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Bu çalışma, 09-13 Eylül 2009 tarihleri arasında Salzburg[Avusturya]’da düzenlenen 28. Annual European-Society-of-Regional-Anaesthesia Congress’da bildiri olarak sunulmuştur. Preperitoneal catheter analgesia following abdominal surgery has attracted interest in the last decade. We conducted this study to evaluate the benefits of preperitoneal catheter analgesia in managing pain after abdominal colon and rectal resections. A total of 50 patients undergoing colon and rectal resections for benign and malignant diseases received analgesic medicines via an epidural catheter placed just prior to surgery and a preperitoneal catheter placed at the end of the surgical procedure. Patients were instructed to use the epidural patient-controlled analgesia (PCA) device freely and were randomized into two groups after obtaining the approval of the Institutional Review Board: Group A received 10 ml of levobupivacaine twice a day postoperatively via preperitoneal catheter and group B received only 10 ml of saline. Demographics, surgical characteristics, pain scores recorded four days following surgery, analgesic volume used from the epidural PCA, clinical outcomes (length of stay, time to first bowel movement, time to first passage of gas or stool, time to first oral intake) and respiratory function test results (preoperative vs. postoperative) were compared. There were no significant differences in demographics or surgical characteristics between both groups. Pain scores were similar. Clinical outcomes and respiratory functions were comparable. The use of analgesic volume via epidural catheter was significantly lower in group A than in group B (P = 0.032). Preperitoneal catheter analgesia significantly decreased the need for epidural drug consumption and proved to be a beneficial adjunct for postoperative pain management of patients who underwent colon and rectal resections. European Soc Reg Anaesthesia

Preliminary evidence has suggested that probiotics may improve eradication rates in patients infected with Helicobacter pylori treated by triple therapy. This study examined the effect of combining triple therapy with kefir, a fermented milk drink containing probiotics. A randomized, double-blind study was carried out on 82 consecutive patients with symptoms of dyspepsia and H. pylori infection confirmed by the urea breath test. Patients were given a two times a day, 14-day course of lansoprazole (30 mg), amoxicillin (1,000 mg), and clarithromycin (500 mg) with either 250 mL of kefir twice daily (triple therapy + kefir, n = 46) or 250 mL of milk containing placebo (triple therapy + placebo, n = 36). Side effects were determined using a standard questionnaire form at 15 days after beginning treatment. Patients returned for urea breath tests 45 days after beginning treatment. Significantly more triple therapy + kefir patients achieved eradication (36 of 46 [78.2%]) compared with triple therapy + placebo patients (18 of 36 [50.0%]) (P = .026, χ(2) test). Side effects were significantly less frequent and less severe in triple therapy + kefir patients than in triple therapy + placebo patients. We conclude that a 14-day regimen of triple therapy with kefir is more effective in achieving H. pylori eradication than is triple therapy alone.

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:25:30Z No. of bitstreams: 0Bitstream added on 2014-05-27T14:31:08Z : No. of bitstreams: 1 2-s2.0-79952197520.pdf: 336059 bytes, checksum: 6887bfb6c66c449f86ed80f9d7459718 (MD5) Made available in DSpace on 2014-05-27T11:25:30Z (GMT). No. of bitstreams: 0 Previous issue date: 2011-03-05 Background: Blood pressure (BP) within pre-hypertensive levels confers higher cardiovascular risk and is an intermediate stage for full hypertension, which develops in an annual rate of 7 out of 100 individuals with 40 to 50 years of age. Non-drug interventions to prevent hypertension have had low effectiveness. In individuals with previous cardiovascular disease or diabetes, the use of BP-lowering agents reduces the incidence of major cardiovascular events. In the absence of higher baseline risk, the use of BP agents reduces the incidence of hypertension. The PREVER-prevention trial aims to investigate the efficacy, safety and feasibility of a population-based intervention to prevent the incidence of hypertension and the development of target-organ damage.Methods: This is a randomized, double-blind, placebo-controlled clinical trial, with participants aged 30 to 70 years, with pre-hypertension. The trial arms will be chlorthalidone 12.5 mg plus amiloride 2.5 mg or identical placebo. The primary outcomes will be the incidence of hypertension, adverse events and development or worsening of microalbuminuria and of left ventricular hypertrophy in the EKG. The secondary outcomes will be fatal or non-fatal cardiovascular events: myocardial infarction, stroke, heart failure, evidence of new sub-clinical atherosclerosis, and sudden death. The study will last 18 months. The sample size was calculated on the basis of an incidence of hypertension of 14% in the control group, a size effect of 40%, power of 85% and P alpha of 5%, resulting in 625 participants per group. The project was approved by the Ethics committee of each participating institution.Discussion: The early use of blood pressure-lowering drugs, particularly diuretics, which act on the main mechanism of blood pressure rising with age, may prevent cardiovascular events and the incidence of hypertension in individuals with hypertension. If this intervention shows to be effective and safe in a population-based perspective, it could be the basis for an innovative public health program to prevent hypertension in Brazil.Trial Registration: Clinical Trials NCT00970931. © 2011 Fuchs et al; licensee BioMed Central Ltd. Hospital de Clínicas de Porto Alegre Universidade Federal do Rio Grande do Sul, Porto Alegre Hospital Universitário Antônio Pedro Universidade Federal Fluminense, Niterói Hospital São Lucas Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre Hospital das Clinicas Universidade de São Paulo, São Paulo Instituto do Coração Universidade de São Paulo, São Paulo Faculdade de Medicina de Ribeirão Preto Universidade de São Paulo, Ribeirão Preto Faculdade de Medicina São José do Rio Preto, São José do Rio Preto Faculdade de Ciências Médicas Universidade de Campinas, Campinas Faculdade de Ciências Farmacêuticas Universidade de São Paulo, Ribeirão Preto Faculdade de Medicina de Botucatu Universidade Estadual de São Paulo, Botucatu Universidade do Estado do Rio de Janeiro, Rio de Janeiro Hospital das Clínicas Universidade Federal de Minas Gerais, Belo Horizonte Hospital das Clínicas de Goiânia Universidade Federal de Goiás, Goiânia Anis Rassi Hospital, Goiânia Hospital Universitário Júlio Muller Universidade Federal de Mato Grosso, Cuiabá Faculdade de Medicina Universidade de Ciências da Saúde Alagoas, Maceió Faculdade de Medicina Universidade Federal de Pernambuco, Recife Instituto de Medicina Integral Prof Fernando Figueira, Recife Hospital Universitário Oswaldo Cruz/PROCAPE Universidade de Pernambuco, Recife Hospital Universitário Valter Cantídio Universidade Federal do Ceará, Fortaleza Hospital Universitário Universidade Federal Maranhão, São Luiz Instituto de Cardiologia Fundação Universitária de Cardiologia, Porto Alegre Faculdade de Medicina Universidade Federal de Pelotas, Pelotas Hospital do Coração, São Paulo Faculdade de Medicina de Botucatu Universidade Estadual de São Paulo, Botucatu

Objective: The aim of this study was to compare the efficacy of ultrasound (US) and ketoprofen phonophoresis (PH) in the treatment of carpal tunnel syndrome (CTS). Design: This study was a prospective, randomised, controlled, double-blinded clinical trial with follow-up at 8 weeks. Fiftyone patients (76 median nerves) with clinical and electrophysiologic evidence of mild or moderate CTS were included in the study. They were randomly assigned to one of three groups; group 1 received sham US and splinting, group 2 received US and splinting, and group 3 received ketoprofen phonophoresis and splinting. Patients were evaluated by use of electrophysiological variables such as median motor distal latency (mMDL), median sensory distal latency (mSDL), functional status scale (FSS), symptom severity scale (SSS) and visual analog scale (VAS). Electrophysiological variables and scales were evaluated at the beginning, end of therapy (2nd week) and 8th week. Results: All the randomised patients were included in the intention-to-treat (ITT) analysis. The per protocol (PP) analysis included only those patients who complied with the study protocol. After completing 2 weeks of treatment, seven out of 51 randomized patients did not finish the study protocol due to non-compliance to splinting, illness and lost to follow-up. Those patients were excluded from PP analysis. Participants were similar in all clinical, electrophysiological and demographic respects (p>0.05). An improvement was found in all parameters (VAS, FSS, SSS, mMDL and mSDL) for all groups at the end of the treatment and 8th week. It was found that pain score was significantly lower in group 3 compared to other treatment groups at 8th week according to ITT and PP analysis (p = 0.002, p = 0.004 and p = 0.001, p = 0.001). Conclusion: Ketoprofen PH as adjuvant therapy on splinting is effective with respect to reduction of pain. Adding US therapy to the splinting is not superior to the splinting alone in patients with CTS. © 2011 - IOS Press and the authors. All rights reserved.

