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To evaluate the effect of cervical pessary, as a strategy to prevent preterm birth (PTB), on the outcome of subsequent pregnancy and maternal quality of life 4 years after the index twin pregnancy.Between 2009 and 2012, the ProTWIN trial randomized women with a multiple pregnancy to pessary use vs standard care for the prevention of PTB. The trial showed no benefit in unselected women with a twin pregnancy, but showed a 60% reduction in poor perinatal outcomes in favor of the pessary group in the subgroup of women with a mid-trimester short cervix (cervical length 38 mm). All women were invited to participate in a follow-up study 4 years after their participation in the ProTWIN trial. In this follow-up study, maternal quality of life was assessed using the EQ-5D-3L questionnaire and women were asked separate questions about subsequent pregnancies. Results were compared between women who were randomized to the pessary vs the control group in the ProTWIN trial by calculating relative risk (RR) and 95% CI. Subgroup analysis was performed for women with a mid-trimester short cervix (cervical length 38 mm).Of the 813 women included in the ProTWIN trial, 408 (50.2%) participated in this follow-up study, comprising 228 randomized to the pessary group and 180 to the control group in the original trial. The median interval between participation in the ProTWIN trial and participation in this follow-up study was 4.1 (interquartile range (IQR), 3.9-7.1) years. Ninety-eight (24.0%) participants tried to conceive after their participation in the ProTWIN trial. Of those, 22 (22.4%) women did not have a subsequent pregnancy (no difference between pessary and control groups), seven (7.1%) women had at least one miscarriage but no live birth, and 67 (68.4%) women had at least one live birth (35 in the pessary vs 32 in the control group; RR, 0.93 (95% CI, 0.8-1.07)). In two women, the pregnancy outcome was unknown. Preterm delivery ( 37 weeks of gestation) of the first live birth occurred in three women in the pessary vs one woman in the control group (all singleton; RR, 2.57 (95% CI, 0.28-23.44)). No differences were found between the pessary and control groups in the subgroup of women with mid-trimester short cervix, but the numbers analyzed were small. The median health state index score was 0.95 (IQR, 0.82-0.95), with no difference between the pessary and control groups.Our findings suggest that there are no long-term effects of pessary use on the outcome of subsequent pregnancies and maternal quality of life. Data on obstetric outcome were limited due to the small numbers. © 2021 The Authors. Ultrasound in ObstetricsGynecology published by John WileySons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

IntroductionPreterm birth is one of the main problems in obstetrics, and the most important cause of neonatal mortality, morbidity and neurodevelopmental impairment. Multiple gestation is an important risk factor for preterm birth, with up to 50% delivering before 37 weeks. Progesterone has a role in maintaining pregnancy and is frequently prescribed to prevent (recurrent) preterm birth and improve pregnancy outcomes in high-risk patients. However, little is known about its long-term effects in multiple gestations. The objective of this follow-up study is to assess long-term benefits and harms of prenatal exposure to progesterone treatment in multiple gestations on child development.Methods and analysisThis is a follow-up study of a multicentre, double-blind, placebo-controlled randomised trial (AMPHIA trial, ISRCTN40512715). Between 2006 and 2009 women with a multiple gestation were randomised at 16–20 weeks of gestation to weekly injections 250 mg 17α-hydroxyprogesterone caproate or placebo, until 36 weeks of gestation or delivery. The current long-term follow-up will assess all children (n=1355) born to mothers who participated in the AMPHIA trial, at 11–14 years of age, with internationally validated questionnaires, completed by themselves, their parents and their teachers.Main outcomes are child cognition and behaviourAdditional outcomes are death (perinatal and up to age 14), gender identity, educational performance and health-related problems. We will use intention-to-treat analyses comparing experimental and placebo group. To adjust for the correlation between twins, general linear mixed-effects models will be used.Ethics and disseminationAmsterdam UMC MEC provided a waiver for the Medical Research Involving Human Subjects Act (W20_234#20.268). Results will be disseminated through peer-reviewed journals and summaries shared with stakeholders, patients and participants. This protocol is published before analysis of the results.Trial registration numberNL8933.

Hyponatraemia due to the syndrome of inappropriate antidiuretic hormone secretion (SIADH) can pose a therapeutic challenge. After fluid restriction, urea is recommended as a second-line treatment by Dutch and European treatment guidelines. Data on this practice are still scarce. We introduced urea for the treatment of SIADH in our hospital and prospectively collected data on its effectiveness and tolerability.In hospitalised patients with a serum sodium level ≤ 129 mmol/l due to SIADH, urea in a dosage of 0.25-0.50 g/kg/day was indicated if prescribed fluid restriction had no effect or could not be applied. Measurement of serum sodium was performed at baseline, after the first and second day of urea therapy and at the end of the first inpatient treatment episode (EIT). The primary outcomes were normonatraemia (serum sodium level 135-145 mmol/l) at EIT and discontinuation of urea due to side effects.Thirteen patients were treated with urea over a median of 5 days (range 2-10 days). The median serum sodium level at baseline was 124 mmol/l (IQR 122-128), which increased to 128 mmol/l (IQR 123-130) (p = 0.003) after the first dose of urea and to 130 mmol/l (IQR 127-133) (p = 0.002) after the second dose of urea. Normonatraemia at EIT was observed in 8 (62%) patients. Seven (54%) patients reported distaste. In one of these patients, urea was discontinued because of nausea. Overcorrection was not observed.Our data show that urea is an effective treatment for hospitalised patients with SIADH. Distaste was a frequent side effect, but usually did not lead to early treatment discontinuation.

Limited evidence supports the efficacy of antimicrobial prophylaxis (AP) in prevention of gunshot woundrelated (GSW-related) infection in resource restricted areas. At Tygerberg Hospital, South Africa, it is standard care for GSW patients to receive one dose of broad-spectrum AP. For various reasons, this protocol is not consistently followed. This study aimed to assess the efficacy of AP in the reduction of in-hospital GSW-related infection and to identify opportunities for practice improvement.All patients admitted with GSW over a three-month period were eligible for inclusion. Patients who did and did not receive AP were identified retrospectively the morning of admission; thereafter, data was collected prospectively. Data regarding circumstances of the incident, injury characteristics, type of AP and surgery was obtained. The occurrence of in-hospital GSW-related infection was recorded over 30 days or until discharge. Propensity score matching (PSM) and inverse probability weighting (IPW) methods were utilised to assess the effect of AP on the prevention of GSW-related infection.165 consecutive patients were assessed, of which 103 received AP according to protocol within 12 hours of admission. PSM showed a reduced in-hospital GSW infection risk of 12% (95% CI, 0.2-24%,Providing AP to GSW patients in a civilian setting appeared to result in a modest but clinically relevant lower risk of in-hospital GSW-related infection. In this study setting, optimisation of AP for all patients with GSWs should significantly lower the burden of wound infection.

Background Evidence for an association between hospital volume and outcomes for liver surgery is abundant. The current Dutch guideline requires a minimum volume of 20 annual procedures per centre. The aim of this study was to investigate the association between hospital volume and postoperative outcomes using data from the nationwide Dutch Hepato Biliary Audit. Methods This was a nationwide study in the Netherlands. All liver resections reported in the Dutch Hepato Biliary Audit between 2014 and 2017 were included. Annual centre volume was calculated and classified in categories of 20 procedures per year. Main outcomes were major morbidity (Clavien–Dindo grade IIIA or higher) and 30‐day or in‐hospital mortality. Results A total of 5590 liver resections were done across 34 centres with a median annual centre volume of 35 (i.q.r. 20–69) procedures. Overall major morbidity and mortality rates were 11·2 and 2·0 per cent respectively. The mortality rate was 1·9 per cent after resection for colorectal liver metastases (CRLMs), 1·2 per cent for non‐CRLMs, 0·4 per cent for benign tumours, 4·9 per cent for hepatocellular carcinoma and 10·3 per cent for biliary tumours. Higher‐volume centres performed more major liver resections, and more resections for hepatocellular carcinoma and biliary cancer. There was no association between hospital volume and either major morbidity or mortality in multivariable analysis, after adjustment for known risk factors for adverse events. Conclusion Hospital volume and postoperative outcomes were not associated., This study analysed the association between hospital volume and postoperative outcomes in the nationwide Dutch Hepato Biliary Audit. A total of 5590 resections was performed across 34 centres with a median annual centre volume of 35 (i.q.r. 20–69) procedures. No association was found between hospital and postoperative outcomes. Cut‐off about right

