The Inclusion of Practical Urology Skills in Intern Induction: A Pilot Programme.

Introduction Intern is the first postgraduate year of training and gives interns the opportunity to practice skills in real-life settings. We aim to examine the undergraduate exposure to urology across all Irish Medical Schools and assess the impact of a mandatory urology training skills session delivered during induction on the preparedness of interns ahead of starting their intern year. Methods In July 2020 all interns mandated to attend the Dublin/Mid-Leinster (DML) network intern induction underwent a 120-minute urology teaching session. The session comprised of formal teaching, followed by practical training and an informal question and answer session. All interns were asked to complete a survey before and after the session that examined undergraduate urology exposure and confidence around practical skills. Results All interns (n=74) who attended induction completed the survey. Less than half [43% (n=32]) reported a compulsory urology placement in medical school and 57% (n=42) reported previous practical training sessions in urology. There was low level of confidence in the management of urological scenarios with only 45 % (n = 33) reporting confidence in the management of urosepsis and 26 % (n = 19) in the insertion of a male catheter. There was a significant increase in self-reported confidence following the teaching session with 78 % (n = 58) interns reporting confidence in the management of urosepsis and 81 % (n = 60) in the insertion of a male catheter. Conclusion To ensure best patient care interns need to be trained in the management of common urology presentations, but our results suggest the current undergraduate curriculum is not sufficient. A dedicated theory and practical urology teaching session during intern induction was able to improve self-reported confidence and better prepare interns. Therefore we support inclusion of practical urology skills session in network intern induction.

Bladder cancer in Ireland: a 21-year review.

INTRODUCTION: Bladder carcinoma is one of the most commonly diagnosed cancers worldwide; however, various studies have reported on marked international variation in incidence and mortality rates. The aim of this study was to report national figures on incidence, survival and risk factors of bladder cancer. This retrospective review is the first to offer a comprehensive analysis of incidence rates, mortality and potential risk factors in the Irish population from 1994 to 2015. METHODS: This was a retrospective study of incidence and survival trends in bladder cancer in the Irish population from 1994 to 2014 based on data from the National Cancer Registry of Ireland (NCRI). Patient demographics, pathology and survival data, as well as potential contributing factors, were studied. RESULTS: A total of 9656 cases of bladder cancer were diagnosed from 1994 to 2015, with majority of cases occurring in males (71%). Survival decreased with increasing age, higher grade and higher stage. Bladder cancer is more common in those with a smoking history and with a higher deprivation score. Urothelial cell carcinoma was the most common pathology (95%), with the majority of patients being stage 1 or 2 (44.7%). CONCLUSION: The overall incidence of bladder cancer in Ireland has fallen, in line with reducing smoking rates. Our data reflects international trends in incidence, survival and contributing risk factors.

Satisfaction rates with the current Special Type Consultation (STC) reimbursement scheme among General Practitioners - A Mixed Methods Study.

The Special Type Consultation (STC) scheme is a fee-for-service reimbursement scheme for General Practitioners (GPs) in Ireland. Introduced in 1989, the scheme includes specified patient services involving the application of a learned skill, e.g. suturing. This study aims to establish the extent to which GPs believe this scheme is appropriate for current General Practice. This is an embedded mixed-methods study combining quantitative data on GPs working experience of and qualitative data on GPs attitudes towards the scheme. Data were collected by means of an anonymous postal questionnaire. The response rate was 60.4% (n=159.) Twenty-nine percent (n=46) disagreed and 65% (n=104) strongly disagreed that the current list of special items is satisfactory. Two overriding themes were identified: economics and advancement of the STC process. This study demonstrates an overwhelming consensus among GPs that the current STC scheme is outdated and in urgent need of revision to reflect modern General Practice.

Somatic CALR mutations in myeloproliferative neoplasms with nonmutated JAK2.

