Continent urinary diversion

During the last decade continent urinary diversion, especially orthotopic bladder substitution has become increasingly popular following radical cystectomy for bladder cancer. In general, if sphincter sparing surgery is possible, orthotopic bladder substitution is performed, if not then continent catheterisable reservoirs are a viable option. Strict patient selection criteria and improved surgical technique have had a positive influence on outcome, not only on survival but also on quality of life issues. It is becoming increasingly obvious, that a nerve sparing surgical technique not only improves sexual function but also continence. In addition, the length of the intestinal segment has an influence on continence and the degree of metabolic consequences, which are discussed in detail. Postoperative surveillance and instruction of patients is of utmost value for good functional results. Overall patient satisfaction and quality of life seem comparable in the various types of continent urinary diversions, and improved when compared to a urinary stoma. Continent urinary diversion offers a good quality of life with few long-term complications and should be considered the treatment of choice in the majority of patients, independent of sex.

Liver transplantation for patients with metastatic endocrine tumors: single-center experience with 15 patients

In contrast to other secondary liver malignancy, orthotopic liver transplantation (OLT) is considered as a treatment modality for nonresectable endocrine liver metastases in selected patients. However, only few series have assessed patient selection criteria and long-term results, and no reports have focused on the impact of new technologies in this regard. Between 1992 and 2004, 28 patients with malignant endocrine tumors underwent evaluation for OLT according to our protocol. Data were entered into a prospective database. During pretransplant evaluation, somatostatin receptor scintigraphy detected extrahepatic metastases not diagnosed in standard imaging in 10 patients. Of them, 3 showed aberrant Ki67 labeling results. One patient was excluded from further evaluation due to severe carcinoid heart. Thus far, 15 patients, 10 men and 5 women, aged 37 to 67 years, were subjected to the transplant procedure (11 deceased donor OLT, 3 living donor liver transplantations, and 1 cluster transplantation). Four patients died during the hospital treatment. The median follow-up of the discharged patients was 60.8 months. The actuarial patient survival was 78.3% at 1 year and 67.2% at 5 years. The actuarial 1-, 2-, and 5-year tumor-free survival amounted to 69.4%, 48.3%, and 48.3%, respectively. Two patients underwent surgery for isolated tumor recurrence. In 2 patients, peptide receptor radiotherapy was carried out because of multilocular recurrent disease. In conclusion, liver transplantation is a realistic therapeutic option for highly selected patients with hepatic metastases of endocrine tumors. Our strategy, which implements strict pretransplant selection and aggressive surgical approach, in case of disease recurrence, in addition to systemic radiopeptide treatment, led to an excellent long-term survival cure, however, is unlikely to be achieved.

Grey literature in meta-analyses of randomized trials of health care interventions

BACKGROUND: The inclusion of grey literature (i.e. literature that has not been formally published) in systematic reviews may help to overcome some of the problems of publication bias, which can arise due to the selective availability of data. OBJECTIVES: To review systematically research studies, which have investigated the impact of grey literature in meta-analyses of randomized trials of health care interventions. SEARCH STRATEGY: We searched the Cochrane Methodology Register (The Cochrane Library Issue 3, 2005), MEDLINE (1966 to 20 May 2005), the Science Citation Index (June 2005) and contacted researchers who may have carried out relevant studies. SELECTION CRITERIA: A study was considered eligible for this review if it compared the effect of the inclusion and exclusion of grey literature on the results of a cohort of meta-analyses of randomized trials. DATA COLLECTION AND ANALYSIS: Data were extracted from each report independently by two reviewers. The main outcome measure was an estimate of the impact of trials from the grey literature on the pooled effect estimates of the meta-analyses. Information was also collected on the area of health care, the number of meta-analyses, the number of trials, the number of trial participants, the year of publication of the trials, the language and country of publication of the trials, the number and type of grey and published literature, and methodological quality. MAIN RESULTS: Five studies met the inclusion criteria. All five studies showed that published trials showed an overall greater treatment effect than grey trials. This difference was statistically significant in one of the five studies. Data could be combined for three of the five studies. This showed that, on average, published trials showed a 9% greater treatment effect than grey trials (ratio of odds ratios for grey versus published trials 1.09; 95% CI 1.03-1.16). Overall there were more published trials included in the meta-analyses than grey trials (median 224 (IQR 108-365) versus 45(IQR 40-102)). Published trials had more participants on average. The most common types of grey literature were abstracts (55%) and unpublished data (30%). There is limited evidence to show whether grey trials are of poorer methodological quality than published trials. AUTHORS' CONCLUSIONS: This review shows that published trials tend to be larger and show an overall greater treatment effect than grey trials. This has important implications for reviewers who need to ensure they identify grey trials, in order to minimise the risk of introducing bias into their review.