Recent theories suggest that self-consciousness, in its most elementary form, is functionally disconnected from the phenomenal body. Patients with psychosis frequently misattribute their thoughts and actions to external sources; and in certain out-of-body experiences, lucid states, and dreams body-ownership is absent but self-identification is preserved. To explain these unusual experiences, we hypothesized that self-identification depends on inferring self-location at the right angular gyrus (i.e., perspective-taking). This process relates to the discrimination of self-produced signals (endogenous attention) from environmental stimulation (exogenous attention). Therefore, when this mechanism fails, this causes altered sensations and perceptions. We combined a Full-body Illusion paradigm with brain stimulation (HD-tDCS) and found a clear causal association between right angular gyrus activation and alterations in self-location (perspective-taking). Anodal versus sham HD-tDCS resulted in: a more profound out-of-body shift (with reduced sense of agency); and a weakened ability to discriminate self from other perspectives. We conclude that self-identification is mediated in the brain by inferring self-location (i.e., perspective-taking). Self-identification can be decoupled from the bodily self, explaining phenomena associated with disembodiment. These findings present novel insights into the relationship between mind and body, and may offer important future directions for treating psychosis symptoms and rehabilitation programs to aid in the recovery from a nervous system injury. The brain's ability to locate itself might be the key mechanism for self-identification and distinguishing self from other signals (i.e., perspective-taking).

To evaluate the results of the national paediatric liver transplantation programme in the University Medical Centre (UMC) Groningen in the Netherlands during the past two decades.Retrospective cohort study.We analysed data from paediatric patients who underwent liver transplantation at UMC Groningen in the period 1995-2016. We compared outcomes from children who had undergone a liver transplantation in the period 1995-2005 (cohort A; n = 126) and in the period 2006-2016 (cohort B; n = 169). We performed a subanalysis in cohort B between liver transplantations with deceased donor livers (n = 132) and living donor liver transplantations (LDLT; n = 37).In cohort A, almost all livers came from deceased donors (99%), whereas in cohort B, 37 LDLTs (22%) were performed. The median age of recipients was significantly higher in cohort A (4.4 vs. 2.5 years; p = 0.015). Postoperative complications were comparable for both cohorts. Re-transplantations within a year after transplantation were more often performed in cohort A than in cohort B (25% vs. 12%; p = 0.004). Following LDLT, there was 2 times (5.4%) an indication for re-transplantation. In cohort B the 5-year survival rate was better than in cohort A (83 vs. 71%; p = 0.014). In cohort B, 5-year survival was higher after LDLT than after transplantation with a deceased donor liver (95 vs. 81%; p = 0.025).Outcomes after paediatric liver transplantation in the Netherlands have further improved during the past two decades. With an actuarial 5-year survival of 83% in the most recent cohort, and as high as 95% following LDLT, we can say that the UMC Groningen has a successful national paediatric liver transplant programme.

BACKGROUND: Biological phenotypes have been identified within several heterogeneous pulmonary diseases, with potential therapeutic consequences. OBJECTIVE: To assess whether distinct biological phenotypes exist within surgical patients, and whether development of postoperative pulmonary complications (PPCs) and subsequent dependence of intra-operative positive end-expiratory pressure (PEEP) differ between such phenotypes. SETTING: Operating rooms of six hospitals in Europe and USA. DESIGN: Secondary analysis of the 'PROtective Ventilation with HIgh or LOw PEEP' trial. PATIENTS: Adult patients scheduled for abdominal surgery who are at risk of PPCs. INTERVENTIONS: Measurement of pre-operative concentrations of seven plasma biomarkers associated with inflammation and lung injury. MAIN OUTCOME MEASURES: We applied unbiased cluster analysis to identify biological phenotypes. We then compared the proportion of patients developing PPCs within each phenotype, and associations between intra-operative PEEP levels and development of PPCs among phenotypes. RESULTS: In total, 242 patients were included. Unbiased cluster analysis clustered the patients within two biological phenotypes. Patients with phenotype 1 had lower plasma concentrations of TNF-α (3.8 [2.4 to 5.9] vs. 10.2 [8.0 to 12.1] pg ml; P

Background Laparoscopic left lateral sectionectomy (LLLS) has been associated with shorter hospital stay and reduced overall morbidity compared with open left lateral sectionectomy (OLLS). Strong evidence has not, however, been provided. Methods In this multicentre double-blind RCT, patients (aged 18–80 years with a BMI of 18–35 kg/m2 and ASA fitness grade of III or below) requiring left lateral sectionectomy (LLS) were assigned randomly to OLLS or LLLS within an enhanced recovery after surgery (ERAS) programme. All randomized patients, ward physicians and nurses were blinded to the procedure undertaken. A parallel prospective registry (open non-randomized (ONR) versus laparoscopic non-randomized (LNR)) was used to monitor patients who were not enrolled for randomization because of doctor or patient preference. The primary endpoint was time to functional recovery. Secondary endpoints were length of hospital stay (LOS), readmission rate, overall morbidity, composite endpoint of liver surgery-specific morbidity, mortality, and reasons for delay in discharge after functional recovery. Results Between January 2010 and July 2014, patients were recruited at ten centres. Of these, 24 patients were randomized at eight centres, and 67 patients from eight centres were included in the prospective registry. Owing to slow accrual, the trial was stopped on the advice of an independent Data and Safety Monitoring Board in the Netherlands. No significant difference in median (i.q.r.) time to functional recovery was observed between laparoscopic and open surgery in the randomized or non-randomized groups: 3 (3–5) days for OLLSversus 3 (3–3) days for LLLS; and 3 (3–3) days for ONRversus 3 (3–4) days for LNR. There were no significant differences with regard to LOS, morbidity, reoperation, readmission and mortality rates. Conclusion This RCT comparing open and laparoscopic LLS in an ERAS setting was not able to reach a conclusion on time to functional recovery, because it was stopped prematurely owing to slow accrual. Registration number: NCT00874224 (https://www.clinicaltrials.gov).

A 71-year-old man was admitted to the emergency room after high-energy trauma. He suddenly deteriorated several hours after an epidural providing local anaesthetics. At that time, his blood was black and the methaemoglobin level was 69 percent. After administration of methylene blue, he made a full clinical and biochemical recovery.

In a multiple-dose-ranging trial, we previously evaluated higher doses of rifampin in patients for 2 weeks. The objectives of the current study were to administer higher doses of rifampin for a longer period to compare the pharmacokinetics, safety/tolerability, and bacteriological activity of such regimens. In a double-blind, randomized, placebo-controlled, phase II clinical trial, 150 Tanzanian patients with tuberculosis (TB) were randomized to receive either 600 mg (approximately 10 mg/kg of body weight), 900 mg, or 1,200 mg rifampin combined with standard doses of isoniazid, pyrazinamide, and ethambutol administered daily for 2 months. Intensive pharmacokinetic sampling occurred in 63 patients after 6 weeks of treatment, and safety/tolerability was assessed. The bacteriological response was assessed by culture conversion in liquid and solid media. Geometric mean total exposures (area under the concentration-versus-time curve up to 24 h after the dose) were 24.6, 50.8, and 76.1 mg · h/liter in the 600-mg, 900-mg, and 1,200-mg groups, respectively, reflecting a nonlinear increase in exposure with the dose ( P < 0.001). Grade 3 adverse events occurred in only 2 patients in the 600-mg arm, 4 patients in the 900-mg arm, and 5 patients in the 1,200-mg arm. No significant differences in the bacteriological response were observed. Higher daily doses of rifampin (900 and 1,200 mg) resulted in a more than proportional increase in rifampin exposure in plasma and were safe and well tolerated when combined with other first-line anti-TB drugs for 2 months, but they did not result in improved bacteriological responses in patients with pulmonary TB. These findings have warranted evaluation of even higher doses of rifampin in follow-up trials. (This study has been registered at ClinicalTrials.gov under identifier NCT00760149.)

