-escalation, hospitalisations, and colectomy during the first year were higher in anti-TNF-exposed patients (40, 43, and 27 % vs. 26, 21, and 11 %, respectively). Patients with primary failure and intolerance to the first anti-TNF and severe disease were associated with worse clinical response. Primary non-response to prior anti-TNF treatment and severe disease were predictive of poorer clinical remission. Low levels of C-reactive protein (CRP) and faecal calprotectin (FC) at baseline were predictors of clinical remission.

Conclusions

In clinical practice, ADA was effective in UC, especially in anti-TNF naïve patients. FC and CRP could be predictors of treatment effectiveness.