Long-Term Experience with Radiofrequency-Induced Hyperthermia Combined with Intravesical Chemotherapy for Non-Muscle Invasive Bladder Cancer.

BACKGROUND: The recurrence rate of non-muscle invasive bladder cancer (NMIBC) is high, despite intravesical treatments. Importantly, patients are frequently unfit or unwilling to undergo a recommended radical cystectomy when standard intravesical treatments fail, due to the substantial risk of morbidity and mortality. For these patients, radiofrequency-induced hyperthermia combined with intravesical chemotherapy (RF-CHT) has shown promising results. We aim to determine treatment outcomes and assess the effect of (ablative) dose. METHODS: 299 intensively pretreated patients treated with RF-CHT were included in safety analysis. Of these, 274 patients who fulfilled induction treatments were included in efficacy analysis. Six-month complete response (CR) and durable response were reported for (concomitant) carcinoma in situ (CIS) patients and recurrence-free survival (RFS) for papillary patients. RESULTS: For CIS, six-month CR-rate was 56.0%; and durable response rates were 79.7%, 66.5%, and 40.3% at one-, two- and five-year, respectively. RFS rates for papillary patients were 77.9%, 57.5%, and 37.2%, respectively. Patients treated with ablative dose are less likely to develop recurrence (adjusted Hazard Ratio 0.54, p = 0.01), compared to adjuvant dose. CONCLUSIONS: RF-CHT is effective in NMIBC patients in whom standard intravesical treatments have failed and should be considered in patients who are unwilling or unfit to undergo radical cystectomy. Patients with CIS or residual papillary tumor at baseline benefit from ablative dose.

The heart rate variability-derived Newborn Infant Parasympathetic Evaluation (NIPE™) Index in pediatric surgical patients from 0 to 2 years under sevoflurane anesthesia-A prospective observational pilot study.

BACKGROUND: The heart rate variability-derived Newborn Infant Parasympathetic Evaluation (NIPE™) Index is a continuous noninvasive tool to assess pain and discomfort in infants <2 years. Initial studies focused on pain monitoring in the neonatal intensive care unit environment. AIMS: The aim of this study was to investigate the performance of the NIPE in infants under sevoflurane anesthesia. The primary objective of this study was to compare the NIPE and heart rate as tools to help recognize the need for additional opioid drugs. Secondary objectives were the course of the NIPE and heart rate around specific standardized noxious procedural mile-stones. METHODS: NIPE and heart rate values recorded during a 120 seconds interval before the anesthetist's decision to administer additional opioid due to the perceived insufficient antinociception and during a 120 seconds interval after drug administration were analyzed by means of a repeated measures ANOVA. The same analyses were performed for datasets around per protocol administration of morphine for postoperative analgesia, performance of a caudal block and surgical incision. RESULTS: In patients with a NIPE value <50, an additional opioid drug administration resulted in a rise of NIPE values, reaching a maximum increase of 5.1 (95% CI: 0.22-9.99) units 120 seconds after drug administration (P = 0.041). There was no evidence of a change in heart rate during these two 120 seconds periods. Per protocol administration of morphine, caudal block, and surgical incision did not result in changes of the NIPE, which was around 65 units on these occasions, and heart rate. CONCLUSION: In infants anesthetized with sevoflurane, NIPE values <50 might be indicative of insufficient antinociception. The results of this observational pilot study might suggest that the NIPE could be a better measure of the nociception/antinociception balance than heart rate.

Development and validation of the TOCO-TURBT tool: a summative assessment tool that measures surgical competency in transurethral resection of bladder tumour.