Intravenous magnesium for acute myocardial infarction

BACKGROUND: Mortality and morbidity from acute myocardial infarction (AMI) remain high. Intravenous magnesium started early after the onset of AMI is thought to be a promising adjuvant treatment. Conflicting results from earlier trials and meta-analyses warrant a systematic review of available evidence. OBJECTIVES: To examine the effect of intravenous magnesium versus placebo on early mortality and morbidity. SEARCH STRATEGY: We searched CENTRAL (The Cochrane Library Issue 3, 2006), MEDLINE (January 1966 to June 2006) and EMBASE (January 1980 to June 2006), and the Chinese Biomedical Disk (CBM disk) (January 1978 to June 2006). Some core Chinese medical journals relevant to the cardiovascular field were hand searched from their starting date to the first-half year of 2006. SELECTION CRITERIA: All randomized controlled trials that compared intravenous magnesium with placebo in the presence or absence of fibrinolytic therapy in addition to routine treatment were eligible if they reported mortality and morbidity within 35 days of AMI onset. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the trial quality and extracted data using a standard form. Odds ratio (OR) were used to pool the effect if appropriate. Where heterogeneity of effects was found, clinical and methodological sources of this were explored. MAIN RESULTS: For early mortality where there was evidence of heterogeneity, a fixed-effect meta-analysis showed no difference between magnesium and placebo groups (OR 0.99, 95%CI 0.94 to 1.04), while a random-effects meta-analysis showed a significant reduction comparing magnesium with placebo (OR 0.66, 95% CI 0.53 to 0.82). Stratification by timing of treatment (< 6 hrs, 6+ hrs) reduced heterogeneity, and in both fixed-effect and random-effects models no significant effect of magnesium was found. In stratified analyses, early mortality was reduced for patients not treated with thrombolysis (OR=0.73, 95% CI 0.56 to 0.94 by random-effects model) and for those treated with less than 75 mmol of magnesium (OR=0.59, 95% CI 0.49 to 0.70) in the magnesium compared with placebo groups.Meta-analysis for the secondary outcomes where there was no evidence of heterogeneity showed reductions in the odds of ventricular fibrillation (OR=0.88, 95% CI 0.81 to 0.96), but increases in the odds of profound hypotension (OR=1.13, 95% CI 1.09 to 1.19) and bradycardia (OR=1.49, 95% CI 1.26 to 1.77) comparing magnesium with placebo. No difference was observed for heart block (OR=1.05, 95% CI 0.97-1.14). For those outcomes where there was evidence of heterogeneity, meta-analysis with both fixed-effect and random-effects models showed that magnesium could decrease ventricular tachycardia (OR=0.45, 95% CI 0.31 to 0.66 by fixed-effect model; OR=0.40, 95% CI 0.19 to 0.84 by random-effects model) and severe arrhythmia needing treatment or Lown 2-5 (OR=0.72, 95% CI 0.60 to 0.85 by fixed-effect model; OR=0.51, 95% CI 0.33 to 0.79 by random-effects model) compared with placebo. There was no difference on the effect of cardiogenic shock between the two groups. AUTHORS' CONCLUSIONS: Owing to the likelihood of publication bias and marked heterogeneity of treatment effects, it is essential that the findings are interpreted cautiously. From the evidence reviewed here, we consider that: (1) it is unlikely that magnesium is beneficial in reducing mortality both in patients treated early and in patients treated late, and in patients already receiving thrombolytic therapy; (2) it is unlikely that magnesium will reduce mortality when used at high dose (>=75 mmol); (3) magnesium treatment may reduce the incidence of ventricular fibrillation, ventricular tachycardia, severe arrhythmia needing treatment or Lown 2-5, but it may increase the incidence of profound hypotension, bradycardia and flushing; and (4) the areas of uncertainty regarding the effect of magnesium on mortality remain the effect of low dose treatment (< 75 mmol) and in patients not treate...

