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Interventions for emergency contraception.

OBJECTIVES: To determine which emergency contraceptive method following unprotected intercourse is the most effective, safe and convenient for use in preventing pregnancy. SEARCH STRATEGY: The search strategy included electronic searches of the Cochrane Controlled Trials Register, Popline, Chinese biomedical databases and HRP emergency contraception database. In addition, references of retrieved papers were searched and researchers in the field and two pharmaceutical companies were contacted. SELECTION CRITERIA: Randomized or quasi-randomized studies including women attending services for emergency contraception following a single act of unprotected intercourse were eligible. DATA COLLECTION AND ANALYSIS: Data on outcomes and trial characteristics were extracted in duplicate by two reviewers. Results were expressed as relative risk using a fixed-effects model with 95 % confidence interval. MAIN RESULTS: Fifteen trials were included in the review. The majority (8/15) of the trials were conducted in China. Most comparisons between different interventions included one or two trials although some trials were appropriately sized with power calculations. Levonorgestrel appears to be more effective than Yuzpe regimen (2 trials, RR: 0.51, 95 % CI: 0.31-0.84) and causes less side-effects (RR: 0.80, 95 % CI: 0.76 to 0.84). Levonorgestrel was less effective than locally manufactured mifepristone in a single, large Chinese study (RR: 2.17, 95 % CI: 1.00 to 4.77). Effectiveness of different doses of mifepristone seem to be similar but the frequency of delay in onset of the subsequent menstrual period increases with increased dose. REVIEWER'S CONCLUSIONS: Levonorgestrel and mifepristone seem to offer the highest efficacy with an acceptable side-effect profile. One disadvantage of mifepristone is that it causes delays in onset of subsequent menses which may induce anxiety. However, this seems to be dose-related and low doses of mifepristone minimise this side-effect without compromising effectiveness. Future studies should compare the effectiveness of mifepristone with levonorgestrel.

Contraceptives, Postcoital↗

Clinical service organisation for heart failure.

BACKGROUND: Chronic heart failure (CHF) is a serious, common condition associated with frequent hospitalisation. Several different disease management interventions (clinical service organisation interventions) for patients with CHF have been proposed. OBJECTIVES: To assess the effectiveness of disease management interventions for patients with CHF. SEARCH STRATEGY: We searched: Cochrane CENTRAL Register of Controlled Trials (to June 2003); MEDLINE (January 1966 to July 2003); EMBASE (January 1980 to July 2003); CINAHL (January 1982 to July 2003); AMED (January 1985 to July 2003); Science Citation Index Expanded (searched January 1981 to March 2001); SIGLE (January 1980 to July 2003); DARE (July 2003); National Research Register (July 2003); NHS Economic Evaluations Database (March 2001); reference lists of articles and asked experts in the field. SELECTION CRITERIA: Randomised controlled trials comparing disease management interventions specifically directed at patients with CHF to usual care. DATA COLLECTION AND ANALYSIS: At least two reviewers independently extracted data information and assessed study quality. Study authors were contacted for further information where necessary. MAIN RESULTS: Sixteen trials involving 1,627 people were included. We classified the interventions into three models: multidisciplinary interventions (a holistic approach bridging the gap between hospital admission and discharge home delivered by a team); case management interventions (intense monitoring of patients following discharge often involving telephone follow up and home visits); and clinic interventions (follow up in a CHF clinic). There was considerable overlap within these categories, however the components, intensity and duration of the interventions varied. Case management interventions tended to be associated with reduced all cause mortality but these findings were not statistically significant (odds ratio 0.86, 95% confidence interval 0.67 to 1.10, P = 0.23), although the evidence was stronger when analysis was limited to the better quality studies (odds ratio 0.68, 95% confidence interval 0.46 to 0.98, P = 0.04). There was weak evidence that case management interventions may be associated with a reduction in admissions for heart failure. It is unclear what the effective components of the case management interventions are. The single RCT of a multidisciplinary intervention showed reduced heart-failure related re-admissions in the short term. At present there is little available evidence to support clinic based interventions. AUTHORS' CONCLUSIONS: The data from this review are insufficient for forming recommendations. Further research should include adequately powered, multi-centre studies. Future studies should also investigate the effect of interventions on patients' and carers' quality of life, their satisfaction with the interventions and cost effectiveness.