Item does not contain fulltext Severe dengue is characterised by thrombocytopenia, plasma leakage and bleeding. Platelets are important for preservation of endothelial integrity. We hypothesised that platelet activation with secondary platelet dysfunction contribute to plasma leakage. In adult Indonesian patients with acute dengue, we measured platelet activation status and the response to the platelet agonist TRAP using flow cytometer-based assays. Patients were monitored daily for plasma leakage by ultrasonography. Acute dengue was associated with platelet activation with an increased expression of the activated fibrinogen receptor (alphaIIbbeta3), the lysosomal marker CD63 and the alpha-granule marker CD62P (P-selectin). Upon maximal platelet activation by TRAP, platelet function defects were observed with a significantly reduced maximal activated alphaIIbbeta3 and CD63 expression and reduced platelet-monocyte and platelet-neutrophil complexes. Patients in the lowest tertile of activated alphaIIbbeta3 and CD63 expression had an odds ratio for plasma leakage of 5.2 (95% confidence interval [CI] 1.3-22.7) and 3.9 (95% CI 1.1-13.7), respectively, compared to the highest tertile. Platelet-derived serotonin has previously been related to plasma leakage and we found increased intra-platelet serotonin concentrations in our patients. In conclusion, platelet activation with platelet function alterations can be found in patients with acute dengue and this may contribute to dengue-associated plasma leakage.

Transfusion-related immunomodulation (TRIM) encompasses immunosuppressive and proinflammatory effects induced by red blood cell (RBC) transfusion. Changes that occur during storage in the RBC product have been hypothesized to underlie TRIM, mediated by tolerance of toll-like receptors (TLR). We investigated whether transfusion of 35-day-stored autologous RBCs alters cytokine production in response to stimulation with lipopolysaccharide (LPS) or lipotheic acid (LTA), in a clinically relevant model of endotoxemia.Eighteen volunteers received 2 ng/kg LPS intravenously, followed by normal saline or 2- or 35-day-stored autologous RBC transfusion. Before LPS, before transfusion, and 6 hours after transfusion blood was collected to measure cytokine gene expression. Whole blood was used for ex vivo stimulation with LPS and LTA, after which cytokine levels were measured with enzyme-linked immunosorbent assay.In vivo LPS induced a biphasic response in cytokine mRNA with peak values 2 hours after LPS infusion. Storage time of RBC transfusion did not influence cytokine mRNA levels. In vivo infusion of LPS resulted in tolerance for ex vivo stimulation with LPS and LTA. However, transfusion of either fresh or stored RBCs did not further affect the capacity to produce cytokines after ex vivo stimulation.In a clinically relevant model of human endotoxemia, autologous transfusion of 35-day-stored RBCs does not influence cytokine mRNA levels nor does it change the capacity of white blood cells in whole blood to produce cytokines after ex vivo stimulation with LPS or LTA.

Objective Transfusion-related acute lung injury is the leading cause of transfusion-related mortality. Preclinical studies have shown that aged RBCs can induce transfusion-related acute lung injury in the presence of a "first hit" (e.g., sepsis). Clinical studies, however, show conflicting results on this matter. We tested whether maximally stored RBCs are able to induce lung injury in the presence of a "first hit" in humans (Dutch Trial Register: NTR4455). Design Open-label, randomized controlled trial. Patients Healthy male volunteers. Interventions Eighteen healthy male volunteers donated one unit of autologous RBCs 2 or 35 days before the experiment. The experiment was started by infusion of 2 ng/kg lipopolysaccharide ("first hit"). After 2 hours, volunteers received normal saline (n = 6), 2-day stored transfusion (n = 6), or 35-day stored transfusion (n = 6) ("second hit"). Blood was sampled hourly. Six hours after transfusion, the diffusion capacity of the lungs for carbon monoxide was tested and volunteers underwent spirometry, chest x-ray study, and a bronchoalveolar lavage. Measurements and main results All volunteers fulfilled sepsis criteria after lipopolysaccharide injection. The stored blood transfusion did not result in significant changes in either hemodynamic or respiratory variables compared with the control groups. Furthermore, chest x-rays, lung function, and PaO2/FIO2 ratios did not differ between groups. Transfusion of stored autologous RBCs did not result in an increased level of protein in the lungs or neutrophil influx. Conclusions Transfusion of 35-day stored autologous RBCs in the presence of endotoxemia does not result in lung injury in humans.

Aim: To investigate the influence of tendinous and synaptic changes induced by unilateral lower limb suspension (ULLS) on the tendon tap reflex. Methods: Eight young men underwent a 23-day period of ULLS. Muscle cross-sectional area (CSA), torque and electromyographic (EMG) activity of the plantar flexor muscles (normalized to the M wave), Achilles tendon–aponeurosis mechanical properties, soleus (SOL) H and T reflexes and associated peak twitch torques were measured at baseline, after 14 and 23 days of ULLS, and 1 week after resuming ambulatory activity. Results: Significant decreases in muscle CSA (−9%), in maximal voluntary torque (−10%) and in the associated SOL EMG activity (−16%) were found after ULLS (P < 0.05). In addition to a 36% (P < 0.01) decrease in tendon–aponeurosis stiffness, normalized H reflex increased by 35% (P < 0.05). An increase in the slope (28%, P < 0.05) and intercept (85%, P < 0.05) of the T reflex recruitment curve pointed to an increase in the gain and to a decrease in the sensitivity of this reflex, possibly resulting from the decrease in the tendon–aponeurosis stiffness at low forces. Following ULLS, changes in tendinous stiffness correlated with changes in neuromuscular efficiency (peak twitch torque to reflex ratio) at higher tendon tap forces. Conclusion: These findings point out the dual and antagonistic influences of spinal and tendinous adaptations upon the tendon tap reflex in humans under conditions of chronic unloading. These observations have potential implications for the sensitivity of the short-latency Ia stretch response involved in rapid compensatory contractions to unexpected postural perturbations.

Renal dysfunction is frequently seen after orthotopic liver transplantation (OLT). Aprotinin is an antifibrinolytic drug which reduces blood loss during OLT. Recent studies in cardiac surgery suggested a higher risk of postoperative renal complications when aprotinin is used. The impact of aprotinin on renal function after OLT, however, is unknown. In 1043 adults undergoing OLT, we compared postoperative renal function in patients who received aprotinin (n = 653) or not (n = 390). Using propensity score stratification (C-index 0.82) and multivariate regression analysis, aprotinin was identified as a risk factor for severe renal dysfunction within the first week, defined as increase in serum creatinine by >= 100% (OR = 1.97, 95% CI = 1.14-3.39; p = 0.02). No differences in renal function were noted at 30 and 365 days postoperatively. Moreover, no significant differences were found in the need for renal replacement therapy (OR = 1.52, 95% CI = 0.94-2.46; p = 0.11) or in 1-year patient survival rate (OR = 1.14, 95% CI = 0.73-1.77; p = 0.64) in patients who received aprotinin or not. In conclusion, aprotinin is associated with a higher risk of transient renal dysfunction in the first week after OLT, but not with a higher need for postoperative renal replacement therapy or an increased risk of mortality.

Postconditioning of myocardial tissue employs short cycles of ischemia or pharmacologic agents during early reperfusion. Effects of helium postconditioning protocols on infarct size and the ischemia/reperfusion-induced immune response were investigated by measurement of protein and mRNA levels of proinflammatory cytokines. Rats were anesthetized with S-ketamine (150 mg/kg) and diazepam (1.5 mg/kg). Regional myocardial ischemia/reperfusion was induced; additional groups inhaled 15, 30, or 60 min of 70% helium during reperfusion. Fifteen minutes of helium reduced infarct size from 43% in control to 21%, whereas 30 and 60 minutes of helium inhalation led to an infarct size of 47% and 39%, respectively. Increased protein levels of cytokine-induced neutrophil chemoattractant (CINC-3) and interleukin-1 beta (IL-1β) were found after 30 or 60 min of helium inhalation, in comparison to control. 30 min of helium increased mRNA levels of CINC-3, IL-1β, interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) in myocardial tissue not directly subjected to ischemia/reperfusion. These results suggest that the effectiveness of the helium postconditioning protocol is very sensitive to duration of noble gas application. Additionally, helium was associated with higher levels of inflammatory cytokines; however, it is not clear whether this is causative of nature or part of an epiphenomenon.

