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PubMed2003

Evidence-based practice in rural and remote clinical practice: where is the evidence?

OBJECTIVE: To critically review the evidence regarding barriers to implementing research findings in rural and remote settings, and the ways those barriers have been addressed. DESIGN: A systematic review that included searching several electronic databases, Internet sites and reference lists of relevant articles, assessment of methodological quality of the studies, and data extraction and analysis where possible. Eligibility for the review was not limited by study design. SETTINGS/PARTICIPANTS: Studies that reported on: (1) barriers to the implementation of evidence by health professionals in rural and remote areas, or (2) interventions for implementing evidence-based practice or an element of evidence-based practice in rural and remote areas. RESULTS: There were no experimental data available on the implementation of research findings in rural and remote clinical settings. The small amounts of empirical research undertaken (surveys) showed that some of the problems experienced by general practitioners were exacerbated by rural and remote location, particularly with relation to isolation, lack of time and locum cover, and poor information technology infrastructure. CONCLUSION: There is a paucity of empirical literature on implementing evidence-based practice in rural and remote settings. This is in contrast to the large amount of literature available on implementing evidence in other clinical settings. A clear finding from the literature was that getting evidence into practice needs to be context-specific and yet very little research has been conducted into the rural and remote context. Research is needed into how evidence can be implemented in contextually specific ways in rural and remote areas.

Data Interpretation, Statistical↗
PubMed2000

Multidisciplinary team interventions for delirium in patients with chronic cognitive impairment.

BACKGROUND: Delirium is common in hospitalized elderly people. In the frail elderly, delirium may occur in 60% of those hospitalized. In the cognitively impaired, 45% have been shown to develop delirium and these patients have longer lengths of stay and a higher rate of complications which, amongst other things, together contribute to an increase in cost of care. The combination of being elderly and chronically cognitively impaired leads to a high risk of delirium with the associated increased risk of prolonged hospital stay, complications, and poor outcomes. The management of delirium has commonly been multifaceted - the primary emphasis has always been on the diagnosis and therapy of the precipitating factors, but as this may not be immediately resolved, symptomatic and supportive care may become of major importance. OBJECTIVES: The objective of this review is to assess the available evidence for the effectiveness, if any, of multidisciplinary team interventions in the coordinated care of patients with delirium superimposed on an underlying chronic cognitive impairment compared with the usual care of older cognitively impaired patients. SEARCH STRATEGY: The Cochrane Controlled Trials Register (Cochrane Library, up to and including Issue 1, 1998) was searched using the terms 'delirium, controlled trial, cognitive'. MEDLINE, EMBASE and Psychlit (Ovid via Winspirs up to Feb 1998) were also searched with the same terms. Other sources including personal communications, ongoing trials, conference proceedings, handsearching and reference lists of published papers and books were all searched for relevant randomized controlled trials. The total yield from searching was 157 from which 8 (eight) were retained for consideration in the review. SELECTION CRITERIA: From the initial search yields, all randomised controlled trials involving the management of elderly patients with delirium were identified. A single reviewer (AMB) discarded irrelevant publications based on the title of the publication and its abstract. In the event that the article could possibly be relevant, it was retrieved for further assessment. All references were compiled in a list with a commentary on type of article, eg review, prospective study etc and this was independently considered by the second reviewer (RR) who agreed to review all randomised controlled studies reported on patients with delirium. Selection for possible inclusion in this review was then made on the basis of the participants reported as having chronic cognitive impairment, who then developed incident delirium and were randomly assigned to either coordinated multidisciplinary care or usual care. The outcomes of interest were length of stay in hospital, morbidity (including complications), patient distress & impact on care environment, mortality, discharge arrangements and follow-up including assessment of cognitive function at 6 months. Studies in which patients with chronic cognitive impairment or dementia, managed for incident delirium, according to ICD 9 criteria (see note) were considered eligible for inclusion in the review. Studies of risk factors and non-randomized studies were excluded. Note: this classification has been widely utilised throughout the English speaking medical literature over the past 20 years: ICD 10 is still being incorporated into clinical coding systems and has not been utilised in studies published in 1996. (ABSTRACT TRUNCATED)

Delirium↗
PubMed1998

Proteins of rat serum: I. Establishing a reference two-dimensional electrophoresis map by immunodetection and microbore high performance liquid chromatography-electrospray mass spectrometry.

In the present investigation, we have identified 56 major spots, or spot rows, corresponding to 22 proteins, in the 2-DE pattern of adult male rats. This was done mainly by applying two complementary techniques, namely immunoblotting and high performance liquid chromatography-mass spectrometry (HPLC-MS) peptide mapping. Glycoproteins were characterized by affinity blotting with six lectins. We have also detailed how rat serum differs from human serum in two main respects: (i) relative abundance of individual proteins, which amounts in some cases to a complete absence in either sample, and (ii) varying molecular parameters for homologous proteins. It was thus possible to establish a first-generation reference map of rat serum proteins, which can be accessed through http://weber.u.washington.edu/ruedilab/aebersold++ +.html. We hope the present database will be a useful reference for the evaluation of changes in serum protein distribution in the course of pharmacological and toxicological studies. The recognition of species-specific proteins appears of special relevance in this respect.

Animals↗
PubMed2000

Deoxyribonuclease for cystic fibrosis.