Full publication of results initially presented in abstracts

BACKGROUND: Abstracts of presentations at scientific meetings are usually available only in conference proceedings. If subsequent full publication of abstract results is based on the magnitude or direction of study results, publication bias may result. Publication bias, in turn, creates problems for those conducting systematic reviews or relying on the published literature for evidence. OBJECTIVES: To determine the rate at which abstract results are subsequently published in full, and the time between meeting presentation and full publication. To assess the association between study characteristics and full publication. SEARCH STRATEGY: We searched MEDLINE, EMBASE, The Cochrane Library, Science Citation Index, reference lists, and author files. Date of most recent search: June 2003. SELECTION CRITERIA: We included all reports that examined the subsequent full publication rate of biomedical results initially presented as abstracts or in summary form. Follow-up of abstracts had to be at least two years. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data. We calculated the weighted mean full publication rate and time to full publication. Dichotomous variables were analyzed using relative risk and random effects models. We assessed time to publication using Kaplan-Meier survival analyses. MAIN RESULTS: Combining data from 79 reports (29,729 abstracts) resulted in a weighted mean full publication rate of 44.5% (95% confidence interval (CI) 43.9 to 45.1). Survival analyses resulted in an estimated publication rate at 9 years of 52.6% for all studies, 63.1% for randomized or controlled clinical trials, and 49.3% for other types of study designs.'Positive' results defined as any 'significant' result showed an association with full publication (RR = 1.30; CI 1.14 to 1.47), as did 'positive' results defined as a result favoring the experimental treatment (RR =1.17; CI 1.02 to 1.35), and 'positive' results emanating from randomized or controlled clinical trials (RR = 1.18, CI 1.07 to 1.30).Other factors associated with full publication include oral presentation (RR = 1.28; CI 1.09 to 1.49); acceptance for meeting presentation (RR = 1.78; CI 1.50 to 2.12); randomized trial study design (RR = 1.24; CI 1.14 to 1.36); and basic research (RR = 0.79; CI 0.70 to 0.89). Higher quality of abstracts describing randomized or controlled clinical trials was also associated with full publication (RR = 1.30, CI 1.00 to 1.71). AUTHORS' CONCLUSIONS: Only 63% of results from abstracts describing randomized or controlled clinical trials are published in full. 'Positive' results were more frequently published than not 'positive' results.

Success rate and efficiency of activator treatment

In a retrospective multicentre study, the success rate and efficiency of activator treatment were analysed. All patients from two University clinics (Giessen, Germany and Berne, Switzerland) that fulfilled the selection criteria (Class II division 1 malocclusion, activator treatment, no aplasia, no extraction of permanent teeth, no syndromes, no previous orthodontic treatment except transverse maxillary expansion, full available records) were included in the study. The subject material amounted to 222 patients with a mean age of 10.6 years. Patient records, lateral head films, and dental casts were evaluated. Treatment was classified as successful if the molar relationship improved by at least half to three-fourths cusp width depending on whether or not the leeway space was used during treatment. Group comparisons were carried out using Wilcoxon two-sample and Kruskal-Wallis tests. For discrete data, chi-square analysis was used and Fisher's exact test when the sample size was small. Stepwise logistic regression was also employed. The success rate was 64 per cent in Giessen and 66 per cent in Berne. The only factor that significantly (P < 0.001) influenced treatment success was the level of co-operation. In approximately 27 per cent of the patients at both centres, the post-treatment occlusion was an 'ideal' Class I. In an additional 38 per cent of the patients, marked improvements in occlusal relationships were found. In subjects with Class II division 1 malocclusions, in which orthodontic treatment is performed by means of activators, a marked improvement of the Class II dental arch relationships can be expected in approximately 65 per cent of subjects. Activator treatment is more efficient in the late than in the early mixed dentition.