Objectives: To investigate the long-term impact of multivessel coronary artery disease (MVD) on cause-specific mortality in patients with ST elevation myocardial infarction (STEMI) treated with reperfusion therapy. Methods and results: Patients with STEMI (n = 395) treated with primary angioplasty or thrombolysis in the setting of a randomised clinical trial were enrolled in the study. Follow up was 8 (2) years. For patients who died all available records were reviewed to assess the specific cause of death. MVD was present in 57% of patients. Patients with MVD were older and more of them had diabetes and previous myocardial infarction. Compared with the non-MVD group, residual left ventricular ejection fraction was lower (45.9% v 49.6%, p = 0.001) and total mortality was higher in patients with MVD (32% v 19%, p = 0.002). After adjustment for potential confounders this association was not significant (hazard ratio 1.4, 95% confidence interval (CI) 0.9 to 2.2). When the specific cause of death was considered, sudden death was comparable between patients with and without MVD (10% v 8%, p = 0.49) but death caused by heart failure was significantly higher in patients with MVD (hazard ratio 7.4, 95% CI 1.7 to 32.2). Conclusion: Patients with STEMI and MVD have a higher long-term mortality than do patients with non-MVD. MVD is not an independent predictor of long-term total mortality or sudden death. However, MVD is a very strong and independent predictor of long-term death caused by heart failure.

Background: Vegetable pollen is a rare source of occupational allergens. Occupational allergy has only been described in the case of paprika pollen and tomato pollen. We describe a new source of occupational pollen allergy. Aim: To study the incidence and the impact of broccoli and cauliflower pollen allergy in employees involved in classical plant breeding. Methods: Fifty-four employees of five companies working with cauliflower (Brassica oleracea botrytis) and broccoli (B. oleracea italica/cymosa) pollen were eligible for complete evaluation. Allergy to cauliflower and broccoli pollen was evaluated by questionnaire and determination of sensitization by radioallergosorbent test (RAST) and skin-prick tests (SPT). SPT and RAST were performed with a panel of commercial and homemade extracts from cauliflower and broccoli pollen. Results: Work-related symptoms such as rhinitis, conjunctivitis, asthma and urticaria caused by B. oleracea pollen were reported by 44% of the participants (24/54), of whom all but one had positive SPT for cauliflower- and/or broccoli-pollen/flower extracts and 58% (14/24) had positive RAST results. Symptoms had developed within the first 2 years in 33% of the patients. Six patients had to stop or change work. Conclusions: Brassica oleracea pollen is a new source of occupational allergen with strong allergenic potential leading to symptoms in almost half of the exposed employees.

Objectives: To study the clinical significance of infarct location during long term follow up in a trial comparing thrombolysis with primary angioplasty. Design: Retrospective longitudinal cohort analysis of prospectively entered data. Setting: Patients with acute ST elevation myocardial infarction (STEMI) treated with primary percutaneous coronary intervention (PCI). Patients: In the Zwolle trial 395 patients with acute STEMI were randomly assigned to intravenous streptokinase or PCI. Main outcome measures: Survival according to infarct location and treatment after 8 (2) years of follow up. Results: 105 patients died: 63 patients in the streptokinase group and 42 patients in the primary PCI group (relative risk (RR) 1.6, 95% confidence interval (CI) 1.0 to 2.6; p = 0.03). In patients with non-anterior STEMI there was no difference in mortality between streptokinase and PCI treated patients (RR 1.1, 95% CI 0.6 to 2.1; p = 0.68) but the streptokinase group had significantly more major adverse cardiac events (MACE) than the PCI group (RR 2.1, 95% CI 1.2 to 3.6). The number needed to treat to prevent one MACE was four. In patients with anterior STEMI, mortality was higher in the streptokinase group than in the PCI group (RR 2.7, 95% CI 1.4 to 5.5; p = 0.004). The number needed to treat to prevent one death was five. Kaplan-Meier analysis confirmed the benefits of primary angioplasty in the first year and showed additional benefit of PCI compared with streptokinase between 1–8 years after the acute event. Conclusions: Patients with anterior STEMI have better long term survival when treated with PCI than with streptokinase. In patients alive one year after the acute event, PCI confers a significant additional survival benefit, probably due to better preserved residual left ventricular function.

Cognitive-behavioural treatment can nowadays be delivered through the Internet. This form of treatment can have various advantages with regard to availability and accessibility. Previous studies showed that Internet-based treatment for chronic pain is effective compared to waiting-list control groups.We conducted a randomized controlled trial comparing an Internet-based cognitive-behavioural intervention with e-mail therapist contact to a face-to-face cognitive-behavioural group intervention. Of the 72 participants who were randomly assigned to an Internet or a group course, 50 participants completed the intervention. Participants were assessed at baseline (T0), immediately after the 7-week course (T1) and at the booster session 2 months later (T2). Pain-related catastrophizing was the primary outcome measure. Pain intensity, fatigue, pain-related interference, locus of control, pain coping, global health-related quality of life and medical expenses were secondary outcome variables.Significant improvement was found on catastrophizing, pain coping, locus of control and aspects of global health-related quality of life in both the Internet and the group courses directly after the course and at the booster session. Pain intensity was improved in both courses at the booster session. At T2, improvement in catastrophizing, pain intensity, pain coping and some quality of life dimensions was significantly greater in completers of the Internet course than in the group course. Furthermore, the Internet course was cost-effective compared to the group course.We conclude that the Internet-based cognitive-behavioural intervention was at least as effective as the face-to-face group intervention and, on some outcome measures appeared to be even more effective.

Background:In the European Rosetta project three separate, previously developed, ICT systems were improved and integrated to create one modular system that helps community-dwelling people with mild cognitive impairment and dementia in different stages of the disease. The system aims to support them in daily functioning, monitor (deviations from) patterns in daily behaviour and to automatically detect emergency situations. The study aimed to inventory the end users’ needs and wishes regarding the development and design of the new integrated Rosetta system, and to describe the to be developed Rosetta system.Methods:Qualitative user-participatory design with in total 50 persons: 14 people with dementia, 13 informal carers, 6 professional carers, 9 dementia experts, 7 care partners within the project, and 1 volunteer. In the Netherlands user focus group sessions were performed and in Germany individual interviews. Dementia experts were consulted by means of a questionnaire, an expert meeting session, and interviews.Results:Persons with dementia and informal carers appreciated the following functionalities most: help in cases of emergencies, navigation support and the calendar function. Dementia experts rated various behaviours relevant to monitor in order to detect timely changes in functioning, e.g. eating, drinking, going to the toilet, taking medicine adequately, performance of activities and sleep patterns. No ethical issues regarding the use of sensors and cameras were mentioned.Conclusion:The user participatory design resulted in valuable input from persons with dementia, informal carers and professional carers/dementia experts, based on which a first prototype Rosetta system was built.

Introduction Induced hypothermia is increasingly applied as a therapeutic intervention in ICUs. One of the underlying mechanisms of the beneficial effects of hypothermia is proposed to be reduction of the inflammatory response. However, a fear of reducing the inflammatory response is an increased infection risk. Therefore, we studied the effect of induced hypothermia on immune response after cardiac arrest. Methods A prospective observational cohort study in a mixed surgical-medical ICU. Patients admitted at the ICU after surviving cardiac arrest were included and during 24 hours body temperature was strictly regulated at 33°C or 36°C. Blood was drawn at three time points: after reaching target temperature, at the end of the target temperature protocol and after rewarming to 37°C. Plasma cytokine levels and response of blood leucocytes to stimulation with toll-like receptor (TLR) ligands lipopolysaccharide (LPS) from Gram-negative bacteria and lipoteicoic acid (LTA) from Gram-positive bacteria were measured. Also, monocyte HLA-DR expression was determined. Results In total, 20 patients were enrolled in the study. Compared to healthy controls, cardiac arrest patients kept at 36°C (n = 9) had increased plasma cytokines levels, which was not apparent in patients kept at 33°C (n = 11). Immune response to TLR ligands in patients after cardiac arrest was generally reduced and associated with lower HLA-DR expression. Patients kept at 33°C had preserved ability of immune cells to respond to LPS and LTA compared to patients kept at 36°C. These differences disappeared over time. HLA-DR expression did not differ between 33°C and 36°C. Conclusions Patients after cardiac arrest have a modest systemic inflammatory response compared to healthy controls, associated with lower HLA-DR expression and attenuated immune response to Gram-negative and Gram-positive antigens, the latter indicative of an impaired immune response to bacteria. Patients with a body temperature of 33°C did not differ from patients with a body temperature of 36°C, suggesting induced hypothermia does not affect immune response in patients with cardiac arrest. Trial registration ClinicalTrials.gov NCT01020916, registered 25 November 2009

