Clinical impact of gastrointestinal bleeding in patients undergoing percutaneous coronary interventions.

BACKGROUND The risk factors and clinical sequelae of gastrointestinal bleeding (GIB) in the current era of drug-eluting stents, prolonged dual antiplatelet therapy, and potent P2Y12 inhibitors are not well established. We determined the frequency, predictors, and clinical impact of GIB after percutaneous coronary interventions (PCIs) in a contemporary cohort of consecutive patients treated with unrestricted use of drug-eluting stents. METHODS AND RESULTS Between 2009 and 2012, all consecutive patients undergoing PCI were prospectively included in the Bern PCI Registry. Bleeding Academic Research Consortium (BARC) GIB and cardiovascular outcomes were recorded within 1 year of follow-up. Among 6212 patients, 84.1% received new-generation drug-eluting stents and 19.5% received prasugrel. At 1 year, GIB had occurred in 65 patients (1.04%); 70.8% of all events and 84.4% of BARC ≥3B events were recorded >30 days after PCI. The majority of events (64.4%) were related to upper GIB with a more delayed time course compared with lower GIB. Increasing age, previous GIB, history of malignancy, smoking, and triple antithrombotic therapy (ie, oral anticoagulation plus dual antiplatelet therapy) were independent predictors of GIB in multivariable analysis. GIB was associated with increased all-cause mortality (adjusted hazard ratio, 3.40; 95% confidence interval, 1.67-6.92; P=0.001) and the composite of death, myocardial infarction, or stroke (adjusted hazard ratio, 3.75; 95% confidence interval, 1.99-7.07; P<0.001) and was an independent predictor of all-cause mortality during 1 year. CONCLUSIONS Among unselected patients undergoing PCI, GIB has a profound effect on prognosis. Triple antithrombotic therapy emerged as the single drug-related predictor of GIB in addition to patient-related risk factors within 1 year of PCI. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT02241291.

Prevention of preterm delivery with vaginal progesterone in women with preterm labour (4P): randomised double-blind placebo-controlled trial.

OBJECTIVE To evaluate the effectiveness of 200 mg of daily vaginal natural progesterone to prevent preterm birth in women with preterm labour. DESIGN Multicentre, randomised, double-blind, placebo-controlled trial. SETTING Twenty-nine centres in Switzerland and Argentina. POPULATION A total of 385 women with preterm labour (24(0/7) to 33(6/7) weeks of gestation) treated with acute tocolysis. METHODS Participants were randomly allocated to either 200 mg daily of self-administered vaginal progesterone or placebo within 48 hours of starting acute tocolysis. MAIN OUTCOME MEASURES Primary outcome was delivery before 37 weeks of gestation. Secondary outcomes were delivery before 32 and 34 weeks, adverse effects, duration of tocolysis, re-admissions for preterm labour, length of hospital stay, and neonatal morbidity and mortality. The study was ended prematurely based on results of the intermediate analysis. RESULTS Preterm birth occurred in 42.5% of women in the progesterone group versus 35.5% in the placebo group (relative risk [RR] 1.2; 95% confidence interval [95% CI] 0.93-1.5). Delivery at <32 and <34 weeks did not differ between the two groups (12.9 versus 9.7%; [RR 1.3; 95% CI 0.7-2.5] and 19.7 versus 12.9% [RR 1.5; 95% CI 0.9-2.4], respectively). The duration of tocolysis, hospitalisation, and recurrence of preterm labour were comparable between groups. Neonatal morbidity occurred in 44 (22.8%) cases on progesterone versus 35 (18.8%) cases on placebo (RR: 1.2; 95% CI 0.82-1.8), whereas there were 4 (2%) neonatal deaths in each study group. CONCLUSION There is no evidence that the daily administration of 200 mg vaginal progesterone decreases preterm birth or improves neonatal outcome in women with preterm labour.

Validation of the Valve Academic Research Consortium Bleeding Definition in Patients With Severe Aortic Stenosis Undergoing Transcatheter Aortic Valve Implantation.