Immediate and early non-occlusal loading of Straumann implants with a chemically modified surface (SLActive) in the posterior mandible and maxilla: interim results from a prospective multicenter randomized-controlled study

OBJECTIVE: Immediate and early loading of dental implants can simplify treatment and increase overall patient satisfaction. The purpose of this 3-year prospective randomized-controlled multicenter study was to assess the differences in survival rates and bone level changes between immediately and early-loaded implants with a new chemically modified surface (SLActive). This investigation shows interim results obtained after 5 months. MATERIAL AND METHODS: Patients > or =18 years of age missing at least one tooth in the posterior maxilla or mandible were enrolled in the study. Following implant placement, patients received a temporary restoration either on the day of surgery (immediate loading) or 28-34 days after surgery (early loading); restorations consisted of single crowns or two to four unit fixed dental prostheses. Permanent restorations were placed 20-23 weeks following surgery. The primary efficacy variable was change in bone level (assessed by standardized radiographs) from baseline to 5 months; secondary variables included implant survival and success rates. RESULTS: A total of 266 patients were enrolled (118 males and 148 females), and a total of 383 implants were placed (197 and 186 in the immediate and early loading groups, respectively). Mean patient age was 46.3+/-12.8 years. After 5 months, implant survival rates were 98% in the immediate group and 97% in the early group. Mean bone level change from baseline was 0.81+/-0.89 mm in the immediate group and 0.56+/-0.73 mm in the early group (P<0.05). Statistical analysis revealed a significant center effect (P<0.0001) and a significant treatment x center interaction (P=0.008). CONCLUSIONS: The results suggested that Straumann implants with an SLActive can be used predictably in time-critical (early or immediate) loading treatment protocols when appropriate patient selection criteria are observed. The mean bone level changes observed from baseline to 5 months (0.56 and 0.81 mm) corresponded to physiological observations from other studies, i.e., were not clinically significant. The presence of a significant center effect and treatment x center interaction indicated that the differences in bone level changes between the two groups were center dependent.

Effects of diabetes mellitus on periodontal and peri-implant conditions: update on associations and risks

OBJECTIVES: To review the evidence for the association between diabetes and periodontal and peri-implant conditions and the impact of periodontal therapy in subjects with diabetes. MATERIAL AND METHODS: A search of MEDLINE-PubMed was performed up to and including December 2007. The search was limited to clinical studies published in English. Publications on animal studies were excluded. The selection criteria included all levels of available evidence. RESULTS: Evidence on the association between diabetes and periodontitis supports the concept of increased severity but not extent of periodontitis in subjects with poorly controlled diabetes. Subjects with controlled diabetes do not show an increase in extent and severity of periodontitis. Periodontitis is associated with poor glycaemic control and diabetes-related complications. It is inconclusive that periodontal therapy with or without the use of antibiotics results in improvements of glycaemic control and of markers of systemic inflammation. Evidence is lacking to indicate that implant therapy in subjects with diabetes yields long-term outcomes comparable with those of non-diabetic subjects. CONCLUSIONS: Poorly controlled diabetes may be considered a risk factor for increased severity of periodontitis. The effects of periodontal therapy on glycaemic control and systemic inflammation is not proven beyond doubt and need to be confirmed in large-scale randomized-controlled clinical trials.