BACKGROUND: Somatic mutations in the Janus kinase 2 gene (JAK2) occur in many myeloproliferative neoplasms, but the molecular pathogenesis of myeloproliferative neoplasms with nonmutated JAK2 is obscure, and the diagnosis of these neoplasms remains a challenge. METHODS: We performed exome sequencing of samples obtained from 151 patients with myeloproliferative neoplasms. The mutation status of the gene encoding calreticulin (CALR) was assessed in an additional 1345 hematologic cancers, 1517 other cancers, and 550 controls. We established phylogenetic trees using hematopoietic colonies. We assessed calreticulin subcellular localization using immunofluorescence and flow cytometry. RESULTS: Exome sequencing identified 1498 mutations in 151 patients, with medians of 6.5, 6.5, and 13.0 mutations per patient in samples of polycythemia vera, essential thrombocythemia, and myelofibrosis, respectively. Somatic CALR mutations were found in 70 to 84% of samples of myeloproliferative neoplasms with nonmutated JAK2, in 8% of myelodysplasia samples, in occasional samples of other myeloid cancers, and in none of the other cancers. A total of 148 CALR mutations were identified with 19 distinct variants. Mutations were located in exon 9 and generated a +1 base-pair frameshift, which would result in a mutant protein with a novel C-terminal. Mutant calreticulin was observed in the endoplasmic reticulum without increased cell-surface or Golgi accumulation. Patients with myeloproliferative neoplasms carrying CALR mutations presented with higher platelet counts and lower hemoglobin levels than patients with mutated JAK2. Mutation of CALR was detected in hematopoietic stem and progenitor cells. Clonal analyses showed CALR mutations in the earliest phylogenetic node, a finding consistent with its role as an initiating mutation in some patients. CONCLUSIONS: Somatic mutations in the endoplasmic reticulum chaperone CALR were found in a majority of patients with myeloproliferative neoplasms with nonmutated JAK2. (Funded by the Kay Kendall Leukaemia Fund and others.).

A critical scoping review of external uses of comfrey (Symphytum spp.).

BACKGROUND: External preparations of the herb comfrey (most commonly Symphytum officinale L.) are widely available for over-the-counter, practitioner and healthcare professional usage. Traditional practice suggests comfrey can be used to treat musculoskeletal disorders, wounds and various other conditions; however a full and critical coverage of the evidence base has not yet been undertaken. METHODS: A critical scoping review was undertaken. Six bibliographic databases, 10 grey literature databases and nine trials registers were searched plus reference lists of included studies and a descriptive overview of comfrey. Randomised or non-randomised clinical trials assessing the external use of comfrey for any indication were included and methodological and reporting quality were assessed. Observational studies were included only in the assessment of adverse events. Studies were grouped and summarised according to the type of indication treated. RESULTS: Of 1348 identified records, 64 full texts were screened for inclusion and 26 were included in the review - 13 RCTs, 5 non-randomised controlled trials and 8 observational studies evaluating treatments for ankle distortion, back pain, abrasion wounds, venous leg ulcers and osteoarthritis. The majority of included trials had an overall unclear risk of bias due to poor quality of reporting. Few adverse events were reported. CONCLUSIONS: Individual clinical trials showed evidence of benefit for ankle distortion, back pain, abrasion wounds and osteoarthritis. Topical application appears to be safe but further rigorous assessment is needed. Systematic reviews focussing on particular indications may clarify the treatment effect and safety of external comfrey preparations.

Systematic review and mixed treatment comparison: dressings to heal diabetic foot ulcers.

AIMS/HYPOTHESIS: Foot ulcers in people with diabetes are a common and serious global health issue. Dressings form a key part of ulcer treatment. Existing systematic reviews are limited by the lack of head-to-head comparisons of alternative dressings in a field where there are several different dressing options. We aimed to determine the relative effects of alternative wound dressings on the healing of diabetic foot ulcers. METHODS: This study was a systematic review involving Bayesian mixed treatment comparison. We included randomised controlled trials evaluating the effects on diabetic foot ulcer healing of one or more wound dressings. There were no restrictions based on language or publication status. RESULTS: Fifteen eligible studies, evaluating nine dressing types, were included. Ten direct treatment comparisons were made. Whilst there was increased healing associated with hydrogel and foam dressings compared with basic wound contact materials, these findings were based on data from small studies at unclear or high risk of bias. The mixed treatment comparison suggested that hydrocolloid-matrix dressings were associated with higher odds of ulcer healing than all other dressing types; there was a high degree of uncertainty around these estimates, which were deemed to be of very low quality. CONCLUSIONS/INTERPRETATION: These findings summarise all available trial evidence regarding the use of dressings to heal diabetic foot ulcers. More expensive dressings may offer no advantages in terms of healing than cheaper basic dressings. In addition, evidence pointing to a difference in favour of 'advanced' dressing types over basic wound contact materials is of low or very low quality.

Lipoxins: update and impact of endogenous pro-resolution lipid mediators.