Case Management↗

Surgery for the resolution of symptoms in malignant bowel obstruction in advanced gynaecological and gastrointestinal cancer.

BACKGROUND: Intestinal obstruction commonly occurs in progressive advanced gynaecological and gastrointestinal cancers. Management of these patients is difficult due to the patients deteriorating mobility and function (performance status), the lack of further chemotherapeutic options and the high mortality and morbidity associated with palliative surgery. There are marked variations in clinical practice concerning surgery in these patients between different countries, gynaecological oncology units, and general hospitals as well as referral patterns from oncologists under whom these patients are often admitted under. There is therefore a need for all the present information to be collated, analysed (with appropriate palliative care outcomes) to establish if surgery is of benefit and what further research is needed. OBJECTIVES: The objective was to locate, appraise and summarise evidence from scientific studies on intestinal obstruction due to advanced gynaecological and gastrointestinal cancer, in order to assess the efficacy of surgery. SEARCH STRATEGY: A comprehensive list of studies was provided by an extensive search of electronic databases, relevant journals, bibliographic databases, conference proceedings, reference lists, the grey literature, personal contact and the world wide web. SELECTION CRITERIA: As the review concentrates on the 'best evidence' available of the role of surgery in malignant bowel obstruction in advanced gynaecological and gastrointestinal cancer the inclusion criteria were kept broad (included both prospective and retrospective studies) so as to include all studies relevant to the question. DATA COLLECTION AND ANALYSIS: Data extraction forms were used to collect data from the studies included in the review. Two researchers extracted the data independently to reduce error. Due to the methodological quality of the studies, only a qualitative assessment was possible. MAIN RESULTS: The role of surgery in malignant bowel obstruction remains controversial, and no firm conclusions from the many retrospective case series can be made. Control of symptoms varies from 42% to over 80%, though it is often unclear how symptoms were measured and whether the tools used to collect symptom scores are validated. There is a large range in the rates of re-obstruction, from 10-50%, though time to re-obstruction was often not included. There is a wide range of postoperative morbidity and mortality, although again the definition of both these surgical outcomes varied between many of the papers. REVIEWER'S CONCLUSIONS: The role of surgery in malignant bowel obstruction needs careful evaluation, using validated outcome measures of symptom control and quality of life scores. Further information would include re-obstruction rates together with the morbidity associated with the various surgical procedures. Currently, bowel obstruction is managed empirically, and there are marked variations in clinical practice by different units. There needs to be a greater standardisation of management so that comparisons between different series can be made.

Female↗

Transcutaneous electrical nerve stimulation (TENS) for chronic pain.

BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) is used in a variety of different clinical settings to treat a range of different acute and chronic pain conditions and has become popular with both patients and health professionals. OBJECTIVES: To evaluate the effectiveness of TENS in chronic pain. SEARCH STRATEGY: The Cochrane Library, Embase, Medline, CINAHL and The Oxford Pain Database were searched. Reference lists from retrieved reports and reviews were examined. Date of the most recent search: March 1999. SELECTION CRITERIA: RCTs were eligible if they included the following treatment comparisons: active TENS versus sham TENS controls active TENS versus no treatment controls active TENS versus active TENS controls (for instance High Frequency TENS vs Low Frequency TENS) Studies of patients suffering chronic pain for three months or more which included subjective outcome measures for pain intensity, or pain relief were eligible for evaluation in this review. No restrictions were made to language or sample size. Data from abstracts, letters, or unpublished studies, and studies of TENS in angina, headache and migraine, and dysmenorrhoea were not included. DATA COLLECTION AND ANALYSIS: Data were extracted and summarised on the following items: patients and details of pain condition, study treatments, study duration, design, methods, subjective pain outcome measures, methodological quality, results for pain outcome measures and adverse effects, and the conclusions made by the authors of the original studies. Extracted data and methodological quality of each report was confirmed by at least three of the reviewers. MAIN RESULTS: Of 107 reports identified from the searches, 88 were excluded as they did not fulfil the pre-defined entry criteria. Nineteen RCTs (from 18 reports) were evaluated. The included trials varied in terms of design, analgesic outcomes, chronic pain conditions, TENS treatments and overall methodological quality. Studies included single and multiple dose treatment comparisons of TENS. The studies were small. The reporting of the methods used and results for the analgesic outcomes were generally poor. TENS treatments and controls were often poorly defined. Few studies evaluated the long-term analgesic effectiveness of TENS and single dose evaluations of TENS are unhelpful in making clinical decisions of the long-term effectiveness of TENS in the management of chronic pain. Meta-analysis was not possible. Overall in 10 of 15 inactive control studies there was a positive analgesic outcome in favour of the active TENS treatments. For the multiple dose treatment comparison studies only three of seven were considered to be in favour of the active TENS treatments. For the active controlled studies, seven studies made direct comparisons between HFTENS and LFTENS. Five of seven studies could find no difference in terms of analgesic efficacy between HFTENS and LFTENS at any time point. REVIEWER'S CONCLUSIONS: The results of this review are inconclusive; the published trials do not provide information on the stimulation parameters which are most likely to provide optimum pain relief, nor do they answer questions about long-term effectiveness. Large multi-centre randomised controlled trials of TENS in chronic pain are urgently needed.