BACKGROUND: The current shift towards competency-based residency training has increased the need for objective assessment of skills. In this study, we developed and validated an assessment tool that measures technical and non-technical competency in transurethral resection of bladder tumour (TURBT). METHODS: The 'Test Objective Competency' (TOCO)-TURBT tool was designed by means of cognitive task analysis (CTA), which included expert consensus. The tool consists of 51 items, divided into 3 phases: preparatory (n = 15), procedural (n = 21), and completion (n = 15). For validation of the TOCO-TURBT tool, 2 TURBT procedures were performed and videotaped by 25 urologists and 51 residents in a simulated setting. The participants' degree of competence was assessed by a panel of eight independent expert urologists using the TOCO-TURBT tool. Each procedure was assessed by two raters. Feasibility, acceptability and content validity were evaluated by means of a quantitative cross-sectional survey. Regression analyses were performed to assess the strength of the relation between experience and test scores (construct validity). Reliability was analysed by generalizability theory. RESULTS: The majority of assessors and urologists indicated the TOCO-TURBT tool to be a valid assessment of competency and would support the implementation of the TOCO-TURBT assessment as a certification method for residents. Construct validity was clearly established for all outcome measures of the procedural phase (all r > 0.5, p < 0.01). Generalizability-theory analysis showed high reliability (coefficient Phi ≥ 0.8) when using the format of two assessors and two cases. CONCLUSIONS: This study provides first evidence that the TOCO-TURBT tool is a feasible, valid and reliable assessment tool for measuring competency in TURBT. The tool has the potential to be used for future certification of competencies for residents and urologists. The methodology of CTA might be valuable in the development of assessment tools in other areas of clinical practice.

Deficiency of fibroblast growth factor 21 (FGF21) promotes hepatocellular carcinoma (HCC) in mice on a long term obesogenic diet.

OBJECTIVE: Non-alcoholic fatty liver (NAFL) associated with obesity is a major cause of liver diseases which can progress to non-alcoholic steatohepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Fibroblast growth factor 21 (FGF21) plays an important role in liver metabolism and is also a potential marker for NAFL. Here we aimed to test the effect of FGF21 deficiency on liver pathology in mice consuming a conventional high fat, high sucrose (HFHS) obesogenic diet for up to 52 weeks. METHODS: C57BL6 WT and FGF21 KO mice were fed a conventional obesogenic diet and were evaluated at 16 and 52 weeks. Evaluation included metabolic assessment, liver pathology, and transcriptomic analysis. RESULTS: With consumption of HFHS diet, FGF21 deficient mice (FGF21 KO) develop excess fatty liver within 16 weeks. Hepatic pathology progresses and at 52 weeks FGF21 KO mice show significantly worse fibrosis and 78% of mice develop HCC; in contrast only 6% of WT mice develop HCC. Well differentiated hepatocellular carcinomas in FGF21 KO mice were characterized by expanded hepatic plates, loss of reticulin network, cytologic atypia, and positive immunostaining for glutamine synthetase. Microarray analysis reveals enrichment of several fibroblast growth factor signaling pathways in the tumors. CONCLUSIONS: In addition to attenuating inflammation and fibrosis in mice under a number of dietary challenges, we show here that FGF21 is required to limit the progression from NAFL to HCC in response to prolonged exposure to an obesogenic diet. The induction of hepatic FGF21 in response to the high fat, high sucrose obesogenic diet may play an important role in limiting progression of liver pathology from NAFL to HCC.

Fibroblast growth factor 21 (FGF21) is robustly induced by ethanol and has a protective role in ethanol associated liver injury.

OBJECTIVE: Excess ethanol consumption has serious pathologic consequences. In humans, repeated episodes of binge drinking can lead to liver damage and have adverse effects on other organs such as pancreas and brain. Long term chronic consumption of ethanol can also result in progressive alcoholic liver disease and cirrhosis. Fibroblast growth factor 21 (FGF21) is a metabolic regulator with multiple physiologic functions. FGF21 is a novel biomarker for non-alcoholic fatty liver disease (NAFLD) in humans and limits hepatotoxicity in mice. Therefore, we explored the possibility that FGF21 plays a role in response to ethanol consumption in both humans and mice. METHODS: We used a binge drinking paradigm in humans to examine the effect of acute ethanol consumption on circulating FGF21. We adapted this paradigm to evaluate the acute response to ethanol in mice. We then examined the role of FGF21 on liver pathology in two models of chronic ethanol consumption in both wild type (WT) mice and mice lacking FGF21 (FGF21-KO). RESULTS: Acute ethanol consumption resulted in a robust induction of serum FGF21 after 6 h in both humans and mice. Serum ethanol peaked at 1 h in both species and was cleared by 6 h. Ethanol clearance was the same in WT and FGF21-KO mice, indicating that FGF21 does not play a major role in ethanol metabolism in a binge paradigm. When FGF21-KO mice were fed the Lieber-DeCarli diet, a high fat diet supplemented with ethanol, a higher mortality was observed compared to WT mice after 16 days on the diet. When FGF21-KO mice consumed 30% ethanol in drinking water, along with a normal chow diet, there was no mortality observed even after 16 weeks, but the FGF21-KO mice had significant liver pathology compared to WT mice. CONCLUSIONS: Acute or binge ethanol consumption significantly increases circulating FGF21 levels in both humans and mice. However, FGF21 does not play a role in acute ethanol clearance. In contrast, chronic ethanol consumption in the absence of FGF21 is associated with significant liver pathology alone or in combination with excess mortality, depending on the type of diet consumed with ethanol. This suggests that FGF21 protects against long term ethanol induced hepatic damage and may attenuate progression of alcoholic liver disease. Further study is required to assess the therapeutic potential of FGF21 in the treatment of alcoholic liver disease.

