[Upper abdominal pain after an elective aortic valve replacement]. / Pijn in de bovenbuik na aortaklepvervanging.

A 69-year-old man came to our emergency department with nausea, vomiting and upper abdominal pain under the suspicion of an ileus. Four weeks before he had had an elective aortic valve replacement. The basal thoracic slides of the abdominal CT-scan revealed a significant amount of pericardial effusion, after which the patient was referred for emergency cardiac surgery. Abdominal complaints are rarely the primary symptoms of severe heart failure.

Predictors of paravalvular aortic regurgitation following self-expanding Medtronic CoreValve implantation: the role of annulus size, degree of calcification, and balloon size during pre-implantation valvuloplasty and implant depth.

OBJECTIVES: We sought to investigate the role of balloon size during pre-implantation valvuloplasty in predicting AR and optimal Medtronic CoreValve (MCS) implantation depth. BACKGROUND: Paravalvular aortic regurgitation (AR) is common following MCS implantation. A number of anatomical and procedural variables have been proposed as determinants of AR including degree of valve calcification, valve undersizing and implantation depth. METHODS: We conducted a multicenter retrospective analysis of 282 patients who had undergone MCS implantation with prior cardiac CT annular sizing between 2007 and 2011. Native valve minimum (Dmin), maximum (Dmax) and arithmetic mean (Dmean) annulus diameters as well as agatston calcium score were recorded. Nominal and achieved balloon size was also recorded. AR was assessed using contrast angiography at the end of each procedure. Implant depth was measured as the mean distance from the nadir of the non- and left coronary sinuses to the distal valve frame angiographically. RESULTS: 29 mm and 26 mm MCS were implanted in 60% and 39% of patients respectively. The majority of patients (N=165) developed AR <2 following MCS implantation. AR ≥3 was observed in 16% of the study population. High agatston calcium score and Dmean were found to be independent predictors of AR ≥3 in multivariate analysis (P<0.0001). Nominal balloon diameter and the number of balloon inflations did not influence AR. However a small achieved balloon diameter-to-Dmean ratio (≤0.85) showed modest correlation with AR ≥3 (P=0.04). This observation was made irrespective of the degree of valve calcification. A small MCS size-to-Dmean ratio is also associated with AR ≥3 (P=0.001). A mean implantation depth of ≥8+2mm was also associated with AR ≥3. Implantation depth of ≥12 mm was associated with small MCS diameter-to-Dmean ratio and increased 30-day mortality. CONCLUSION: CT measured aortic annulus diameter and agatston calcium score remain important predictors of significant AR. Other procedural predictors include valve undersizing and low implantation depth. A small achieved balloon diameter-to-Dmean ratio might also predict AR ≥3. Our findings confirm that a small achieved balloon size during pre-implantation valvuloplasty predicts moderate-severe AR in addition to previously documented factors.

Patients with aortic stenosis referred for TAVI: treatment decision, in-hospital outcome and determinants of survival.

AIMS: To assess treatment decision and outcome in patients referred for transcatheter aortic valve implantation (TAVI) in addition to predictive factors of mortality after TAVI. METHODS: Three-centre prospective observational study including 358 patients. Endpoints were defined according to the Valve Academic Research Consortium. RESULTS: Of the 358 patients referred for TAVI, TAVI was performed in 235 patients (65%), surgical aortic valve replacement (AVR) in 24 (7%) and medical therapy (MT) in 99 (28%). Reasons to decline TAVI in favour of AVR/MT were patient preference (29%), peripheral vascular disease (15%) and non-severe aortic stenosis (11%). The logistic EuroSCORE was significantly higher in patients who underwent TAVI and MT in comparison with those undergoing AVR (19 vs. 10%, p = 0.007). At 30 days, all-cause mortality and the combined safety endpoint were 9 and 24% after TAVI and 8 and 25% after AVR, respectively. All-cause mortality was significantly lower in the TAVI group compared with the MT group at 6 months, 1 year and 2 years (12% vs. 22%, 21% vs. 33% and 31% vs. 55%, respectively, p < 0.001). Multivariable analysis revealed that blood transfusion (HR: 1.19; 95% CI: 1.05-1.33), pre-existing renal failure (HR: 1.18; 95% CI: 1.06-1.33) and STS score (HR: 1.06; 95% CI: 1.02-1.10) were independent predictors of mortality at a median of 10 (IQR: 3-23) months after TAVI. CONCLUSIONS: Approximately two-thirds of the patients referred for TAVI receive this treatment with gratifying short- and long-term survival. Another 7% underwent AVR. Prognosis is poor in patients who do not receive valve replacement therapy.