In an investigation of condom breakage in commercial sex, we found a high proportion of multiple condoms use. This study sought to ascertain the characteristics of brothel-based commercial sex workers (CSWs) and their clients; to identify the decision makers (clients and/or CSWs) active in choosing multiple condom use; and to determine whether there is an implicit hierarchy of condom use negotiation.To identify factors associated with multiple condom use in commercial sex and to provide an understanding of how this innovation developed in this setting.Sixty-seven brothel-based CSWs in Lamphun Province who participated in a study of condom breakage participated in a case-control study of multiple versus single condom use, which determined CSW and client characteristics for evidence of multiple condom use. Interviews and focus groups were used to determine decision making for condom use and the contexts for multiple use. Association between characteristics of CSWs/clients and multiple condom use was analyzed using X2 for trend.No official program encouraged multiple condom use; this appeared to be a community-devised strategy to increase protection from human immunodeficiency virus (HIV) and other sexually transmitted diseases (STDs). CSWs working in daytime brothels had significantly greater multiple condom use than those working in nighttime brothels; mean percentages + SD of multiple simultaneous use were 57.5% + 28.6 and 35.5% + 22.4, respectively (p0.001). Day CSWs were older, had more pregnancies, reported higher frequency of STD symptoms and history of pelvic inflammatory disease, and had more clients per day but had a lower number of sex acts per client than night CSWs. Among factors associated with multiple condoms, only age was significant. The decision to use single or multiple condoms for a sex act was primarily (78.2% in single and 79.3% in multiple) made by the CSW herself. The main reason given for multiple condom use was protection from HIV/STD.There is high compliance between CSWs in Lamphun province and the Ministry of Public Health-sponsored 100% condom use campaign, and CSWs are attempting to further reduce their risks of HIV/STD exposure by using multiple condoms for sex with their clients.

To verify the acclaimed accuracy of ultrasound (US) combined with US-guided fine-needle aspiration biopsy (FNAB) in the detection of lymph node metastasis in the neck and to evaluate the interobserver variability.In a prospective, multicenter study of 185 patients with head and neck squamous cell carcinoma, US (n=238 neck sides) with US-guided FNAB (n=178 neck sides) was used for evaluation of the lymph node status of the neck. Findings were correlated with those of histopathologic examination in 238 neck sides.US with US-guided FNAB had a sensitivity of 77% and a specificity of 100%. Nineteen of 178 aspirations were nondiagnostic. There were no significant differences between the four participating hospitals or the individual sonologists (P.05).Sensitivity of US with US-guided FNAB was slightly lower compared with previous reports. Specificity was similar to previous reports. Interobserver variability appeared to be low. The validity of US with US-guided FNAB is high and warrants widespread use of the procedure for evaluation of the neck.

Introduction Uric acid released from injured tissue is considered a major endogenous danger signal and local instillation of uric acid crystals induces acute lung inflammation via activation of the NLRP3 inflammasome. Ventilator-induced lung injury (VILI) is mediated by the NLRP3 inflammasome and increased uric acid levels in lung lavage fluid are reported. We studied levels in human lung injury and the contribution of uric acid in experimental VILI. Methods Uric acid levels in lung lavage fluid of patients with acute lung injury (ALI) were determined. In a different cohort of cardiac surgery patients, uric acid levels were correlated with pulmonary leakage index. In a mouse model of VILI the effect of allopurinol (inhibits uric acid synthesis) and uricase (degrades uric acid) pre-treatment on neutrophil influx, up-regulation of adhesion molecules, pulmonary and systemic cytokine levels, lung pathology, and regulation of receptors involved in the recognition of uric acid was studied. In addition, total protein and immunoglobulin M in lung lavage fluid and pulmonary wet/dry ratios were measured as markers of alveolar barrier dysfunction. Results Uric acid levels increased in ALI patients. In cardiac surgery patients, elevated levels correlated significantly with the pulmonary leakage index. Allopurinol or uricase treatment did not reduce ventilator-induced inflammation, IκB-α degradation, or up-regulation of NLRP3, Toll-like receptor 2, and Toll-like receptor 4 gene expression in mice. Alveolar barrier dysfunction was attenuated which was most pronounced in mice pre-treated with allopurinol: both treatment strategies reduced wet/dry ratio, allopurinol also lowered total protein and immunoglobulin M levels. Conclusions Local uric acid levels increase in patients with ALI. In mice, allopurinol and uricase attenuate ventilator-induced alveolar barrier dysfunction.

Background. Little is known about the rehabilitation outcomes of long-term survivors following treatment for head and neck cancer. There are, for example, no studies on physical and psychosocial rehabilitation outcomes of T1 glottic larynx carcinoma, despite the fact that these form the majority of head and neck cancer sites. Thus, this investigation afforded a unique opportunity for examining similarities and differences among T1 glottic larynx patients, laryngectomy patients, and those who had surgery for cancer of the oral cavity and/or oropharynx along a variety of physical and psychosocial dimensions. Methods. To describe the impact of these three types of head and neck cancer and their treatment on the physical and psychosocial functioning of long-term survivors, a selfreport questionnaire was completed by 110 patients treated between 2 and 6 years previously in a major cancer center. Results. Data indicate that a higher percentage of patients treated with laryngectomy or commando procedures still experience severe psychosocial distress between 2 and 6 years after their last treatment than do patients treated with radiotherapy for a T1 carcinoma of the glottic larynx. Psychosocial and physical complaints are still reported by many laryngectomy patients, apparently the result of problems in effective communication with others. Many commando procedure patients experience problems with respect to food intake, and with disfigurement and its consequences. T1 Iarynx patients mainly experience a considerable number of physical complaints. The greater the time that had elapsed since treatment, the fewer the psychosocial problems associated with head and neck tumors. Open discussion of the illness in the family, social support, and perceptions of adequate information from the specialist are the most important predictors of positive rehabilitation outcomes. Conclusions. This study indicates that T1 Iarynx patients report many physical complaints even though several years had elapsed since treatment. Also, Iaryngectomy patients may need psychosocial guidance for a longer posttreatment period and that health care personnel must involve the partner as much as possible in all communications. Commando procedure patients in particular feel hindered by their disfigurement and its consequences. Future research with respect to validation of the specific head and neck modules is needed.

The mechanisms underlying obesity-related hypertension are incompletely understood. Microvascular dysfunction might play a role by increasing peripheral vascular resistance (PVR). Metabolic and microvascular effects of insulin are impaired in obesity, but how these impairments contribute to disturbed blood pressure homeostasis is unclear. Specifically, it is unknown whether local microvascular vasoactive effects of insulin play a role in determining systemic vascular resistance. The aim of this study was to investigate the association between PVR and local microvascular effects of insulin.Thirty-seven healthy, overweight subjects (age 25-55 years, BMI 25-30 kg/m(2) ) were cross-sectionally studied. Local insulin-mediated vasodilation was measured using skin laser Doppler fluxmetry combined with transcutaneous iontophoresis of insulin. For comparison, local vasodilatory effects of acetylcholine and sodium nitroprusside were measured. PVR was calculated from mean arterial pressure and cardiac output, assessed by pulse-dye densitometry.PVR was inversely correlated with insulin-mediated vasodilation (r = -0.50; P0.01). This finding was maintained after adjustment for age, sex, blood pressure, and smoking. PVR was not associated with local microvascular effects of acetylcholine.Our study in overweight subjects suggests that insulin's role in the microvasculature may contribute to blood pressure control.

Catastrophizing is a defining factor in the pain experience and strongly contributes to the prediction of various aspects of health. Catastrophizing is not just present in pain patients, but may also be present in people with non-clinical pain. The aim of the present study is to investigate levels of catastrophizing in pain patients and people with pain from the general population. Also, the relationship between catastrophizing and pain intensity, specialist consultation and use of pain medication is studied.A cross-sectional survey design was used, including 150 pain patients and 376 respondents from the general population.The results show that pain is highly prevalent in the general population. The pain patients reported significantly higher levels of pain intensity and catastrophizing than the community pain sample. In both samples, significant positive correlations between catastrophizing and pain intensity were found. The data show a linear relationship between catastrophizing and pain intensity, which can be interpreted as evidence for a dose-response pattern in pain-related catastrophizing. Furthermore, catastrophizing predicted specialist consultation and medication use in the community pain sample.It can be concluded that pain-related catastrophizing is present in pain patients as well as people with pain from the general population in a dose-response pattern. Catastrophizing seems to be an important factor determining certain aspects of pain-related medical consumption, even in non-clinical pain, and should therefore be a target of the screening procedure and early intervention.