Lipoxins (LXs) are endogenously produced eicosanoids that are typically generated by transcellular biosynthesis. These trihydroxytetraene-containing lipid mediators and their stable synthetic analogues possess a wide spectrum of anti-inflammatory and pro-resolution bioactions both in vitro and in vivo. More recently, LXs have emerged as potential anti-fibrotic mediators that may influence pro-fibrotic cytokines and matrix-associated gene expression in response to platelet-derived growth factor (PDGF). Here we review the biosynthesis, metabolism and bioactions of LXs and LX analogues and their therapeutic potential.

Antibiotics and antiseptics for venous leg ulcers.

BACKGROUND: Venous leg ulcers are a type of chronic wound affecting up to 1% of adults in developed countries at some point during their life. Many of these wounds are colonised by bacteria or show signs of clinical infection. The presence of infection may delay ulcer healing. There are two main strategies used to prevent and treat clinical infection in venous leg ulcers: systemic antibiotics and topical antibiotics or antiseptics. OBJECTIVES: The objective of the review is to determine the effects of systemic antibiotics and topical antibiotics and antiseptics on the healing of venous ulcers. SEARCH STRATEGY: The following databases were searched up to October 2007: the Cochrane Wounds Group Specialised Register; the Cochrane Central Register of Controlled Trials; MEDLINE; EMBASE; and CINAHL. In addition, the reference lists of included studies and relevant review articles were examined. SELECTION CRITERIA: Randomised controlled trials recruiting people with venous leg ulceration that evaluated at least one systemic antibiotic, topical antibiotic or topical antiseptic and reported an objective assessment of wound healing (e.g. time to complete healing, frequency of complete healing, change in ulcer surface area) were eligible for inclusion. Selection decisions were made by three authors working independently. DATA COLLECTION AND ANALYSIS: Information on the characteristics of participants, interventions and outcomes were recorded on a standardised data extraction form. In addition, aspects of trial methods were extracted, including methods of randomisation and allocation concealment, use of blinded outcome assessment, intention-to-treat analysis, reporting of patient follow-up and study group comparability at baseline. Data extraction and validity assessment were conducted by one author and checked by a second. MAIN RESULTS: Twenty two trials were identified of different antibiotics and antiseptics, including systemic antibiotics (5 trials). The remainder were topical preparations: cadexomer iodine (10 trials); povidone iodine (2 trials); peroxide-based preparations (3 trials); ethacridine lactate (1 trial); and mupirocin (1 trial). For the systemic antibiotics, the only comparison where a statistically significant between-group difference was detected was that in favour of the antihelminthic levamisole when compared with placebo. This trial, in common with the other evaluations of systemic antibiotics, was small and so the observed effect could have occurred by chance. In terms of topical preparations, there is some evidence to suggest that cadexomer iodine generates higher healing rates than standard care. One study showed a statistically significant result in favour of cadexomer iodine when compared with standard care (not involving compression) in terms of frequency of complete healing at six weeks (RR 2.29, 95% CI 1.10 to 4.74). The intervention regimen used was intensive, involving daily dressing changes, and so these findings may not be generalisable to most everyday clinical settings. When cadexomer iodine was compared with standard care with all patients receiving compression, the pooled estimate from two trials for frequency of complete healing at 4 to 6 weeks indicated significantly higher healing rates for cadexomer iodine (RR 6.72, 95% CI 1.56 to 28.95). Surrogate healing outcomes such as change in ulcer surface area and daily or weekly healing rate showed favourable results for cadexomer iodine, peroxide-based preparations and ethacridine lactate in some studies. These surrogate outcomes may not be valid proxies for complete healing of the wound. Most of the trials were small and many had methodological problems such as poor baseline comparability between groups, failure to use (or report) true randomisation, adequate allocation concealment, blinded outcome assessment and analysis by intention-to-treat. AUTHORS' CONCLUSIONS: At present, there is no existing evidence to support the routine use of systemic antibiotics to promote healing in venous leg ulcers. However, the lack of reliable evidence means that it is not possible to recommend the discontinuation of any of the agents reviewed. In terms of topical preparations, there is some evidence to support the use of cadexomer iodine. Further good quality research is required before definitive conclusions can be made about the effectiveness of systemic antibiotics and topical preparations such as povidone iodine, peroxide-based preparations, ethacridine lactate and mupirocin in healing venous leg ulceration. In light of the increasing problem of bacterial resistance to antibiotics, current prescribing guidelines recommend that antibacterial preparations should only be used in cases of defined infection and not for bacterial colonisation.