BACKGROUND: Recombinant human deoxyribonuclease is currently used to treat pulmonary disease (the major cause of morbidity and mortality) in cystic fibrosis. OBJECTIVES: To determine whether the use of recombinant human deoxyribonuclease in cystic fibrosis is associated with improved mortality and morbidity as compared to placebo and to identify any adverse events associated with its use. To compare the efficacy of recombinant human deoxyribonuclease with other mucolytics. SEARCH STRATEGY: The Cochrane Cystic Fibrosis and Genetic Disorders Group specialist trials register which comprises references identified from comprehensive electronic database searches, hand searching relevant journals and abstracts from conferences. The company producing recombinant human deoxyribonuclease was also contacted. Date of the most recent search of the Group's specialised register: November 1999. SELECTION CRITERIA: All randomised and quasi-randomised trials where recombinant human deoxyribonuclease was compared to either placebo, standard therapy or another mucolytic for any duration, dose regimen and age of patient with cystic fibrosis of any disease severity. DATA COLLECTION AND ANALYSIS: Trials were independently assessed for inclusion criteria, methodological quality and data extraction by the two reviewers. Comparisons were between recombinant human deoxyribonuclease and placebo and recombinant human deoxyribonuclease and other mucolytics. The following outcomes were recorded: Mean % change from baseline in forced vital capacity (FVC), forced expiratory voloume at one second (FEV1) and weight, mean number of respiratory tract exacerbations, days intravenous and oral antibiotics used, mean number of days as inpatient, number of deaths, adverse events and the cost of therapy. MAIN RESULTS: Seven primary clinical trials were identified, totalling 1710 patients. Two further studies examined the health care cost of patients from one of the clinical trials. No eligible studies compared recombinant human deoxyribonuclease to another mucolytic. Five trials presented outcomes at up to one month, one at three months and one at six months. No reduction in mortality for treated patients was identified (Relative Risk (RR) at six month 1.01, 95%Confidence Interval (CI) 0.09, 11.11). Lung function improved to a greater extent in the treated groups (at six months Weighted Mean Difference (WMD) FEV1 5.7, 95%CI 4.18, 7.23, at three months 7.3, 95%CI 4.04, 10.65). Pooled data from the five trials of up to one month gave WMD 9.2 95%CI 0.93, 17. 6 although there was significant heterogeneity). Recombinant human deoxyribonuclease was well tolerated with no excess of serious adverse events (RR haemoptysis 0.89, 95%CI 0.54, 1.45, pneumothorax 0.97 95%CI 0.19, 4.96). Voice alteration was, however, reported more frequently in the treated groups (RR 2.33 95%CI 1.38, 3.93). No study analysed our pre-defined outcome measure for respiratory exacerbations and insufficient data was available to analyse differences in antibiotic treatment, inpatient stay and quality of life. REVIEWER'S CONCLUSIONS: Studies are of insufficient duration to identify a reduction in mortality or number of respiratory exacerbations. Further trials are required to answer these important questions. Recombinant human deoxyribonuclease therapy is associated with an improvement in lung function after six months treatment, but it is not possible to assess whether this effect on lung function is sustained in the long-term. No studies were identified that compared recombinant human deoxyribonuclease to another mucolytic.

Cystic Fibrosis↗
PubMed2001

Local treatments for cutaneous warts.

BACKGROUND: Viral warts caused by the human papilloma virus represent one of the most common diseases of the skin. Any area of skin can be affected although the hands and feet are by far the commonest sites. A very wide range of local treatments are available. OBJECTIVES: To assess the effects of different local treatments for cutaneous, non-genital warts in healthy people. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (March 1999), the Skin Group trials register (March 1999), MEDLINE (1966 to August 2000), EMBASE (1980 to August 2000) and a number of other key biomedical and health economics databases. In addition the cited references of all trials identified and key review articles were searched. Pharmaceutical companies involved in local treatments for warts and experts in the field were contacted. SELECTION CRITERIA: Randomized controlled trials of local treatments for cutaneous non-genital viral warts in immunocompetent human hosts were included. DATA COLLECTION AND ANALYSIS: Study selection and assessment of methodological quality were carried out by two independent reviewers. MAIN RESULTS: Forty-nine trials were identified which fulfilled the criteria for inclusion in the review. The evidence provided by these studies was generally weak because of poor methodology and reporting. In 17 trials with placebo groups that used participants as the unit of analysis the average cure rate of placebo preparations was 30% (range 0 to 73%) after an average period of 10 weeks (range 4 to 24 weeks). The best available evidence was for simple topical treatments containing salicylic acid, which are clearly better than placebo. Data pooled from six placebo-controlled trials show a cure rate of 144/191 (75%) compared with 89/185 (48%) in controls, odds ratio 3.91 (95% confidence interval 2.40 to 6.36), random effects model. Most of the bigger trials of cryotherapy studied different regimens rather than comparing cryotherapy with other treatments or placebo. Pooled data from two small trials that included cryotherapy and placebo or no treatment, showed no significant difference in cure rates. In two other trials comparing cryotherapy with salicylic acid no significant difference in efficacy was demonstrated. There was no consistent evidence for the effectiveness of intralesional bleomycin. Four studies, using warts rather than individuals as the unit of analysis, had widely varying results which could not be meaningfully pooled. There was some evidence for the efficacy of dinitrochlorobenzene, a potent contact sensitizer. Pooled data from two small studies comparing dinitrochlorobenzene with placebo showed cure rates of 32/40 (80%) and 17/40 (43%) respectively, odds ratio 5.42 (95% confidence interval 1.99 to 14.75), random effects model. Only limited evidence was found for the efficacy of topical 5-fluorouracil, intralesional interferons and photodynamic therapy. Bleomycin, dinitrochlorobenzene, 5-fluorouracil, interferons and photodynamic therapy are potentially hazardous or toxic treatments. REVIEWER'S CONCLUSIONS: There is a considerable lack of evidence on which to base the rational use of the local treatments for common warts. The reviewed trials are highly variable in method and quality. Cure rates with placebo preparations are variable but nevertheless considerable. There is certainly evidence that simple topical treatments containing salicylic acid have a therapeutic effect. There is less evidence for the efficacy of cryotherapy and no convincing evidence that it is any more effective than simple topical treatments. Dinitrochlorobenzene appears to be effective but no more so than the safer, simpler and cheaper topical treatments containing salicylic acid. The benefits and risks of 5-fluorouracil, bleomycin, interferons and photodynamic therapy remain to be determined.