Plasma Cytokine Profiles in Long-Term Strenuous Exercise.

The open window theory indicates altered immunity 3 to 72 hours after exercise. The J-curve describes the risk of illness in response to exercise. The aim of this study was to examine the secretion of proinflammatory and anti-inflammatory cytokines before and after long-term strenuous exercise. Fourteen marathon and 16 half-marathon runners and 10 military cadets participating in a military ranger-training course were recruited to this study. Within-subject design was used measuring levels of plasma cytokines before, during, and after exercise. Plasma cytokines were measured using Luminex multiplex technology and ELISA. Comparing pre/post plasma levels both the marathon- and the half-marathon runners showed heavily increased levels of IL-6, IL-10, and IL-8 (P < 0.001). LPS stimulation among the half-marathon runners decreased the postrace levels of IL-6, IL-1b, and TNFα by 45%, 24%, and 43%, respectively (P < 0.01). During the ranger training course the spontaneous and LPS-stimulated levels of IL-6, IL-8, IL-10, IL-1b, and TNFα changed in a similar fashion as in the half-marathon runners although the fluctuations were smaller. Our study supports the open window and the J-curve theory; the immune system is more activated and the subjects are more threatened to infectious pathogens after intensive physical activity and in the period after exercise.

Effect of postpartum pelvic floor muscle training on vaginal symptoms and sexual dysfunction-secondary analysis of a randomised trial.

OBJECTIVE: Evaluate effect of pelvic floor muscle training (PFMT) on vaginal symptoms and sexual matters, dyspareunia and coital incontinence in primiparous women stratified by major or no defects of the levator ani muscle. DESIGN: Randomised controlled trial (RCT). SETTING: Akershus University Hospital, Norway. SAMPLE: About 175 primiparous women with a singleton vaginal delivery. METHODS: Two-armed assessor blinded parallel group RCT from 6 weeks to 6 months postpartum comparing effect of PFMT versus control. MAIN OUTCOME MEASURES: International Consultation on Incontinence Modular Questionnaire-vaginal symptoms questionnaire (ICIQ-VS) and ICIQ sexual matters module (ICIQ-FLUTSsex). RESULTS: Overall, analysis (n = 175) showed no difference between training and control groups in women having vaginal symptoms or symptoms related to sexual dysfunction 6 months postpartum. The majority of women (88%) had intercourse and there was no difference between groups. Unadjusted subgroup analysis of women with a major defect of the levator ani muscle (n = 55) showed that women in the training group had 45% less risk of having the symptom 'vagina feels loose or lax' compared with the control group (relative risk 0.55, 95% confidence interval 0.31, 0.95; P = 0.03). CONCLUSIONS: Unadjusted analysis showed that in women with major defect of the levator ani muscle, significantly fewer in the training group had the symptom 'vagina feels loose or lax' compared with the control group. No difference was found between groups for symptoms related to sexual dysfunction. More studies are needed to explore effect of PFMT on vaginal symptoms and sexual dysfunction. TWEETABLE ABSTRACT: Unadjusted analysis shows that PFMT might prevent symptoms of 'vagina feels loose or lax'.

The Simbla TURBT Simulator in Urological Residency Training: From Needs Analysis to Validation.