Patient acceptability of larval therapy for leg ulcer treatment: a randomised survey to inform the sample size calculation of a randomised trial.

BACKGROUND: A trial was commissioned to evaluate the effectiveness of larval therapy to debride and heal sloughy and necrotic venous leg ulcers. Larval therapy in the trial was to be delivered in either loose or bagged form. Researchers were concerned that resistance to larval therapy may threaten the feasibility of the trial. Additionally there was concern that the use of larval therapy may require a larger effect size in time to healing than originally proposed by the investigators. METHODS: To formally evaluate patient preferences a survey using two randomly allocated, nurse administered questionnaires was undertaken. Patients were randomised to receive one of the two following questionnaires (i) preferences between loose larvae and standard treatment (hydrogel) or (ii) patient preferences between bagged larvae and standard therapy (hydrogel). The study was undertaken in a Vascular Clinic, in an Outpatients Department of a large teaching hospital in the North of England. The sample consisted of 35 people aged 18 years and above with at least one leg ulcer of venous or mixed (venous and arterial) aetiology. RESULTS: Approximately 25% of participants would not consider the use of larval therapy as an acceptable treatment option for leg ulcers, regardless of the method of containment. For the patients that would consider the use of larval therapy, different preferences in healing times required to use the therapy were observed depending upon the method of containment. The median response of those participants questioned about bagged larvae found that they would be willing to use this therapy even if they were equally able to achieve healing with the use of hydrogel by 20 weeks. For those participants questioned about the use of loose larvae complete healing would have to have taken place over 17 weeks for them to choose larvae as their preferred option rather than hydrogel. This difference was not significant (p = 0.075). CONCLUSION: We found no evidence of widespread resistance to the utilisation of larval therapy from patients regardless of the method of larval therapy containment. These methods have the potential to inform sample size calculations where there are concerns of patient acceptability.

A series of systematic reviews to inform a decision analysis for sampling and treating infected diabetic foot ulcers.

OBJECTIVES: To review systematically the evidence on the performance of diagnostic tests used to identify infection in diabetic foot ulcers (DFUs) and of interventions to treat infected DFUs. To use estimates derived from the systematic reviews to create a decision analytic model in order to identify the most effective method of diagnosing and treating infection and to identify areas of research that would lead to large reductions in clinical uncertainty. DATA SOURCES: Electronic databases covering period from inception of the database to November 2002. REVIEW METHODS: Selected studies were assessed against validated criteria and described in a narrative review. The structure of a decision analytic model was derived for two groups of patients in whom diagnostic tests were likely to be used. RESULTS: Three studies that investigated the performance of diagnostic tests for infection on populations including people with DFUs found that there was no evidence that single items on a clinical examination checklist were reliable in identifying infection in DFUs, that wound swabs perform poorly against wound biopsies, and that semi-quantitative analysis of wound swabs may be a useful alternative to quantitative analysis. However, few people with DFUs were included, so it was not possible to tell whether diagnostic performance differs for DFUs relative to wounds of other aetiologies. Twenty-three studies investigated the effectiveness (n = 23) or cost-effectiveness (n = 2) of antimicrobial agents for DFUs. Eight studied intravenous antibiotics, five oral antibiotics, four different topical agents such as dressings, four subcutaneous granulocyte colony stimulating factor (G-CSF), one evaluated oral and topical Ayurvedic preparations and one compared topical sugar versus antibiotics versus standard care. The majority of trials were underpowered and were too dissimilar to be pooled. There was no strong evidence for recommending any particular antimicrobial agent for the prevention of amputation, resolution of infection or ulcer healing. Topical pexiganan cream may be as effective as oral antibiotic treatment with ofloxacin for the resolution of local infection. Ampicillin and sulbactam were less costly than imipenem and cilastatin, a growth factor (G-CSF) was less costly than standard care and cadexomer iodine dressings may be less costly than daily dressings. A decision analytic model was derived for two groups of people, those for whom diagnostic testing would inform treatment--people with ulcers which do not appear infected but whose ulcer is not progressing despite optimal concurrent treatment--and those in whom a first course of antibiotics (prescribed empirically) have failed. There was insufficient information from the systematic reviews or interviews with experts to populate the model with transition probabilities for the sensitivity and specificity of diagnosis of infection in DFUs. Similarly, there was insufficient information on the probabilities of healing, amputation or death in the intervention studies for the two populations of interest. Therefore, we were unable to run the model to inform the most effective diagnostic and treatment strategy. CONCLUSIONS: The available evidence is too weak to be able to draw reliable implications for practice. This means that, in terms of diagnosis, infection in DFUs cannot be reliably identified using clinical assessment. This has implications for determining which patients need formal diagnostic testing for infection, on whether empirical treatment with antibiotics (before the results of diagnostic tests are available) leads to better outcomes, and on identifying the optimal methods of diagnostic testing. With respect to treatment, it is not known whether treatment with systemic or local antibiotics leads to better outcomes or whether any particular agent is more effective. Limited evidence suggests that both G-CSF and cadexomer iodine dressings may be less expensive than 'standard' care, that ampicillin/sulbactam may be less costly than imipenem/cilastatin, and that an unlicensed cream (pexiganan) may be as effective as oral ofloxacin. Further research is needed to ascertain the characteristics of infection in people with DFUs that influence healing and amputation outcomes, to determine whether detecting infection prior to treatment offers any benefit over empirical therapy, and to establish the most effective and cost-effective methods for detecting infection, as well as the relative effectiveness and cost-effectiveness of antimicrobial interventions for DFU infection.