Administration, Topical↗
PubMed2004

Commonly used types of postmenopausal estrogen for treatment of hot flashes: scientific review.

CONTEXT: Recommendations for postmenopausal hormone therapy have changed since the Women's Health Initiative indicated that estrogen was harmful for use in disease prevention; however, treatment of menopausal symptoms with low-dose estrogen remains an approved indication for use. OBJECTIVE: To compare the short-term efficacy and adverse effects of 2 commonly used estrogens, conjugated equine estrogen (CEE) and 17beta-estradiol, for reducing menopausal hot flashes by systematically reviewing randomized controlled trials. DATA SOURCES: MEDLINE, EMBASE, the Cochrane Database of Systematic Reviews, and Cochrane Controlled Trials Registry were searched from the database start dates to July 2003 using database-specific key words. Reference lists of published articles, experts, and pharmaceutical manufacturers were also consulted. STUDY SELECTION: English-language abstracts of double-blind, randomized, placebo-controlled trials and systematic evidence reviews of oral CEE and oral and transdermal 17beta-estradiol, and treatment of menopausal hot flashes and their adverse effects. DATA EXTRACTION: Study design, population characteristics, eligibility criteria, interventions, withdrawals, adverse effects, and results for each outcome. Study quality was assessed using predefined criteria based on parameters developed with the US Preventive Services Task Force and the UK National Health Services Centre. DATA SYNTHESIS: A total of 32 trials including 4 head-to-head comparisons met inclusion criteria; 14 trials met criteria for meta-analysis. All estrogen agents significantly reduced the weekly number of hot flashes compared with placebo (CEE, 1 trial: mean change, -19.1; 95% confidence interval [CI], -33.0 to -5.1; oral 17beta-estradiol, 5 trials: pooled weighted mean difference, -16.8; 95% CI, -23.4 to -10.2; transdermal 17beta-estradiol, 6 trials: pooled weighted mean difference, -22.4; 95% CI, -35.9 to -10.4); differences between agents were not significant. Breast tenderness and atypical vaginal bleeding were the most frequently reported adverse effects among estrogen users. The influence of progestin or progesterone use, cyclic and continuous regimens, and differences in adverse effects could not be determined. CONCLUSION: Conjugated equine estrogen and 17beta-estradiol have consistent and comparable effects on treatment of menopausal hot flashes and may have similar short-term adverse effects.

Estradiol↗
PubMed2006

Recommendations for the care of individuals with an inherited predisposition to Lynch syndrome: a systematic review.

CONTEXT: About 2% of all colorectal cancer occurs in the context of the autosomal dominantly inherited Lynch syndrome, which is due to mutations in mismatch repair genes. Potential risk-reducing interventions are recommended for individuals known to have these mutations. OBJECTIVES: To review cancer risks and data on screening efficacy in the context of Lynch syndrome (hereditary nonpolyposis colorectal cancer) and to provide recommendations for clinical management for affected families, based on available evidence and expert opinion. DATA SOURCES AND STUDY SELECTION: A systematic literature search using PubMed and the Cochrane Database of Systematic Reviews, reference list review of retrieved articles, manual searches of relevant articles, and direct communication with other researchers in the field. Search terms included hereditary non-polyposis colon cancer, Lynch syndrome, microsatellite instability, mismatch repair genes, and terms related to the biology of Lynch syndrome. Only peer-reviewed, full-text, English-language articles concerning human subjects published between January 1, 1996, and February 2006 were included. The US Preventive Services Task Force's 2-tier system was adapted to describe the quality of evidence and to assign strength to the recommendations for each guideline. EVIDENCE SYNTHESIS: The evidence supports colonoscopic surveillance for individuals with Lynch syndrome, although the optimal age at initiation and frequency of examinations is unresolved. Colonoscopy is recommended every 1 to 2 years starting at ages 20 to 25 years (age 30 years for those with MSH6 mutations), or 10 years younger than the youngest age of the person diagnosed in the family. While fully acknowledging absence of demonstrated efficacy, the following are also recommended annually: endometrial sampling and transvaginal ultrasound of the uterus and ovaries (ages 30-35 years); urinalysis with cytology (ages 25-35 years); history, examination, review of systems, education and genetic counseling regarding Lynch syndrome (age 21 years). Regular colonoscopy was favored for at-risk persons without colorectal neoplasia. For individuals who will undergo surgical resection of a colon cancer, subtotal colectomy is favored. Evidence supports the efficacy of prophylactic hysterectomy and oophorectomy. CONCLUSIONS: The past 10 years have seen major advances in the understanding of Lynch syndrome. Current recommendations regarding cancer screening and prevention require careful consultation between clinicians, clinical cancer genetic services, and well-informed patients.

Adult↗
PubMed2004

Acupuncture for chronic asthma.