Chronic Disease↗

'Human' insulin versus animal insulin in people with diabetes mellitus.

BACKGROUND: Human insulin was introduced for the routine treatment of diabetes mellitus in the early 1980s without adequate comparison of efficacy to animal insulin preparations. First reports of altered hypoglycaemia awareness after transfer to human insulin made physicians and especially patients uncertain about potential adverse effects of human insulin. OBJECTIVES: To assess the effects of different insulin species by evaluating their efficacy (in particular glycaemic control) and adverse effects profile (mainly hypoglycaemia). SEARCH STRATEGY: A highly sensitive search for randomised controlled trials combined with key terms for identifying studies on human versus animal insulin was performed using The Cochrane Library, MEDLINE and EMBASE. We also searched reference lists and databases of ongoing trials. Date of latest search: July 2004. SELECTION CRITERIA: We included randomised controlled clinical trials with diabetic patients of all ages that compared human to animal (for the most part purified porcine) insulin. Trial duration had to be at least one month in order to achieve reliable results on the main outcome parameter glycated haemoglobin. DATA COLLECTION AND ANALYSIS: Trial selection as well as evaluation of study quality was performed by two independent reviewers. The quality of reporting of each trial was assessed according to a modification of the quality criteria as specified by Schulz and by Jadad. MAIN RESULTS: Altogether 2156 participants took part in the 45 randomised controlled studies that were discovered through extensive search efforts. Though many studies had a randomised, double-blind design, most studies were of poor methodological quality. Purified porcine and semi-synthetic insulin were most often investigated. No significant differences in metabolic control or hypoglycaemic episodes between various insulin species could be elucidated. Insulin dose and insulin antibodies did not show relevant dissimilarities. AUTHORS' CONCLUSIONS: A comparison of the effects of human and animal insulin as well as of the adverse reaction profile did not show clinically relevant differences. Many patient-oriented outcomes like health-related quality of life or diabetes complications and mortality were never investigated in high-quality randomised clinical trials. The story of the introduction of human insulin might be repeated by contemporary launching campaigns to introduce pharmaceutical and technological innovations that are not backed up by sufficient proof of their advantages and safety.

Animals↗

Nonoxynol-9 for preventing vaginal acquisition of HIV infection by women from men.

BACKGROUND: There is a need for female-controlled methods of HIV prevention. Vaginal microbicides, substances inserted into the vagina to prevent women acquiring HIV and sexually transmitted infections (STIs) from men, could be useful in this regard. One potential vaginal microbicide is the widely used spermicide, nonoxynol-9 (N-9). OBJECTIVES: To determine the safety and effectiveness of N-9 in preventing vaginal acquisition of HIV infection by women from men. SEARCH STRATEGY: Extensive searches of electronic databases, conference abstracts, reference lists of relevant studies and contact with experts and funders. SELECTION CRITERIA: Randomised controlled trials meeting pre-determined quality criteria with HIV infection as the outcome. DATA COLLECTION AND ANALYSIS: Data were extracted by one reviewer and checked by the another. Any discrepancies were adjudicated by a third reviewer. MAIN RESULTS: Five trials were included in the review and four contributed to a meta-analysis. Overall, the risk of HIV infection was not statistically significantly different among women receiving N-9 (relative risk [RR] 1.12, 95% CI 0.88-1.42; p=0.4). The risk of genital lesions was statistically significantly greater among women receiving N-9 (RR 1.18, 95%CI 1.02-1.36; p=0.02). REVIEWER'S CONCLUSIONS: There is no evidence that nonoxynol-9 protects against vaginal acquisition of HIV infection by women from men. There is evidence that it may do harm by increasing the frequency of genital lesions.