Systematic review of methods to diagnose infection in foot ulcers in diabetes.

AIM: To undertake a systematic review of the diagnostic performance of clinical examination, sample acquisition and sample analysis in infected foot ulcers in diabetes. METHODS: Nineteen electronic databases plus other sources were searched. To be included, studies had to fulfil the following criteria: (i) compare a method of clinical assessment, sample collection or sample analysis with a reference standard; (ii) recruit diabetic individuals with foot ulcers; (ii) present 2 x 2 diagnostic data. Studies were critically appraised using a 12-item checklist. RESULTS: Three eligible studies were identified, one each on clinical examination, sample collection and sample analysis. For all three, study groups were heterogeneous with respect to wound type and a small proportion of participants had foot ulcers due to diabetes. No studies identified an optimum reference standard. Other methodological problems included non-blind interpretation of tests and the time lag between index and reference tests. Individual signs or symptoms of infection did not prove to be useful tests when assessed against punch biopsy as the reference standard. The wound swab did not perform well when assessed against tissue biopsy. Semiquantitative analysis of wound swab might be a useful alternative to quantitative analysis. The limitations of these findings and their impact on recommendations from relevant clinical guidelines are discussed. CONCLUSION: Given the importance of this topic, it is surprising that only three eligible studies were identified. It was not possible to describe the optimal methods of diagnosing infection in diabetic patients with foot ulceration from the evidence identified in this systematic review.

Systematic review of antimicrobial treatments for diabetic foot ulcers.

BACKGROUND: Foot ulcers in diabetes are associated with increased mortality, illness and reduced quality of life. Ulcer infection impairs healing and antimicrobial interventions may cure infection, aid healing and reduce amputation rates. OBJECTIVES: To systematically review the evidence for antimicrobial interventions for foot ulcers in diabetes. METHODS: We searched 16 databases, 11 Internet sites, three books, conference proceedings, a journal and bibliographies in November 2002. We included randomized controlled trials (RCTs) or controlled clinical trials (CCTs). RESULTS: Twenty-three studies investigated the effectiveness or cost-effectiveness of antimicrobial agents: intravenous antibiotics (n = 8); oral antibiotics (n = 5); topical antimicrobials (n = 4); subcutaneous granulocyte-colony stimulating factor (G-CSF) (n = 4); Ayurvedic preparations (n = 1): and sugar vs. antibiotics vs. standard care (n = 1). The trials were small and too dissimilar to be pooled. There is no strong evidence for any particular antimicrobial agent for the prevention of amputation, resolution of infection, or ulcer healing. Pexiganan cream may be as effective as oral ofloxacin for resolution of infection. Ampicillin and sulbactam cost less than imipenem/cilastatin, G-CSF cost less than standard care and cadexomer iodine dressings may cost less than daily dressings. CONCLUSIONS: The evidence is too weak to recommend any particular antimicrobial agent. Large studies are needed of the effectiveness and cost-effectiveness of antimicrobial interventions.

Clinical effectiveness, tolerability and cost-effectiveness of newer drugs for epilepsy in adults: a systematic review and economic evaluation.