BACKGROUND: Acupuncture has traditionally been used to treat asthma in China and is used increasingly for this purpose internationally. OBJECTIVES: The objective of this review was to assess the effects of acupuncture for the treatment of asthma or asthma-like symptoms. SEARCH STRATEGY: We searched the Cochrane Airways Group trials register (searched August 2003), the Cochrane Complementary Medicine Field trials register, the Alternative Medicine Database (August 2003) and reference lists of articles. We also contacted trialists and researchers in the field of complementary and alternative medical research. SELECTION CRITERIA: Randomised and possibly randomised trials using needle acupuncture or other forms of stimulation of acupuncture. Any form of control treatment was considered (no treatment in addition to conventional asthma treatment, sham or placebo interventions, active comparator interventions). Studies were included provided outcome was assessed at one week or more. DATA COLLECTION AND ANALYSIS: At least two reviewers independently assessed trial quality. A reviewer experienced in acupuncture assessed the adequacy of the active and sham acupunctures used in the studies. Study authors were contacted for missing information. MAIN RESULTS: Eleven studies met the inclusion criteria with 324 participants. Trial reporting was poor and trial quality was deemed inadequate to generalise findings. There was variation in the type of active and sham acupunctures, the outcomes measured and time-points presented. The points used in the sham arm of some studies are used for the treatment of asthma according to traditional Chinese medicine. Two studies used individualised treatment strategies and one study used a combination strategy of formula acupuncture with the addition of individualised points. No statistically significant or clinically relevant effects were found for acupuncture compared to sham acupuncture. Data from two small studies were pooled for lung function (post-treatment FEV1): Standardised Mean Difference 0.12, 95% confidence interval -0.31 to 0.55). REVIEWER'S CONCLUSIONS: There is not enough evidence to make recommendations about the value of acupuncture in asthma treatment. Further research needs to consider the complexities and different types of acupuncture.

Acupuncture Therapy↗
PubMed2005

Cyclosporine for induction of remission in Crohn's disease.

BACKGROUND: Cyclosporine was first found to be an effective and well-tolerated immunosuppressive agent in organ transplant recipients, and subsequently in several autoimmune diseases. It was reported in open studies that cyclosporine is effective for induction of remission in Crohn's disease. Four randomized controlled trials have been performed to determine whether the results observed in these open studies were valid. This systematic review summarizes the evidence on the use of oral cyclosporine for the induction of remission in Crohn's disease. OBJECTIVES: To evaluate the effectiveness of oral cyclosporine for induction of remission in patients with active Crohn's disease in the presence and absence of concomitant steroid therapy. Secondary objectives were to evaluate clinical response rates and adverse events associated with cyclosporine. SEARCH STRATEGY: Computer-assisted searches of the on-line bibliographic databases MEDLINE and EMBASE were performed to identify potentially relevant publications between 1980 and July 2004. The MeSH terms "Crohn Disease" or "Inflammatory Bowel disease" and "Cyclosporin" (exploded) were used to perform key word searches of the databases. Manual searches of reference lists from potentially relevant papers were performed in order to identify additional studies that may have been missed. Abstracts from major gastroenterological meetings, The Cochrane Central Register of Controlled Trials and the Cochrane Inflammatory Bowel Disease Group Specialized Trials Register were also searched for relevant studies. Appropriate officials at Sandoz Corporation were contacted to seek information on any unpublished trials. SELECTION CRITERIA: Prospective, randomized, double-blinded, placebo-controlled trials of parallel design with treatment duration of a minimum 12 weeks comparing oral cyclosporine therapy with placebo for treatment of patients with active Crohn's disease were eligible for inclusion. DATA COLLECTION AND ANALYSIS: All data were analyzed on an intention-to-treat basis. Data were extracted from the original research articles and converted into 2x2 tables (cyclosporine vs. placebo). Where available, individual 2x2 tables for strata within studies were also used. Heterogeneity was assessed using the chi-square test (p < 0.10 was regarded as statistically significant). For non-pooled data, p-values were derived using the chi-square test. For pooled data, summary test statistics were derived using the Peto odds ratio and 95% confidence intervals. A fixed effects model was used for pooling of data. For continuous data, summary test statistics were derived using the weighted mean difference and 95% confidence intervals. The definitions of treatment success, remission and clinical improvement were set by the authors of each paper, and the data were combined for analysis only if these definitions were sufficiently similar. MAIN RESULTS: Brynskov 1989a found that patients receiving high dose cyclosporine (median 7.6 mg/kg/day) had statistically significant clinical improvement at 12 weeks compared to placebo patients. None of the other studies found any statistically significant benefit for clinical improvement or induction of remission for low dose cyclosporine treatment (5 mg/kg/day) used by itself or in combination with corticosteroids compared to placebo. Cyclosporine was associated with a significantly higher proportion of adverse events and withdrawals due to adverse events relative to placebo. AUTHORS' CONCLUSIONS: Brynskov 1989a enrolled a small number of patients and the modified clinical grading scale used in the study has not been validated in other studies. Furthermore, statistically significant clinical improvement does not imply induction of clinical remission. Indeed, Brynskov 1989a found no statistically significant differences in the mean Crohn's Disease Activity Index score at 12 weeks indicating that cyclosporine was no more effective than placebo for induction of remission in Crohn's disease. The results of this review demonstrate that low dose (5 mg/kg/day) oral cyclosporine is not effective for the induction of remission in Crohn's disease. Patients treated with low dose oral cyclosporine are more likely than placebo treated patients to experience adverse events including renal dysfunction. The use of low dose oral cyclosporine for the treatment of chronic active Crohn's disease does not appear to be justified. Oral dosing at higher levels or parenteral administration of cyclosporine have not been adequately evaluated in controlled clinical trials. Higher doses of cyclosporine are not likely to be useful for the long-term management of Crohn's disease because of the risk of nephrotoxicity and the availability of other proven interventions.

Crohn Disease↗
PubMed2006

Extramedullary fixation implants and external fixators for extracapsular hip fractures in adults.