Coitus↗

Nonoxynol-9 for preventing vaginal acquisition of sexually transmitted infections by women from men.

BACKGROUND: The incidence and prevalence of sexually transmitted infections (STI) and other reproductive tract infections (RTI) is high in much of the developing and parts of the developed worlds. STIs and RTIs are associated with the vaginal transmission of HIV. Additional strategies to improve STI control are needed, and vaginal microbicides are a possible strategy. One potential vaginal microbicide is the widely used spermicide, nonoxynol-9 (N-9). OBJECTIVES: To determine the safety and effectiveness of N-9 in preventing vaginal acquisition of sexual transmitted infections (exclusive of HIV) by women from men. SEARCH STRATEGY: Systematic search of electronic databases, conference abstracts, reference lists of relevant studies and contact with experts and funders. SELECTION CRITERIA: Randomised controlled trials meeting pre-determined quality criteria with STI as the outcome. DATA COLLECTION AND ANALYSIS: Data were extracted by one reviewer and checked by another. MAIN RESULTS: Ten of 12 identified randomised controlled trials were included and findings among them were broadly consistent. In meta-analysis, the risks of gonorrhoea (relative risk [RR] 0.91, 95%CI 0.67-1.24), cervical infection (RR 1.01, 0.84-1.22), trichomoniasis (RR 0.84, 0.69-1.02), bacterial vaginosis (0.88, 0.74-1.04), chlamydia (RR 0.88, 0.77-1.01) and candidiasis (RR 0.97, 0.84-1.12) were not statistically significantly different in women receiving N-9 compared with placebo. Genital lesions were more common in the N-9 users (RR 1.17, 95%CI 1.02-1.35). REVIEWER'S CONCLUSIONS: There is good evidence that nonoxynol-9 does not protect against sexually transmitted infections, and there is some evidence that it may be harmful by increasing the rate of genital ulceration. As such, this product cannot be recommended for STI prevention.

Female↗

Lay health workers in primary and community health care.

BACKGROUND: Lay health workers (LHWs) are widely used to provide care for a broad range of health issues. However, little is known about the effectiveness of LHW interventions. OBJECTIVES: To assess the effects of LHW interventions in primary and community health care on health care behaviours, patients' health and wellbeing, and patients' satisfaction with care. SEARCH STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care and Consumers and Communication specialised registers (to August 2001); the Cochrane Central Register of Controlled Trials (to August 2001); MEDLINE (1966- August 2001); EMBASE (1966-August 2001); Science Citations (to August 2001); CINAHL (1966-June 2001); Healthstar (1975-2000); AMED (1966-August 2001); the Leeds Health Education Effectiveness Database and the reference lists of articles. SELECTION CRITERIA: Randomised controlled trials of any intervention delivered by LHWs (paid or voluntary) in primary or community health care and intended to promote health, manage illness or provide support to patients. A 'lay health worker' was defined as any health worker carrying out functions related to health care delivery; trained in some way in the context of the intervention; and having no formal professional or paraprofessional certificated or degreed tertiary education. There were no restrictions on the types of consumers. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data onto a standard form and assessed study quality. Studies that compared broadly similar types of interventions were grouped together. Where feasible, the results of included studies were combined and an estimate of effect obtained. MAIN RESULTS: Forty three studies met the inclusion criteria, involving more than 210,110 consumers. These showed considerable diversity in the targeted health issue and the aims, content and outcomes of interventions. Most were conducted in high income countries (n=35), but nearly half of these focused on low income and minority populations (n=15). Study diversity limited meta-analysis to outcomes for five subgroups (n=15 studies) (LHW interventions to promote the uptake of breast cancer screening, immunisation and breastfeeding promotion [before two weeks and between two weeks and six months post partum] and to improve diagnosis and treatment for selected infectious diseases). Promising benefits in comparison with usual care were shown for LHW interventions to promote immunisation uptake in children and adults (RR=1.30 [95% CI 1.14, 1.48] p=0.0001) and LHW interventions to improve outcomes for selected infectious diseases (RR=0.74 [95% CI 0.58, 0.93) p=0.01). LHWs also appear promising for breastfeeding promotion. They appear to have a small effect in promoting breast cancer screening uptake when compared with usual care. For the remaining subgroups (n=29 studies), the outcomes were too diverse to allow statistical pooling. We can therefore draw no general conclusions on the effectiveness of these subgroups of interventions. AUTHORS' CONCLUSIONS: LHWs show promising benefits in promoting immunisation uptake and improving outcomes for acute respiratory infections and malaria, when compared to usual care. For other health issues, evidence is insufficient to justify recommendations for policy and practice. There is also insufficient evidence to assess which LHW training or intervention strategies are likely to be most effective. Further research is needed in these areas.

