Immediate versus delayed removal of urinary catheter after laparoscopic hysterectomy: a randomised controlled trial.

OBJECTIVE: To evaluate if immediate catheter removal (ICR) after laparoscopic hysterectomy is associated with similar retention outcomes compared with delayed removal (DCR). STUDY DESIGN: Non-inferiority randomised controlled trial. POPULATION: Women undergoing laparoscopic hysterectomy in six hospitals in the Netherlands. METHODS: Women were randomised to ICR or DCR (between 18 and 24 hours after surgery). PRIMARY OUTCOME: The inability to void within 6 hours after catheter removal. RESULTS: One hundred and fifty-five women were randomised to ICR (n = 74) and DCR (n = 81). The intention-to-treat and per-protocol analysis could not demonstrate the non-inferiority of ICR: ten women with ICR could not urinate spontaneously within 6 hours compared with none in the delayed group (risk difference 13.5%, 5.6-24.8, P = 0.88). However, seven of these women could void spontaneously within 9 hours without additional intervention. Regarding the secondary outcomes, eight women from the delayed group requested earlier catheter removal because of complaints (9.9%). Three women with ICR (4.1%) had a urinary tract infection postoperatively versus eight with DCR (9.9%, risk difference -5.8%, -15.1 to 3.5, P = 0.215). Women with ICR mobilised significantly earlier (5.7 hours, 0.8-23.3 versus 21.0 hours, 1.4-29.9; P ≤ 0.001). CONCLUSION: The non-inferiority of ICR could not be demonstrated in terms of urinary retention 6 hours after procedure. However, 70% of the women with voiding difficulties could void spontaneously within 9 hours after laparoscopic hysterectomy. It is therefore questionable if all observed urinary retention cases were clinically relevant. As a result, the clinical advantages of ICR may still outweigh the risk of bladder retention and it should therefore be considered after uncomplicated laparoscopic hysterectomy. TWEETABLE ABSTRACT: The advantages of immediate catheter removal after laparoscopic hysterectomy seem to outweigh the risk of bladder retention.

Standardization of allergen products: 3. Validation of candidate European Pharmacopoeia standard methods for quantification of major birch allergen Bet v 1.

BACKGROUND: The BSP090 project aims at establishing European Pharmacopoeia Reference Substances in combination with the corresponding ELISA methods for the quantification of major allergens in allergen products. Two sandwich ELISAs proved suitable for quantification of Bet v 1, the major birch pollen allergen, in preceding phases of BSP090. METHODS: Two Bet v 1-specific ELISA systems were compared with respect to accuracy and precision in a ring trial including 13 laboratories. Model samples containing recombinant rBet v 1.0101 as well as native birch pollen extracts were measured independently at least three times in each facility. The assessment was completed with a comparative quantification of Bet v 1 in 30 marketed birch allergen products in one laboratory, simulating the future use as reference method. RESULTS: In the collaborative study, both candidate ELISAs confirmed their suitability to quantify recombinant and native Bet v 1. ELISA-A showed higher precision and lower interlaboratory variability, yet ELISA-B exhibited slightly higher accuracy. Subsequent parallel measurement of Bet v 1 in a panel of 'real-life' birch allergen products indicated better repeatability of ELISA-B. Both systems detected substantial differences in Bet v 1 content between allergen products, but the effect was more pronounced using ELISA-B due to persistently higher values compared to ELISA-A. CONCLUSIONS: In the collaborative study, no deciding differences were observed between the two candidate ELISAs. Further comparison under conditions simulating the intended use combined with the criterion of long-term availability enabled the selection of one Bet v 1-specific ELISA for proposal as European Pharmacopoeia standard method.

Disseminated leiomyoma cells can be identified following conventional myomectomy.