OBJECTIVES: To examine the clinical effectiveness, tolerability and cost-effectiveness of gabapentin (GBP), lamotrigine (LTG), levetiracetam (LEV), oxcarbazepine (OXC), tiagabine (TGB), topiramate (TPM) and vigabatrin (VGB) for epilepsy in adults. DATA SOURCES: Electronic databases. Internet resources. Pharmaceutical company submissions. REVIEW METHODS: Selected studies were screened and quality assessed. Separate analyses assessed clinical effectiveness, serious, rare and long-term adverse events and cost-effectiveness. An integrated economic analysis incorporating information on costs and effects of newer and older antiepileptic drugs (AEDs) was performed to give direct comparisons of long-term costs and benefits. RESULTS: A total of 212 studies were included in the review. All included systematic reviews were Cochrane reviews and of good quality. The quality of randomised controlled trials (RCTs) was variable. Assessment was hampered by poor reporting of methods of randomisation, allocation concealment and blinding. Few of the non-randomised studies were of good quality. The main weakness of the economic evaluations was inappropriate use of the cost-minimisation design. The included systematic reviews reported that newer AEDs were effective as adjunctive therapy compared to placebo. For newer versus older drugs, data were available for all three monotherapy AEDs, although data for OXC and TPM were limited. There was limited, poor-quality evidence of a significant improvement in cognitive function with LTG and OXC compared with older AEDs. However, there were no consistent statistically significant differences in other clinical outcomes, including proportion of seizure-free patients. No studies assessed effectiveness of AEDs in people with intellectual disabilities or in pregnant women. There was very little evidence to assess the effectiveness of AEDs in the elderly; no significant differences were found between LTG and carbamazepine monotherapy. Sixty-seven RCTs compared adjunctive therapy with placebo, older AEDs or other newer AEDs. For newer AEDs versus placebo, a trend was observed in favour of newer drugs, and there was evidence of statistically significant differences in proportion of responders favouring newer drugs. However, it was not possible to assess long-term effectiveness. Most trials were conducted in patients with partial seizures. For newer AEDs versus older drugs, there was no evidence to assess the effectiveness of LEV, LTG or OXC, and evidence for other newer drugs was limited to single studies. Trials only included patients with partial seizures and follow-up was relatively short. There was no evidence to assess effectiveness of adjunctive LEV, OXC or TPM versus other newer drugs, and there were no time to event or cognitive data. No studies assessed the effectiveness of adjunctive AEDs in the elderly or pregnant women. There was some evidence from one study (GBP versus LTG) that both drugs have some beneficial effect on behaviour in people with learning disabilities. Eighty RCTs reported the incidence of adverse events. There was no consistent or convincing evidence to draw any conclusions concerning relative safety and tolerability of newer AEDs compared with each other, older AEDs or placebo. The integrated economic analysis for monotherapy for newly diagnosed patients with partial seizures showed that older AEDs were more likely to be cost-effective, although there was considerable uncertainty in these results. The integrated analysis suggested that newer AEDs used as adjunctive therapy for refractory patients with partial seizures were more effective and more costly than continuing with existing treatment alone. Combination therapy, involving new AEDs, may be cost-effective at a threshold willingness to pay per quality-adjusted life year (QALY) greater than 20,000 pounds, depending on patients' previous treatment history. There was, again, considerable uncertainty in these results. There were few data available to determine effectiveness of treatments for patients with generalised seizures. LTG and VPA showed similar health benefits when used as monotherapy. VPA was less costly and was likely to be cost-effective. The analysis indicated that TPM might be cost-effective when used as an adjunctive therapy, with an estimated incremental cost-effectiveness ratio of 34,500 pounds compared with continuing current treatment alone. CONCLUSIONS: There was little good-quality evidence from clinical trials to support the use of newer monotherapy or adjunctive therapy AEDs over older drugs, or to support the use of one newer AED in preference to another. In general, data relating to clinical effectiveness, safety and tolerability failed to demonstrate consistent and statistically significant differences between the drugs. The exception was comparisons between newer adjunctive AEDs and placebo, where significant differences favoured newer AEDs. However, trials often had relatively short-term treatment durations and often failed to limit recruitment to either partial or generalised onset seizures, thus limiting the applicability of the data. Newer AEDs, used as monotherapy, may be cost-effective for the treatment of patients who have experienced adverse events with older AEDs, who have failed to respond to the older drugs, or where such drugs are contraindicated. The integrated economic analysis also suggested that newer AEDs used as adjunctive therapy may be cost-effective compared with the continuing current treatment alone given a QALY of about 20,000 pounds. There is a need for more direct comparisons of the different AEDs within clinical trials, considering different treatment sequences within both monotherapy and adjunctive therapy. Length of follow-up also needs to be considered. Trials are needed that recruit patients with either partial or generalised seizures; that investigate effectiveness and cost-effectiveness in patients with generalised onset seizures and that investigate effectiveness in specific populations of epilepsy patients, as well as studies evaluating cognitive outcomes to use more stringent testing protocols and to adopt a more consistent approach in assessing outcomes. Further research is also required to assess the quality of life within trials of epilepsy therapy using preference-based measures of outcomes that generate cost-effectiveness data. Future RCTs should use CONSORT guidelines; and observational data to provide information on the use of AEDs in actual practice, including details of treatment sequences and doses.