OBJECTIVE: To investigate the value of the physical Simbla Transurethral Resection of a Bladder Tumor (TURBT) simulator as an educational tool within urological residency training, by means of a training needs analysis (TNA) and assessment of its feasibility, acceptability, and face, content, and construct validity. METHODS: To analyze the training needs for TURBT, procedural steps and pitfalls were identified and the TNA was completed during an expert consensus meeting. Participants (n = 76) were divided into three groups based on their experience in TURBT: novices, intermediates, and experts. Participants performed two standardized TURBT procedures on the simulator. Face validity and content validity, as well as feasibility and acceptability, were assessed with a quantitative survey. Construct validity was assessed by comparing the performance of novices, intermediates, and experts on resection time, quality of tumor resection, and overall performance. RESULTS: Of the 21 procedural steps and 17 pitfalls defined in TNA, 13 steps and 8 pitfalls were covered by the Simbla. Participants rated the Simbla's overall realism (face validity) with a score of 8 of 10 (range 6-9). The simulator was judged to be most useful (content validity) for learning eye-hand coordination: score 8 (6-10). All aspects regarding realism and usefulness were rated above the acceptability threshold of 6/10. Intermediates (100%) and experts (96%) considered the Simbla to be a useful educational tool within the urological curriculum. Resection time was longer for novices than for experts (p < 0.05; construct validity). In addition, the overall performance of novices was rated lower compared with intermediates and experts, and novices showed more irradical resections and bladder perforations (all p < 0.05). CONCLUSIONS: The Simbla TURBT simulator is a valid, feasible, and acceptable educational tool for training procedural skills and may be implemented in the urological curriculum to complement learning in clinical practice. TNA is valuable in defining training objectives and evaluating the educational value of a simulator.

The levator ani muscle during pregnancy and major levator ani muscle defects diagnosed postpartum: a three- and four-dimensional transperineal ultrasound study.

OBJECTIVE: To investigate associations between levator hiatus area and levator ani muscle function during pregnancy and major levator ani muscle defects postpartum. DESIGN: Observational prospective cohort study. SETTING: University hospital, Norway. SAMPLE: A cohort of 234 nulliparous women at 21 and 37 weeks of gestation, and at 6 weeks postpartum. METHODS: Ultrasound measurements of the levator hiatus at rest, during pelvic floor muscle contraction, and during the Valsalva manoeuvre were taken at 21 and 37 weeks of gestation. Levator ani muscle function was estimated as the percentage changes in levator ani muscle length from rest to contraction, and the level of muscle stretch during the Valsalva manoeuvre. Major levator ani muscle defects were diagnosed at 6 weeks postpartum using tomographic ultrasound imaging. MAIN OUTCOME MEASURES: Associations between ultrasound measurements antepartum and major levator ani muscle defects postpartum. RESULTS: Women with major levator ani muscle defects postpartum had significantly smaller levator hiatus area at rest and during the Valsalva manoeuvre at mid-pregnancy (mean difference 1.03 cm(2) , 95% CI 0.31-1.76; 2.92 cm(2) , 95% CI 1.77-4.07), and at 37 weeks of gestation (mean difference 1.47 cm(2) , 95% CI 0.62-2.32; 2.84 cm(2) , 95% CI 0.88-4.80), than women without such defects. They also had significantly less shortening of the levator ani muscle during contraction at 37 weeks of gestation. CONCLUSIONS: Smaller levator hiatus area at rest and during the Valsalva manoeuvre at mid and late pregnancy, and less shortening of the levator ani muscle during contraction at 37 weeks of gestation, are associated with major levator ani muscle defects postpartum.

Dyspareunia and pelvic floor muscle function before and during pregnancy and after childbirth.

INTRODUCTION AND HYPOTHESIS: There is limited knowledge on dyspareunia during pregnancy and postpartum and the role of the pelvic floor muscles (PFM) in women with dyspareunia. Aims of the study were to investigate the presence of dyspareunia before and during pregnancy and postpartum, and to compare vaginal resting pressure (VRP), PFM strength, and endurance between women with and those without dyspareunia. It was hypothesized that there is no difference in PFM variables between women with and those without dyspareunia. METHODS: Three hundred nulliparous women participated in this prospective cohort and answered questions about dyspareunia and the level of bother at gestational weeks 22 and 37, 6 and 12 months postpartum, and retrospectively prior to their pregnancies using ICIQ-FLUTSsex. PFM variables were assessed by manometer at gestational week 22, and 6 and 12 months postpartum. Comparisons between groups were analyzed using independent samples t test. RESULTS: Twenty-eight and 30 % of the women reported dyspareunia at pre-pregnancy and at gestational week 22 respectively. At gestational week 37, and 6 and 12 months postpartum, the percentages were 40, 45, and 33 respectively. No difference in PFM variables was found between women with and those without dyspareunia. Level of bother was higher postpartum than before and during pregnancy. CONCLUSIONS: Symptoms of dyspareunia were common at all time points. No link could be made between PFM function and dyspareunia. Women suffering from dyspareunia postpartum reported it as being bothersome. Our findings suggest that women should be asked about symptoms of dyspareunia related to pregnancy, and that future research should aim for preventative and therapeutic strategies.