A retrospective analysis of patients referred for implant placement to a specialty clinic: indications, surgical procedures, and early failures

Purpose: This retrospective study analyzed the pool of patients referred for treatment with dental implants over a 3-year period in a referral specialty clinic. Materials and Methods: All patients receiving dental implants between 2002 and 2004 in the Department of Oral Surgery and Stomatology, University of Bern, were included in this retrospective study. Patients were analyzed according to age, gender, indications for implant therapy, location of implants, and type and length of implants placed. A cumulative logistic regression analysis was performed to identify and analyze potential risk factors for complications or failures. Results: A total of 1,206 patients received 1,817 dental implants. The group comprised 573 men and 633 women with a mean age of 55.2 years. Almost 60% of patients were age 50 or older. The most frequent indication for implant therapy was single-tooth replacement in the maxilla (522 implants or 28.7%). A total of 726 implants (40%) were inserted in the esthetically demanding region of the anterior maxilla. For 939 implants (51.7%), additional bone-augmentation procedures were required. Of these, ridge augmentation with guided bone regeneration was performed more frequently than sinus grafting. Thirteen complications leading to early failures were recorded, resulting in an early failure rate of 0.7%. The regression analysis failed to identify statistically significant failure etiologies for the variables assessed. Conclusions: From this study it can be concluded that patients referred to a specialty clinic for implant placement were more likely to be partially edentulous and over 50 years old. Single-tooth replacement was the most frequent indication (> 50%). Similarly, additional bone augmentation was indicated in more than 50% of cases. Adhering to strict patient selection criteria and a standardized surgical protocol, an early failure rate of 0.7% was experienced in this study population

Psychosocial interventions for smoking cessation in patients with coronary heart disease

BACKGROUND: Quitting smoking improves prognosis after a cardiac event, but many patients continue to smoke, and improved cessation aids are urgently required. OBJECTIVES: To assess the effectiveness of psychosocial interventions such as behavioural therapeutic intervention, telephone support and self-help interventions in helping people with coronary heart disease (CHD) to quit smoking. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (issue 2 2003), MEDLINE, EMBASE, PsycINFO and PSYNDEX were searched from the start of the database to August 2003. Results were supplemented by cross-checking references, and handsearches in selected journals and systematic reviews. SELECTION CRITERIA: Randomised controlled studies (RCTs) in patients with CHD with a minimum follow-up of 6 months. After initial selection of the studies three trials with methodological flaws (e.g. high drop out) were excluded. DATA COLLECTION AND ANALYSIS: Abstinence rates were computed according to an intention to treat analysis if possible, or if not on follow-up results only. MAIN RESULTS: We found 16 RCTs meeting inclusion criteria. Interventions consist of behavioural therapeutic approaches, telephone support and self-help material and were either focused on smoking cessation alone or addressed several risk factors. The trials mostly included older male patients with CHD, predominantly myocardial infarction. Overall there was a positive effect of interventions on abstinence after 6 to 12 months (odds ratio (OR) 1.66, 95% confidence interval (CI) 1.25 to 2.22), but substantial heterogeneity between trials. Studies with validated assessment of smoking status at follow-up had lower efficacy (OR 1.44, 95% CI 0.99 to 2.11) than non-validated trials (OR 1.92, 95% CI 1.26 to 2.93). Studies were clustered by intervention strategy and intensity of the intervention. Clustering reduced heterogeneity, although many trials used more than one type of intervention. The ORs for different strategies were similar (behavioural therapies OR 1.69, 95% CI 1.33 to 2.14; telephone support OR 1.58, 95% CI 1.28 to 1.97; self-help OR 1.48, 95% CI 1.11 to 1.96). More intense interventions showed increased quit rates (OR 1.98, 95% CI 1.49 to 2.65) whereas brief interventions did not appear effective (OR 0.92, 95% CI 0.70 to 1.22). Two trials had longer term follow-up, and did not show any benefits after 5 years. AUTHORS' CONCLUSIONS: Psychosocial smoking cessation interventions are effective in promoting abstinence at 1 year, provided they are of sufficient duration. Further studies, with longer follow-up, should compare different psychosocial intervention strategies, or the addition of a psychosocial intervention strategy to pharmacological therapy (e.g. nicotine replacement therapy) compared with pharmacological treatment alone.