BACKGROUND & AIMS: Tenofovir disoproxil fumarate (TDF), a nucleotide analogue and potent inhibitor of hepatitis B virus (HBV) polymerase, showed superior efficacy to adefovir dipivoxil in treatment of chronic hepatitis B through 48 weeks. We evaluated long-term efficacy and safety of TDF monotherapy in patients with chronic hepatitis B who were positive or negative for hepatitis B e antigen (HBeAg+ or HBeAg-). METHODS: After 48 weeks of double-blind comparison of TDF to adefovir dipivoxil, patients who underwent liver biopsy were eligible to continue the study on open-label TDF for 7 additional years; data presented were collected up to 3 years (week 144) from 85% of participants. Primary efficacy end points at week 144 included levels of HBV DNA and alanine aminotransferase, development of resistance mutations, and presence of HBeAg or hepatitis B surface antigen (HBsAg). RESULTS: At week 144, 87% of HBeAg- and 72% of HBeAg+ patients treated with TDF had levels of HBV DNA

Acute mountain sickness (AMS) is a common and disabling condition that occurs in healthy individuals ascending to high altitude. Based on the ability of iron to influence cellular oxygen sensing pathways, we hypothesized that iron supplementation would protect against AMS. To examine this hypothesis, 24 healthy sea-level residents were randomized to receive either intravenous iron(III)-hydroxide sucrose (200 mg) or saline placebo, before ascending rapidly to Cerro de Pasco, Peru (4340 m). The Lake Louise scoring system was used to assess incidence and severity of AMS at sea level and on the first full day at altitude. No significant difference in absolute AMS score was detected between the two groups either at baseline or at high altitude. However, the mean increase in AMS score was 65% smaller in the iron group than in the saline group (p

This prospective, randomized, double-blind study compared the effects on thromboelastography (TEG) of preloading with two different colloid fluids prior to spinal anaesthesia for caesarean section. Healthy full-term parturients received either 500 ml 6% hydroxyethyl starch 130/0.4 (HES, n = 25) or 500 ml 4% succinylated gelatine (GEL, n = 25) prior to spinal anaesthesia. TEG parameters including reaction time (r-time), clot formation time (k-time), clot formation rate (α-angle) and maximum amplitude (MA) were measured immediately before and after pre-loading. Both groups had significantly shorter r-time and lower MA after pre-loading. The α-angle was significantly decreased after pre-loading with HES but not with GEL. No significant differences in k-time were induced pre-loading. In conclusion, preloading with HES or GEL was associated with a mild hypocoagulable effect in healthy parturients presenting for elective caesarean section; however, all TEG parameters in both groups remained within or very close to the normal range after pre-loading.

Neurocysticercosis is the most common cause of acquired epilepsy in the world. Antiparasitic treatment of viable brain cysts is of clinical benefit, but current antiparasitic regimes provide incomplete parasiticidal efficacy. Combined use of two antiparasitic drugs may improve clearance of brain parasites. Albendazole (ABZ) has been used together with praziquantel (PZQ) before for geohelminths, echinococcosis and cysticercosis, but their combined use is not yet formally recommended and only scarce, discrepant data exist on their pharmacokinetics when given together. We assessed the pharmacokinetics of their combined use for the treatment of neurocysticercosis. METHODS A randomized, double-blind, placebo-controlled phase II evaluation of the pharmacokinetics of ABZ and PZQ in 32 patients with neurocysticercosis was carried out. Patients received their usual concomitant medications including an antiepileptic drug, dexamethasone, and ranitidine. Randomization was stratified by antiepileptic drug (phenytoin or carbamazepine). Subjects had sequential blood samples taken after the first dose of antiparasitic drugs and again after 9days of treatment, and were followed for 3months after dosing. RESULTS Twenty-one men and 11 women, aged 16 to 55 (mean age 28)years were included. Albendazole sulfoxide concentrations were increased in the combination group compared with the ABZ alone group, both in patients taking phenytoin and patients taking carbamazepine. PZQ concentrations were also increased by the end of therapy. There were no significant side effects in this study group. CONCLUSIONS Combined ABZ + PZQ is associated with increased albendazole sulfoxide plasma concentrations. These increased concentrations could independently contribute to increased cysticidal efficacy by themselves or in addition to a possible synergistic effect.

We evaluated the overall agreement between colposcopically directed biopsies and the definitive excisional specimens within the context of three clinical trials. A total of 737 women aged 16-45 who had a cervical biopsy taken within 6 months before their definitive therapy were included. Per-protocol, colposcopists were to also obtain a representative cervical biopsy immediately before definitive therapy. Using adjudicated histological diagnoses, the initial biopsies and the same day biopsies were correlated with the surgically excised specimens. The overall agreement between the biopsies taken within 6 months of definitive therapy, and the definitive therapy diagnoses was 42% (weighted kappa = 0.34) (95% CI: 0.29-0.39). The overall underestimation of cervical intraepithelial neoplasia grade 2/3 or adenocarcinoma in situ (CIN2-3/AIS) and CIN3/AIS was 26 and 42%, respectively. When allowing for one degree of variance in the correlation, the overall agreement was 92% for CIN2-3/AIS. The overall agreement between the same day biopsy and definitive therapy specimen was 56% (weighted kappa = 0.41) (95% CI: 0.36-0.47), and the underestimation of CIN2-3/AIS was 57%. There were significant associations in the agreement between biopsies and excisional specimen diagnoses when patients were stratified by age, number of biopsies, lesion size, presence of human papillomavirus (HPV)16/18 and region. Of 178 diagnostic endocervical curettages performed, 14 (7.9%) found any HPV disease. Colposcopic accuracy improved when CIN2 and CIN3/AIS were grouped as a single predictive measure of high-grade disease. Colposcopy functioned well when allowed a one-degree difference between the biopsy and the surgical histologic interpretations, as done in clinical practice. Taking more than one biopsy improved colposcopic accuracy and could improve patient management. Copyright © 2010 UICC.