BACKGROUND: Extramedullary fixation of hip fractures involves the application of a plate and screws to the lateral side of the proximal femur. In external fixators, the stabilising component is held outside the thigh by pins or screws driven into the bone. OBJECTIVES: To compare different types of extramedullary fixation implants and external fixators for fixing extracapsular hip fracture in adults. SEARCH STRATEGY: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (July 2005), various other databases, conference proceedings and reference lists. SELECTION CRITERIA: All randomised or quasi-randomised controlled trials comparing extramedullary implants or external fixators for fixing extracapsular hip fracture in adults. DATA COLLECTION AND ANALYSIS: Two authors independently selected trials, assessed trial quality and extracted data. Data were pooled where appropriate. MAIN RESULTS: The 14 included trials tested seven comparisons in a total of 2222 mainly female and older participants. All trials had methodological flaws that may affect the validity of their results. Three trials comparing a fixed nail plate (Jewett or McLaughlin) with the sliding hip screw (SHS) found an increased risk of fixation failure for fixed nail plates. The two trials comparing the Resistance Augmented Bateaux (RAB) plate with the SHS had contrasting results, notably in terms of operative complications, fixation failure and anatomical restoration. One trial comparing the Pugh nail and the SHS found no significant difference between implants. Two trials compared the Medoff plate with the SHS. One trial reported higher blood losses and longer operation times for the Medoff plate. There was a lower risk of fixation failure with the Medoff plate for unstable trochanteric fractures. Two trials compared the Medoff plate with three different screw-plate systems. There were no statistically significant differences in outcome for trochanteric fractures. For subtrochanteric fractures, there was a lower fixation failure rate for the Medoff plate, but no evidence for differences in longer-term outcomes. Two trials comparing the Gotfried percutaneous plate with a SHS found a reduced blood loss with the Gotfried plate. A higher intra-operative fixation failure rate of the Gotfried plate may indicate some restriction to its use. Two trials found less operative trauma for external fixation when compared with the SHS. Final outcome appeared similar. AUTHORS' CONCLUSIONS: The markedly increased fixation failure rate of fixed nail plates compared with the SHS is a major consideration and thus the SHS appears preferable. There was insufficient evidence from other comparisons to draw definite conclusions.

Bone Plates↗
PubMed2004

Mobilisation strategies after hip fracture surgery in adults.

BACKGROUND: Hip fracture, which happens in predominantly elderly populations, often results in a reduction in mobility. Care programmes after hip fracture surgery include strategies for mobilisation, such as early weight bearing and gait retraining. Other mobilisation strategies, such as exercises and physical training, are used at various stages in rehabilitation including after discharge from hospital. OBJECTIVES: To evaluate the effects of different mobilisation strategies and programmes after hip fracture surgery. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group Specialised Register (May 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 2, 2004), MEDLINE and other databases, conference proceedings and reference lists of articles. SELECTION CRITERIA: All randomised or quasi-randomised trials comparing different mobilisation strategies/programmes after hip fracture surgery. DATA COLLECTION AND ANALYSIS: The reviewers independently assessed trial quality and extracted data. MAIN RESULTS: Our third update, which extended the review scope to cover the whole rehabilitation period, included four new trials. Most of the 10 included trials were small and all had methodological limitations, including inadequate follow up. Seven trials evaluated mobilisation strategies started soon after hip fracture surgery. One trial (273 participants) found no statistically significant differences in unfavourable outcomes for weight bearing started at two versus 12 weeks after internal fixation of a displaced intracapsular fracture. Of two trials (188 participants) comparing a more with a less intensive regimen of physiotherapy, one reported a lack of demonstrable difference in recovery of the two patient groups, and the other found a higher level of drop-out in the more intensive group with no difference in length of hospital stay. One trial (80 participants) comparing two-week programmes of weight-bearing versus non-weight-bearing exercise found some short-term improvement in mobility and balance in the weight-bearing exercise group. One trial (80 participants) found improved mobility, leg extension power and Barthel score in those given a quadriceps muscle strengthening exercise programme. One trial (40 participants) found no statistically significant difference in recovery of mobility and time to hospital discharge after a treadmill versus conventional gait retraining programme. One trial (27 participants) comparing neuromuscular stimulation of the quadriceps muscle with placebo found a greater recovery of pre-fracture mobility in the stimulation group. The interventions tested by the three remaining trials started after hospital discharge. One trial (28 participants) found improved outcome after 12 weeks of intensive physical training. One trial (120 participants) found improved outcome after home-based exercises started around 22 weeks from injury. One trial (44 participants) found home-based weight-bearing exercises starting at seven months produced no statistically significant differences aside, perhaps, for greater quadriceps strength. REVIEWERS' CONCLUSIONS: There is insufficient evidence from randomised trials to determine the effectiveness of the various mobilisation strategies examined in this review that start either in the early post-operative period or during the later rehabilitation period. Further research is required to establish the possible benefits of the additional provision of interventions primarily aimed at enhancing mobility.

Adult↗
PubMed2000

SSRIs versus other antidepressants for depressive disorder.