Allied Health Personnel↗

Substitution treatment of injecting opioid users for prevention of HIV infection.

BACKGROUND: Injecting drug users are vulnerable to infection with HIV and other blood borne viruses as a result of collective use of injecting equipment as well as sexual behaviour. OBJECTIVES: To assess the effect of oral substitution treatment for opioid dependent injecting drug users on rates of HIV infections, and high risk behaviours. SEARCH STRATEGY: Multiple electronic databases were searched. Reference lists of retrieved studies, reviews and conference abstracts were handsearched. SELECTION CRITERIA: Studies were required to consider the incidence of risk behaviours, or the incidence of HIV infection related to substitution treatment of opioid dependence. All types of original studies were considered. DATA COLLECTION AND ANALYSIS: Each potentially relevant study was independently assessed by two reviewers. For studies that met the inclusion criteria, key information was extracted by one reviewer and confirmed by consultation between all four reviewers. MAIN RESULTS: Twenty-eight studies, involving 7900 participants, were included. The majority were not randomised controlled studies. Issues of confounding and bias are discussed. The studies varied in several aspects limiting the extent of quantitative analysis. REVIEWERS' CONCLUSIONS: Oral substitution treatment for opioid-dependent injecting drug users is associated with statistically significant reductions in illicit opioid use, injecting use and sharing of injecting equipment. It is also associated with reductions in the proportion of injecting drug users reporting multiple sex partners or exchanges of sex for drugs or money, but has little effect on condom use. It appears that the reductions in risk behaviours related to drug use do translate into reductions in cases of HIV infection. The lack of data from randomised controlled studies limits the strength of the evidence presented in this review. However, these findings add to the stronger evidence of effectiveness of substitution treatment on drug use, and treatment retention outcomes shown by other systematic reviews. On this basis, the provision of substitution treatment for opioid dependence in countries with emerging HIV and injecting drug use problems as well as in countries with established populations of injecting drug users should be supported.

Administration, Oral↗

EMLA and amethocaine for reduction of children's pain associated with needle insertion.