OBJECTIVE: Uncontained morcellation of leiomyomas during laparoscopic surgery has recently been discouraged, as undetected malignant tumours, namely leiomyosarcomas, could be fragmented which may result in upstaged disease. However, enucleating leiomyomas per se may be inappropriate from an oncological perspective because complete, radical resection of malignant tumours to prevent further tumour growth or recurrence is not achieved. Thus, the aim of this study was to determine whether spillage of leiomyoma cells occurs during laparotomic myomectomy. DESIGN: Observational study. SETTING: Tertiary academic centre in the Netherlands. POPULATION: Women undergoing laparotomic myomectomy were included in the study. METHODS: Peritoneal abdominal washings were obtained on two occasions during the myomectomy procedure; the first one immediately after opening the abdomen and the second one after resection of the leiomyoma(s). Cytological evaluation of the fluids was performed. MAIN OUTCOME MEASURES: The presence of leiomyoma cells in any of the washings. RESULTS: Five patients were included in this pilot study. All first washings were negative for leiomyoma cells. However, cytology positive for the presence of leiomyoma cells was found in three of the five second, post-myomectomy washings. CONCLUSION: Tissue spillage from leiomyoma(s) occurs during conventional open myomectomy. The clinical relevance of tissue dissemination after myomectomy is unclear but it cannot be excluded that this may negatively affect the patient's outcome if there is malignant change within the enucleated leiomyoma(s). Therefore, it is questionable whether morcellation in specially designed containment bags after laparoscopic myomectomy, guarantees any additional oncological safety. TWEETABLE ABSTRACT: Even during conventional myomectomy, tissue spillage occurs during resection of leiomyoma(s).

Milk processing quality of suckled/milked goats: effects of milk accumulation interval and milking regime.

Milk with a high concentration of fat and casein is required for cheese production, and these components have a major impact for both quality and yield of the curd. Recent observations have shown that suckling can elevate milk fat concentration in goats and our aim was therefore to check the hypothesis that animal welfare and cheese-processing properties of goat milk could be optimised by appropriate management of suckled/milked goats. Twelve Swedish dairy goats were kept together with one kid each in 4 different mixed management-systems (milking combined with partial suckling) in a cross-over design. Two milk accumulation intervals were tested; Short = dams and kids were together for 16 h (T16) and Long = ; dams and kids were together for 8 h (T8 h). In addition, two milking regimes were used; Suckled Before Milking = S and Milked Before Suckling = M. Milk accumulation interval referred to how long dams and kids were separated. The milk yield available for processing (milk offtake), was weighed and analysed from each milking occasion and the suckled milk yield was estimated by a weigh-suckle-weigh method (WSW) in combination with observing the suckling behaviour during the free suckling periods. Milking managements, such as 'suckling before milking (S)', increased milk fat concentration compared to milking before suckling (M) and 'Short accumulation treatments (T16)' gave higher milk fat, casein concentration and individual curd yield (%) compared to the 'Long accumulation treatment (T8)'. The total individual curd yield (g) was the same despite treatment, but the animal welfare was most likely higher in T16 where dams and kids spent more time together.

Dexamethasone for postoperative nausea and vomiting prophylaxis in cesarean delivery and a delayed diagnosis of neonatal congenital adrenal hyperplasia.

The case of a false-negative newborn screen for congenital adrenal hyperplasia in a 37 weeks' gestation 46,XX neonate, thought to be due to maternal administration of dexamethasone intra-operatively prior to umbilical cord clamping, for postoperative nausea and vomiting prophylaxis after neuraxial anesthesia, is described.

[Optimising postoperative recovery at home; individualised discharge policy and task division between GP and medical specialist]. / Optimaliseren van postoperatief herstel thuis.

In the last decennia, the length of hospital stay of admitted patients has significantly decreased in all medical fields. As a result, postoperative recovery mainly takes place at home, inherently leading to new challenges. Here, two patients are being discussed for whom the postoperative period was substandard. To guarantee optimal quality of care in the home situation, the medical specialist and the general practitioner need to make the necessary arrangements. We would first of all recommend providing each discharged patient with specific, structured and individualised advices regarding postoperative recovery but also regarding alarm symptoms and logistics (e.g. who to call in case of emergency). Finally, we believe that, as (serious) complications are rare, it should be agreed on the fact that the responsible medical specialist is the coordinator of the postoperative period and the first contact point for postoperative patients.

Validation of ELISA methods for quantification of the major birch allergen Bet v 1 (BSP090).