Background “Patient-Reported Outcome” (PRO) is used as an umbrella term for different concepts for measuring subjectively perceived health status e. g. as treatment effects. Their common characteristic is, that the appraisal of the health status is reported by the patient himself. In order to describe the informative value of PRO in Health Technology Assessment (HTA) first an overview of concepts, classifications and methods of measurement is given. The overview is complemented by an empirical analysis of clinical trials and HTA-reports on rheumatoid arthritis and breast cancer in order to report on type, frequency and consequences of PRO used in these documents. Methods For both issues systematic reviews of the literature have been performed. The search for methodological literature covers the publication period from 1990 to 2009, the search for clinical trials of rheumatoid arthritis and breast cancer covers the period 2005 to 2009. Both searches were performed in the medical databases of the German Institute of Medical Documentation and Information (DIMDI). The search for HTA-reports and methodological papers of HTA-agencies was performed in the CRD-Databases (CRD = Centre for Reviews and Dissemination) and by handsearching the websites of INAHTA member agencies (INAHTA = International Network of Agencies for Health Technology Assessment). For all issues specific inclusion and exclusion criteria were defined. The methodological quality of randomized controlled trials (RCT) was assessed by a modified version of the Cochrane Risk of Bias Tool. For the methodological part information extraction from the literature is structured by the report’s chapters, for the empirical part data extraction sheets were constructed. All information is summarized in a qualitative manner. Results Concerning the methodological issues the literature search retrieved 158 documents (87 documents related to definition or classification, 125 documents related to operationalisation of PRO). For the empirical analyses 225 RCT (rheumatoid arthritis: 77; breast cancer: 148) and 40 HTA-reports and method papers were found. The analysis of the methodological literature confirms the role of PRO as an umbrella term for a variety of different concepts. The newest classification system facilitates the description of PRO measures by construct, target population and the method of measurement. Steps of operationalisation involve defining a conceptual framework, instrument development, exploration of measurement properties or, possibly, the modification of existing instruments. Seven out of 59 RCT analysing the effects of antibody therapy for rheumatoid arthritis define PRO as the primary endpoint, 38 trials utilize composite measures (ACR, DAS) and ten trials report clinical or radiological parameters as the primary endpoint. Six out of 123 chemotherapy trials for breast cancer define PRO as the primary endpoint, while 98 trials report clinical endpoints (survival, tumour response, progression) in their primary analyses. Discrepancies in the number of trials result from inaccurate specifications of endpoints in the publications. This distribution is reflected in the HTA-reports: while almost all reports on rheumatoid arthritis refer to PRO, this is only the case in about half of the reports on breast cancer. Conclusions As definition and classification of PRO are concerned, coherent concepts are found in the literature. Their operationalisation and implementation must be guided by scientific principles. The type and frequency of PRO used in clinical trials largely depend on the disease analysed. The HTA-community seems to pursue the utilization of PRO proactively – in case of missing data the need for further research is stated., GMS Health Technology Assessment; 7:Doc01; ISSN 1861-8863

Vitamin A supplementation is associated with divergent clinical norovirus (NoV) outcomes in Mexican children. Fecal cytokine concentrations following NoV genogroup infections among 127 Mexican children 5-15 mo old enrolled in a randomized, double-blind, placebo-controlled, vitamin A supplementation trial were determined to clarify the role the gut immune response plays in these associations. Stools collected from supplemented children [20,000 IU retinol (3.3 IU = 1 μg retinol) for children < 12 mo of age; 45,000 IU for children ≥ 12 mo] or children in the placebo group were screened for NoV genogroups I (GI) and II (GII). Monocyte chemoattractant protein-1 (MCP-1), TNFα, IL-5, IL-6, IL-8, IL-4, IFNγ, and IL-10 fecal concentrations were also determined. Differences in cytokine levels between the 2 groups following GI and GII infections were determined using ordered logistic regression models. MCP-1 and IL-8 levels were greater among GI- and GII-infected children, respectively, compared with uninfected children, whereas IL-5 levels were greater following both genogroup infections. MCP-1, IL-8, and IL-6 fecal levels were reduced among supplemented children with GII-associated diarrhea compared with the placebo group. Vitamin A-supplemented, GII-infected children had reduced MCP-1 and TNFα levels compared with GII-infected children in the placebo group (P-interaction = 0.02 and 0.03, respectively). Supplemented children with GI-associated diarrhea had higher TNFα and IL-4 levels compared with children in the placebo group with diarrhea (P-interaction = 0.02 and 0.02, respectively). The divergent effects of supplementation on NoV outcomes may result from the different effects vitamin A has on the genogroup-specific immune responses.

Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-27T11:24:47Z No. of bitstreams: 0 Made available in DSpace on 2014-05-27T11:24:47Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-09-01 We report on the results of a double-blind, randomized, controlled clinical trial comparing two preparations of ethinylestradiol and cyproterone acetate in the treatment of women of reproductive age presenting menstrual irregularities of hyper-androgenic origin. After obtaining informed consent, subjects were randomized to a 4-month treatment period consisting of one daily dose of 0.035mg ethinylestradiol + 2mg cyproterone acetate. The treatment regimen cycle consisted of one pill, once daily for 21 days, followed by a 7-day pill-free period. We compared the efficacy of two presentations of the drug combination after each treatment cycle (Visits 2, 3, 4, and 5) in establishment and maintenance of menstrual regulation, intensity of menstrual flow, and dysmenorrhea, as well as a comparison of the two presentations in terms of Global Satisfaction and Drug Satisfaction assessments performed by the patients and the investigating physician. At each study visit, drug compliance and use of concomitant medications, as well as incidence, severity and duration of adverse events were recorded. A total of 86 subjects were randomized to treatment, with 43 subjects in each treatment group. At Visit 2 and each subsequent visit, all patients in both treatment groups reported an episode of withdrawal bleeding during the 7-day hormone-free period. We observed a statistically significant (p

BACKGROUND: Testosterone increases lean mass and may help to counter the changes in muscle architecture associated with sarcopenia. This study was designed to investigate the effects of testosterone replacement therapy on skeletal muscle architecture in intermediate-frail and frail elderly men. METHODS: A subgroup of 30 intermediate-frail and frail elderly men (65-89 years) with low to borderline-low testosterone levels were enrolled from a single-center randomized, double-blind placebo-controlled trial. Participants received either a transdermal testosterone (50 mg) or placebo gel daily for 6 months. Architecture (muscle thickness, fascicle length, and pennation angle) of the gastrocnemius medialis muscle was assessed by ultrasound imaging at baseline and after 6 months of treatment. RESULTS: Serum testosterone increased from 11.6 +/- 3.5 to 18.0 +/- 8.1 nmol/L by 10 days after randomization in the active group (but not the placebo group) and was maintained throughout the treatment period. Testosterone treatment resulted in a preservation of muscle thickness at 6 months while it decreased in the placebo group (effect size 1.4 [95% confidence interval = 0.3-2.5; p = .015]). There was no significant effect of treatment on fascicle length (effect size 1.9 mm [95% confidence interval = -1.2 to 5.0 mm; p = .22]) or pennation angle (effect size 1.2 degrees [95% confidence interval = -1.3 to 3.7 degrees ; p = .32]). CONCLUSIONS: Testosterone replacement in intermediate-frail and frail elderly men is associated with preservation of muscle thickness. The results suggest that testosterone mitigates sarcopenia by improving muscle tissue to maintain a state of normality in aging men.

Background: We describe the incidence and duration of cervical human papillomavirus (HPV) infection episodes along with the risk of infection reappearance following a period of nondetection. Methods: Women (1,788) ages 16 to 23 years underwent cytologic testing and PCR-based testing of cervical swab samples for HPV DNA (HPV-16/18/31/33/35/45/52/58/59) at ∼6-month intervals for up to 4 years in the context of a phase 3 clinical trial (placebo arm). HPV type–specific incidence rates were estimated per 100 person-years. Duration of type-specific cervical infection episodes and risk of reappearance following a period of nondetection were estimated using Kaplan-Meier methods. Results: HPV-16 exhibited the highest (5.9), and HPV-35 and HPV-33 exhibited the lowest (1.0) incidence rates per 100 person-years. Mean cervical infection durations ranged from 13 months for HPV-59 to 20 months for HPV-16 and 58 (with ongoing infections censored at the time of treatment, if done). The risk of cervical infection reappearance within ∼3 years following a period of nondetection ranged from 0% to 16% across HPV types, with a mean of 8%. Limited evidence was found for a role of false-positive HPV tests, missed infections that were above the threshold for detection, or new acquisition of infection in accounting for patterns of infection reappearance. Conclusions: Incidence of high-risk cervical infection was observed to vary considerably more across HPV types than infection duration. A nontrivial proportion of women exhibited infection reappearance following a period of nondetection, with a potential explanation for many such events observed within this analysis being a return to detectable levels of a previously acquired infection. Impact: The risk of HPV infection reappearance following a period of nondetection has not been previously reported for individual HPV types, and this study finds that a nontrivial proportion of infected women exhibit reappearances. Future studies could ascertain subject-level factors that potentially modify the risk of infection reappearance. Cancer Epidemiol Biomarkers Prev; 19(6); 1585–94. ©2010 AACR.