BACKGROUND: Children often experience pain from needle insertion procedures; therefore, several topical anaesthetics have been developed. OBJECTIVES: To compare the topical anaesthetics amethocaine and an eutectic mixture of local anaesthetics (EMLA) in terms of anaesthetic efficacy, ease of needle insertion and adverse events when used for intravenous cannulation and venipuncture in children. SEARCH STRATEGY: An exhaustive search that included over 30 databases and handsearching reference lists and journals. Language restrictions were not imposed. SELECTION CRITERIA: Randomized controlled trials were selected that compared EMLA and amethocaine for relieving children's pain from intravenous cannulation or venipuncture. DATA COLLECTION AND ANALYSIS: Two review authors independently determined eligibility for inclusion by assessing trial quality. Details of eligible studies were summarized. One author was contacted for additional information. Information about adverse events was obtained from the text of the trial reports. Review Manager 4.2 was used to perform a meta-analysis and compute relative risks (RR) with 95% confidence intervals. MAIN RESULTS: Six trials consisting of 534 children, three months to 15 years of age, were included in this review. A meta-analysis was done comparing amethocaine with EMLA on anaesthetic efficacy, ease of needle procedure and resultant skin changes. For anaesthetic efficacy, amethocaine significantly reduced the risk of pain compared to EMLA when all pain data were combined into a common pain metric (RR 0.78, 95% CI 0.62 to 0.98); when pain was self-reported by children (RR 0.63, 95% CI 0.45 to 0.87); or when pain was observed by researchers (sensitivity analysis: RR 0.71, 95% CI 0.52 to 0.96). Compared to EMLA, amethocaine significantly reduced the risk of pain when drugs were applied for the following durations: for 30 to 60 minutes (RR 0.61, 95% CI 0.41 to 0.91); when applied according to manufacturer's instructions (sensitivity analysis: RR 0.64, 95% CI 0.46 to 0.89); and when applied for over 60 minutes (RR 0.70, 95% CI 0.51 to 0.96). Amethocaine was also significantly more efficacious than EMLA when used specifically for intravenous cannulation (RR 0.70, 95% CI 0.55 to 0.88). Insufficient data were available to compare anaesthetic efficacy for venipuncture.A comparison of amethocaine and EMLA for ease of a needle procedure was not significant; only one trial reported data that could be included. For skin changes, EMLA was favoured in the analysis of erythema (RR 14.83, 95% CI 2.28 to 96.36). Erythema was observed after use of amethocaine whereas blanching was observed after using EMLA. Adverse effects included itching and one case of conjunctival irritation. AUTHORS' CONCLUSIONS: Although EMLA is an effective topical anaesthetic for children, amethocaine is superior in preventing pain associated with needle procedures.

Adolescent↗

Endoscopic mucosal resection for early gastric cancer.

BACKGROUND: The treatment of early gastric cancer (EGC) using an endoscopy, namely, endoscopic mucosal resection (EMR), has been adopted for about 20 years, but the effectiveness and the safety of the modality are still controversial. The quality of these trials has not been assessed systematically. OBJECTIVES: The purpose of this review was to compare the effectiveness and the safety of EMR with gastrectomy for the treatment of EGC. SEARCH STRATEGY: Searches were conducted on the Cochrane Central Register of Controlled Trials - CENTRAL (which includes the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group Trials Register) on The Cochrane Library (Issue 1 2005) MEDLINE (1966 to March 2005) and EMBASE (1980 to March 2005), CINAHL (1985-March 2005) and CBM (Chinese BioMedical Database 1982 -2002). Reference lists from trials selected by electronic searching were handsearched to identify further relevant trials. Published abstracts from conference proceedings from the United European Gastroenterology Week (published in Gut) and Digestive Disease Week (published in Gastroenterology) were handsearched. Members of the Cochrane UGPD Group, and experts in the field were contacted and asked to provide details of outstanding clinical trials and any relevant unpublished materials SELECTION CRITERIA: All randomised controlled trials of EGC patients involving a treatment arm of EMR and a comparison arm of gastrectomy were to be included, but no RCTs were found. DATA COLLECTION AND ANALYSIS: Three reviewers (YP Wang, C Bennett and T Pan) independently assessed the eligibility of potential trials and extracted the data. MAIN RESULTS: There are no included randomised control trials for the systematic review. Available evidence derived from non-randomised controlled trials is discussed in the main text of this review. AUTHORS' CONCLUSIONS: There is a lack of randomised controlled trials in which EMR is compared with gastrectomy for EGC. There is a need for well designed randomised controlled trials to determine the effects of EMR compared to gastrectomy.

Gastrectomy↗

A combined application of reaction prediction and infrared spectra simulation for the identification of degradation products of s-triazine herbicides.

Substance identification in analytical chemistry is usually performed by comparing an experimental spectrum with a reference spectrum. Especially in environmental chemistry, reference spectra from databases are only available for a limited number of compounds. The combination of the reaction prediction system EROS and of infrared spectra simulation is a powerful tool for computer-assisted substance identification. First, possible degradation products of a chemical are predicted and then the infrared spectra of all these compounds are simulated. Comparison of the simulated infrared spectra with experimental spectra allows one to identify the structure of compounds. The method is demonstrated with the example of s-triazine herbicides.

Computer Simulation↗

Systematic review comparing laparoscopic and open repair for perforated peptic ulcer.