Percutaneus treatment of varicose veins with bipolar radiofrequency ablation.

UNLABELLED: The traditional surgical treatment of an incompetent great saphenous vein (GSV) and small saphenous vein (SSV) is challenged by endovenous techniques. Bipolar radio frequency induced thermo therapy (RFITT) is a new endovenous treatment, which occludes the vein by using the venous wall as a conductor. Linear endovenous energy density (LEED) describes the amount of energy used for vein closure. MATERIAL/METHODS: From March 2007 till April 2009, two cohorts (23 W and 20 W) were compared, respectively 280 and 178 patients. GSV and SSV were separately analyzed. Follow-up was performed at 3 weeks and 1 year post-operatively with duplex ultrasound, to assess vein closure and perioperative complaints. A visual analog scale (VAS) pain score (range 0-10) was documented. For patients operated after October 2008 follow-up was performed at least 6 months after surgery. RESULTS: 528 GSV and 76 SSV were treated. For the GSV a significant difference in LEED 40.8 17.1 in the 20 W cohort was found, resulting in higher occlusion rates 90.6% compared to 82.7% after 3 weeks. Follow-up of 1 year in the 20 W cohort showed 88.7% occlusion. Multivariate analysis showed that pullback speed (OR 3.7, CI 1.1-12.4) and CEAP classification (OR 3.1, CI 1.7-5.6) were significant predictors for vein occlusion. Despite a higher LEED, post-operative complaints were not significantly worse. CONCLUSION: RFITT is a safe and effective method to treat incompetent saphenous veins. Slower pullback speed with higher LEED results in higher closure rates without causing more pain.

Validation of the New Zealand Physical Activity Questionnaire (NZPAQ-LF) and the International Physical Activity Questionnaire (IPAQ-LF) with accelerometry.

BACKGROUND: Validation of instruments used to measure physical activity patterns is essential when attempting to assess the effectiveness of physical activity interventions. OBJECTIVES: To assess the validity of two self-report physical activity questionnaires on a representative sample of New Zealand adults. METHODS: 70 adults aged 18-65 years from around Christchurch, New Zealand were required to wear an ActiGraph GT1M accelerometer during all waking hours for 7 consecutive days. Immediately following the 7 day accelerometer period participants were required to complete the long forms of both the New Zealand Physical Activity Questionnaire (NZPAQ-LF) and the International Physical Activity Questionnaire (IPAQ-LF). RESULTS: Both the NZPAQ-LF and the IPAQ-LF questionnaires showed small to moderate correlations with ActiGraph data for time spent in moderate-intensity physical activity (r=0.19-0.30) and total physical activity (sum of moderate and vigorous-intensity physical activity, r=0.30-0.32). In comparison with the ActiGraph data, both self-report questionnaires tended to overestimate activity levels by approximately 165%. Total physical activity levels gathered from both questionnaires were strongly correlated with each other (r=0.79) and showed good levels of agreement in the Bland-Altman plots. CONCLUSIONS: The long forms of the NZPAQ and IPAQ were found to have acceptable validity when detecting participants' ability to meet activity guidelines based on exercise duration, but a significant amount of overestimation was evident. This presents a need for both instruments to be further developed and tested in order to increase validity.

Key transcriptional regulators of the vasoprotective effects of shear stress.

Atherosclerotic plaque rupture and subsequent thrombosis is the main cause of sudden coronary death. Remarkably, atherosclerosis only develops in certain predisposed areas of the vasculature. Endothelial cells in these predisposed areas experience low or oscillatory shear stress, which activates the proinflammatory and procoagulant transcription factors activator protein 1 (AP-1) and nuclear factor kappaB (NFkappaB), thus inducing a proinflammatory, procoagulant surface. In contrast, healthy endothelial cells that are exposed to prolonged high laminar shear stress, express anti-inflammatory and anticoagulant genes. The key shear stress-induced transcription factors that govern the expression of these genes are Krüppel-like factor 2 (KLF2) and nuclear factor erythroid 2-like 2 (Nrf2). Together KLF2 and Nrf2 govern approximately 70% of the shear stress-elicited gene sets. Nrf2 potently induces anti-inflammatory/antioxidant enzymes, while KLF2 induces anti-inflammatory and anticoagulant proteins, most specifically endothelial Nitric oxide synthase (eNOS) and thrombomodulin (TM). KLF2 also inhibits proinflammatory and antifibrinolytic genes through inhibition of the proinflammatory transcription factors AP-1 and NFkappaB. The widespread beneficial effects of the key transcription factors KLF2 and Nrf2 on endothelial phenotype, holds the promise that their targeted modulation might lead to a new class of cardiovascular drugs.