Systemic prokinetic pharmacologic treatment for postoperative adynamic ileus following abdominal surgery in adults

BACKGROUND: Postoperative adynamic bowel atony interferes with recovery following abdominal surgery. Prokinetic pharmacologic drugs are widely used to accelerate postoperative recovery. OBJECTIVES: To evaluate the benefits and harms of systemic acting prokinetic drugs to treat postoperative adynamic ileus in patients undergoing abdominal surgery. SEARCH STRATEGY: Trials were identified by computerised searches of the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and the Cochrane Colorectal Cancer Group specialised register. The reference lists of included trials and review articles were tracked and authors contacted. SELECTION CRITERIA: Randomised controlled parallel-group trials (RCT) comparing the effect of systemically acting prokinetic drugs against placebo or no intervention. DATA COLLECTION AND ANALYSIS: Four reviewers independently extracted the data and assessed trial quality. Trial authors were contacted for additional information if needed. MAIN RESULTS: Thirty-nine RCTs met the inclusion criteria contributing a total of 4615 participants. Most trials enrolled a small number of patients and showed moderate to poor (reporting of) methodological quality, in particular regarding allocation concealment and intention-to-treat analysis. Fifteen systemic acting prokinetic drugs were investigated and ten comparisons could be summarized. Six RCTs support the effect of Alvimopan, a novel peripheral mu receptor antagonist. However, the trials do not meet reporting guidelines and the drug is still in an investigational stage. Erythromycin showed homogenous and consistent absence of effect across all included trials and outcomes. The evidence is insufficient to recommend the use of cholecystokinin-like drugs, cisapride, dopamine-antagonists, propranolol or vasopressin. Effects are either inconsistent across outcomes, or trials are too small and often of poor methodological quality. Cisapride has been withdrawn from the market due to adverse cardiac events in many countries. Intravenous lidocaine and neostigmine might show a potential effect, but more evidence on clinically relevant outcomes is needed. Heterogeneity among included trials was seen in 10 comparisons. No major adverse drug effects were evident. AUTHORS' CONCLUSIONS: Alvimopan may prove to be beneficial but proper judgement needs adherence to reporting standards. Further trials are needed on intravenous lidocaine and neostigmine. The remaining drugs can not be recommended due to lack of evidence or absence of effect.

Erythropoietin or Darbepoetin for patients with cancer--meta-analysis based on individual patient data

BACKGROUND: Erythropoiesis-stimulating agents (ESAs) reduce anemia in cancer patients and may improve quality of life, but there are concerns that ESAs might increase mortality. OBJECTIVES: Our objectives were to examine the effect of ESAs and identify factors that modify the effects of ESAs on overall survival, progression free survival, thromboembolic and cardiovascular events as well as need for transfusions and other important safety and efficacy outcomes in cancer patients. SEARCH STRATEGY: We searched the Cochrane Library, Medline, Embase and conference proceedings for eligible trials. Manufacturers of ESAs were contacted to identify additional trials. SELECTION CRITERIA: We included randomized controlled trials comparing epoetin or darbepoetin plus red blood cell transfusions (as necessary) versus red blood cell transfusions (as necessary) alone, to prevent or treat anemia in adult or pediatric cancer patients with or without concurrent antineoplastic therapy. DATA COLLECTION AND ANALYSIS: We performed a meta-analysis of randomized controlled trials comparing epoetin alpha, epoetin beta or darbepoetin alpha plus red blood cell transfusions versus transfusion alone, for prophylaxis or therapy of anemia while or after receiving anti-cancer treatment. Patient-level data were obtained and analyzed by independent statisticians at two academic departments, using fixed-effects and random-effects meta-analysis. Analyses were according to the intention-to-treat principle. Primary endpoints were on study mortality and overall survival during the longest available follow-up, regardless of anticancer treatment, and in patients receiving chemotherapy. Tests for interactions were used to identify differences in effects of ESAs on mortality across pre-specified subgroups. The present review reports only the results for the primary endpoint. MAIN RESULTS: A total of 13933 cancer patients from 53 trials were analyzed, 1530 patients died on-study and 4993 overall. ESAs increased on study mortality (combined hazard ratio [cHR] 1.17; 95% CI 1.06-1.30) and worsened overall survival (cHR 1.06; 95% CI 1.00-1.12), with little heterogeneity between trials (I(2) 0%, p=0.87 and I(2) 7.1%, p=0.33, respectively). Thirty-eight trials enrolled 10441 patients receiving chemotherapy. The cHR for on study mortality was 1.10 (95% CI 0.98-1.24) and 1.04; 95% CI 0.97-1.11) for overall survival. There was little evidence for a difference between trials of patients receiving different cancer treatments (P for interaction=0.42). AUTHORS' CONCLUSIONS: ESA treatment in cancer patients increased on study mortality and worsened overall survival. For patients undergoing chemotherapy the increase was less pronounced, but an adverse effect could not be excluded.