Background: Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Objective: It was hypothesized that specific dietary components are able to reduce low-grade inflammation as well as metabolic and oxidative stress. Design: Dietary products [resveratrol, green tea extract, α-tocopherol, vitamin C, n-3 (omega-3) polyunsaturated fatty acids, and tomato extract] selected for their evidence-based antiinflammatory properties were combined and given as supplements to 36 healthy overweight men with mildly elevated plasma C-reactive protein concentrations in a double-blind, placebo-controlled, crossover study with treatment periods of 5 wk. Inflammatory and oxidative stress defense markers were quantified in plasma and urine. Furthermore, 120 plasma proteins, 274 plasma metabolites (lipids, free fatty acids, and polar compounds), and the transcriptomes of peripheral blood mononuclear cells and adipose tissue were quantified. Results: Plasma adiponectin concentrations increased by 7%, whereas C-reactive protein (principal inflammation marker) was unchanged. However, a multitude of subtle changes were detected by an integrated analysis of the "omics" data, which indicated modulated inflammation of adipose tissue, improved endothelial function, affected oxidative stress, and increased liver fatty acid oxidation. Conclusion: An intervention with selected dietary products affected inflammatory processes, oxidative stress, and metabolism in humans, as shown by large-scale profiling of genes, proteins, and metabolites in plasma, urine, and adipose tissue. This trial was registered at clinical trials.gov as NCT00655798. © 2010 American Society for Nutrition.

Background. The aim of this study was to compare spinal anesthesia effects of low-dose hyperbaric levobupivacaine and low-dose hyperbaric bupivacaine for transurethral procedures. Methods. In this double-blind, randomized, controlled study, a total of 60 patients who were ASA I-III were randomized into two groups. Group B received 7.5 mg hyperbaric bupivacaine plus 25 µg fentanyl, and Group L received 7.5 mg hyperbaric levobupivacaine plus 25 µg fentanyl intrathecally. The onset time to T10 dermatome, times to maximum sensory and motor block levels, time to two-segment regression of sensory block, time to Bromage score zero, time to full recovery of sensory block, and hemodynamic values, as well as adverse effects, were recorded. The primary outcome was the time to complete regression of motor block. Results. The onset time of block to T10, time to maximum sensory block, and time to two-segment regression were similar in both groups. The time to maximum motor block was shorter in Group B (7 ± 3 min) than in Group L (12±5 min), (P

As we contemplate the astonishing successes of human papillomavirus (HPV) vaccines, it is worthwhile to consider whether randomized controlled trials of the sort recently published in the Journal can ever show reductions in cervical cancer rates (1). In their excellent article, Munoz et al. (1) reported nearly complete efficacy of quadrivalent HPV vaccine against vulvar and cervical intraepithelial neoplasia, adenocarcinoma in situ, and genital warts that contained viral types in the vaccine. Of course, this study did not show differences in cervical cancer because that was never its intent. However, the hope that one day randomized controlled trials like these will finally show that HPV vaccines prevent cervical cancer is nicely summarized by the conclusion of a recent systematic review (2) of HPV vaccine trials, “To evaluate cervical cancer incidence and mortality, a longer follow-up is necessary.” But is this really true? Assessing clinical trial outcomes related to cervical disease typically requires regular Papanicolaou test screenings, and ethics require that women with abnormal screening results receive follow-up and treatment, as appropriate. This combination of screening and treatment should prevent all but the most aggressive interval cervical cancers (3). Indeed, one of the most interesting findings reported by Munoz et al. was that none of the women in the trial developed cervical cancer during the approximately 63 000 women-years reported. Because their study participants had at least annual screening for cervical abnormalities to assess the main outcomes, clinicians treated abnormalities identified during the tests with procedures known to be effective in preventing cervical cancer and thus vastly reduced the chances the women would get cervical cancer. We can think of this risk reduction as reflecting a “cervical cancer Heisenberg principle,” according to which studying intermediate outcomes obliterates more severe ones. One way that researchers have devised to get around this Heisenbergian challenge is to design studies that continue past the duration of most efficacy trials (ie, beyond 4–6 years) (3). Women remain randomly assigned to condition, but they no longer receive regular testing as part of the trial. Instead, the researchers follow the women over the next decades by linking their identities to national cancer registries. The ethical justification is that routine screening and medical treatment outside the trial are the standard of care. In contrast, HPV vaccine provision to older women is not the standard of care, and the majority of HPV infections will have already occurred during the ages in which women were enrolled in the trial. The other alternative to get around this Heisenbergian challenge is to evaluate HPV vaccine impact at the population level by use of one of the many alternatives that we have previously reviewed elsewhere (4). These evaluations have to rely on prospective cohort studies and other nonexperimental study designs that yield weaker evidence than randomized controlled trials. One such study (5) recently reported decreases in the incidence of genital warts after implementation of a national HPV vaccination program in Australia. It is highly likely that additional studies, many of which are under way, will provide similar correlational evidence for the population-level impact of HPV vaccine on cervical cancer. While we wait for further evidence to accumulate, it is important to remember that most randomized controlled trials cannot and will not tell us whether HPV vaccines prevent cervical cancer.

Calcium channel blockers, antiarrhythmic drugs, such as verapamil and diltiazem, may decrease the symptoms of tardive dyskinesia. The efficacy and safety of administering 60 mg diltiazem hydrochloride, four times daily for a period of 3 weeks, was studied in a random, double-blind, crossover trial in which the drug was compared with placebo in 17 neuroleptic-treated, chronic psychiatric inpatients of both genders with (tardive) dyskinesia. The severity of the dyskinesia was assessed using the Abnormal Involuntary Movement Scale. Neither diltiazem nor placebo produced a significant decrease in the severity of the dyskinesia. Diltiazem did not influence the psychiatric state of the patients, nor did it have a significant effect on either the blood pressure or electrocardiographic parameters. No significant adverse drug reactions were elicited.

Calcium channel blockers, antiarrhythmic drugs, such as verapamil and diltiazem, may decrease the symptoms of tardive dyskinesia. The efficacy and safety of administering 60 mg diltiazem hydrochloride, four times daily for a period of 3 weeks, was studied in a random, double-blind, crossover trial in which the drug was compared with placebo in 17 neuroleptic-treated, chronic psychiatric inpatients of both genders with (tardive) dyskinesia. The severity of the dyskinesia was assessed using the Abnormal Involuntary Movement Scale. Neither diltiazem nor placebo produced a significant decrease in the severity of the dyskinesia. Diltiazem did not influence the psychiatric state of the patients, nor did it have a significant effect on either the blood pressure or electrocardiographic parameters. No significant adverse drug reactions were elicited.