Reduce the rads: a quality assurance project on reducing unnecessary chest X-rays in children with asthma.

OBJECTIVES: To quantify and then reduce the number of unnecessary chest X-rays (CXR) being performed on children presenting with asthma. METHODS: A retrospective review of case notes of all children, aged 1-15 years, who presented with asthma and had a CXR performed. The setting was two General Hospitals that see all children presenting to an emergency department in the region. The period of review was before and after the development and implementation of a simple guide for staff, with an education programme, outlining when CXR were deemed unnecessary (known asthmatic, primary diagnosis asthma, improving with treatment, pneumothorax not suspected, and not in Intensive Care Unit). RESULTS: In the 12 months prior to the education programme, 466 children presented with asthma: 260 had a CXR, of which 211 (81.1%) were unnecessary. During the 6 month period following implementation of the programme 197 presented with asthma: 72 had a CXR, of which 56 (78%) were deemed unnecessary. However the percentage of all children presenting with asthma who had an unnecessary CXR fell from 45.3% (211/466) to 28.4% (56/197): P = 0.00005. There was also a decrease in the admission rate from 46% before to 31% after the period of education. CONCLUSION: This study determined that an unacceptably high rate of unnecessary CXR was being ordered in children presenting to hospital with asthma. It also showed how a clinically and statistically significant reduction in the overall number of CXR could be achieved, through a simple and easy to implement educational programme. Further measures are needed in addition to ongoing education in order to improve on this achievement.

Profiling penciclovir susceptibility and prevalence of resistance of herpes simplex virus isolates across eleven clinical trials.

Asusceptibility testing program was established to determine the prevalence of resistance to penciclovir among herpes simplex virus isolates collected from patients participating in 11 world-wide clinical trials involving penciclovir (topical or intravenous formulations) or famciclovir, the oral prodrug of penciclovir. These trials represented nine randomised double blind, placebo or aciclovir-controlled studies and two open-label studies. Groups surveyed included immunocompetent or immunocompromised patients receiving 2 to 12 months chronic suppressive therapy for genital herpes, immunocompetent patients with recurrent herpes labialis treated for four days, and immunocompromised patients with mucocutaneous herpes simplex virus (HSV). Another subset of patients had been identified as non-responders to aciclovir or to valaciclovir. This program assessed the susceptibility profile for a total of 2145 herpes simplex virus isolates from 913 immunocompetent and 288 immunocompromised patients treated with penciclovir, famciclovir, aciclovir or placebo (depending on trial design). HSV isolates were tested for susceptibility to penciclovir using the plaque reduction assay (PRA) in MRC-5 cells. Resistance was defined as an IC(50)>or=2.0 microg/ml or an IC(50)> 10-fold above the wild type control virus IC(50) within that particular assay. Penciclovir-resistant HSV was isolated from 0.22% immunocompetent patients, and 2.1% of immunocompromised patients overall and therefore the frequency of penciclovir-resistant herpes simplex virus in the immunocompetent population approximates that of aciclovir-resistant herpesvirus reported previously. Penciclovir-resistant HSV isolates were more common in isolates from immunocompromised patients, consistent with aciclovir clinical experience. Treatment with penciclovir (intravenous formulation) was associated with the development of resistant HSV in only one severely immunocompromised patient (day 7 isolate IC(50) = 2.01 microg/ml), although treatment was effective and resulted in the complete clearance of the lesion by day 8. No patients receiving topical penciclovir developed treatment-associated penciclovir-resistant HSV, and a single immunocompromised patient developed resistant HSV upon treatment with oral famiciclovir.

A randomized, double-blind trial of famciclovir versus acyclovir for the treatment of localized dermatomal herpes zoster in immunocompromised patients.

In this randomized, double-blind, multicenter, acyclovir-controlled study, the efficacy and safety of famciclovir were evaluated for the treatment of herpes zoster in patients who were immunocompromised following bone marrow or solid organ transplantation or oncology treatment. A total of 148 patients, 12 years or older with clinical evidence of localized herpes zoster, received either oral famciclovir, 500 mg three times daily, or acyclovir, 800 mg five times daily, for 10 days. Famciclovir was equivalent to acyclovir with respect to the numbers of patients reporting new lesion formation while on therapy (77% vs. 73%, respectively). There were no significant differences between the groups in the time to cessation of new lesion formation, full crusting, complete healing of lesions, or loss of acute phase pain. Treatment with famciclovir was well tolerated, with a safety profile comparable to that of acyclovir. Thus oral famciclovir is a convenient, effective, and well-tolerated regimen for immunocompromised patients with herpes zoster.