How well can pelvic floor muscles with major defects contract? A cross-sectional comparative study 6 weeks after delivery using transperineal 3D/4D ultrasound and manometer.

OBJECTIVE: To investigate ability to contract, vaginal resting pressure (VRP), pelvic floor muscle (PFM) strength and PFM endurance 6 weeks after vaginal delivery in primiparous women, with and without major defects of the levator ani (LA) muscle. DESIGN: Cross-sectional comparative study. SETTING: Akershus University Hospital, Norway. SAMPLE: A cohort of 175 singleton primiparous women delivering vaginally after more than 32 weeks of gestation. METHODS: Major LA defects were assessed by 3D/4D transperineal ultrasound at maximal PFM contraction, using tomographic imaging. VRP, PFM strength and PFM endurance were measured vaginally by manometer. Data were analysed by independent-samples Student's t test, chi-square test, and standard multiple and simple linear regression. MAIN OUTCOME MEASURES: VRP, PFM strength and PFM endurance. RESULTS: Of the women included in the study, 4% were not able to contract their PFM 6 weeks after delivery. Women with major LA defects (n = 55) had 47% lower PFM strength and 47% lower endurance when compared with women without major LA defects (n = 120). Mean differences were 7.5 cmH2O (95% CI 5.1-9.9, P < 0.001) and 51.2 cmH2O seconds (95% CI 32.8-69.6, P < 0.001), respectively. These estimates were unchanged by adjustment in multivariable linear regression for potentially confounding demographic and obstetric factors. No difference was found regarding VRP (P = 0.670). CONCLUSIONS: Women with major LA defects after vaginal delivery had pronounced lower PFM strength and endurance than women without such defects; however, most women with major LA defects were able to contract the PFM. This indicates a potential capacity by non-injured muscle fibres to compensate for loss in muscle strength, even at an early stage after delivery.

The evolution of hypertension treatment in Belgium, a pharmacoepidemiological study.

OBJECTIVES: The aim of this paper is to study the number of patients treated for hypertension and the evolution in usage of different classes of antihypertensive medication. METHODS: Data from 1997 to 2009 was extracted from Pharmanet, a nation-wide database of prescriptions of reimbursed medication in Belgium. RESULTS: In 2009, 25% of women and 20% of men were prescribed at least one antihypertensive drug. Prescription rates rose with age but already 25% of the population aged between 41 and 60 years were treated. More than 50% of the Belgians above 60 years took antihypertensive medication. From 1997 to 2009, a rise in absolute prescription rate was observed for all antihypertensive drug classes. Diuretics and beta blockers remain by far the most frequently delivered drugs with stable prescription rates of 30% over this period. The largest rise is observed for angiotensin II receptor blockers (ARBs), which were only sporadically prescribed in 1997 and now account for 10.5% of the delivered antihypertensive drugs. A small rise is also noted for angiotensin-converting enzyme inhibitors (ACE-inhibitors) (12.3% in 1997 vs 15.6% in 2009). Their success comes at the expense of calcium antagonists, of which the delivered amount declined from 19.8% in 1997 tot 14.1% in 2009. A progressive rise in the prescription of fixed combination products is observed (from 15% in 1997 to 21% in 2009), and can probably be attributed to their growing availability but also to the recent guidelines, promoting their usage. CONCLUSION: Above age 60, the majority of the Belgians are treated with antihypertensive medication. There is a growing tendency for the use of renin angiotensin aldosterone system (RAAS) blockers and fixed combination products.

Long-term electrical capsular stimulation in patients with obsessive-compulsive disorder.