BACKGROUND The Valve Academic Research Consortium (VARC) has proposed a standardized definition of bleeding in patients undergoing transcatheter aortic valve interventions (TAVI). The VARC bleeding definition has not been validated or compared to other established bleeding definitions so far. Thus, we aimed to investigate the impact of bleeding and compare the predictivity of VARC bleeding events with established bleeding definitions. METHODS AND RESULTS Between August 2007 and April 2012, 489 consecutive patients with severe aortic stenosis were included into the Bern-TAVI-Registry. Every bleeding complication was adjudicated according to the definitions of VARC, BARC, TIMI, and GUSTO. Periprocedural blood loss was added to the definition of VARC, providing a modified VARC definition. A total of 152 bleeding events were observed during the index hospitalization. Bleeding severity according to VARC was associated with a gradual increase in mortality, which was comparable to the BARC, TIMI, GUSTO, and the modified VARC classifications. The predictive precision of a multivariable model for mortality at 30 days was significantly improved by adding the most serious bleeding of VARC (area under the curve [AUC], 0.773; 95% confidence interval [CI], 0.706 to 0.839), BARC (AUC, 0.776; 95% CI, 0.694 to 0.857), TIMI (AUC, 0.768; 95% CI, 0.692 to 0.844), and GUSTO (AUC, 0.791; 95% CI, 0.714 to 0.869), with the modified VARC definition resulting in the best predictivity (AUC, 0.814; 95% CI, 0.759 to 0.870). CONCLUSIONS The VARC bleeding definition offers a severity stratification that is associated with a gradual increase in mortality and prognostic information comparable to established bleeding definitions. Adding the information of periprocedural blood loss to VARC may increase the sensitivity and the predictive power of this classification.

Effects of dialysis modality on blood loss, bleeding complications and transfusion requirements in critically ill patients with dialysis-dependent acute renal failure.

Blood loss and bleeding complications may often be observed in critically ill patients on renal replacement therapies (RRT). Here we investigate procedural (i.e. RRT-related) and non-procedural blood loss as well as transfusion requirements in regard to the chosen mode of dialysis (i.e. intermittent haemodialysis [IHD] versus continuous veno-venous haemofiltration [CVVH]). Two hundred and fifty-two patients (122 CVVH, 159 male; aged 61.5±13.9 years) with dialysis-dependent acute renal failure were analysed in a sub-analysis of the prospective randomised controlled clinical trial-CONVINT-comparing IHD and CVVH. Bleeding complications including severity of bleeding and RRT-related blood loss were assessed. We observed that 3.6% of patients died related to severe bleeding episodes (between group P=0.94). Major all-cause bleeding complications were observed in 23% IHD versus 26% of CVVH group patients (P=0.95). Under CVVH, the rate of RRT-related blood loss events (57.4% versus 30.4%, P=0.01) and mean total blood volume lost was increased (222.3±291.9 versus 112.5±222.7 ml per patient, P <0.001). Overall, transfusion rates did not differ between the study groups. In patients with sepsis, transfusion rates of all blood products were significantly higher when compared to cardiogenic shock (all P <0.01) or other conditions. In conclusion, procedural and non-procedural blood loss may often be observed in critically ill patients on RRT. In CVVH-treated patients, procedural blood loss was increased but overall transfusion rates remained unchanged. Our data show that IHD and CVVH may be regarded as equivalent approaches in critically ill patients with dialysis-dependent acute renal failure in this regard.

Bleeding on probing as it relates to smoking status in patients enrolled in supportive periodontal therapy for at least 5 years

AIM To relate the mean percentage of bleeding on probing (BOP) to smoking status in patients enrolled in supportive periodontal therapy (SPT). MATERIALS AND METHODS Retrospective data on BOP from 8'741 SPT visits were related to smoking status among categories of both periodontal disease severity and progression (instability) in patients undergoing dental hygiene treatment at the Medi School of Dental Hygiene (MSDH), Bern, Switzerland 1985-2011. RESULTS A total of 445 patients were identified with 27.2% (n = 121) being smokers, 27.6% (n = 123) former smokers and 45.2% (n = 201) non-smokers. Mean BOP statistically significantly increased with disease severity (p = 0.0001) and periodontal instability (p = 0.0115) irrespective of the smoking status. Periodontally stable smokers (n = 30) categorized with advanced periodontal disease demonstrated a mean BOP of 16.2% compared to unstable smokers (n = 15) with a mean BOP of 22.4% (p = 0.0291). Assessments of BOP in relation to the percentage of sites with periodontal probing depths (PPD) ≥ 4 mm at patient-level yielded a statistically significantly decreased proportion of BOP in smokers compared to non-smokers and former smokers (p = 0.0137). CONCLUSIONS Irrespective of the smoking status, increased mean BOP in SPT patients relates to disease severity and periodontal instability while smokers demonstrate lower mean BOP concomitantly with an increased prevalence of residual PPDs.