OBJECTIVES: To examine the relative efficacy of selective serotonin reuptake inhibitors (SSRIs) compared to other antidepressants. SEARCH STRATEGY: The search strategy included a search of (a) Electronic bibliographic databases (MEDLINE, EMBASE); (b) reference lists of related reviews (c) reference lists of all located studies (d) contact with the manufacturer and (e) the Cochrane Group register of controlled trials SELECTION CRITERIA: Randomised controlled trials comparing selective serotonin reuptake inhibitors with other kinds of antidepressants in the treatment of patients with depressive disorders. The outcome measures assessed included measures of the severity of depression. DATA COLLECTION AND ANALYSIS: Data were collected from each study the main outcome measurefrom each study. These included: mean Hamilton depression rating scale, mean Montgomery & Asberg depression rating scale, Clinical Global Impression rating scale. An analysis of standardised mean difference of these scales was performed using Review Manager 3. 1 software. The presence of heterogeneity of treatment effect was assessed MAIN RESULTS: Ninety-eight trials contributed data to the analysis of the relative efficacy of SSRIs and related drugs with comparator antidepressants (Figure 3 & Appendix 3). Analysis of efficacy was based upon 5044 patients treated with an SSRI or related drug, and 4510 treated with an alternative antidepressant. The standardised effect size for SSRIs and related drugs together versus alternative antidepressants using a fixed effects model was 0. 035 (95% CI -0.006 to 0.076; Q = 149.25, df = 97, p < 0.001). REVIEWER'S CONCLUSIONS: There are no clinically significant differences in effectiveness between selective serotonin reuptake inhibitors and tricyclic antidepressants. Treatment decisions need to be based on considerations of relative patient acceptability, toxicity and cost.

Antidepressive Agents↗
PubMed2001

Hypothermia to reduce neurological damage following coronary artery bypass surgery.

BACKGROUND: Coronary artery bypass surgery (CABG) may be life saving, but known side effects include neurological damage and cognitive impairment. The temperature used during cardiopulmonary bypass (CPB) may be important with regard to these adverse outcomes, where hypothermia is used as a means of neuroprotection. OBJECTIVES: To assess the effectiveness of hypothermia during CABG in reducing neurological damage and subsequent cognitive deficits. SEARCH STRATEGY: The Cochrane Controlled Trials Register was searched for randomised controlled trials (RCT) and this was updated by searching MEDLINE and EMBASE to December 1999 using database specific RCT filters. Reference lists of retrieved articles were searched and experts in the field were contacted. SELECTION CRITERIA: Only RCTs were considered. All patients undergoing CABG, either first time or revisions, elective or emergency procedures, were included. Any hypothermia protocol was considered. Only trials reporting neurological outcomes were included. DATA COLLECTION AND ANALYSIS: Studies were selected independently and data were extracted from the source papers independently by two reviewers. Authors were contacted for further information. Studies were combined with meta-analysis where appropriate, and meta-regression was used to explore heterogeneity. MAIN RESULTS: There was a trend towards a reduction in the incidence of non fatal strokes in the hypothermic group (OR 0.68 (0.43, 1.05)). Conversely, there was a trend for the number of non stroke related perioperative deaths to be higher in the hypothermic group (OR 1.46 (0.9, 2.37)). Hypothermia had no effect on the incidence of non fatal myocardial infarction (OR 1.05 (0.81, 1.37)), but the incidence of another marker of myocardial damage, low output syndrome, was higher in the hypothermic group (OR 1.21 (0.99, 1.48). When pooling all "bad" outcomes (stroke, perioperative death, myocardial infarction, low output syndrome, intra aortic balloon pump use) there was no significant advantage of either hypothermia or normothermia (OR 1.07 (0.92, 1.24)). Only 4 of 17 trials reported neuropsychological function as an outcome. REVIEWER'S CONCLUSIONS: This review could find no definite advantage of hypothermia over normothermia in the incidence of clinical events. Hypothermia was associated with a reduced stroke rate, but this is off set by a trend towards an increase in non stroke related perioperative mortality and myocardial damage. There is insufficient data to date to draw any conclusions about the use of mild hypothermia. Similarly, there is insufficient data to date to comment on the effect of temperature during CPB on subtle neurological deficits, and further trials are needed in these areas.

Cardiac Output, Low↗
PubMed2001

Concomitant chemotherapy and radiation therapy for cancer of the uterine cervix.

BACKGROUND: The National Cancer Institute (USA) alert in February 1999 stated that concomitant chemoradiotherapy should be considered for all patients with cervical cancer, based on evidence from five randomised controlled trials. OBJECTIVES: To review all known randomised clinical controlled trials (RCTs) comparing concomitant chemotherapy and radiation therapy with radiotherapy for locally advanced cervical cancer. SEARCH STRATEGY: We searched electronic databases, trials registers and reference lists of published trial reports and review articles were also searched. SELECTION CRITERIA: This review includes RCTs in cervical cancer comparing concomitant chemotherapy and radiotherapy with radiotherapy. In the experimental arm, further adjuvant chemotherapy was allowable. Hydroxyurea was considered inactive and allowable. Trials using radiosensitisers or radioprotectors in the experimental arm were excluded. DATA COLLECTION AND ANALYSIS: Two authors reviewed trials for inclusion and extracted data. For meta-analyses of time-to-event outcomes (survival, progression-free survival), a hazard ratio (HR) was extracted or estimated from trial reports, where possible. Only overall rates of local and distant recurrence were presented in many reports so only an odds ratios (OR) of recurrence rates could be calculated, which takes no account of time to recurrence or censoring. The HRs and ORs for individual trials were combined across all trials, using the fixed effect model. Few trials reported acute toxicity adequately. Data were therefore grouped and the number of toxic events was used to calculate a single OR for each site and grade. Late toxicity was rarely described so could only be reviewed qualitatively. MAIN RESULTS: Nineteen trials (17 published, two unpublished) were identified including 4580 patients, although due to patient exclusion and differential reporting 62-78% were available for the various analyses. The review strongly suggests chemoradiation improves overall survival and progression free survival, whether platinum was used or not with absolute benefits of 12% and 16% respectively. There was, however, statistical heterogeneity for these outcomes There was some evidence that the effect was greater in trials including a high proportion of stage I and II patients. Chemoradiation also showed significant benefit for both local and distant recurrence. Haematological and gastrointestinal toxicity was significantly greater in the concomitant chemoradiation group. Details of late morbidity were sparse. REVIEWER'S CONCLUSIONS: Concomitant chemotherapy and radiotherapy appears to improve overall survival and progression-free survival in locally advanced cervical cancer. It also reduces local and distant recurrence suggesting concomitant chemotherapy may afford cytotoxic and sensitisation effects. Some acute toxicity is increased, but data on long term side effects were sparse.