A systematic review of the clinical effectiveness of orlistat used for the management of obesity.

The aim of this paper is to assess the clinical effectiveness of orlistat used for the management of obesity. Nineteen electronic databases were searched for randomized controlled trials evaluating the effectiveness of orlistat for weight loss or maintenance of weight loss in overweight or obese patients. Each included trial was assessed for methodological quality. Statistical pooling was performed when trials were considered to be sufficiently similar. Twenty-three trials were eligible for inclusion. Placebo-controlled trials recruiting patients with uncomplicated obesity reported statistically significant differences in favour of orlistat for weight loss and changes in obesity-related risk factors at all time points. Trials in obese patients with defined risk factors at baseline showed similar results, however, smaller effect sizes were observed in patients with type 2 diabetes. The effectiveness of orlistat relative to other anti-obesity drugs is currently unclear. When orlistat was added to simvastatin, this proved to be more effective for weight loss than either drug used individually. Orlistat use is associated with a higher incidence of gastrointestinal adverse events compared with placebo. In conclusion, orlistat is more effective than placebo in promoting weight loss, maintenance of weight loss, and improving cardiovascular risk factor profiles. Baseline parameters of patients seen in clinical practice should be taken into account when considering treatment.

The prevention and treatment of childhood obesity.

The effectiveness of interventions used in the prevention and treatment of childhood obesity published in a recent issue of Effective Heath Care is reviewed.

Interventions for preventing obesity in children.

BACKGROUND: The prevalence of obesity and overweight is increasing in both adult and child populations throughout the world. Obesity in children impacts on their health in both the short and longer term, and obesity prevention is an international public health priority. However, the efficacy of prevention strategies is poorly understood. OBJECTIVES: To assess the effectiveness of educational, health promotion and/or psychological/family/behavioural therapy/counselling/management interventions that focussed on diet, physical activity and/or lifestyle and social support, and were designed to prevent obesity in childhood. SEARCH STRATEGY: The following databases were searched: MEDLINE, Psyclit, EMBASE, Science Citation Index, Social Science Citation Index, CINAHL, Cochrane Controlled Trials Register (CCTR) and the Cochrane Heart Group's specialised register from 1985 to July 2001. Non English language papers were included. Experts were contacted to seek additional references or unpublished studies. SELECTION CRITERIA: RCTs and non-randomised trials with concurrent control group that observed participants for a minimum of three months were included DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed study quality. MAIN RESULTS: Ten studies were included; seven were long-term (children observed for at least one year), three were shorter term (at least 3 months). Eight were school/nursery-based interventions, one was a community-based intervention targeting low-income African-American families, and one was a family-based intervention that targeted non-obese children of obese parents. The studies included were diverse in terms of study design and quality, target population, theoretical underpinning of intervention approach, and outcome measures, so it was not possible to combine study findings using statistical methods. Three of the four long-term studies that combined dietary education and physical activity interventions resulted in no difference in overweight, whereas one study reported an improvement in favour of the intervention group. In two studies of dietary education alone, a multimedia action strategy appeared to be effective but other strategies did not. The one long term study that only focussed on physical activity resulted in a slightly greater reduction in overweight in favour of the intervention group, as did two short term studies of physical activity. REVIEWER'S CONCLUSIONS: There is limited high quality data on the effectiveness of obesity prevention programs and no generalisable conclusions can be drawn. However, concentration on strategies that encourage reduction in sedentary behaviours and increase in physical activity may be fruitful. The need for well-designed studies that examine a range of interventions remains a priority, although a number of important studies are underway.