To date, the potency of allergen products in Europe is expressed in manufacturer-specific units relative to a product-specific in-house reference. Consequently, cross-product comparability of allergen products from different manufacturers with respect to strength and efficacy is impossible. The Biological Standardisation Programme (BSP) project BSP090 addresses this issue via the establishment of reference standards in conjunction with ELISA methods for the quantification of major allergens in allergen products. Since the initiation of BSP090, the recombinant major allergen Bet v 1 has been adopted by the European Pharmacopoeia Commission as a Chemical Reference Substance (CRS). In parallel, two sandwich ELISA systems for quantification of Bet v 1 were found suitable in preliminary phases of BSP090 to be validated in a large collaborative study. In this study, the candidate ELISA systems were compared with respect to accuracy, precision and variability. Thirteen participating laboratories tested model samples containing the CRS as well as spiked and unspiked birch pollen extracts. Both in pre-testing and in the collaborative study, the 2 candidate ELISA systems confirmed their suitability to quantify recombinant and native Bet v 1. As no clear-cut decision for one of the ELISA systems could be made based on the results of the collaborative study, a post-study testing was performed. Bet v 1 content of 30 birch pollen allergen products was determined in parallel in both ELISA systems. Consequently, 1 candidate ELISA system was selected to be proposed as the future European Pharmacopoeia standard method for Bet v 1 quantification.

Patient preference for oral or intravenous chemotherapy: a randomised cross-over trial comparing capecitabine and Nordic fluorouracil/leucovorin in patients with colorectal cancer.

Until recently, fluorouracil (F) and leucovorin (L) had been considered the standard therapy for patients with colorectal cancer. However, several studies have shown that oral therapy with UFT/L or capecitabine is as effective as intravenous (i.v.) therapy and in addition it is claimed that patients prefer oral to i.v. therapy as long as efficacy is not compromised. In a previous crossover study by Borner et al., it was shown that 26 out of 31 patients preferred oral therapy with UFT/L to i.v. FL (Mayo regimen) [Borner M, Schöffski P, de Wit R, et al. Patient preferences and pharmacokinetics of oral modulated UFT versus intravenous fluorouracil and leucovorin: a randomised crossover trial in advanced colorectal cancer. Eur J Cancer 2002;38:349-58]. The objective of the present study was to investigate patient preference between i.v. FL and oral capecitabine using the design described by Borner. The Nordic FL schedule is a bolus regimen with efficacy comparable to other i.v. regimens and at the same time a very tolerable and easy administered regimen. We randomised 60 patients with colorectal cancer (53 patients received adjuvant therapy and seven patients received palliative therapy) to start therapy with either oral capecitabine or Nordic bolus FL. After 6 weeks of therapy (two courses of capecitabine or three courses of Nordic FL) patients were crossed over to the other regimen. After having completed 12 weeks of therapy the patients (49 evaluable patients) were asked to choose one of the regimens for a further 12 weeks of therapy. Patients had more side-effect when treated with capecitabine and a total of 30 out of 49 (61%) preferred the Nordic FL regimen and 19 (39%) preferred capecitabine. We conclude that patients prefer the regimen with less toxicity and that it is of minor importance whether the medication is administrated orally at home or i.v. at the hospital.

Collaborative study to establish human immunoglobulin BRP batch 3 and human immunoglobulin (molecular size) BRP batch 1.

A study was carried out by the European Directorate for the Quality of Medicines (EDQM) as part of the joint Biological Standardisation Programme of the Council of Europe and the European Commission with the aim to establish replacement batches of the European Pharmacopoeia (Ph. Eur.) human immunoglobulin Biological Reference Preparation (BRP) batch 2. Twenty-eight laboratories participated in this study. The suitability of the candidate reference preparations to serve as working references in the tests for distribution of the molecular size, anticomplementary activity and Fc function, in accordance with the specifications of the Ph. Eur. monographs Human normal immunoglobulin for intravenous administration (0918), Human normal immunoglobulin (0338) and Anti-T lymphocyte immunoglobulin for human use, animal (1928) was demonstrated. The candidates were therefore established as human immunoglobulin BRP batch 3 and Human immunoglobulin (molecular size) BRP batch 1. The prescribed use of the latter BRP is limited to the test for distribution of molecular size.

