Mood and nonmood components of perceived stress and exacerbation of Crohnʼs disease

BACKGROUND: Diverse psychological factors are involved in the pathophysiology of stress. In order to devise effective intervention strategies, it is important to elucidate which factors play the most important role in the association between psychological stress and exacerbation of Crohn's disease (CD). We hypothesized that the association between perceived stress and exacerbation of CD would remain after removal of mood and anxiety components, which are largely involved in stress perception. METHODS: In all, 468 adults with CD were recruited and followed in different hospitals and private practices of Switzerland for 18 months. At inclusion, patients completed the Perceived Stress Questionnaire and anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. During the follow-up, gastroenterologists assessed whether patients presented with a CD exacerbation. By means of binary logistic regression analysis, we estimated the factor by which one standard deviation of perceived stress would increase the odds of exacerbation of CD with and without controlling for anxiety and depression. RESULTS: The odds of exacerbation of CD increased by 1.85 times (95% confidence interval 1.43-2.40, P < 0.001) for 1 standard deviation of perceived stress. After removing the anxiety and depression components, the residuals of perceived stress were no longer associated with exacerbation of CD. CONCLUSIONS: The association between perceived stress and exacerbation of CD was fully attributable to the mood components, specifically anxiety and depression. Future interventional studies should evaluate the treatment of anxiety and depression as a strategy for potential prevention of CD exacerbations. (Inflamm Bowel Dis 2011;).

Cardiogoniometric parameters for detection of coronary artery disease at rest as a function of stenosis localization and distribution

Cardiogoniometry (CGM), a spatiotemporal electrocardiologic 5-lead method with automated analysis, may be useful in primary healthcare for detecting coronary artery disease (CAD) at rest. Our aim was to systematically develop a stenosis-specific parameter set for global CAD detection. In 793 consecutively admitted patients with presumed non-acute CAD, CGM data were collected prior to elective coronary angiography and analyzed retrospectively. 658 patients fulfilled the inclusion criteria, 405 had CAD verified by coronary angiography; the 253 patients with normal coronary angiograms served as the non-CAD controls. Study patients--matched for age, BMI, and gender--were angiographically assigned to 8 stenosis-specific CAD categories or to the controls. One CGM parameter possessing significance (P < .05) and the best diagnostic accuracy was matched to one CAD category. The area under the ROC curve was .80 (global CAD versus controls). A set containing 8 stenosis-specific CGM parameters described variability of R vectors and R-T angles, spatial position and potential distribution of R/T vectors, and ST/T segment alterations. Our parameter set systematically combines CAD categories into an algorithm that detects CAD globally. Prospective validation in clinical studies is ongoing.

Three-year results of visual outcome with disease activity-guided ranibizumab algorithm for the treatment of exudative age-related macular degeneration

PURPOSE To evaluate 3-year follow-up treatment outcomes with ranibizumab (Lucentis(®)) 0.5 mg administered either monthly or quarterly on a pro re nata (PRN) basis according to a disease activity-guided monitoring and treatment algorithm. METHODS A total of 316 treatment-naive eyes of 316 patients with exudative age-related macular degeneration met the criteria for inclusion in this retrospective, interventional case series. Patients were treated with ranibizumab 0.5 mg according to a disease activity-guided algorithm with monthly monitoring. Optical coherence tomography and fluorescein angiography were routinely used to assess disease activity: active lesions were treated with a series of three monthly injections, whereas inactive lesions were treated with quarterly injections. RESULTS Mean Early Treatment Diabetic Retinopathy Study best-corrected visual acuity improved from 52 letters at baseline to 59 letters at 12 months, achieved with a mean of 7.1 injections, 61 letters at 24 months with a mean of 5.0 injections administered in the second year and 60 letters at 36 months with a mean number of 5.2 injections. CONCLUSIONS Monthly visits and a morphology-driven PRN regimen with 3 injections in case of recurrence plus quarterly injections in case of inactive CNV resulted in an average VA gain of 7-9 letters that could be maintained over 3 years.