OBJECTIVE: Because of the irreversibility of lesioning procedures and their possible side effects, we studied the efficacy of replacing bilateral anterior capsulotomy with chronic electrical capsular stimulation in patients with severe, long-standing, treatment-resistant obsessive-compulsive disorder. METHODS: We stereotactically implanted quadripolar electrodes in both anterior limbs of the internal capsules into six patients with severe obsessive-compulsive disorder. Psychiatrists and psychologists performed a double-blind clinical assessment. A blinded random crossover design was used to assess four of those patients, who underwent continuous stimulation thereafter. RESULTS: The psychiatrist-rated Yale-Brown Obsessive Compulsive Scale score was lower in the stimulation-on condition (mean, 19.8 +/- 8.0) than in the postoperative stimulator-off condition (mean, 32.3 +/- 3.9), and this stimulation-induced effect was maintained for at least 21 months after surgery. The Clinical Global Severity score decreased from 5 (severe; standard deviation, 0) in the stimulation-off condition to 3.3 (moderate to moderate-severe; standard deviation, 0.96) in the stimulation-on condition. The Clinical Global Improvement scores were unchanged in one patient and much improved in the other three during stimulation. During the stimulation-off period, symptom severity approached baseline levels in the four patients. Bilateral stimulation led to increased signal on functional magnetic resonance imaging studies, especially in the pons. Digital subtraction analysis of preoperative [(18)F]2-fluoro-2-deoxy-d-glucose positron emission tomographic scans and positron emission tomographic scans obtained after 3 months of stimulation showed decreased frontal metabolism during stimulation. CONCLUSION: These observations indicate that capsular stimulation reduces core symptoms 21 months after surgery in patients with severe, long-standing, treatment-refractory obsessive-compulsive disorder. The stimulation elicited changes in regional brain activity as measured by functional magnetic resonance imaging and positron emission tomography.

Diffusing wave spectroscopy used to study the influence of shear on aggregation.

In this study, diffusing wave spectroscopy (DWS) is used to investigate the effect of shear on a food-related aggregating emulsion. The principle of the method is validated using a nonaggregating, nearly monodisperse latex suspension. In general, with increasing shear rate the diffusive motion of the scatterers becomes negligible compared to the convective motion. This causes a decrease in the decay time of the autocorrelation curves and a change in the form of the autocorrelation curves from nearly exponential to Gaussian. This is reflected in the exponent of the mean square displacement that changes from 1 to 2. The effect of shear on the acidification of a sodium caseinate-stabilized emulsion was studied by DWS and by rheometry. The emulsion droplets in the food-related emulsion were uniformly dispersed at neutral pH. Upon acidification down to a pH of 5.2 +/- 0.05, the emulsion showed Newtonian behavior with constant viscosity over the whole pH range. At pH 5.17 +/- 0.05, independent of the applied shear rate during acidification, the viscosity suddenly increased. From this point on, the emulsion showed shear-thinning behavior. The photon-transport mean free path ( l*) was not influenced by the applied shear rate and did not change down to pH 5.2 +/- 0.05. Close to this pH, l* increased, and the decay of the autocorrelation curves shifted to longer correlation times when shear rates smaller than 1 s (-1) were applied. At lower pH (5.05 +/- 0.05), l* started to fluctuate, and the autocorrelation curves no longer decayed to zero, indicating that at these shear rates the system behaved nonergodicly. Assuming that the convective motion and the Brownian motion are independent of each other, the mean square displacement as a result of Brownian motion was determined. From this, the sol-gel point and the radius of the aggregates at this point as a function of the shear rate was determined. The results indicated that the radius of the aggregates at the sol-gel transition decreased with increasing shear rate and suggested that shear will result in a more open structure of the network formed by the aggregates.

WITHDRAWN: Advice to stay active as a single treatment for low-back pain and sciatica.

BACKGROUND: Low back pain is one of the most common conditions managed in primary care. Restricted activity, rest, and symptomatic analgesics are the most commonly prescribed treatment for low back pain and sciatica. OBJECTIVES: To assess the effects of advice to stay active as single treatment for patients with low back pain. SEARCH STRATEGY: Computerised searches in MEDLINE, EMBASE, Sport, The Cochrane Controlled Trials Register, Musculoskeletal Group's Trials Register and Scisearch, and scanning of reference lists from relevant articles were undertaken. Relevant studies were also traced by contacting authors. Date of the most recent searches: December 1998. SELECTION CRITERIA: We included all randomised trials or quasi-randomised trials where the study population consisted of adult patients with low back pain or sciatica, in which one comparison group was advised to stay active. The main outcomes of interest were pain, functional status, recovery and return to work. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion, assessed the validity of included trials and extracted data. Investigators were contacted to collect missing data or for clarification when needed. MAIN RESULTS: Four trials, with a total of 491 patients, were included. Advice to stay active was compared to advice to rest in bed in all trials. Two trials were assessed to have low risk of bias and two to have moderate to high risk of bias. The results were heterogeneous. Results from one high quality trial of patients with acute simple LBP found small differences in functional status [Weighted Mean Difference (on a 0-100 scale) 6.0 (95% CI: 1.5, 10.5)] and length of sick leave [WMD 3.4 days (95% CI: 1.6, 5.2)] in favour of staying active compared to advice to stay in bed for two days. The other high quality trial compared advice to stay active with advice to rest in bed for 14 days for patients with sciatic syndrome, and found no differences between the groups. One of the high quality trials also compared advice to stay active with exercises for patients with acute simple LBP, and found improvement in functional status and reduction in sick leave in favour of advice to stay active. AUTHORS' CONCLUSIONS: The best available evidence suggests that advice to stay active alone has small beneficial effects for patients with acute simple low back pain, and little or no effect for patients with sciatica. There is no evidence that advice to stay active is harmful for either acute low back pain or sciatica. If there is no major difference between advice to stay active and advice to rest in bed, and there is potential harmful effects of prolonged bed rest, then it is reasonable to advise people with acute low back pain and sciatica to stay active. These conclusions are based on single trials.