JUSTIFICATIVA E OBJETIVOS: Avaliar a sedação, a pressão intraocular e as alterações hemodinâmicas com o uso de doses baixas de clonidina, 100 µg e 200 µg por via oral, como medicação pré-anestésica para operações de catarata em regime ambulatorial. MÉTODO: O trabalho foi realizado pela Universidade Federal de São Paulo, sendo um estudo clínico aleatório e duplamente encoberto em 60 pacientes, de ambos os sexos, estado físico ASA 1 e 2, com idade mínima de 18 anos e máxima de 80 anos. Os pacientes foram divididos em três grupos: placebo, clonidina 100 µg e 200 µg. As medidas de pressão intraocular, frequência cardíaca e pressão arterial, além da avaliação de sedação, foram feitas antes e após 90 minutos da administração da clonidina. Os níveis de sedação foram classificados de acordo com a escala de sedação de Ramsay. RESULTADOS: Pacientes que receberam placebo e 100 µg de clonidina não apresentaram redução da frequência cardíaca com diferença estatística significativa, enquanto os que receberam 200 µg de clonidina, sim. Os que receberam clonidina na dose de 200 µg apresentaram redução na pressão arterial sistólica e diastólica (p < 0,05). Um paciente que utilizou 200 µg de clonidina desenvolveu hipotensão arterial grave com pressão sistólica < 80 mmHg. Os pacientes tratados com clonidina apresentaram redução da pressão intraocular (p < 0,05). Quanto à sedação, 90 minutos após a administração de placebo e clonidina 100 µg e 200 µg por via oral, 25%, 60% e 80% dos pacientes encontravam-se, respectivamente, em Ramsay 3 ou 4. CONCLUSÕES: A dose de 100 µg de clonidina pode ser indicada como medicação pré-anestésica para facectomia, possuindo efeito na sedação, diminuição da pressão intraocular e ausência de efeitos adversos na pressão arterial sistêmica e frequência cardíaca. BACKGROUND AND OBJECTIVES: The objective of the present study was to evaluate the degree of sedation, intraocular pressure, and hemodynamic changes with premedication with low doses of oral clonidine, 100 µg and 200 µg, in outpatient cataract surgeries. METHODS: This is a randomized, double-blind, clinical study undertaken at the Universidade Federal de São Paulo with 60 patients of both genders, physical status ASA 1 and 2, ages 18 to 80 years. Patients were separated into three groups: placebo, clonidine 100 µg, and clonidine 200 µg. Intraocular pressure, heart rate, and blood pressure besides assessment of sedation were measured before and 90 minutes after the administration of clonidine. Sedation levels were classified according to the Ramsay sedation scale. RESULTS: Patients who received placebo and 100 µg of clonidine did not show reduction in heart rate, while a reduction in heart rate was observed in patients who received 200 µg of clonidine, and this difference was statistically significant. Patients who received 200 µg of clonidine also had a reduction in systolic and diastolic blood pressure (p < 0.05). One patient who received 200 µg of clonidine developed severe hypotension, with systolic pressure < 80 mmHg. Patients treated with clonidine had a reduction in intraocular pressure (p < 0.05). Ninety minutes after the oral administration of placebo and 100 µg and 200 µg of clonidine, 25%, 60%, and 80% of the patients respectively were classified as Ramsay 3 or 4. CONCLUSIONS: Clonidine 100 µg can be indicated as premedication for fasciectomies, being effective in sedation and reduction of intraocular pressure, without adverse effects on blood pressure and heart rate. JUSTIFICATIVA Y OBJETIVOS: Evaluar la sedación, la presión intraocular y las alteraciones hemodinámicas con el uso de bajas dosis de clonidina, 100 µg y 200 µg por vía oral, como medicación preanestésica para operaciones de catarata en el ambulatorio. MÉTODO: El trabajo fue realizado por la Universidad Federal de São Paulo, siendo un estudio clínico aleatorio y doble ciego en 60 pacientes de los dos sexos, estado físico ASA 1 y 2, con edad mínima de 18 años y máxima de 80 años. Los pacientes fueron divididos en tres grupos: placebo, clonidina 100 µg y 200 µg. Las medidas de presión intraocular, frecuencia cardiaca y presión arterial, además de la evaluación de sedación, fueron hechas antes y después de los 90 minutos iniciales en que se administró la clonidina. Los niveles de sedación se clasificaron de acuerdo con la escala de sedación de Ramsay. RESULTADOS: Los pacientes que recibieron placebo y 100 µg de clonidina, no presentaron una reducción de la frecuencia cardiaca con diferencia estadística significativa, mientras que los que recibieron 200 µg de clonidina, sí la presentaron. Los que recibieron clonidina en dosis de 200 µg presentaron una reducción en la presión arterial sistólica y diastólica (p < 0,05). Un paciente que utilizó 200 µg de clonidina, debutó con hipotensión arterial grave y presión sistólica < 80 mm Hg. Los pacientes tratados con clonidina, presentaron una reducción de la presión intraocular (p < 0,05). En cuanto a la sedación, 90 minutos después de la administración del placebo y la clonidina 100 µg y 200 µg por vía oral, 25%, 60% y 80% de los pacientes estaba respectivamente en Ramsay 3 ó 4. CONCLUSIONES: La dosis de 100 µg de clonidina puede ser indicada como una medicación preanestésica para facectomía, con efecto en la sedación, reducción de la presión intraocular y ausencia de efectos adversos en la presión arterial sistémica y en la frecuencia cardiaca.

Background. Human papillomavirus (HPV)-6/11/16/18 vaccine reduces the risk of HPV-6/11/16/18-related cervical intraepithelial neoplasia (CIN) 1-3 or adenocarcinoma in situ (AIS). Here, its impact on CIN1-3/AIS associated with nonvaccine oncogenic HPV types was evaluated. Methods. We enrolled 17,622 women aged 16-26 years. All underwent cervicovaginal sampling and Pap testing at regular intervals for up to 4 years. HPV genotying was performed for biopsy samples, and histological diagnoses were determined by a pathology panel. Analyses were conducted among subjects who were negative for 14 HPV types on day 1. Prespecified analyses included infection of-6 months' duration and CIN1-3/AIS due to the 2 and 5 most common HPV types in cervical cancer after HPV types 16 and 18, as well as all tested nonvaccine types. Results. Vaccination reduced the incidence of HPV-31/45 infection by 40.3% (95% confidence interval [CI], 13.9% to 59.0%) and of CIN1-3/AIS by 43.6% (95% CI, 12.9% to 64.1%), respectively. The reduction in HPV-31/ 33/45/52/58 infection and CIN1-3/AIS was 25.0% (95% CI, 5.0% to 40.9%) and 29.2% (95% CI, 8.3% to 45.5%), respectively. Efficacy for CIN2-3/AIS associated with the 10 nonvaccine HPV types was 32.5% (95% CI, 6.0% to 51.9%). Reductions were most notable for HPV-31. Conclusions. HPV-6/11/16/18 vaccine reduced the risk of CIN2-3/AIS associated with nonvaccine types responsible for 20% of cervical cancers. The clinical benefit of cross-protection is not expected to be fully additive to the efficacy already observed against HPV-6/11/16/18-related disease, because women may have >1 CIN lesion, each associated with a different HPV type. Trial registration. ClinicalTrials.gov identifiers: NCT00092521, NCT00092534, and NCT00092482. © 2009 by the Infectious Diseases Society of America.

Objective: NMDA receptor antagonists were found to be effective treating alcohol withdrawal syndrome, preventing seizures, and decreasing daily alcohol intake in preclinical studies. But there were only few studies on the efficacy of NMDA receptor antagonists in humans. In this current study, we evaluated the effects of memantine, an NMDA receptor antagonist on alcohol withdrawal syndrome. Methods: The study was planned as a prospective, randomized; double-blind study. In total, 32 patients enrolled in study. 16 patients were randomized to benzodiazepine plus memantine group and 16 were randomized to benzodiazepine plus placebo group. Memantine was administered to patients as 10 mg/day in first week of study and 20 mg/day in second week of study. Severity of alcohol withdrawal was measured by Revised Clinical Institute Withdrawal Assessment for Alcohol scale (CIWA-AR). Mean Corpuscular Volume (MCV), Gama Glutamyl transferase (GGT), Carbohydrate Deficient Transferrine (CDT), and Alcohol Using Disorders Identity Test (AUDIT) tests were also administered to evaluate patients. CIWA-AR scores of the two groups were compared with Mann-Whitney U test at 1(st), 4(th), 7(th), 10(th), and 15(th) days of treatment. P values were corrected for multiple comparisons. Results: Two groups were identical on age, sex, marital status, education and employment. There were also no differences in AUDIT, CDT, MCV, and GGT scores between two groups at the beginning of the study. Mean CIWA-AR score of the memantine group was 23.63 +/- 7.24 and mean CIWA-AR score of the placebo group was 22.94 +/- 7.47 at the beginning of the study. The difference between two groups was not statistically significant. CIWA-AR scores of the memantine group were 7.88 +/- 4,37, 2.44 +/- 2.03, 0.94 +/- 0.99, and 0.25 +/- 0.44 respectively on the 4(th), 7(th), 10(th) and 15(th) measurement days. CIWA-AR scores of the placebo group were 8.63 +/- 4,79, 4.19 +/- 2.10, 2.50 +/- 1.82, and 1.13 +/- 0.96 respectively on the 4(th), 7(th), 10(th) and 15(th) measurement days. Although the decline in CIWA-AR scores was higher in memantine group, there was no statistically significant difference between memantine and placebo group. Memantine group had better improvement in tremor and sweating subscales of CIWA-AR but this difference was not statistically significant. Discussion: Despite the previous results that were mentioning that memantine was effective in alcohol withdrawal syndrome, we could not find statistically significant difference between two groups. Although memantine was not superior to placebo in our setting, randomized placebo controlled studies with more subjects and no extra medication might be helpful for showing efficacy of memantine and other antiglutamatergic agents in alcohol withdrawal syndrome.