Beneficial effect of recruitable collaterals: a 10-year follow-up study in patients with stable coronary artery disease undergoing quantitative collateral measurements

BACKGROUND: The prognostic relevance of the collateral circulation is still controversial. The goal of this study was to assess the impact on survival of quantitatively obtained, recruitable coronary collateral flow in patients with stable coronary artery disease during 10 years of follow-up. METHODS AND RESULTS: Eight-hundred forty-five individuals (age, 62+/-11 years), 106 patients without coronary artery disease and 739 patients with chronic stable coronary artery disease, underwent a total of 1053 quantitative, coronary pressure-derived collateral measurements between March 1996 and April 2006. All patients were prospectively included in a collateral flow index (CFI) database containing information on recruitable collateral flow parameters obtained during a 1-minute coronary balloon occlusion. CFI was calculated as follows: CFI = (P(occl) - CVP)/(P(ao) - CVP) where P(occl) is mean coronary occlusive pressure, P(ao) is mean aortic pressure, and CVP is central venous pressure. Patients were divided into groups with poorly developed (CFI < 0.25) or well-grown collateral vessels (CFI > or = 0.25). Follow-up information on the occurrence of all-cause mortality and major adverse cardiac events after study inclusion was collected. Cumulative 10-year survival rates in relation to all-cause deaths and cardiac deaths were 71% and 88%, respectively, in patients with low CFI and 89% and 97% in the group with high CFI (P=0.0395, P=0.0109). Through the use of Cox proportional hazards analysis, the following variables independently predicted elevated cardiac mortality: age, low CFI (as a continuous variable), and current smoking. CONCLUSIONS: A well-functioning coronary collateral circulation saves lives in patients with chronic stable coronary artery disease. Depending on the exact amount of collateral flow recruitable during a brief coronary occlusion, long-term cardiac mortality is reduced to one fourth compared with the situation without collateral supply.

Psychosocial interventions for smoking cessation in patients with coronary heart disease

BACKGROUND: Quitting smoking improves prognosis after a cardiac event, but many patients continue to smoke, and improved cessation aids are urgently required. OBJECTIVES: To assess the effectiveness of psychosocial interventions such as behavioural therapeutic intervention, telephone support and self-help interventions in helping people with coronary heart disease (CHD) to quit smoking. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (issue 2 2003), MEDLINE, EMBASE, PsycINFO and PSYNDEX were searched from the start of the database to August 2003. Results were supplemented by cross-checking references, and handsearches in selected journals and systematic reviews. SELECTION CRITERIA: Randomised controlled studies (RCTs) in patients with CHD with a minimum follow-up of 6 months. After initial selection of the studies three trials with methodological flaws (e.g. high drop out) were excluded. DATA COLLECTION AND ANALYSIS: Abstinence rates were computed according to an intention to treat analysis if possible, or if not on follow-up results only. MAIN RESULTS: We found 16 RCTs meeting inclusion criteria. Interventions consist of behavioural therapeutic approaches, telephone support and self-help material and were either focused on smoking cessation alone or addressed several risk factors. The trials mostly included older male patients with CHD, predominantly myocardial infarction. Overall there was a positive effect of interventions on abstinence after 6 to 12 months (odds ratio (OR) 1.66, 95% confidence interval (CI) 1.25 to 2.22), but substantial heterogeneity between trials. Studies with validated assessment of smoking status at follow-up had lower efficacy (OR 1.44, 95% CI 0.99 to 2.11) than non-validated trials (OR 1.92, 95% CI 1.26 to 2.93). Studies were clustered by intervention strategy and intensity of the intervention. Clustering reduced heterogeneity, although many trials used more than one type of intervention. The ORs for different strategies were similar (behavioural therapies OR 1.69, 95% CI 1.33 to 2.14; telephone support OR 1.58, 95% CI 1.28 to 1.97; self-help OR 1.48, 95% CI 1.11 to 1.96). More intense interventions showed increased quit rates (OR 1.98, 95% CI 1.49 to 2.65) whereas brief interventions did not appear effective (OR 0.92, 95% CI 0.70 to 1.22). Two trials had longer term follow-up, and did not show any benefits after 5 years. AUTHORS' CONCLUSIONS: Psychosocial smoking cessation interventions are effective in promoting abstinence at 1 year, provided they are of sufficient duration. Further studies, with longer follow-up, should compare different psychosocial intervention strategies, or the addition of a psychosocial intervention strategy to pharmacological therapy (e.g. nicotine replacement therapy) compared with pharmacological treatment alone.