Transitions in structure in oil-in-water emulsions as studied by diffusing wave spectroscopy.

Transitions in structure of sodium caseinate stabilized emulsions were studied using conventional rheometry as well as diffusing wave spectroscopy (DWS). Structural differences were induced by different amounts of stabilizer, and transitions in structure were induced by acidification. Special attention was given to the sol-gel transition. In this study the criterion of the sol-gel transition being frequency independent was verified for emulsions using DWS. It was shown that this sol-gel transition did not correspond to the so-called ergodic-nonergodic transition. Differences, as a function of the pH, were found for emulsions containing different amounts of stabilizer. The emulsion droplets in an emulsion without extra stabilizer formed a continuous network upon acidification, while the droplets in emulsions with an excess of stabilizer formed a network of oil droplets at neutral pH. Upon acidification of the latter one, the initial network of oil droplets fell apart, and eventually a network of sodium caseinate, in which the oil droplets were embedded, was formed. This caused the appearance of two sol-gel transitions. The breaking of the initial network as well as the network formation of sodium caseinate in time was observed by DWS.

Bed rest for acute low-back pain and sciatica.

BACKGROUND: Low-back pain (LBP) is a common reason for consulting a general practitioner, and advice on daily activities is an important part of the primary care management of low-back pain. OBJECTIVES: To assess the effects of advice to rest in bed for patients with acute LBP or sciatica. SEARCH STRATEGY: We searched the Cochrane Back Group Specialized Registry, CENTRAL, MEDLINE, EMBASE, Sport, and SCISEARCH to March 2003, reference lists of relevant articles, and contacted authors of relevant articles. SELECTION CRITERIA: Randomised or controlled clinical trials with quasi-randomisation (alternate allocation, case record numbers, dates of birth, etc.), in any language, where the effectiveness of advice to rest in bed was evaluated. The main outcomes of interest were pain, functional status, recovery and return to work. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion, assessed the internal validity of included trials and extracted data. Investigators were contacted to obtain missing information. MAIN RESULTS: Eleven trials (1963 patients) were included in this updated version. There is high quality evidence that people with acute LBP who are advised to rest in bed have a little more pain [Standardised Mean Difference (SMD) 0.22 (95% Confidence Interval (CI): 0.02, 0.41)] and a little less functional recovery [SMD 0.29 (95% CI: 0.05, 0.45)] than those advised to stay active. For patients with sciatica, there is moderate quality evidence of little or no difference in pain [SMD -0.03 (95% CI: -0.24, 0.18)] or functional status [SMD 0.19 (95% CI: -0.02, 0.41)] between bed rest and staying active. For patients with acute LBP, there is moderate quality evidence of little or no difference in pain intensity or functional status between bed rest and exercises. For patients with sciatica, there is moderate quality evidence of little or no difference in pain intensity between bed rest and physiotherapy, but small improvements in functional status [Weighted Mean Difference 6.9 (on a 0-100 scale) (95% CI: 1.09, 12.74)] with physiotherapy. There is moderate quality evidence of little or no difference in pain intensity or functional status between two to three days and seven days of bed rest. REVIEWERS' CONCLUSIONS: For people with acute LBP, advice to rest in bed is less effective than advice to stay active. For patients with sciatica, there is little or no difference between advice to rest in bed and advice to stay active. There is little or no difference in the effect of bed rest compared to exercises or physiotherapy, or seven days of bed rest compared with two to three.