Prophylactic antibiotics or G-CSF for the prevention of infections and improvement of survival in cancer patients undergoing chemotherapy

BACKGROUND: Febrile neutropenia (FN) and other infectious complications are some of the most serious treatment-related toxicities of chemotherapy for cancer, with a mortality rate of 2% to 21%. The two main types of prophylactic regimens are granulocyte (G-CSF) or granulocyte-macrophage colony stimulating factors (GM-CSF); and antibiotics, frequently quinolones or cotrimoxazole. Important current guidelines recommend the use of colony stimulating factors when the risk of febrile neutropenia is above 20% but they do not mention the use of antibiotics. However, both regimens have been shown to reduce the incidence of infections. Since no systematic review has compared the two regimens, a systematic review was undertaken. OBJECTIVES: To compare the effectiveness of G-CSF or GM-CSF with antibiotics in cancer patients receiving myeloablative chemotherapy with respect to preventing fever, febrile neutropenia, infection, infection-related mortality, early mortality and improving quality of life. SEARCH STRATEGY: We searched The Cochrane Library, MEDLINE, EMBASE, databases of ongoing trials, and conference proceedings of the American Society of Clinical Oncology and the American Society of Hematology (1980 to 2007). We planned to include both full-text and abstract publications. SELECTION CRITERIA: Randomised controlled trials comparing prophylaxis with G-CSF or GM-CSF versus antibiotics in cancer patients of all ages receiving chemotherapy or bone marrow or stem cell transplantation were included for review. Both study arms had to receive identical chemotherapy regimes and other supportive care. DATA COLLECTION AND ANALYSIS: Trial eligibility and quality assessment, data extraction and analysis were done in duplicate. Authors were contacted to obtain missing data. MAIN RESULTS: We included two eligible randomised controlled trials with 195 patients. Due to differences in the outcomes reported, the trials could not be pooled for meta-analysis. Both trials showed non-significant results favouring antibiotics for the prevention of fever or hospitalisation for febrile neutropenia. AUTHORS' CONCLUSIONS: There is no evidence for or against antibiotics compared to G(M)-CSFs for the prevention of infections in cancer patients.