The effect of heart rate reduction by ivabradine on collateral function in patients with chronic stable coronary artery disease

Objective To evaluate the effect of heart rate reduction by ivabradine on coronary collateral function in patients with chronic stable coronary artery disease (CAD). Methods This was a prospective randomised placebo-controlled monocentre trial in a university hospital setting. 46 patients with chronic stable CAD received placebo (n=23) or ivabradine (n=23) for the duration of 6 months. The main outcome measure was collateral flow index (CFI) as obtained during a 1 min coronary artery balloon occlusion at study inclusion (baseline) and at the 6-month follow-up examination. CFI is the ratio between simultaneously recorded mean coronary occlusive pressure divided by mean aortic pressure both subtracted by mean central venous pressure. Results During follow-up, heart rate changed by +0.2±7.8 beats/min in the placebo group, and by –8.1±11.6 beats/min in the ivabradine group (p=0.0089). In the placebo group, CFI decreased from 0.140±0.097 at baseline to 0.109±0.067 at follow-up (p=0.12); it increased from 0.107±0.077 at baseline to 0.152±0.090 at follow-up in the ivabradine group (p=0.0461). The difference in CFI between the 6-month follow-up and baseline examination amounted to −0.031±0.090 in the placebo group and to +0.040±0.094 in the ivabradine group (p=0.0113). Conclusions Heart rate reduction by ivabradine appears to have a positive effect on coronary collateral function in patients with chronic stable CAD.

Penetrating or stricturing diseases are the major determinants of time to first and repeat resection surgery in Crohn's disease

BACKGROUND About 80% of patients with Crohn's disease (CD) require bowel resection and up to 65% will undergo a second resection within 10 years. This study reports clinical risk factors for resection surgery (RS) and repeat RS. METHODS Retrospective cohort study, using data from patients included in the Swiss Inflammatory Bowel Disease Cohort. Cox regression analyses were performed to estimate rates of initial and repeated RS. RESULTS Out of 1,138 CD cohort patients, 417 (36.6%) had already undergone RS at the time of inclusion. Kaplan-Meier curves showed that the probability of being free of RS was 65% after 10 years, 42% after 20 years, and 23% after 40 years. Perianal involvement (PA) did not modify this probability to a significant extent. The main adjusted risk factors for RS were smoking at diagnosis (hazard ratio (HR) = 1.33; p = 0.006), stricturing with vs. without PA (HR = 4.91 vs. 4.11; p < 0.001) or penetrating disease with vs. without PA (HR = 3.53 vs. 4.58; p < 0.001). The risk factor for repeat RS was penetrating disease with vs. without PA (HR = 3.17 vs. 2.24; p < 0.05). CONCLUSION The risk of RS was confirmed to be very high for CD in our cohort. Smoking status at diagnosis, but mostly penetrating and stricturing diseases increase the risk of RS.

Disease progression and recurrence in women treated for vulvovaginal intraepithelial neoplasia

OBJECTIVE The malignant potential of intraepithelial neoplasia of the vulva and vagina after treatment is not well defined. Our objective was to examine risk factors for recurrence and invasive disease. METHODS Four hundred sixty-four women with biopsy proven high-grade intraepithelial neoplasia of the vulva and vagina were identified in the electronic databases of four colposcopy clinics. Inclusion criteria were a follow-up of more than one year, no history of invasive cancer and no invasive cancer within the first year after initial treatment. We investigated the potential factors associated with recurrence and progression using a logistic regression analysis to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS Of the 411 eligible patients, 123 patients (29.9%) recurred later than one year after initial treatment and 24 patients (5.8%) progressed to invasive disease. According to multivariate analyses, the risk factors associated with recurrence were multifocality (OR, 3.33; 95% CI, 2.02 to 5.51), immunosuppression (OR, 2.51; 95% CI, 1.09 to 5.81), excision as initial treatment (vs. laser evaporation; OR, 1.79; 95% CI, 1.11 to 2.91) and smoking (OR, 1.61; 95% CI, 1.02 to 2.55). Risk factors for progression to invasive disease were immunosuppression (OR, 4.00; 95% CI, 1.30 to 12.25), multifocality (OR, 3.05; 95% CI, 1.25 to 7.43) and smoking (OR, 2.97; 95% CI, 1.16 to 7.60), but not treatment modality. CONCLUSION Laser evaporation combined with extensive biopsy is at least as efficacious as initial treatment of intraepithelial neoplasia with excision. Smoking is a risk factor for both recurrence and progression to invasive disease. Hence, smoking cessation should be advised and maintaining a long follow-up period due to late relapses is necessary.