BACKGROUND Patients with unstable angina despite intensive medical therapy, ie, refractory angina, are at high risk for developing thrombotic complications: myocardial infarction or coronary occlusion during percutaneous transluminal coronary angioplasty (PTCA). Chimeric 7E3 (c7E3) Fab is an antibody fragment that blocks the platelet glycoprotein (GP) IIb/IIIa receptor and potently inhibits platelet aggregation. METHODS AND RESULTS To evaluate whether potent platelet inhibition could reduce these complications, 60 patients with dynamic ST-T changes and recurrent pain despite intensive medical therapy were randomized to c7E3 Fab or placebo. After initial angiography had demonstrated a culprit lesion suitable for PTCA, placebo or c7E3 Fab was administered as 0.25 mg/kg bolus injection followed by 10 micrograms/min for 18 to 24 hours until 1 hour after completion of second angiography and PTCA. During study drug infusion, ischemia occurred in 9 c7E3 Fab and 16 placebo patients (P = .06). During hospital stay, 12 major events occurred in 7 placebo patients (23%), including 1 death, 4 infarcts, and 7 urgent interventions. In the c7E3 Fab group, only 1 event (an infarct) occurred (3%, P = .03). Angiography showed improved TIMI flow in 4 placebo and 6 c7E3 Fab patients and worsening of flow in 3 placebo patients but in none of the c7E3 Fab patients. Quantitative analysis showed significant improvement of the lesion in the patients treated with c7E3 Fab, which was not observed in the placebo group, although the difference between the two treatment groups was not significant. Measurement of platelet function and bleeding time demonstrated > 90% blockade of GPIIb/IIIa receptors, > 90% reduction of ex vivo platelet aggregation to ADP, and a significantly prolonged bleeding time during c7E3 Fab infusion, without excess bleeding. CONCLUSIONS Combined therapy with c7E3 Fab, heparin, and aspirin appears safe. These pilot study results support the concept that effective blockade of the platelet GPIIb/IIIa receptors can reduce myocardial infarction and facilitate PTCA in patients with refractory unstable angina.

This qualitative explorative survey aimed at investigating the personal experiences of elderly people with early-stage dementia with regard to their illness and the extent to which they experience their situation as 'suffering'. In the Netherlands insight in this suffering is relevant with regard to ongoing debate on euthanasia and physician assisted death in early dementia. Participants in the study were 24 elderly (mean age 76.3 years) diagnosed with early-stage Alzheimer's disease. The semi-structured interviews were transcribed verbatim, and qualitatively analyzed. The elderly were found to be very capable of sharing experiences about their disease. They indicated not to experience their situation 'as a whole' as one of dreadful suffering. The gradual progression, which is distinctive of Alzheimer's disease, also allows people to adapt and adjust to their changing situation. As a result, the actual experiences of the disease can, in a positive manner, deviate from their anticipatory beliefs. The experiences of the participants appeared less negative than the ideas 'healthy' elderly often have about a life with dementia. The results from this study emphasize the importance of listening to the voices of people with dementia. Communication with elderly with Alzheimer's disease, is in the early stages quite possible and essential for advance care planning to be adjusted to their actual wishes and needs.

Background: Most infants born through meconium-stained amniotic fluid (MSAF) are observed clinically for 24 h postnatally. Only 5% of infants born through MSAF develop the meconium aspiration syndrome (MAS), a serious condition requiring medical intervention. Objective: To evaluate the value of 24-h postnatal observation of infants born through MSAF. Methods: A cohort of 394 term neonates born through MSAF was studied. Data were collected on Apgar scores, the development of MAS and other perinatal factors. Results: Nineteen of the 394 (4.8%) infants born through MSAF developed MAS. 298 (76%) infants had a 5-minute Apgar score (5′AS) of ⩾9. In this group the number of infants developing MAS (1; 0.3%) was significantly lower compared with the 5′AS ⩽8 group (18; 19%). Conclusion: MAS develops rarely in infants born through MSAF with 5′AS above 8. These infants can be safely discharged from the hospital shortly after birth.

An experiment was conducted to assess the effects of different types of sentences and recording methods on naive judges' evaluations of the speech communication effectiveness of four patients who had undergone surgery for oral cancer. As expected, judges understood patients better if they read meaningful rather than meaningless sentences and if their speech was evaluated under video rather than audio conditions. However, these general findings were qualified because of the powerful influence of individual differences among patients. For example, whereas the intelligibility of three of the patients increased under the audio condition if the sentences being read were meaningful, one patient was poorly understood no matter what type of sentence he read under the same condition. The results suggested that the identification of the unique personality characteristics of patients that are related to their intelligibility merits serious consideration by both researchers and rehabilitation clinicians.

AIM: The present study investigated the influence of muscle architectural changes on muscle torque during 3-week unilateral lower limb suspension (ULLS). METHODS: Plantarflexion maximal voluntary contraction (MVC), soleus (SOL), gastrocnemius medialis (GM) and lateralis (GL) muscle volume (VOL), GL fascicle length (L(f)) and pennation angle (theta), physiological cross-sectional area (PCSA), and electromyographic (EMG) activity were assessed in eight healthy men (aged 19 +/- 0 years) after days 14 and 23 of ULLS. RESULTS: After 14 day of ULLS, MVC and SOL EMG decreased (P < 0.05) by 10% and 29%, respectively, but did not further decline between days 14 and 23. SOL, GM and GL muscle VOL decreased by 5%, 6% and 5%, respectively (P < 0.05), on day 14, and by 7% (SOL), 10% (GM) and 6% (GL) on day 23. In GL, theta and L(f) were reduced by 3% (P < 0.05) and 2% (NS), respectively, on day 14, and by 5% (P < 0.05) and 4% (P < 0.05), respectively, on day 23. Consequently, GL PCSA declined by 3% (P < 0.05) on day 14, but did not further decrease on day 23. Similarly, the 7% (P < 0.05) loss in GL force/PCSA observed on day 14 persisted until the end of the unloading period. CONCLUSION: These findings suggest that rapid muscle architecture remodelling occurs with lower limb unloading in humans, with changes occurring within 14 days of weight bearing removal. These adaptations, mitigating the decline in muscle PCSA, might protect from a larger loss of muscle force.

In 1987, a thoroughly renewed TNM classification was published; the revision was a conjunct effort of the International Union Against Cancer (UICC) and American Joint Committee on Cancer (AJCC). With respect to the former UICC classification, a major change was introduced regarding the regional lymph node subcategories in head and neck cancer; that is compared to the 1978 edition the subjective subcategory of fixation was eliminated and size of the lymph node has become of paramount importance. To see whether the 1987 UICC classification system is indeed more predictive and discriminatory than the 1978 edition, we have analysed patients with supraglottic cancer with clinically detectable lymph node metastasis (TI -4, N+). All patients treated between 1965 and 1980 by radiation therapy only were staged according to both editions of the UICC classification system. From these data we conclude that the prognosis of patients with lymph nodal involvement indeed worsens from N1 to N3 when classified according to the 1987 edition; in contrast, no difference is seen between the NI, N2 or N3 subcategories when staged according to the 1978 classification rules.

Objective: To evaluate the prognostic role of postprocedural single-lead residual ST-segment deviation for electrocardiographic evaluation of myocardial perfusion in patients with ST-segment elevation myocardial infarction (STEMI) treated by primary angioplasty. Design: Prospective observational clinical cohort study. Setting: Tertiary referral centre. Patients: 1660 patients treated with primary angioplasty for STEMI. Main outcome measure: Mortality at 1-year follow-up. Results: Single-lead ST-segment deviation significantly correlated with infarct size, predischarge ejection fraction, distal embolisation and myocardial blush grade 3. At 1-year follow-up, 63 patients had died. The method correlated well with 1-year mortality. At multivariate analysis, after correction for baseline demographic, clinical and angiographic variables, postprocedural single-lead ST-segment deviation showed better accuracy than residual single-lead ST-segment elevation or resolution and residual 12-lead ST-segment deviation. Conclusions: This study showed that maximal residual ST-segment deviation in a single lead at 3 hours after the procedure is an easy and accurate predictor of 1-year mortality after primary angioplasty for STEMI.