Consumption of fructo-oligosaccharides (FOS) has been shown to improve mineral absorption in the short term, but no long-term effects were studied in girls with a low calcium intake. Therefore, we hypothesized that short- and long-term consumption of short-chain FOS (sc-FOS) improves calcium and magnesium absorption in girls with a low habitual calcium intake. Fourteen girls aged between 12 and 14 years received, for 36 days, 10 g sc-FOS (sc-FOS) or maltodextrin (placebo). Short-chain FOS were taken daily for 8 days followed by an intermittent intake mode on 28 random days to mimic noncontinuous intake. In a crossover design, true calcium and magnesium absorption was computed on the 8th and 36th day of each treatment period from isotope enrichment in urine. In addition, the parathyroid hormone and vitamin D in serum and markers of bone resorption in urine (pyridinoline and deoxypyridinoline) were determined. Short-chain FOS increased magnesium absorption by 18% after 36 days (30.1% ± 9.1% vs 35.4% ± 12.8%). Magnesium absorption did not change after the initial 8 days of long-term sc-FOS intake. Short-chain FOS did not affect calcium absorption. In addition, sc-FOS did not affect vitamin D, parathyroid hormone, or markers of bone resorption. It is concluded that consumption of sc-FOS for 36 days stimulated magnesium absorption in girls but did not affect calcium absorption. © 2009 Elsevier Inc. All rights reserved.

Premature ejaculation (PE) is thought to be the most common male sexual dysfunction; however, the prevalence of lifelong (LL)-PE is relatively low. The aim of this study was to investigate the effects of on-demand vardenafil (10 mg) to modify the intravaginal ejaculatory latency time (IELT) in men with LL-PE without erectile dysfunction. Forty-two men (18-35 years) were enrolled in a 16-week, double-blind, placebo-controlled, cross-over study. Primary end point was the modification from baseline of IELT assessed by stopwatch technique; secondary end points were post-ejaculatory refractory time (PERT) and variations of scores at the Index of Premature Ejaculation questionnaire. The changes in geometric mean IELT were superior after taking vardenafil (0.6+/-0.3 vs 4.5+/-1.1 min, P

Consumption of fructo-oligosaccharides (FOS) has been shown to improve mineral absorption in the short term, but no long-term effects were studied in girls with a low calcium intake. Therefore, we hypothesized that short- and long-term consumption of short-chain FOS (sc-FOS) improves calcium and magnesium absorption in girls with a low habitual calcium intake. Fourteen girls aged between 12 and 14 years received, for 36 days, 10 g sc-FOS (sc-FOS) or maltodextrin (placebo). Short-chain FOS were taken daily for 8 days followed by an intermittent intake mode on 28 random days to mimic noncontinuous intake. In a crossover design, true calcium and magnesium absorption was computed on the 8th and 36th day of each treatment period from isotope enrichment in urine. In addition, the parathyroid hormone and vitamin D in serum and markers of bone resorption in urine (pyridinoline and deoxypyridinoline) were determined. Short-chain FOS increased magnesium absorption by 18% after 36 days (30.1% ± 9.1% vs 35.4% ± 12.8%). Magnesium absorption did not change after the initial 8 days of long-term sc-FOS intake. Short-chain FOS did not affect calcium absorption. In addition, sc-FOS did not affect vitamin D, parathyroid hormone, or markers of bone resorption. It is concluded that consumption of sc-FOS for 36 days stimulated magnesium absorption in girls but did not affect calcium absorption. © 2009 Elsevier Inc. All rights reserved.

Midazolam has only sedative properties. However, dexmedetomidine has both analgesic and sedative properties that may prolong the duration of sensory and motor block obtained with spinal anesthesia. This study was designed to compare intravenous dexmedetomidine with midazolam and placebo on spinal block duration, analgesia, and sedation in patients undergoing transurethral resection of the prostate. In this double-blind randomized placebo-controlled trial, 75 American Society of Anesthesiologists' I and II patients received dexmedetomidine 0.5 mu g center dot A kg(-1), midazolam 0.05 mg center dot A kg(-1), or saline intravenously before spinal anesthesia with bupivacaine 0.5% 15 mg (n = 25 per group). The maximum upper level of sensory block and sensory and motor regression times were recorded. Postoperative analgesic requirements and sedation were also recorded. Sensory block was higher with dexmedetomidine (T 4.6 +/- A 0.6) than with midazolam (T 6.4 +/- A 0.9; P < 0.001) or saline (T 6.4 +/- A 0.8; P < 0.001). Time for sensory regression of two dermatomes was 145 +/- A 26 min in the dexmedetomidine group, longer (P < 0.001) than in the midazolam (106 +/- A 39 min) or the saline (97 +/- A 27 min) groups. Duration of motor block was similar in all groups. Dexmedetomidine also increased the time to first request for postoperative analgesia (P < 0.01 compared with midazolam and saline) and decreased analgesic requirements (P < 0.05). The maximum Ramsay sedation score was greater in the dexmedetomidine and midazolam groups than in the saline group (P < 0.001). Intravenous dexmedetomidine, but not midazolam, prolonged spinal bupivacaine sensory blockade. It also provided sedation and additional analgesia.

Objective: To study cardiovascular risk markers in women taking estradiol/trimegestone or estradiol/dydrogesterone. Design: Multicenter, randomized, prospective, double-blind study of 184 healthy post-menopausal women randomized to 6 cycles of either estradiol (2 mg) + trimegestone (0.5 mg) (T-group) or estradiol (2 mg) + dydrogesterone (10 mg) (DYDR group). Cardiovascular risk markers were measured before, after cycle 1, 3 and 6 and at 4 weeks post-treatment. Results: Fibrinogen was reduced in both groups but more markedly in the DYDR group. Factor VIIc activity levels decreased in both groups with a greater change in the T-group. Factor VII antigen was increased in both groups with a greater increase in the DYDR group. Factor VIIa was increased in the DYDR group only. Plasminogen levels were also increased in both groups with a greater increase in the T-group. There were no statistically significant changes in lipid variables between the different regimens. Changes in total cholesterol and LDL cholesterol were correlated positively with changes in factor VIIc in the DYDR group and negatively with changes in factor VIIc in the T-group. Trigemestone was associated with a better bleeding pattern. Conclusions: Trimegestone was associated with less procoagulant changes in factor VIIa and factor VIIc activity and larger decrease in PAI-1 activity compared with the dydrogesterone preparation. These results reflect less androgenic properties of the trimegestone preparation. The fibrinogen level and Lp(a) were more decreased during dydrogesterone treatment. Further investigation is required to clarify the relative importance of beneficial effects with respect to cardiovascular risk. © 2009.

This is a prospective, randomized, controlled trial that compared the efficacy of different protocols of local tissue infiltration with levobupivacaine or levobupivacaine-methylprednisolone at the surgical site for pain relief after lumbar discectomy. The objective of the study was to determine the efficacy of preemptive wound infiltration with levobupivacaine and levobupivacaine-methylprednisolone at the surgical site for pain relief. Patients usually suffer significant pain after lumbar discectomy. Wound infiltration with local anesthetics with or without corticosteroids is one method to address this. A total of 100 patients were randomly allocated to five equal groups as follows: Group I had the musculus multifidi near the operated level infiltrated with 30 mL 0.25% levobupivacaine and 40 mg methylprednisolone just before wound closure; Group II had the same region infiltrated with 30 mL 0.25% levobupivacaine alone before closure; Group III had this region infiltrated with 30 mL 0.25% levobupivacaine and 40 mg methylprednisolone before the incision was made; in Group IV this region was infiltrated with 30 mL 0.25% levobupivacaine alone before incision; and in Group C (controls) this region was infiltrated with 30 mL 0.9% NaCl just before wound closure. Demographics, vital signs, postoperative pain scores and morphine usage were recorded. All four treatment groups showed significantly better results than the control group for most parameters. The treated groups had lower parenteral opioid requirements after surgery, lower incidences of nausea and shorter hospital stays. Further, the data indicate that, compared with infiltration of these drugs at wound closure, preemptive injection of levobupivacaine or levobupivacaine-methylprednisolone into the muscle near the operative site provides more effective analgesia after lumbar discectomy. Our data suggest that preemptive infiltration of the wound site with levobupivacaine alone or combined with methylprednisolone provides effective pain control with reduced opiate dose after unilateral lumbar discectomy.