BACKGROUND: The advantages of laparoscopic over open repair for perforated peptic ulcer are not as obvious as they may seem. This paper summarizes the published trials comparing the two approaches. METHODS: Two randomized prospective, five non-randomized prospective and eight retrospective studies were included in the analysis. Relevant trials were identified from the Medline/Pubmed database and the reference lists of the retrieved papers were then analysed. The outcome measures used were operating time, postoperative analgesic requirements, length of hospital stay, return to normal diet and usual activities, and complication and mortality rates. Published data were tested for heterogeneity by means of a chi2 test. Meta-analysis methods were used to measure the pooled estimate of the effect size. In total, 1113 patients are represented from 15 selected studies, of whom 535 were treated by laparoscopic repair and 578 by open repair; 102 patients (19.1 per cent) underwent conversion to open repair. RESULTS: Statistically significant findings in favour of laparoscopic repair were less analgesic use, shorter hospital stay, less wound infection and lower mortality rate. Shorter operating time and less suture-site leakage were advantages of open repair. Three variables (hospital stay, operating time and analgesic use) were significantly heterogeneous in the papers analysed. CONCLUSION: Laparoscopic repair seems better than open repair for low-risk patients. However, limited knowledge about its benefits and risks compared with open repair suggests that the latter, more familiar, approach may be more appropriate in high-risk patients. Further studies are needed.

Analgesics↗

Young age and outcome for women with early-stage invasive breast carcinoma.

BACKGROUND: Patients with invasive breast carcinoma who are ages 35-40 years or younger at the time of diagnosis have been found in several studies to have worse prognosis and higher local failure rates after breast-conserving therapy (BCT) compared with older patients. However, it is uncertain whether specific clinical, pathologic, or treatment factors affect these results, or whether mastectomy yields a better outcome. METHODS: Articles addressing how patient age at the time of diagnosis affects treatment outcome were identified through the MEDLINE and CancerLit databases and the reference lists of relevant articles. RESULTS: Young age was found to remain an independent risk factor for worse outcome after either BCT or mastectomy. Limited evidence did not demonstrate a superior outcome with mastectomy compared with BCT. Recent studies of BCT still reported young age to be associated with higher local recurrence rates compared with that for older patients, but their interpretation was hampered by inadequate margin assessment for ductal carcinoma in situ. Adjuvant chemotherapy has been found to improve local control rates substantially for young patients after BCT. CONCLUSIONS: To the authors' knowledge, there are insufficient data to determine whether young patients have superior long-term outcome if treated by mastectomy compared with BCT, or whether having truly uninvolved margins abrogates their increased risk of local failure after BCT. When meticulous attention is given to surgical techniques and margin status, it appears that young age at the time of diagnosis need not be a contraindication to BCT.

Adult↗

A systematic review of the clinical effectiveness of donepezil, rivastigmine and galantamine on cognition, quality of life and adverse events in Alzheimer's disease.

BACKGROUND: The use of cholinesterase inhibitors for Alzheimer's disease (AD) is currently being appraised by the National Institute for Clinical Evidence (NICE). This article provides the latest evidence that NICE will be using as part of this appraisal process. OBJECTIVE: To provide a systematic review of the best quality evidence of the effects of donepezil, rivastigmine and galantamine on cognition, quality of life and adverse events in people with mild to moderately-severe AD. DESIGN: Electronic databases were searched, references of all retrieved articles were checked, and experts were contacted for advice, peer review and to identify additional references. Randomised controlled trials (RCTs) were included if they fulfilled pre-specified criteria. Data were synthesised through a narrative review. RESULTS: Twenty-six RCTs that compared any one of the cholinesterase inhibitors with either a control group or with another cholinesterase inhibitor were included. The quality of reporting and methodology was varied. Treatment with donepezil, rivastigmine or galantamine resulted in significantly better cognitive performance using the ADAS-cog scale when compared with placebo. These findings were generally supported using the MMSE scale. Results from head to head comparisons were limited by the low number of studies and the study quality; generally showing no robust support for any one drug. Few studies evaluated quality of life. Adverse events were generally related to the gastrointestinal system, with a tendency for these to be more common in the treatment arms. CONCLUSIONS: The cholinesterase inhibitors donepezil, rivastigmine, and galantamine can delay cognitive impairment in patients with mild to moderately-severe AD for at least 6 months duration.