Effects of litter provision during early rearing and environmental enrichment during the production phase on feather pecking and feather damage in laying hens.

Feather pecking is a multi-factorial behavioral disorder and a serious welfare issue in the poultry industry. Several studies report early life experience with litter to be a major determinant in the development of feather pecking. The current study aimed to test the large-scale on-farm efficiency of a simple and cheap husbandry procedure applied during the rearing period with the ultimate goal of reducing the incidence of feather pecking and plumage damage during the production stage in laying hens. Five laying hen-rearing farmers from across Norway participated in the study. These farmers were asked to create divisions within their hen rearing houses and to separate their chicks into 2 groups: one reared with access to a paper substrate from the first d of age, the other a control group without access to paper substrate during rearing. All flocks were visited at the production farms at 30 wk of age and observed for pecking behavior and feather damage. Birds in the control group had higher odds of having more feather damage compared to the birds from the treatment group. In addition, flocks provided with environmental enrichment at the production farms had a reduced incidence of feather pecking, irrespective of the treatment. These results indicate that husbandry procedures during both rearing and production stages have the potential to alleviate feather pecking and increase laying hen welfare.

Dose-effect study of carboplatin in ovarian cancer: a Danish Ovarian Cancer Group study.

PURPOSE: To elucidate the effect of a doubled carboplatin dose-intensity in epithelial ovarian cancer in combination with a fixed dose of cyclophosphamide. PATIENTS AND METHODS: A total of 222 patients with epithelial ovarian cancer stages II to IV were included in the study. Following surgery, patients were randomly assigned to receive carboplatin at an area under the concentration-versus-time curve (AUC) of 4 (AUC4) or carboplatin at an AUC of 8 (AUC8) and cyclophosphamide 500 mg/m2 given every 4 weeks for six courses. The AUC was calculated according to Calvert's formula. In 123 patients, the carboplatin AUC was also measured based on a single-sample method and the results were compared with the calculated AUC. The end points of the trial were complete pathologic remission (CPR) and crude survival. RESULTS: Approximately 50% of patients in both arms underwent second-look surgery. The frequency of CPR was 32% and 30%, respectively. The survival curves showed no significant difference (P = .84). The dose-intensity of cyclophosphamide was almost identical in the two arms, whereas that of carboplatin was different. In the AUC8 arm, the dose-intensity was 1.86 times that of the AUC4 arm. The results also demonstrated good agreement between the calculated and the measured AUC in most patients. Bone marrow toxicity was significantly higher in the AUC8 arm. CONCLUSION: A doubling of the carboplatin dose-intensity did not result in any significant improvement of pathologic remission or survival. Calvert's formula can be used to give a fairly accurate estimate of the carboplatin AUC. Bone marrow toxicity increased with higher dose-intensity, and a further increase of dose is only feasible with growth-factor or stem-cell support.

Systematic overview of cost-utility assessments in oncology.

PURPOSE: Cost-utility analyses (CUAs) present the value of an intervention as the ratio of its incremental cost divided by its incremental survival benefit, with survival weighted by utilities to produce quality-adjusted life years (QALYs). We critically reviewed the CUA literature and its role in informing clinical oncology practice, research priorities, and policy. METHODS: The English-language literature was searched between 1975 and1997 for CUAs. Two readers abstracted from each article descriptions of the clinical situation and patients, the methods used, study perspective, the measures of effectiveness, costs included, discounting, and whether sensitivity analyses were performed. The readers then made subjective quality assessments. We also extracted utility values from the reviewed papers, along with information on how and from whom utilities were measured. RESULTS: Our search yielded 40 studies, which described 263 health states and presented 89 cost-utility ratios. Both the number and quality of studies increased over time. However, many studies are at variance with current standards. Only 20% of studies took a societal perspective, more than a third failed to discount both the costs and QALYs, and utilities were often simply estimates from the investigators or other physicians. CONCLUSION: The cost-utility literature in oncology is not large but is rapidly expanding. There remains much room for improvement in the methodological rigor with which utilities are measured. Considering quality-of-life effects by incorporating utilities into economic studies is particularly important in oncology, where many therapies obtain modest improvements in response or survival at the expense of nontrivial toxicity.