Admission hyperglycaemia is associated with an increased risk of mortality after myocardial infarction. Whether long-term glucose dysregulation (assessed by HbA1c) is more important than acute hyperglycaemia is unknown. We evaluated the prognostic value of admission glucose and HbA1c levels in nondiabetic patients with ST-segment elevation acute myocardial infarction (STEMI).In 504 unselected, consecutive patients with STEMI, glucose and HbA1c levels were measured on admission. Glucose was categorised as11.1 mmol/l (n=422) andor= 11.1 mmol/l (n=82). HbA1c levels were categorised as6.0% (n=416) andor=6.0% (n=88). Mean follow-up was 1.6+/-0.6 years.Patients with hyperglycaemia on admission were comparable with those with normoglycaemia. However,patients with HbA1cor=6.0%, as compared with those with HbA1c6%, were older, were more often on beta-blockers and more frequently had multivessel disease. Thirty-day mortality in the subsequent glucose categories (11.1 mmol/l andor=11.1 mmol/l) was 4% and 19% (p0.001) and in the subsequent HbA1c categories (6% andor=6%) was 5% and 12% (p=0.03). After multivariable analyses, admission glucose (OR 4.91,95% CI 2.03 to 11.9, p0.001) but not HbA1c (OR 1.33, 95%CI 0.48 to 3.71, p=0.58) was significantly associated with 30-day mortality. Among 30-day survivors, neither admission glucose nor HbA1c were predictors of long-term mortality.Elevated admission glucose is an important predictor of 30-day outcome after STEMI, while prior long-term glucose dysregulation is a covariate of other high-risk clinical characteristics. Among 30-day survivors, neither admission blood glucose nor HbA1c were predictors of long-term outcome.

Purpose: We investigated the prognostic value of plasma soluble urokinase plasminogen activator receptor (suPAR) on day 1 in patients with the acute respiratory distress syndrome (ARDS) for intensive care unit (ICU) mortality and compared it with established disease severity scores on day 1. Methods: suPAR was determined batchwise in plasma obtained within 24 h after admission. Results: 632 ARDS patients were included. Significantly (P = 0.02) higher median levels of suPAR were found with increasing severity of ARDS: 5.9 ng/ml [IQR 3.1–12.8] in mild ARDS (n = 82), 8.4 ng/ml [IQR 4.1–15.0] in moderate ARDS (n = 333), and 9.0 ng/ml [IQR 4.5–16.0] in severe ARDS (n = 217). Non-survivors had higher median levels of suPAR [12.5 ng/ml (IQR 5.1–19.5) vs. 7.4 ng/ml (3.9–13.6), P

The introduction of molecular detection of infectious organisms has led to increased numbers of positive findings, as observed for pathogens causing gastroenteritis (GE). However, because little is known about the prevalence of these pathogens in the healthy asymptomatic population, the clinical value of these additional findings is unclear. A case–control study was carried out in a population of patients served by general practitioners in the Netherlands. A total of 2710 fecal samples from case and matched control subjects were subjected to multiplex real-time PCR for the 11 most common bacterial and four protozoal causes of GE. Of 1515 case samples, 818 (54%) were positive for one or more target organisms. A total of 49% of the controls were positive. Higher positivity rates in cases compared to controls were observed for Campylobacter spp., Salmonella spp., Clostridium difficile, enteroinvasive Escherichia coli/Shigella spp., enterotoxigenic E. coli, enteroaggregative E. coli, atypical enteropathogenic E. coli (EPEC), Cryptosporidium parvum/hominis, and Giardia lamblia. However, Dientamoeba fragilis and Shiga-like toxigenic E. coli were detected significantly less frequent in cases than in controls, while no difference in prevalence was found for typical EPEC and enterohemorrhagic E. coli. The association between the presence of microorganisms and GE was the weakest in children aged 0 to 5 years. Higher relative loads in cases further support causality. This was seen for Campylobacter spp., Salmonella spp., enterotoxigenic E. coli, and C. parvum/hominis, and for certain age categories of those infected with C. difficile, enteroaggregative E. coli, and atypical EPEC. For D. fragilis and Shiga-like toxigenic E. coli/enterohemorrhagic E. coli, pathogen loads were lower in cases. Application of molecular diagnostics in GE is rapid, sensitive and specific, but results should be interpreted with care, using clinical and additional background information.

A drug-eluting stent was implanted in four patients, a man aged 67 and a woman aged 42 with acute myocardial infarction, a woman aged 41 with unstable angina pectoris and a man aged 41 with stable angina pectoris. All suffered stent thrombosis after discontinuation (in three cases prematurely) of clopidogrel therapy. Reasons for discontinuation included allergic reaction, a dental procedure and refusal of reimbursement by the insurer. In order to restore stent patency they were treated by percutaneous coronary intervention and all patients suffered irreversible myocardial damage. Combination therapy using acetylsalicylic acid and clopidogrel during and after angioplasty for the prevention of long- and short-term complications is necessary. Stent thrombosis after drug-eluting stent implantation usually occurs within 1-4 weeks following discontinuation ofantiplatelet medication. These cases stress the importance of antiplatelet therapy after stent implantation. Physicians, dentists and patients must be aware of the risk of the early discontinuation ofantiplatelet therapy.

The onset of whole muscle hypertrophy in response to overloading is poorly documented. The purpose of this study was to assess the early changes in muscle size and architecture during a 35-day high-intensity resistance training (RT) program. Seven young healthy volunteers performed bilateral leg extension three times per week on a gravity-independent flywheel ergometer. Cross-sectional area (CSA) in the central (C) and distal (D) regions of the quadriceps femoris (QF), muscle architecture, maximal voluntary contraction (MVC), and electromyographic (EMG) activity were measured before and after 10, 20, and 35 days of RT. By the end of the training period, MVC and EMG activity increased by 38.9 ± 5.7 and 34.8% ± 4.7%, respectively. Significant increase in QF CSA (3.5 and 5.2% in the C and D regions, respectively) was observed after 20 days of training, along with a 2.4 ± 0.7% increase in fascicle length from the 10th day of training. By the end of the 35-day training period, the total increase in QF CSA for regions C and D was 6.5 ± 1.1 and 7.4 ± 0.8%, respectively, and fascicle length and pennation angle increased by 9.9 ± 1.2 and 7.7 ± 1.3%, respectively. The results show for the first time that changes in muscle size are detectable after only 3 wk of RT and that remodeling of muscle architecture precedes gains in muscle CSA. Muscle hypertrophy seems to contribute to strength gains earlier than previously reported; flywheel training seems particularly effective for inducing these early structural adaptations.

Fatigue resistance of knee extensor muscles is higher during voluntary isometric contractions at short compared with longer muscle lengths. In the present study we hypothesized that this would be due to lower energy consumption at short muscle lengths. Ten healthy male subjects performed isometric contractions with the knee extensor muscles at a 30, 60, and 90° knee angle (full extension = 0°). At each angle, muscle oxygen consumption (mV̇o2) of the rectus femoris, vastus lateralis, and vastus medialis muscle was obtained with near-infrared spectroscopy. mV̇o2 was measured during maximal isometric contractions and during contractions at 10, 30, and 50% of maximal torque capacity. During all contractions, blood flow to the muscle was occluded with a pressure cuff (450 mmHg). mV̇o2 significantly ( P < 0.05) increased with torque and at all torque levels, and for each of the three muscles mV̇o2 was significantly lower at 30° compared with 60° and 90° and mV̇o2 was similar ( P > 0.05) at 60° and 90°. Across all torque levels, average (± SD) mV̇o2 at the 30° angle for vastus medialis, rectus femoris, and vastus lateralis, respectively, was 70.0 ± 10.4, 72.2 ± 12.7, and 75.9 ± 8.0% of the average mV̇o2 obtained for each torque at 60 and 90°. In conclusion, oxygen consumption of the knee extensors was significantly lower during isometric contractions at the 30° than at the 60° and 90° knee angle, which probably contributes to the previously reported longer duration of sustained isometric contractions at relatively short muscle lengths.