Famciclovir in chronic hepatitis B: results of a dose-finding study.

BACKGROUND/AIMS: Famciclovir, an orally available nucleoside analogue with potent in vitro activity against HBV, is being investigated for treatment of chronic hepatitis B. METHODS: A dose-finding study was conducted in patients with hepatitis B e antigen present in serum. Patients received famciclovir 125 mg, 250 mg, 500 mg three times daily (tid) or placebo for 16 weeks, followed by 8 months post-treatment observation, and 16 weeks open-label treatment. More than 90% of patients had previously received alpha-interferon or had baseline characteristics indicating a high likelihood of poor response to alpha-interferon. RESULTS: Famciclovir induced rapid, dose-dependent suppression of viral replication and reduction in alanine aminotransferase (ALT), with greatest efficacy in the 500-mg tid treatment group. HBV DNA reduction was maintained throughout the treatment period. ALT also steadily declined during the treatment period. Approximately 40% of patients with pretreatment ALT>upper limit of normal (ULN) receiving famciclovir 500 mg tid, experienced sustained normalization of ALT at the end of the 8-month follow-up. Anti-HBe seroconversion occurred more frequently in patients receiving famciclovir 500 mg tid compared with placebo (p=0.04). Famciclovir was generally well tolerated; the incidence of adverse events was comparable to placebo. Exacerbation of liver disease or serious ALT flares were not observed. CONCLUSION: Famciclovir 500 mg three times daily may offer an alternative to alpha-interferon for treatment for chronic hepatitis B. Anti-HBe seroconversion in the famciclovir 500-mg tid group suggests that 16 weeks treatment has the potential for HBV clearance. Further studies with a longer treatment duration are warranted.

Penciclovir cream for the treatment of sunlight-induced herpes simplex labialis: a randomized, double-blind, placebo-controlled trial. Penciclovir Cream Herpes Labialis Study Group.

OBJECTIVE: The purpose of this study was to further define the therapeutic value of penciclovir cream in the treatment of sunlight-induced herpes labialis by comparing its efficacy and tolerability with those of an inactive control (purified water). METHODS: In this randomized, double-blind, placebo-controlled, parallel-group clinical trial, lesions were induced by exposure to sunlight. Treatment was self-initiated within 1 hour of development of the signs or symptoms of a recurrence. RESULTS: Healthy male and female patients (mean age, 38.3 years; range, 18 to 81 years) who had a history of sunlight-induced herpes labialis (mean of 6 recurrences in previous 12 months) applied either penciclovir cream (n = 266) or purified water (n = 275). Penciclovir cream significantly decreased the time to lesion healing (P < 0.001), with a reduction in median time of up to 2 days. The efficacy of penciclovir cream was further supported by a significant reduction in maximum lesion area (P = 0.008), a faster loss of lesion-associated symptoms (P = 0.026), and significant reductions in daily assessments of pain (P < or = 0.040), itching (P < or = 0.032), burning (P < or = 0.028), and tenderness (P < or = 0.026) as moderate or severe. These effects were reinforced by the results of the daily self-assessment of lesion attributes, with significantly fewer severe/extreme assessments of lesion size (P < or = 0.003), noticeability (P < or = 0.003), amount of scab/crust (P < or = 0.003), raised/ swollen area (P < or = 0.040), soreness/tenderness (P < or = 0.043), and overall severity (P < or = 0.001) throughout the study period. CONCLUSIONS: Penciclovir cream has demonstrated efficacy for a broad range of clinically important outcomes. Significant effects on lesion area, lesion symptoms, and other lesion attributes extend the clinical efficacy of penciclovir cream beyond lesion healing.

Postherpetic neuralgia: impact of famciclovir, age, rash severity, and acute pain in herpes zoster patients.