Alzheimer Disease↗

The proteome and secretome of human arterial smooth muscle cells.

Smooth muscle cells (SMCs) play a crucial role in cardiovascular disorders. A differential proteomic approach should help to elucidate SMC dysfunctions involved in these diseases. With this goal in mind, we plotted the first 2-dimensional (2-D) maps of the proteome and secretome of human arterial smooth muscle cell (ASMC). Intracellular and secreted proteins were extracted from a primary culture of SMCs obtained from patients undergoing coronary artery bypass surgery (n = 11) and separated by 2-dimensional gel electrophoresis. Silver-stained gels were analyzed using Progenesis software. A high level of between-gel reproducibility was obtained, allowing us to generate two protein patterns specific to the ASMC proteome and secretome, respectively. A total of 121 and 40 distinct intracellular and secreted polypeptide spots, corresponding to 83 and 18 different proteins, respectively, were identified by matrix-assisted laser desorption/ionization mass spectrometry. The 2-D reference maps and database resulting from this study confirm that SMCs are involved in a wide range of biological functions. They could constitute a useful tool for a wide range of investigators involved in vascular biology, allowing them to investigate SMC protein changes associated with cardiovascular disorders or environmental stimuli.

Cells, Cultured↗

2-D reference map of Bacillus anthracis vaccine strain A16R proteins.

Bacillus anthracis has always been an important pathogen because it can cause lethal inhalational anthrax, and may be used as a bioweapon or by bioterrorists. In this study, a 2-DE reference map and database of B. anthracis A16R was constructed. In total, 534 spots were processed, and 406 spots representing 299 proteins were identified. Gel-estimated pIs and molecular masses mostly matched well with their theoretical predictions, but some discrepancies also existed. Spot and protein corresponding analysis revealed that post-translational modifications might be common in B. anthracis. Through the MASCOT search, the similarity of B. anthracis, B. cereus and B. thuringiensis was further verified by protein level and a possible annotation error in B. anthracis strain Ames 0581 genome was found. Proteins of energy metabolism, fatty acid and phospholipid metabolism, protein synthesis, and cellular processes represented a large part of the most abundant proteins. At the same time, 27 hypothetical proteins were experimentally proved. There were 28 proteins also identified as spore composition in recently spore-related research, which indicated that they might play some roles in different phases such as growth, sporulation and outgrowth. Maps and information about all identified proteins are available on the Internet at http://www.mpiib-berlin.mpg.de/2D-PAGE and http://www.proteomics.com.cn.

Anthrax Vaccines↗

Systematic review of surgery in malignant bowel obstruction in advanced gynecological and gastrointestinal cancer. The Systematic Review Steering Committee.

OBJECTIVE: The objective was to locate, appraise, and summarize evidence from scientific studies on intestinal obstruction due to advanced gynecological and gastrointestinal cancer in order to assess the efficacy of surgery. MATERIALS AND METHODS DATA SOURCES: A comprehensive list of studies was provided by an extensive search of electronic databases, relevant journals, bibliographic databases, conference proceedings, reference lists, the gray literature, personal contact, and the worldwide web. DATA SYNTHESIS: Two researchers extracted the data independently. Due to the methodological quality of the studies, only a qualitative assessment was possible. RESULTS: The role of surgery in malignant bowel obstruction remains controversial, and no firm conclusions from the many retrospective case series can be made. Control of symptoms varies from 42% to over 80%, although it is often unclear how symptoms were measured and whether the symptom scores used are validated. There is a large range in the rates of reobstruction, from 10 to 50%, although time to reobstruction was often not included. There is a wide range of postoperative morbidity and mortality, although again the definition of both of these surgical outcomes varied among many of the papers. CONCLUSION: The role of surgery in malignant bowel obstruction needs careful evaluation, using validated outcome measures on symptom control and quality of life scores. Further information would include reobstruction rates together with the morbidity associated with the various surgical procedures. Currently, bowel obstruction is managed empirically, and there are marked variations in clinical practice by different units. There needs to be a greater standardization of management so that comparisons between different series can be made.

Female↗