Dose-response relationship of epirubicin in the treatment of postmenopausal patients with metastatic breast cancer: a randomized study of epirubicin at four different dose levels performed by the Danish Breast Cancer Cooperative Group.

PURPOSE: To test for possible correlations between dose of single-drug epirubicin and efficacy/toxicity in postmenopausal women with metastatic breast cancer. The study also included analysis of a correlation between pharmacokinetic and pharmacodynamic parameters. PATIENTS AND METHODS: Two hundred eighty-seven women were randomized to receive either 40, 60, 90, or 135 mg/m2 of epirubicin intravenously (IV) every 3 weeks. Treatment consisted of first-line cytotoxic therapy for metastatic disease. In patients with early progressive disease after either 40 or 60 mg/m2, dose escalation to 135 mg/m2 was performed. A full pharmacokinetic analysis was performed in 78 patients. RESULTS: Among 263 eligible patients, an increase in response rate and time to progression was found with an increase in dose from 40 to 90 mg/m2, while no increase in efficacy was found from 90 to 135 mg/m2. Multivariate analysis, using the Cox proportional hazards model with time to progression as the end point, confirmed that epirubicin dose more than 60 mg/m2 was an independent prognostic covariate. Furthermore, a significant association was established between randomized dose and both hematologic and nonhematologic toxicity. No association between pharmacokinetic parameters and efficacy parameters was demonstrated. On the other hand, a significant correlation between pharmacokinetic parameters and both hematologic and nonhematologic toxicity was found. CONCLUSION: An increase in dose of epirubicin from 40 to 90 mg/m2 is accompanied by increased efficacy. Further increases in dose do not yield increased efficacy. A positive correlation between epirubicin dose and toxicity, as well as a correlation between pharmacokinetic parameters and toxicity, was also established.

Comparison of early and late mortality in men and women after isolated coronary artery bypass graft surgery in Stockholm, Sweden, 1980 to 1989.

OBJECTIVES: We sought to analyze early and late mortality after coronary artery bypass graft surgery (CABG) in relation to gender. BACKGROUND: Early mortality after CABG is generally higher in women than in men, but the causes are controversial. Few studies have investigated long-term mortality after CABG in relation to gender. METHODS: In all, 3,326 men and 607 women underwent isolated CABG in Stockholm from 1980 to 1989. Mortality for these patients was followed by means of the National Cause of Death Register, from the time of operation until the end of 1990. Survival was evaluated by life-table methods and by proportional hazards regression. RESULTS: Early mortality (within 30 days) was 3% in women and 1.7% in men, corresponding to a relative risk of 1.8 (95% confidence interval [CI] 1.0 to 3.0) in women compared with men. When age and body surface area were taken into account, the relative risk was 1.0 (95% CI 0.5 to 2.0), which was not markedly different but multivariate analyses that included hypertension, diabetes mellitus, previous myocardial infarction, left ventricular function and number of diseased vessels. Only small gender differences in mortality were observed for 5 years after the operation among those who survived for 30 days. CONCLUSIONS: The results suggest that men and women run similar risks of early and late mortality after CABG when patient characteristics are taken into account.

Low HEMA conjugation induces high autoantibody titer in mice.

2-hydroxyethylmethacrylate (HEMA) is a known causal agent of hypersensitivity to resin composites. We have reported that immunization with HEMA conjugated to mouse serum albumin (MSA) induces an autoantibody response in mice. In this study, we investigated both the activity and the avidity of autoantibodies induced by immunization with various HEMA conjugations to MSA. Female Balb/c mice were given MSA carrying 3, 7, 15, or 22 HEMA molecules. Antigen-specific IgG and IgE antibodies were determined by ELISA, and average antibody avidity by thiocyanate dissociation. Immunization with MSA carrying the lowest number of HEMA molecules induced a significantly higher IgG and IgE anti-MSA autoantibody response, with significantly higher IgG antibody avidity, than did the more heavily conjugated preparations. The results suggest that the lower the degree of HEMA conjugation to self-protein, the higher the risk for autoantibody production to the carrier protein. These findings suggest a mechanism of potential relevance in humans.