SummaryEpidemiological studies have shown that hormone therapy (HT) increases the risk of venous thromboembolism in post menopausal women. The mechanism of this increased risk is unknown; however, activation of the haemostatic system is known to contribute to the pathogenesis of venous thromboembolism. In post-menopausal women the estrogen /progestogen composition of the HT can influence the level of haemostatic activation. It was the objective of this study to compare changes in inhibitors and activation markers of the haemostatic system in healthy post-menopausal women taking estradiol (2 mg) combined with dydrogesterone or a new progestin, trimegestone. A multicentre study of 186 women randomised to six months therapy with either estradiol (2 mg) +trimegestone (0.5 mg) or estradiol (2 mg) +dydrogesterone (10 mg) was performed. Antithrombin and protein S activity was decreased and activated protein C (APC) resistance, D-dimer and prothrombin fragment 1.2, were increased in both groups on treatment. Protein C activity was decreased and plasmin-antiplasmin complex was increased in the trimegestone group only. The increase in plasmin-antiplasmin complex and D-dimer was greater after six cycles of treatment in the trimegestone group compared with the dydro-gesterone group. In conclusion, decreased levels of inhibitors of blood coagulation and increased thrombin production were found in both groups however a greater increase in the levels of plasmin-antiplasmin complex and D-dimer was found in the tri-megestone group. This suggests an enhanced fibrinolytic response in this group. Further studies are required to determine the significance of this finding with respect to venous thrombosis risk.

The efficacy of the quadrivalent Human Papillomavirus (HPV) vaccine is thought to be mediated by humoral immunity. We evaluated the correlation between quadrivalent HPV vaccine-induced serum anti-HPV responses and efficacy. 17,622 women were vaccinated at day 1, and months 2 and 6. At day 1 and at 6-12 months intervals for up to 48 months, subjects underwent Papanicolaou and genital HPV testing. No immune correlate of protection could be found due to low number of cases. Although 40% of vaccine subjects were anti-HPV 18 seronegative at end-of-study, efficacy against HPV 18-related disease remained high (98.4%; 95% CI: 90.5-100.0) despite high attack rates in the placebo group. These results suggest vaccine-induced protection via immune memory, or lower than detectable HPV 18 antibody titers. © 2008 Elsevier Ltd. All rights reserved.

Study objective To evaluate the quality of analgesia and the severity of side effects of intrathecal morphine administered for a dose range of 0.0 to 0.4 mg for postcesarean analgesia with low-dose bupivacaine. Design Double-blind, randomized study. Setting University hospital. Patients 100 ASA physical status I and II term parturients undergoing cesarean delivery with spinal anesthesia in the operating room. Interventions Patients were randomized to one of 5 groups to receive 0.0, 0.1, 0.2, 0.3, or 0.4 mg intrathecal morphine in addition to low-dose (7.5 mg) heavy bupivacaine. Each patient received intravenous (IV) patient-controlled analgesia (PCA) with morphine after the operation. Measurements 24-hour IV PCA morphine use and visual analog scores for pain were recorded. The severity score (4-point scale) of nausea, vomiting, and pruritus were assessed intraoperatively and at 4-hour intervals during the first 24 hours postoperatively. Main results PCA morphine use was higher in the control group (0.0 mg) than in groups receiving 0.1, 0.2, 0.3, or 0.4 mg intrathecal morphine. There was no difference in IV PCA morphine use between the 0.1 and 0.4-mg groups, despite a 4-fold increase in intrathecal morphine dose. There was no difference between groups in nausea and vomiting, but pruritus increased in direct proportion to the dose of intrathecal morphine (linear regression, P = 0.0001). Conclusions The dose of 0.1 mg intrathecal morphine produces analgesia comparable with doses as high as 0.4 mg, with significantly less pruritus when combined with low-dose bupivacaine.

Knowledge on the effects of the additive bronchodilatory effects of short-acting agents on the top of the effect of long-acting bronchodilators is limited. In this trial, we examined the influence of higher than conventional doses of the short-acting inhaled β 2 -adrenergic agent salbutamol and the short-acting anticholinergic drug ipratropium bromide on bronchodilation induced by a regular treatment with the long-acting anticholinergic drug tiotropium 18 μg/day in 30 patients with stable COPD. On 3 separate days, a dose-response curve to inhaled salbutamol (100 μg puff-1), ipratropium bromide (20 μg puff-1) or placebo was constructed 3 h after inhalation of the last dose of tiotropium, using one puff, one puff, two puffs and two puffs, for a total cumulative dose of 600 μg salbutamol or 120 μg ipratropium bromide. Doses were given at 30-min intervals and measurements made 15 min after each dose. At the highest cumulative dose, salbutamol showed a trend to be more effective than ipratropium bromide in improving FEV1 (0.157 L vs 0.125 L), and reducing sRaw (−4.52 kPa/s vs 3.57 kPa/s), although the differences between the two treatments were always not significant (p > 0.05), whereas there was no substantial difference between the two drugs in changing FVC (0.179 L vs 0.168 L), IC (0.254 L vs 0.240 L), TGV (−0.444 L vs −0.441 L), TLC (−0.334 L vs −0.318 L) and RV (−0.467 L vs −0.498 L). Both drugs did not affect heart rate and SpO2. Our results indicate that there is not much difference in bronchodilation between adding higher than conventional doses of salbutamol or ipratropium bromide to tiotropium in patients with stable COPD. Effective improvement of the pulmonary function may be achieved in such a type of patients by adding salbutamol 600 μg or ipratropium bromide 120 μg to regular tiotropium. These is an interesting finding mainly for those COPD patients suffering from cardiovascular co-morbidities that are at highest risk of myocardial infarction, congestive heart failure , cardiac arrest and sudden cardiac death when treated with elevated doses of a β 2-agonist (EudraCT number: 2007-001597-82).

Objective: To examine the effects of aerobic exercise or vitamin B supplementation on cognitive function in older adults with mild cognitive impairment (MCI). Design: Randomised placebo-controlled trial. Setting: General community. Participants: Community-dwelling adults aged 70-80 with MCI. Interventions : The 152 participants were randomly assigned to two interventions: (1) a twice-weekly, group-based, moderate-intensity walking programme (WP, n = 77) or a low-intensity placebo activity programme (n = 75) for one year; and (2) daily vitamin pill containing 5 mg folic acid, 0.4 mg vitamin B-12, 50 mg vitamin B-6 (FA/B12/B6, n = 78) or placebo pill (n = 74) for one year. Outcome measures: Cognitive function, measured with neuropsychological tests at baseline and after six and 12 months. Results: Median session attendance at the exercise programmes (25th-75th percentile) was 63% (2%-81%) and median compliance with taking pills (25th-75th percentile) was 100% (99%-100%). Gender was an effect modifier. Intention-to-treat analysis revealed no main intervention effect for either intervention. In women in the WP, attention (Stroop combination task) improved by 0.3 seconds (p = 0.04) and memory (auditory verbal learning test) by 0.04 words (p = 0.06) with each percentage increase in session attendance. In men attending at least 75% of the sessions, the WP improved memory (β 1.5 (95% CI: 0.1 to 3.0) words). Conclusion: The walking programme and/or FA/B12/B6 supplementation were not effective in improving cognition within one year. The walking programme, however, was efficacious in improving memory in men and memory and attention in women with better adherence. Trial registration: International Standard Randomised Controlled Trial Number Register, 19227688, http://www.controlled-trials.com/isrctn/. Chemicals / CAS: Folic Acid, 59-30-3; Vitamin B 12, 68-19-9; Vitamin B 6, 8059-24-3