Vaginal cytokines do not correlate with postmenopausal vulvovaginal symptoms.

OBJECTIVES Exploratory pilot study to determine the correlation between postmenopausal vulvovaginal symptoms and vaginal cytokine levels. METHODS Postmenopausal women (n = 34) not using menopausal hormone therapy and presenting with or without symptoms of vulvovaginal irritation were screened. Each participant underwent a vaginal examination and screening for vaginitis. A cervicovaginal lavage (CVL) with sterile saline and a peripheral blood sample were obtained. Main outcome measures were assessed by Luminex® X-map method on the Bio-Plex® platform. Main outcome measures were cervicovaginal and serum interleukin (IL)-4, IL-5, IL-10, IL-12, IL-13, TNF-α, GM-CSF, MIP-1-alpha and RANTES level. Cervicovaginal cytokines were adjusted to total protein concentration [pg/mcg protein]. RESULTS Twenty-six postmenopausal women were enrolled (symptomatic: n = 15; asymptomatic: n = 11). There were no significant differences between groups: age, age at menopause, vaginal pH and all CVL and serum cytokines (IL-4, IL-5, IL-10, IL-12, IL-13, TNF-α, GM-CSF, MIP-1-alpha and RANTES). GM-CSF was the most abundant vaginal cytokine (symptomatic: 146.5 ± 165.6 pg/mcg protein; asymptomatic: 146.0 ± 173.5 pg/mcg protein; p = 0.99). CONCLUSIONS Postmenopausal vulvovaginal symptoms did not correlate with vaginal inflammatory marker. There was no difference in serum or CVL cytokines between symptomatic and asymptomatic postmenopasual women. Vaginal symptoms after menopause are not related to the vaginal cytokine changes associated with loss of estrogen.

Efficacy and safety of non-hormonal remedies for vaginal dryness: open, prospective, randomized trial

OBJECTIVES To prove non-inferiority of the first non-hormonal vaginal cream in Germany, Vagisan(®) Moisturising Cream (CREAM), compared to a non-hormonal vaginal gel (GEL) for vulvovaginal atrophy (VVA) symptom relief. METHOD This was a 12-week multicenter, open-label, prospective, randomized, two-period, cross-over phase-III trial. The primary endpoint was the cumulative VVA subjective symptom score of the respective treatment period. Secondary endpoints were assessment of single VVA subjective and objective symptoms, VVA objective symptom score, vaginal pH, safety parameters, overall assessment of efficacy, tolerability and evaluation of product properties. In total, 117 women were randomly allocated to either one of the two treatments, each administered for 4 weeks; 92 women were included in the per-protocol analysis (primary analysis). The main outcome measure was cumulative VVA subjective symptom score. RESULTS Regarding VVA symptom relief, results confirmed non-inferiority of CREAM compared to GEL and even indicated superiority of CREAM. Frequency and intensity of subjective symptoms and objective findings were clearly reduced, with CREAM showing better results compared to GEL. Mean VVA objective symptom score significantly decreased; improvement was significantly greater with CREAM. Vaginal pH decreased only following CREAM treatment. Tolerability was superior for CREAM: burning and itching, mostly rated as mild, occurred markedly less often with CREAM than with GEL. Overall satisfaction with treatment efficacy, tolerability and most product properties were rated significantly superior for CREAM. CONCLUSIONS Subjective and objective VVA symptoms were reliably and safely reduced by both non-hormonal topical products. However, efficacy and tolerability of CREAM were shown to be superior to GEL.