Squamous carcinoma of the external ear canal is a rare disease and a challenge to treat. Some controversy exists regarding the best options for treatment. Reported 5-year survival varies between 35% and 63%. Since 1976, we have adopted a conservative approach to these tumours, with patients undergoing a specific protocol of meticulous tumour debulking followed by a course of repeated topical 5-fluoro-uracil (5-FU) cream application and necrotectomy. Data was collected prospectively. From 1976 to 1998, 23 patients underwent primary treatment according to our protocol. Nine patients had T1 disease whereas six had T2 and eight had T3 disease. The 5- and 10-year overall survivals were 74% and 60% respectively. These results compare very favourably with those in the literature and surgical debulking with topical 5-FU and necrotectomy remains our primary treatment of choice for squamous cell carcinoma of the external auditory canal.

Early-life stress is a critical risk factor for developing psychopathological alterations later in life. This early adverse environment has been modeled in rats by exposure to stress during the peripubertal period-that is, corresponding to childhood and puberty-and has been shown to lead to increased emotionality, decreased sociability and pathological aggression. The amygdala, particularly its central nucleus (CeA), is hyperactivated in this model, consistent with evidence implicating this nucleus in the regulation of social and aggressive behaviors. Here, we investigated potential changes in the gene expression of molecular markers of excitatory and inhibitory neurotransmission in the CeA. We found that peripubertal stress led to an increase in the expression of mRNA encoding NR1 (the obligatory subunit of the N-methyl D-aspartate (NMDA) receptor) but to a reduction in the level of mRNA encoding glutamic acid decarboxylase 67 (GAD67), an enzyme that is critically involved in the activity-dependent synthesis of GABA, and to an increase in the vesicular glutamate transporter 1 (VGLUT1)/vesicular GABA transporter (VGAT) ratio in the CeA. These molecular alterations were present in addition to increased novelty reactivity, sociability deficits and increased aggression. Our results also showed that the full extent of the peripubertal protocol was required for the observed behavioral and neurobiological effects because exposure during only the childhood/prepubertal period (Juvenile Stress) or the male pubertal period (Puberty Stress) was insufficient to elicit the same effects. These findings highlight peripuberty as a period in which stress can lead to long-term programming of the genes involved in excitatory and inhibitory neurotransmission in the CeA.

Evaluation of the results of CO2 laser treatment of recurrent glottic carcinoma after radiotherapy.Records of all patients treated in the University Hospital Rotterdam and the Dr. Daniel den Hoed Cancer Center between 1980 and 1996 by CO2 laser for recurrent glottic carcinoma were studied.Forty patients were treated by laser surgery. Average follow-up was 77 months. Twenty-three patients (58%) had another recurrence develop after laser surgery. Three were cured by a second laser procedure. Therefore, 20 patients (50%) were successfully treated with laser surgery. In 23 patients the recurrence did not extend into the anterior commissure; in 57% a total laryngectomy could be avoided. In 17 patients the recurrence did extend into the anterior commissure; in 41% a total laryngectomy was avoided.Most patients with recurrent carcinoma of the larynx after radiotherapy can be cured by laser surgery if the tumor does not extend into the anterior commissure.

The burden of HIV in stable relationships places emotional, economic and physical stresses on families. We compared the influence of HIV notification on marital partnerships in northern Thailand among a cohort of HIV discordant couples, and identified factors associated with marital disruption. Data were collected using in-depth interviews with both members of six separated or divorced couples and 13 couples whose relationship remained intact. Five factors influenced marital stability following HIV notification: longer duration of relationship; economic constraints, extended family members' opinions, especially parents; the existence of children from the marriage; and fear of stigmatization by community members. Social influences, both overt and perceived, are important in shaping marital behaviour and decision-making in HIV epidemic areas. HIV counselling needs to be extended beyond the individual seeking testing to include stable partners (and perhaps further, to include the extended family), although it is recognized that this is not the norm for most HIV testing centres.This study investigates the factors influencing marital stability among HIV discordant couples in northern Thailand. The influence of HIV notification on marital partnerships was compared between 6 separated or divorced couples and 13 couples whose relationship remained intact after positive HIV diagnosis of the husband through in-depth interviews. An ethnographic field guide was used in the interview, which addressed premarital background, marital relationships, and changes in the spousal relationship following notification of the husband's HIV test results. The results indicated that 5 factors influenced marital stability following HIV notification: 1) a longer duration of relationship; 2) economic constraints; 3) opinions of extended family; 4) presence of children; and 5) fear of stigmatization by community members. Separation and divorce usually occurred in short-duration, childless marriages and among high-income women. The findings suggest the need for culturally fitting HIV prevention and counseling programs with both the infected individual and his partner.

Pseudoaneurysm is a rare complication of surgery or trauma around the knee. A 30-year-old man presented 10 days following anterior cruciate ligament repair with a 2 cm pulsatile swelling on the medial side of the knee. Angiography demonstrated a pseudoaneurysm of the medial inferior genicular artery. Surgical exploration and ligation of the feeding vessel to the aneurysm was performed and the patient made a full recovery. Vascular injury must be suspected in patients presenting with a haemarthrosis or pulsatile swelling following surgery on the knee.

To establish the prevalence of 'silent ischaemia' of the myocardium in male patients with type 1 diabetes mellitus using a non-invasive cardiac examination, and to determine what clinical variables are related to silent ischaemia.Prospective, cross-sectional.Males aged 20-69 years who visited the outpatient department of Internal Medicine of the De Weezenlanden Hospital in Zwolle between 1 February 1992 and 31 January 1995, and who showed no symptoms of ischaemic cardiopathy (angina pectoris, myocardial infarction or arrhythmias) or of chronic obstructive pulmonary disease, were examined for cardiac ischaemia by means of a 24-hour Holter registration and a perfusion scintigram after administration of dipyridamol. In order to demonstrate a possible connection between cardiovascular risk factors and silent ischaemia, the patients with an abnormal and those with a normal scintigram were compared by means of multivariate analysis.Data were collected on 92 successive patients, with a median age of 40 years (range 22-69). There were 19 patients (21%) with an abnormal myocardial scintigram. On average they were older and had a longer history of diabetes mellitus. An abnormal Holter registration was observed in 14 patients (15%), abnormality of either the Holter registration or the myocardial scintigram in 28 patients (30%) and abnormality of both the myocardial scintigram and the Holter registration in 5 patients (5%). The duration of the diabetes mellitus, and a diastolic blood pressureor = 90 mm Hg were statistically significant and independent predictors of an abnormal myocardial scintigram (relative risks 1.08 and 3.4 per year, respectively).The prevalence of cardiac ischaemia in males with type 1 diabetes mellitus without cardiac symptoms is approximately 20%. Abnormal test results were associated with a longer duration of the diabetes mellitus and a diastolic blood pressureor = 90 mm Hg.

It has been shown that primary percutaneous transluminal coronary angioplasty (PTCA) for acute myocardial infarction results in higher patency rates than thrombolytic therapy. However, no data are available on differences in long-term angiographic outcome after successful primary PTCA compared with successful thrombolysis. Therefore, we compared angiographic data of the Antithrombotics in the Prevention of Reocclusion In COronary Thrombolysis (APRICOT) trial and the Zwolle primary PTCA trial. In the APRICOT trial 248 patients underwent coronary angiography at a mean of 24 hours after thrombolysis and had a patent infarct-related vessel (Thrombolysis In Myocardial Infarction-3 trial flow) when entering the study. Reocclusion rates were assessed at a second angiography after 3 months. In the Zwolle trial 136 patients had a successful primary PTCA. At 3 months 131 patients underwent a second angiography. Quantitative coronary angiography showed a significant lower mean diameter stenosis of the infarct-related vessel after primary PTCA (27 +/- 12% vs 57 +/-12%; p = 0.00001). At 3 months this difference was sustained (35 +/- 22% vs 63 +/- 26%; p = 0.00001). After thrombolysis the reocclusion rate at 3 months was 29% compared with 5% after primary PTCA (p = 0.0001). Results show that compared with successful thrombolytic therapy, primary PTCA for acute myocardial infarction results in an improved infarct-related vessel status not only short term but also long term, with a low reocclusion rate.