Combined Modality Therapy↗
PubMed2005

Concomitant chemotherapy and radiation therapy for cancer of the uterine cervix.

BACKGROUND: The National Cancer Institute (USA) alert in February 1999 stated that concomitant chemoradiotherapy should be considered for all patients with cervical cancer, based on evidence from five randomised controlled trials (RCTs). OBJECTIVES: To review all known RCTs comparing concomitant chemotherapy and radiation therapy with radiotherapy for locally advanced cervical cancer. SEARCH STRATEGY: We searched electronic databases, trials registers and reference lists of published trial reports and review articles were also searched. SELECTION CRITERIA: This review includes RCTs in cervical cancer comparing concomitant chemoradiation with radiotherapy in the experimental arm. Trials allowing further adjuvant chemotherapy or hydroxyurea were included. Trials using radiosensitisers or radioprotectors in the experimental arm were excluded. DATA COLLECTION AND ANALYSIS: Two authors reviewed trials for inclusion and extracted data. For meta-analyses of time-to-event outcomes (survival, progression-free survival), a hazard ratio (HR) was extracted or estimated from trial reports, where possible. Only overall rates of local and distant recurrence were presented in many reports so only odds ratios (OR) of recurrence rates could be calculated, which takes no account of time to recurrence or censoring. Few trials reported acute toxicity adequately, but where possible ORs were calculated for the main types and severities of acute toxicity. The HRs and ORs for individual trials were combined across all trials, using the fixed effect model. Late toxicity was rarely described in sufficient detail so could only be reviewed qualitatively. MAIN RESULTS: The original review was based on nineteen trials (17 published and two unpublished) including 4580 patients. This update includes twenty four trials (21 published, 3 unpublished) and 4921 patients, although due to patient exclusion and differential reporting 61% to 75% were available for the analyses. The review strongly suggests chemoradiation improves overall survival and progression free survival, whether or not platinum was used with absolute benefits of 10% and 13% respectively. There was, however, statistical heterogeneity for these outcomes. There was some evidence that the effect was greater in trials including a high proportion of stage I and II patients. Chemoradiation also showed significant benefit for local recurrence and a suggestion of a benefit for distant recurrence. Acute haematological and gastrointestinal toxicity was significantly greater in the concomitant chemoradiation group. Late effects of treatment were not well reported and so the impact of chemoradiation on these effects could not be determined adequately. Treatment-related deaths were rare. AUTHORS' CONCLUSIONS: Concomitant chemoradiation appears to improve overall survival and progression-free survival in locally advanced cervical cancer. It also appears to reduce local and distant recurrence suggesting concomitant chemotherapy may afford radiosensitisation and systemic cytotoxic effects. Some acute toxicity is increased, but the long-term side effects are still not clear.

Combined Modality Therapy↗
PubMed2003

Fluoride toothpastes for preventing dental caries in children and adolescents.

BACKGROUND: Fluoride toothpastes have been widely used for over three decades and remain a benchmark intervention for the prevention of dental caries. OBJECTIVES: To determine the effectiveness and safety of fluoride toothpastes in the prevention of caries in children and to examine factors potentially modifying their effect. SEARCH STRATEGY: We searched the Cochrane Oral Health Group's Trials Register (May 2000), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2000), MEDLINE (1966 to January 2000), plus several other databases. We handsearched journals, reference lists of articles and contacted selected authors and manufacturers. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials with blind outcome assessment, comparing fluoride toothpaste with placebo in children up to 16 years during at least one year. The main outcome was caries increment measured by the change in decayed, missing and filled tooth surfaces (D(M)FS). DATA COLLECTION AND ANALYSIS: Inclusion decisions, quality assessment and data extraction were duplicated in a random sample of one third of studies, and consensus achieved by discussion or a third party. Authors were contacted for missing data. The primary measure of effect was the prevented fraction (PF) that is the difference in caries increments between the treatment and control groups expressed as a percentage of the increment in the control group. Random effects meta-analyses were performed where data could be pooled. Potential sources of heterogeneity were examined in random effects meta-regression analyses. MAIN RESULTS: Seventy-four studies were included. For the 70 that contributed data for meta-analysis (involving 42,300 children) the D(M)FS pooled PF was 24% (95% confidence interval (CI), 21 to 28%; p<0.0001). This means that 1.6 children need to brush with a fluoride toothpaste (rather than a non-fluoride toothpaste) over three years to prevent one D(M)FS in populations with caries increment of 2.6 D(M)FS per year. In populations with caries increment of 1.1 D(M)FS per year, 3.7 children will need to use a fluoride toothpaste for three years to avoid one D(M)FS. There was clear heterogeneity, confirmed statistically (p<0.0001). The effect of fluoride toothpaste increased with higher baseline levels of D(M)FS, higher fluoride concentration, higher frequency of use, and supervised brushing, but was not influenced by exposure to water fluoridation. There is little information concerning the deciduous dentition or adverse effects (fluorosis). REVIEWER'S CONCLUSIONS: Supported by more than half a century of research, the benefits of fluoride toothpastes are firmly established. Taken together, the trials are of relatively high quality, and provide clear evidence that fluoride toothpastes are efficacious in preventing caries.