New and previously reported analyses of the data from a placebo-controlled trial of famciclovir are reviewed in light of recently proposed recommendations for the analysis of pain in herpes zoster trials. The analyses examined the effect of famciclovir treatment on the duration of postherpetic neuralgia (PHN), which was defined as pain persisting after rash healing, pain persisting > 30 days after study enrollment, or pain persisting > 3 months after study enrollment; the baseline characteristics of patients in the famciclovir and placebo groups who developed PHN; the impact of famciclovir treatment on the duration of PHN, while controlling for significant covariates; and the prevalence of PHN at monthly intervals from 30 to 180 days after enrollment. The results of these analyses indicated that greater age, rash severity, and acute pain severity are risk factors for prolonged PHN. In addition, they demonstrated that treatment of acute herpes zoster patients with famciclovir significantly reduces both the duration and prevalence of PHN.

Oral famciclovir for the suppression of recurrent genital herpes: a randomized controlled trial. Collaborative Famciclovir Genital Herpes Research Group.

CONTEXT: Recurrent genital herpes simplex virus (HSV) may be treated episodically, but this may not be sufficient for patients with frequent recurrences. OBJECTIVE: To determine the efficacy and safety of famciclovir in the suppression of recurrent genital HSV infection. DESIGN: A randomized, double-blind, placebo-controlled, parallel-group study. SETTING: Thirty university, hospital, or private outpatient referral centers in Canada and Europe. PATIENTS: A total of 455 patients (223 men, 232 women) aged 18 years or older with a history of 6 or more episodes of genital herpes during 12 of the most recent 24 months, in the absence of suppressive therapy, received study medication. INTERVENTION: Oral famciclovir, 125 mg or 250 mg 3 times daily or 250 mg twice daily, or placebo for 52 weeks. MAIN OUTCOME MEASURES: Time to the first recurrence of genital HSV infection; the proportion of patients remaining free of HSV recurrence at 6 months; frequency of adverse events. RESULTS: In an intent-to-treat analysis, famciclovir significantly delayed the time to the first recurrence of genital herpes at all dose regimens (hazard ratios, 2.9-3.3; P<.001); median time to recurrence for famciclovir recipients was 222 to 336 days compared with 47 days for placebo recipients. The proportion of patients remaining free of HSV recurrence was approximately 3 times higher in famciclovir recipients (79%-86%) than in placebo recipients (27%) at 6 months (relative risks, 2.9-3.1; P<.001); efficacy was maintained at 12 months. Famciclovir was well tolerated with an adverse experience profile comparable to placebo. CONCLUSIONS: Oral famciclovir (125 mg or 250 mg 3 times daily or 250 mg twice daily) is an effective, well-tolerated treatment for the suppression of genital HSV infection in patients with frequent recurrences.

Famciclovir for the suppression of symptomatic and asymptomatic herpes simplex virus reactivation in HIV-infected persons. A double-blind, placebo-controlled trial.

BACKGROUND: Herpes simplex virus (HSV) infection is one of the most common opportunistic infections in HIV-infected persons. However, most documentation of the effectiveness of antiviral therapy in reducing HSV reactivation is anecdotal. OBJECTIVE: To evaluate the quantitative effect of antiviral therapy on the frequency of HSV reactivation in HIV-infected persons. DESIGN: Double-blind, placebo-controlled, crossover trial. SETTING: Research clinic at a university hospital. PATIENTS: 48 persons (45 men and 3 women) who were HIV positive and HSV seropositive. INTERVENTION: Patients were randomly assigned to receive famciclovir, 500 mg orally twice daily, or placebo for 8 weeks. They then crossed over to receive the other regimen after a 1-week washout period. MEASUREMENTS: Patients obtained daily cultures of their perirectal, urethral, oral, and genital areas and kept dairy records of signs and symptoms of genital and oral-labial herpes. RESULTS: The median CD4 cell count at study entry was 384 cells/mm3. In the intention-to-treat analysis of the first study period, HSV was isolated on 122 of 1114 (11%) placebo days compared with 9 of 1071 (1%) famciclovir days (relative risk, 0.15; P < 0.001). For patients who completed the crossover, the median difference in days with symptoms between placebo and famciclovir was 13.8% of days and the median difference in days on which HSV was isolated was 5.4% of days (P < 0.001 for both). Percentage of days with HSV-2 shedding was reduced from 9.7% to 1.3%. Breakthrough reactivations that occurred while patients were receiving famciclovir were infrequent, short, and often asymptomatic, HSV-2 isolates from these reactivations were susceptible to penciclovir in vitro. CONCLUSIONS: Antiviral chemotherapy with famciclovir results in clinically and statistically significant reductions in the symptoms associated with HSV infection and the symptomatic and asymptomatic shedding of HSV among HIV-positive persons.