Doxycycline for osteoarthritis of the knee or hip

BACKGROUND: Osteoarthritis is a chronic joint disease that involves degeneration of articular cartilage. Pre-clinical data suggest that doxycycline might act as a disease-modifying agent for the treatment of osteoarthritis, with the potential to slow cartilage degeneration. OBJECTIVES: To examine the effects of doxycycline compared with placebo or no intervention on pain and function in patients with osteoarthritis of the hip or knee. SEARCH STRATEGY: We searched CENTRAL ( The Cochrane Library 2008, issue 3), MEDLINE, EMBASE and CINAHL up to 28 July 2008, checked conference proceedings, reference lists, and contacted authors. SELECTION CRITERIA: We included studies if they were randomised or quasi-randomised controlled trials that compared doxycycline at any dosage and any formulation with placebo or no intervention in patients with osteoarthritis of the knee or hip. DATA COLLECTION AND ANALYSIS: We extracted data in duplicate. We contacted investigators to obtain missing outcome information. We calculated differences in means at follow-up between experimental and control groups for continuous outcomes and risk ratios for binary outcomes. MAIN RESULTS: We found one randomised controlled trial that compared doxycycline with placebo in 431 obese women. After 30 months of treatment, clinical outcomes were similar between the two treatment groups, with a mean difference of -0.20 cm (95% confidence interval (CI) -0.77 to 0.37 cm) on a visual analogue scale from 0 to 10 cm for pain and -1.10 units (95% CI -3.86 to 1.66) for function on the WOMAC disability subscale, which ranges from 17 to 85. These differences correspond to clinically irrelevant effect sizes of -0.08 and -0.09 standard deviation units for pain and function, respectively. The difference in changes in minimum joint space narrowing was in favour of doxycycline (-0.15 mm, 95% CI -0.28 to -0.02 mm), which corresponds to a small effect size of -0.23 standard deviation units. More patients withdrew from the doxycycline group compared with placebo due to adverse events (risk ratio 1.69, 95% CI 1.03 to 2.75). AUTHORS' CONCLUSIONS: The symptomatic benefit of doxycycline is minimal to non-existent. The small benefit in terms of joint space narrowing is of questionable clinical relevance and outweighed by safety problems. Doxycycline should not be recommended for the treatment of osteoarthritis of the knee or hip.

S-Adenosylmethionine for osteoarthritis of the knee or hip

BACKGROUND: Osteoarthritis is the most common form of joint disease and the leading cause of pain and disability in the elderly. S-Adenosylmethionine may be a viable treatment option but the evidence about its effectiveness and safety is equivocal. OBJECTIVES: We set out to compare S-Adenosylmethionine (SAMe) with placebo or no specific intervention in terms of effects on pain and function and safety outcomes in patients with knee or hip osteoarthritis. SEARCH STRATEGY: We searched CENTRAL, MEDLINE, EMBASE, CINAHL and PEDro up to 5 August 2008, checked conference proceedings and reference lists, and contacted authors. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials that compared SAMe at any dosage and in any formulation with placebo or no intervention in patients with osteoarthritis of the knee or hip. DATA COLLECTION AND ANALYSIS: Two independent authors extracted data using standardised forms. We contacted investigators to obtain missing outcome information. We calculated standardised mean differences (SMDs) for pain and function, and relative risks for safety outcomes. We combined trials using inverse-variance random-effects meta-analysis. MAIN RESULTS: Four trials including 656 patients were included in the systematic review, all compared SAMe with placebo. The methodological quality and the quality of reporting were poor. For pain, the analysis indicated a small SMD of -0.17 (95% CI -0.34 to 0.01), corresponding to a difference in pain scores between SAMe and placebo of 0.4 cm on a 10 cm VAS, with no between trial heterogeneity (I(2) = 0). For function, the analysis suggested a SMD of 0.02 (95% CI -0.68 to 0.71) with a moderate degree of between-trial heterogeneity (I2 = 54%). The meta-analyses of the number of patients experiencing any adverse event, and withdrawals or drop-outs due to adverse events, resulted in relative risks of 1.27 (95% CI 0.94 to 1.71) and 0.94 (95% CI 0.48 to 1.86), respectively, but confidence intervals were wide and tests for overall effect were not significant. No trial provided information concerning the occurrence of serious adverse events. AUTHORS' CONCLUSIONS: The current systematic review is inconclusive, hampered by the inclusion of mainly small trials of questionable quality. The effects of SAMe on both pain and function may be potentially clinically relevant and, although effects are expected to be small, deserve further clinical evaluation in adequately sized randomised, parallel-group trials in patients with knee or hip osteoarthritis. Meanwhile, routine use of SAMe should not be advised.