Long-term electrical capsular stimulation in patients with obsessive-compulsive disorder.

OBJECTIVE: Because of the irreversibility of lesioning procedures and their possible side effects, we studied the efficacy of replacing bilateral anterior capsulotomy with chronic electrical capsular stimulation in patients with severe, long-standing, treatment-resistant obsessive-compulsive disorder. METHODS: We stereotactically implanted quadripolar electrodes in both anterior limbs of the internal capsules into six patients with severe obsessive-compulsive disorder. Psychiatrists and psychologists performed a double-blind clinical assessment. A blinded random crossover design was used to assess four of those patients, who underwent continuous stimulation thereafter. RESULTS: The psychiatrist-rated Yale-Brown Obsessive Compulsive Scale score was lower in the stimulation-on condition (mean, 19.8 +/- 8.0) than in the postoperative stimulator-off condition (mean, 32.3 +/- 3.9), and this stimulation-induced effect was maintained for at least 21 months after surgery. The Clinical Global Severity score decreased from 5 (severe; standard deviation, 0) in the stimulation-off condition to 3.3 (moderate to moderate-severe; standard deviation, 0.96) in the stimulation-on condition. The Clinical Global Improvement scores were unchanged in one patient and much improved in the other three during stimulation. During the stimulation-off period, symptom severity approached baseline levels in the four patients. Bilateral stimulation led to increased signal on functional magnetic resonance imaging studies, especially in the pons. Digital subtraction analysis of preoperative [(18)F]2-fluoro-2-deoxy-d-glucose positron emission tomographic scans and positron emission tomographic scans obtained after 3 months of stimulation showed decreased frontal metabolism during stimulation. CONCLUSION: These observations indicate that capsular stimulation reduces core symptoms 21 months after surgery in patients with severe, long-standing, treatment-refractory obsessive-compulsive disorder. The stimulation elicited changes in regional brain activity as measured by functional magnetic resonance imaging and positron emission tomography.

Advice to stay active as a single treatment for low back pain and sciatica.

BACKGROUND: Low back pain is one of the most common conditions managed in primary care. Restricted activity, rest, and symptomatic analgesics are the most commonly prescribed treatment for low back pain and sciatica. OBJECTIVES: To assess the effects of advice to stay active as single treatment for patients with low back pain. SEARCH STRATEGY: Computerised searches in MEDLINE, EMBASE, Sport, The Cochrane Controlled Trials Register, Musculoskeletal Group's Trials Register and Scisearch, and scanning of reference lists from relevant articles were undertaken. Relevant studies were also traced by contacting authors. Date of the most recent searches: December 1998. SELECTION CRITERIA: We included all randomised trials or quasi-randomised trials where the study population consisted of adult patients with low back pain or sciatica, in which one comparison group was advised to stay active. The main outcomes of interest were pain, functional status, recovery and return to work. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion, assessed the validity of included trials and extracted data. Investigators were contacted to collect missing data or for clarification when needed. MAIN RESULTS: Four trials, with a total of 491 patients, were included. Advice to stay active was compared to advice to rest in bed in all trials. Two trials were assessed to have low risk of bias and two to have moderate to high risk of bias. The results were heterogeneous. Results from one high quality trial of patients with acute simple LBP found small differences in functional status [Weighted Mean Difference (on a 0-100 scale) 6.0 (95% CI: 1.5, 10.5)] and length of sick leave [WMD 3.4 days (95% CI: 1.6, 5.2)] in favour of staying active compared to advice to stay in bed for two days. The other high quality trial compared advice to stay active with advice to rest in bed for 14 days for patients with sciatic syndrome, and found no differences between the groups. One of the high quality trials also compared advice to stay active with exercises for patients with acute simple LBP, and found improvement in functional status and reduction in sick leave in favour of advice to stay active. REVIEWER'S CONCLUSIONS: The best available evidence suggests that advice to stay active alone has small beneficial effects for patients with acute simple low back pain, and little or no effect for patients with sciatica. There is no evidence that advice to stay active is harmful for either acute low back pain or sciatica. If there is no major difference between advice to stay active and advice to rest in bed, and there is potential harmful effects of prolonged bed rest, then it is reasonable to advise people with acute low back pain and sciatica to stay active. These conclusions are based on single trials.