Early-onset Crohn's disease is a risk factor for smaller final height.

OBJECTIVES Growth retardation is a frequent complication of paediatric inflammatory bowel disease (IBD). Only a few studies report the final height of these patients, with controversial results. We compared adult height of patients with paediatric IBD with that of patients with adult-onset disease. METHODS Height data of 675 women 19-44 years of age and 454 men 23-44 years of age obtained at inclusion in the Swiss IBD cohort study registry were grouped according to the age at diagnosis: (a) prepubertal (men≤13, women≤11 years), (b) pubertal (men 13-22, women 11-18 years) and (c) adult (men>22, women>18 years of age), and compared with each other and with healthy controls. RESULTS Male patients with prepubertal onset of Crohn's disease (CD) had significantly lower final height (mean 172±6 cm, range 161-182) compared with men with pubertal (179±6 cm, 161-192) or adult (178±7 cm, 162-200) age at onset and the general population (178±7 cm, 142-204). Height z-scores standardized against heights of the normal population were significantly lower in all patients with a prepubertal diagnosis of CD (-0.8±0.9) compared with the other patient groups (-0.1±0.8, P<0.001). Prepubertal onset of CD emerged as a risk factor for reduced final height in patients with prepubertal CD. No difference for final height was found between patients with ulcerative or unclassified IBD diagnosed at prepubertal, pubertal or adult age. CONCLUSION Prepubertal onset of CD is a risk for lower final height, independent of the initial disease location and the necessity for surgical interventions.

Serum ficolin-2 correlates worse than fecal calprotectin and CRP with endoscopic Crohn's disease activity.

BACKGROUND AND AIMS Ficolin-2 is an acute phase reactant produced by the liver and targeted to recognize N-acetyl-glucosamine which is present in bacterial and fungal cell walls. We recently showed that ficolin-2 serum levels were significantly higher in CD patients compared to healthy controls. We aimed to evaluate serum ficolin-2 concentrations in CD patients regarding their correlation with endoscopic severity and to compare them with clinical activity, fecal calprotectin, and CRP. METHODS Patients provided fecal and blood samples before undergoing ileo-colonoscopy. Disease activity was scored clinically according to the Harvey-Bradshaw Index (HBI) and endoscopically according to the simplified endoscopic score for CD (SES-CD). Ficolin-2 serum levels and fecal calprotectin levels were measured by ELISA. RESULTS A total of 136 CD patients were prospectively included (mean age at inclusion 41.5±15.4 years, 37.5% females). Median HBI was 3 [2-6] points, median SES-CD was 5 [2-8], median fecal calprotectin was 301 [120-703] μg/g, and median serum ficolin-2 was 2.69 [2.02-3.83] μg/mL. SES-CD correlated significantly with calprotectin (R=0.676, P<0.001), CRP (R=0.458, P<0.001), HBI (R=0.385, P<0.001), and serum ficolin-2 levels (R=0.171, P=0.047). Ficolin-2 levels were higher in CD patients with mild endoscopic disease compared to patients in endoscopic remission (P=0.015) but no difference was found between patients with mild, moderate, and severe endoscopic disease. CONCLUSIONS Ficolin-2 serum levels correlate worse with endoscopic CD activity when compared to fecal calprotectin or CRP.