The thalamus and the schizophrenia phenotype: failure to replicate reduced volume.

BACKGROUND: Thalamic abnormalities resulting in impaired attention and information processing may form a foundation for cognitive and perceptual disturbances in schizophrenia. Measurements of the thalamus in patients with schizophrenia have shown reductions relative to normal comparison subjects. METHODS: In the current project, magnetic resonance images of the brain were obtained in 10 male and 11 female subjects with paranoid-type schizophrenia, and 15 male and 12 female normal comparison subjects. Total brain and bilateral thalamic volumes were calculated. RESULTS: There were no significant diagnosis, hemisphere, or gender differences in thalamic volumes. CONCLUSIONS: Structural thalamic abnormalities are not likely to universally and parsimoniously explain the schizophrenia phenotype. Abnormal thalamic size in patients with schizophrenia should be understood as reflecting one of several possible structural abnormalities contributing to production of the schizophrenia phenotype, but must be regarded with caution unless paired with functional studies.

One and one-half syndrome with supranuclear facial weakness: magnetic resonance imaging localization.

OBJECTIVE: To provide clinicoanatomical correlation for a small pontine tegmental ischemic stroke producing the one and one-half syndrome associated with supranuclear facial weakness. DESIGN: Case report. SETTING: Tertiary care center. PATIENT: A 70-year-old man developed left-sided facial weakness sparing the forehead, a left internuclear ophthalmoplegia, and a complete left horizontal gaze palsy immediately after percutaneous transluminal coronary angioplasty. Magnetic resonance imaging demonstrated a small lesion in the left paramedian aspect of the dorsal pontine tegmentum. MAIN OUTCOME AND RESULTS: Electromyographic findings were consistent with supranuclear facial involvement. The patient had nearly complete recovery after 1 year. CONCLUSIONS: To our knowledge, this is the first report of supranuclear facial weakness in association with the one and one-half syndrome. The location of the lesion provides evidence of the existence of corticofugal fibers that extend to the facial nucleus in the dorsal paramedian pontine tegmentum.

Atypical herpes simplex virus encephalitis diagnosed by PCR amplification of viral DNA from CSF.

OBJECTIVE: To determine the frequency of mild/atypical herpes simplex virus encephalitis (HSVE) among patients with CSF specimens submitted to a university diagnostic virology laboratory for HSV PCR. BACKGROUND: HSVE is the most commonly recognized cause of acute sporadic encephalitis in the United States. Recognized clinical features are based on autopsy- or brain biopsy-confirmed cases. This is likely to produce ascertainment bias for features associated with severe disease and under-recognition of mild or atypical cases. Amplification of HSV DNA by PCR from CSF provides a sensitive and specific method for diagnosis of HSVE. METHODS: Results of all HSV CSF PCR tests sent to a university diagnostic virology laboratory (January 1, 1993, to December 31, 1996) were reviewed. Clinical information was prospectively collected and retrospectively reviewed. Patients with positive HSV CSF PCR tests were classified as having meningitis, encephalitis, or neonatal infection. Encephalitis was considered typical or atypical based on published criteria. RESULTS: A total of 7.6% of 1,224 CSF specimens were positive for HSV DNA. CSF HSV DNA-positive patients had meningitis (52%), encephalitis (26%), neonatal infection (17%), or nonclassifiable disease (5%). A total of 17% of HSVE patients had mild or atypical disease characterized by the absence of focal findings and slow progression in the absence of antiviral therapy. Atypical HSVE was associated with HSV-2 infection (two of the four patients), immunosuppression by steroid therapy or coexisting HIV infection (three of the four patients), or disease predominantly involving the nondominant temporal lobe (two of the four patients). CONCLUSIONS: Approximately one-fifth of HSVE patients have mild or atypical disease. CSF PCR for HSV DNA should be performed in patients with febrile encephalopathy even in the absence of focal features, initial CSF pleocytosis, or abnormal CT. Mild or atypical HSVE may be associated with infection with either HSV-1 or HSV-2. Mild or atypical HSVE was frequently associated with immunocompromise or asymmetric HSV infection affecting predominantly the nondominant temporal lobe.