Preoperative single, high-dose methylprednisolone administration improves postoperative outcomes after colonic surgery. Several randomized studies, including major surgeries, assessed various high-dose steroid regimens; however, evidence about the effect of administration of lower doses on postoperative outcomes in colorectal surgery is not available. The aim of the present study is to determine whether the administration of a single, low dose of dexamethasone before surgery would confer an outcome advantage after colorectal surgery. Thirty patients undergoing colorectal surgery were included in this randomized, double-blind study. Patients received 8 mg dexamethasone or serum physiologic preoperatively. Levels of Interleukin-6 and C-reactive protein, pain scores, postoperative nausea and vomiting, mobilization, complications, hospital stay, and readmissions were compared. Age, sex, indications, and operations were similar in both groups (P > 0.05). C-reactive protein and Interleukin-6 levels increased significantly postoperatively in each group (P < 0.05), but there were no differences between groups when compared (P > 0.05). There were also no significant differences between pain scores, bowel functions, mobilization, hospital stay, complication rates, and readmission rates between the two groups (P > 0.05). Preoperative 8 mg dexamethasone administration has no significant effect on reducing postoperative inflammatory response and also does not improve outcomes of colorectal. surgery.

Background Low back pain (LBP) and neck pain (NP) are a major public health problem with considerable costs for individuals, companies and society. Therefore, prevention is imperative. The Stay@Work study investigates the (cost-)effectiveness of Participatory Ergonomics (PE) to prevent LBP and NP among workers. Methods In a randomised controlled trial (RCT), a total of 5,759 workers working at 36 departments of four companies is expected to participate in the study at baseline. The departments consisting of about 150 workers are pre-stratified and randomised. The control departments receive usual practice and the intervention departments receive PE. Within each intervention department a working group is formed including eight workers, a representative of the management, and an occupational health and safety coordinator. During a one day meeting, the working group follows the steps of PE in which the most important risk factors for LBP and NP, and the most adequate ergonomic measures are identified on the basis of group consensus. The implementation of ergonomic measures at the department is performed by the working group. To improve the implementation process, so-called 'ergocoaches' are trained. The primary outcome measure is an episode of LBP and NP. Secondary outcome measures are actual use of ergonomic measures, physical workload, psychosocial workload, intensity of pain, general health status, sick leave, and work productivity. The cost-effectiveness analysis is performed from the societal and company perspective. Outcome measures are assessed using questionnaires at baseline and after 6 and 12 months. Data on the primary outcome as well as on intensity of pain, sick leave, work productivity, and health care costs are collected every 3 months. Discussion Prevention of LBP and NP is beneficial for workers, employers, and society. If the intervention is proven (cost-)effective, the intervention can have a major impact on LBP and NP prevention and, thereby, on work disability prevention. Results are expected in 2010. Trial registration ISRCTN27472278

Appetite suppressants may be one strategy in the fight against obesity. This study evaluated whether Korean pine nut free fatty acids (FFA) and triglycerides (TG) work as an appetite suppressant. Korean pine nut FFA were evaluated in STC-1 cell culture for their ability to increase cholecystokinin (CCK-8) secretion vs. several other dietary fatty acids from Italian stone pine nut fatty acids, oleic acid, linoleic acid, alpha-linolenic acid, and capric acid used as a control. At 50 μM concentration, Korean pine nut FFA produced the greatest amount of CCK-8 release (493 pg/ml) relative to the other fatty acids and control (46 pg/ml). A randomized, placebo-controlled, double-blind cross-over trial including 18 overweight post-menopausal women was performed. Subjects received capsules with 3 g Korean pine (Pinus koraiensis) nut FFA, 3 g pine nut TG or 3 g placebo (olive oil) in combination with a light breakfast. At 0, 30, 60, 90, 120, 180 and 240 minutes the gut hormones cholecystokinin (CCK-8), glucagon like peptide-1 (GLP-1), peptide YY (PYY) and ghrelin, and appetite sensations were measured. A wash-out period of one week separated each intervention day. CCK-8 was higher 30 min after pine nut FFA and 60 min after pine nut TG when compared to placebo (p < 0.01). GLP-1 was higher 60 min after pine nut FFA compared to placebo (p < 0.01). Over a period of 4 hours the total amount of plasma CCK-8 was 60% higher after pine nut FFA and 22% higher after pine nut TG than after placebo (p < 0.01). For GLP-1 this difference was 25% after pine nut FFA (P < 0.05). Ghrelin and PYY levels were not different between groups. The appetite sensation "prospective food intake" was 36% lower after pine nut FFA relative to placebo (P < 0.05). This study suggests that Korean pine nut may work as an appetite suppressant through an increasing effect on satiety hormones and a reduced prospective food intake. © 2008 Pasman et al; licensee BioMed Central Ltd.

Venous leg ulcers are an important medical issue due to their high incidence in the elderly and the lack of a standard curative approach. Apart from surgical therapy, different medical treatments to effect ulcer wound repair and regeneration are currently being investigated. Sucralfate is a cytoprotective agent employed to prevent or treat several gastrointestinal diseases such as gastroesophageal reflux, gastritis, peptic ulcer, stress ulcer and dyspepsia. In this study we evaluated the efficacy, safety and tolerability of topical sucralfate (SUC-LIS 95) on the healing of chronic venous leg ulcers in 50 patients by a double-blind, placebo-controlled, randomized study. Our results indicated that the daily application of SUC-LIS 95 to non-infected post-phlebitis/vascular ulcers, for a median period of 42.0 days, led to complete healing in 95.6% of patients, against only 10.9% of cases with a matched placebo. A significant improvement was obtained in the SUC-LIS 95-treated patient group with regard to local tissue inflammation as well as pain and burning, and consequently, in ulcer size and the evolution of granulation tissue. Our findings were corroborated for selected patients by the morphological analysis of biopsies obtained before and after treatment. Using ultrastructural analysis we demonstrated that the topical use of SUC-LIS 95 was able to affect neoangiogenesis, increase wound contraction, promote re-epithelialization of the wound area and diminish the inflammatory reaction. Overall, our results indicated that patients with chronic venous ulcers show improvement after the use of topical sucralfate.

Background. Low back pain (LBP) and neck pain (NP) are a major public health problem with considerable costs for individuals, companies and society. Therefore, prevention is imperative. The Stay@Work study investigates the (cost-)effectiveness of Participatory Ergonomics (PE) to prevent LBP and NP among workers. Methods. In a randomised controlled trial (RCT), a total of 5,759 workers working at 36 departments of four companies is expected to participate in the study at baseline. The departments consisting of about 150 workers are pre-stratified and randomised. The control departments receive usual practice and the intervention departments receive PE. Within each intervention department a working group is formed including eight workers, a representative of the management, and an occupational health and safety coordinator. During a one day meeting, the working group follows the steps of PE in which the most important risk factors for LBP and NP, and the most adequate ergonomic measures are identified on the basis of group consensus. The implementation of ergonomic measures at the department is performed by the working group. To improve the implementation process, so-called 'ergocoaches' are trained. The primary outcome measure is an episode of LBP and NP. Secondary outcome measures are actual use of ergonomic measures, physical workload, psychosocial workload, intensity of pain, general health status, sick leave, and work productivity. The cost-effectiveness analysis is performed from the societal and company perspective. Outcome measures are assessed using questionnaires at baseline and after 6 and 12 months. Data on the primary outcome as well as on intensity of pain, sick leave, work productivity, and health care costs are collected every 3 months. Discussion. Prevention of LBP and NP is beneficial for workers, employers, and society. If the intervention is proven (cost-)effective, the intervention can have a major impact on LBP and NP prevention and, thereby, on work disability prevention. Results are expected in 2010. Trial registration. ISRCTN27472278. © 2008 Driessen et al; licensee BioMed Central Ltd.