Analysis of TNF-antagonist switch over time and associated risk factors in the Swiss Inflammatory Bowel Disease Cohort

BACKGROUND AND AIMS Limited data from large cohorts are available on tumor necrosis factor (TNF) antagonists (infliximab, adalimumab, certolizumab pegol) switch over time. We aimed to evaluate the prevalence of switching from one TNF antagonist to another and to identify associated risk factors. METHODS Data from the Swiss Inflammatory Bowel Diseases Cohort Study (SIBDCS) were analyzed. RESULTS Of 1731 patients included into the SIBDCS (956 with Crohn's disease [CD] and 775 with ulcerative colitis [UC]), 347 CD patients (36.3%) and 129 UC patients (16.6%) were treated with at least one TNF antagonist. A total of 53/347 (15.3%) CD patients (median disease duration 9 years) and 20/129 (15.5%) of UC patients (median disease duration 7 years) needed to switch to a second and/or a third TNF antagonist, respectively. Median treatment duration was longest for the first TNF antagonist used (CD 25 months; UC 14 months), followed by the second (CD 13 months; UC 4 months) and third TNF antagonist (CD 11 months; UC 15 months). Primary nonresponse, loss of response and side effects were the major reasons to stop and/or switch TNF antagonist therapy. A low body mass index, a short diagnostic delay and extraintestinal manifestations at inclusion were identified as risk factors for a switch of the first used TNF antagonist within 24 months of its use in CD patients. CONCLUSION Switching of the TNF antagonist over time is a common issue. The median treatment duration with a specific TNF antagonist is diminishing with an increasing number of TNF antagonists being used.

Independent at heart: persistent association of altitude with ischaemic heart disease mortality after consideration of climate, topography and built environment.

BACKGROUND Living at higher altitude was dose-dependently associated with lower risk of ischaemic heart disease (IHD). Higher altitudes have different climatic, topographic and built environment properties than lowland regions. It is unclear whether these environmental factors mediate/confound the association between altitude and IHD. We examined how much of the altitude-IHD association is explained by variations in exposure at place of residence to sunshine, temperature, precipitation, aspect, slope and distance to main road. METHODS We included 4.2 million individuals aged 40-84 at baseline living in Switzerland at altitudes 195-2971 m above sea level (ie, full range of residence), providing 77 127 IHD deaths. Mortality data 2000-2008, sociodemographic/economic information and coordinates of residence were obtained from the Swiss National Cohort, a longitudinal, census-based record linkage study. Environment information was modelled to residence level using Weibull regression models. RESULTS In the model not adjusted for other environmental factors, IHD mortality linearly decreased with increasing altitude resulting in a lower risk (HR, 95% CI 0.67, 0.60 to 0.74) for those living >1500 m (vs<600 m). This association remained after adjustment for all other environmental factors 0.74 (0.66 to 0.82). CONCLUSIONS The benefit of living at higher altitude was only partially confounded by variations in climate, topography and built environment. Rather, physical environment factors appear to have an independent effect and may impact on cardiovascular health in a cumulative way. Inclusion of additional modifiable factors as well as individual information on traditional IHD risk factors in our combined environmental model could help to identify strategies for the reduction of inequalities in IHD mortality.

Vaccination of cattle with the N terminus of LppQ of Mycoplasma mycoides subsp. mycoides results in type III immune complex disease upon experimental infection.

Contagious bovine pleuropneumonia (CBPP) is a serious respiratory disease of cattle caused by Mycoplasma mycoides subsp. mycoides. Current vaccines against CBPP induce short-lived immunity and can cause severe postvaccine reactions. Previous studies have identified the N terminus of the transmembrane lipoprotein Q (LppQ-N') of M. mycoides subsp. mycoides as the major antigen and a possible virulence factor. We therefore immunized cattle with purified recombinant LppQ-N' formulated in Freund's adjuvant and challenged them with M. mycoides subsp. mycoides. Vaccinated animals showed a strong seroconversion to LppQ, but they exhibited significantly enhanced postchallenge glomerulonephritis compared to the placebo group (P = 0.021). Glomerulonephritis was characterized by features that suggested the development of antigen-antibody immune complexes. Clinical signs and gross pathological scores did not significantly differ between vaccinated and placebo groups. These findings reveal for the first time the pathogenesis of enhanced disease as a result of antibodies against LppQ during challenge and also argue against inclusion of LppQ-N' in a future subunit vaccine for CBPP.