Adolescent↗
PubMed2003

Fluoride mouthrinses for preventing dental caries in children and adolescents.

BACKGROUND: Fluoride mouthrinses have been used extensively as a caries-preventive intervention in school-based programmes and individually at home. OBJECTIVES: To determine the effectiveness and safety of fluoride mouthrinses in the prevention of dental caries in children and to examine factors potentially modifying their effect. SEARCH STRATEGY: We searched the Cochrane Oral Health Group's Trials Register (May 2000), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2000), MEDLINE (1966 to January 2000), plus several other databases. We handsearched journals, reference lists of articles and contacted selected authors and manufacturers. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials with blind outcome assessment, comparing fluoride mouthrinse with placebo or no treatment in children up to 16 years during at least 1 year. The main outcome was caries increment measured by the change in decayed, missing and filled tooth surfaces (D(M)FS). DATA COLLECTION AND ANALYSIS: Inclusion decisions, quality assessment and data extraction were duplicated in a random sample of one third of studies, and consensus achieved by discussion or a third party. Authors were contacted for missing data. The primary measure of effect was the prevented fraction (PF) that is the difference in mean caries increments between the treatment and control groups expressed as a percentage of the mean increment in the control group. Random effects meta-analyses were performed where data could be pooled. Potential sources of heterogeneity were examined in random effects metaregression analyses. MAIN RESULTS: Thirty-six studies were included. For the 34 that contributed data for meta-analysis (involving 14,600 children) the D(M)FS pooled PF was 26% (95% confidence interval (CI), 23% to 30%; p < 0.0001). Heterogeneity was not substantial, but confirmed statistically (p = 0.008). No significant association between estimates of D(M)FS prevented fractions and baseline caries severity, background exposure to fluorides, rinsing frequency and fluoride concentration was found in metaregression analyses. A funnel plot of the 34 studies indicated no relationship between prevented fraction and study precision. There is little information concerning possible adverse effects or acceptability of treatment in the included trials. REVIEWER'S CONCLUSIONS: This review suggests that the supervised regular use of fluoride mouthrinse at two main strengths and rinsing frequencies is associated with a clear reduction in caries increment in children. In populations with caries increment of 0.25 D(M)FS per year, 16 children will need to use a fluoride mouthrinse (rather than a non-fluoride rinse) to avoid one D(M)FS; in populations with a caries increment of 2.14 D(M)FS per year, 2 children will need to rinse to avoid one D(M)FS. There is a need for complete reporting of side effects and acceptability data in fluoride mouthrinse trials.

Adolescent↗
PubMed2004

One topical fluoride (toothpastes, or mouthrinses, or gels, or varnishes) versus another for preventing dental caries in children and adolescents.

BACKGROUND: Topical fluorides in the form of toothpaste, mouthrinse, varnish and gel are effective caries preventive measures. However, there is uncertainty about the relative value of these interventions. OBJECTIVES: To compare the effectiveness of one form of topical fluoride intervention with another when used for the prevention of dental caries in children. SEARCH STRATEGY: We searched the Cochrane Oral Health Group's Trials Register (May 2000), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2000), MEDLINE (1966 to January 2000), plus several other databases. We handsearched journals, reference lists of articles and contacted selected authors and manufacturers. SELECTION CRITERIA: Randomized or quasi-randomized controlled trials with blind outcome assessment, comparing fluoride varnish, gel, mouthrinse, or toothpaste with each other in children up to 16 years during at least 1 year. The main outcome was caries increment measured by the change in decayed, missing and filled tooth surfaces (D(M)FS). DATA COLLECTION AND ANALYSIS: Inclusion decisions, quality assessment and data extraction were duplicated in a random sample of one third of studies, and consensus achieved by discussion or a third party. Authors were contacted for missing data. The primary measure of effect was the prevented fraction (PF) that is the difference in mean caries increments between the 'experimental' and 'control' groups expressed as a percentage of the mean increment in the control group. Random effects meta-analyses were performed where data could be pooled. MAIN RESULTS: There were 17 studies included, and 15 contributed data for the meta-analyses. Fluoride toothpaste was not significantly different from mouthrinse (pooled DMFS PF 0%; 95% CI, -18% to 19%; p = 0.94), or gel (pooled DMFS PF 0%; 95% CI, -21% to 21%; p = 1), or both gel and mouthrinse (pooled DMFS PF 1%; 95% CI, -13% to 14%; p = 0.94); heterogeneity was substantial. Results from the single trial comparing toothpaste with varnish (in deciduous teeth) were inconclusive (dfs PF 5%; CI not obtainable). The pooled results from the comparisons of fluoride varnish with mouthrinse was a non-significant difference favouring varnish (DMFS PF 10%; 95% CI, -12% to 32%; p = 0.40), but this result was not robust to sensitivity analysis performed, and heterogeneity was considerable. Results from the single trial comparing varnish with gel (14%, 95% CI, -12% to 40%; p = 0.30) and the single trial comparing gel with mouthrinse (-14% DMFS PF; 95% CI, -40% to 12%; p = 0.30) were inconclusive (favoured varnish and mouthrinse respectively). REVIEWER'S CONCLUSIONS: Fluoride toothpastes in comparison to mouthrinses or gels appear to have a similar degree of effectiveness for the prevention of dental caries in children. There is no clear suggestion that fluoride varnish is more effective than mouthrinses and the evidence for the comparative effectiveness of fluoride varnishes and gels, and mouthrinses and gels is inconclusive. No conclusions about adverse effects could be reached, because no data were reported on in the trials. Acceptance is likely to be greater for fluoride toothpaste.

Adolescent↗