Heterogeneity in outcome selection, definition and measurement in studies assessing the treatment of cryptoglandular anal fistula: findings from a systematic review.

BACKGROUND: Treatment for cryptoglandular anal fistula (AF) is challenging and a lack of uniform outcomes in the literature prevents direct comparison of treatments. This can be addressed by developing a core outcome set, a standardised set of outcomes reported in all interventional studies for a specific condition. The aim of this systematic review is to assess the range of outcomes, their definitions, and the measurement instruments currently utilised in interventional studies for adult patients with AF. This will inform the development of an AF core outcome set. METHODS: Medline, Embase and The Cochrane Library were searched to identify all patient- and clinician-reported outcomes in studies assessing medical, surgical or combination treatment of adult patients with AF published from January 2008 to May 2020. The resulting outcomes were categorized according to the Core Outcome Measurement in Effectiveness Trials (COMET) taxonomy to better understand their distribution. RESULTS: In total, 155 studies were included, 552 outcomes were extracted, with a median of three outcomes (interquartile range 2-5) per study. Only 25% of studies demonstrated high-quality outcome reporting. The outcomes were merged into 52 unique outcomes and structured into four core areas and 14 domains, with the majority in the domain of physiological or clinical (gastrointestinal) outcomes. The most commonly reported outcomes were healing (77%), incontinence (63%), and recurrence (40%), with no single outcome assessed across all studies. There was a wide variation in outcome definitions and measurement instruments used. CONCLUSIONS: There is substantial heterogeneity in outcomes, definitions, and measurement instruments reported in interventional studies for cryptoglandular anal fistula. This emphasises the need for standardised outcome reporting and measurement.

European Society of ColoProctology: guideline for haemorrhoidal disease.

AIM: The goal of this European Society of ColoProctology project was to establish a multidisciplinary, international guideline for haemorrhoidal disease (HD) and to provide guidance on the most effective (surgical) treatment for patients with HD. METHODS: The development process consisted of six phases. In phase one we defined the scope of the guideline. The patient population included patients with all stages of haemorrhoids. The target group for the guideline was all practitioners treating patients with haemorrhoids and, in addition, healthcare workers and patients who desired information regarding the treatment management of HD. The guideline needed to address both the diagnosis of and the therapeutic modalities for HD. Phase two consisted of the compilation of the guideline development group (GDG). All clinical members needed to have affinity with the diagnosis and treatment of haemorrhoids. Further, attention was paid to the geographical distribution of the clinicians. Each GDG member identified at least one patient in their country who could read English to comment on the draft guideline. In phase three review questions were formulated, using a reversed process, starting with possible recommendations based on the GDG's knowledge. In phase four a literature search was performed in MEDLINE (Ovid), PubMed, Embase (Ovid) and the Cochrane Database of Systematic Reviews. The search was focused on existing systematic reviews addressing each review question, supplemented by other studies published after the time frame covered by the systematic reviews. In phase five data of the included papers were extracted by the surgical resident (RT) and checked by the methodologist (JK) and the GDG. If needed, meta-analysis of the systematic reviews was updated by the surgical resident and the methodologist using Review Manager. During phase six the GDG members decided what recommendations could be made based on the evidence found in the literature using GRADE. RESULTS: There were six sections: (i) symptoms, diagnosis and classification; (ii) basic treatment; (iii) outpatient procedures; (iv) surgical interventions; (v) special situations; (vi) other surgical techniques. Thirty-four recommendations were formulated. CONCLUSION: This international, multidisciplinary guideline provides an up to date and evidence based summary of the current knowledge of the management of HD and may serve as a useful guide for patients and clinicians.

Towards a core outcome set for hemorrhoidal disease-a systematic review of outcomes reported in literature.

PURPOSE: Previously published literature regarding treatment of hemorrhoidal disease (HD) revealed a lack of uniform defined outcomes. These differences between outcomes among studies limit transparency and lead to incomparability of results. The aim of this study was to systematically list the types of outcomes used in HD studies. This list will be used to develop a core outcome set. METHODS: We searched Medline (Pubmed), Embase (OVID), and Cochrane for interventional studies for adult patients with HD. Two authors independently identified and reviewed eligible studies. This resulted in a list of outcomes reported by each clinical trial. All outcomes were categorized using the conceptual framework OMERACT filter 2.0. RESULTS: A total of 34 randomized controlled trials and prospective observational studies were included in this study. A total of 59 different types of outcomes were identified. On average, 5.8 different outcomes (range 2-8) were used per study. The outcomes were structured into three core areas and10 ten domains. The most commonly reported core area was pathophysiological manifestations including the domain symptoms, complications, and recurrence. The most frequently reported outcomes were pain (91%), blood loss (94%), prolapse (71%), and incontinence (56%). There was a high variation in definitions of the common outcomes. And often there was no definition at all. CONCLUSION: This study shows a substantial heterogeneity in the types of outcomes in HD studies. We provided an overview of the types of outcomes reported in HD studies and identified a list of potentially relevant outcomes required for the development of a COS.

[Algorithm for Choosing the Study Design in Systematic Reviews]. / Algorithmus zur Auswahl von Studientypen in systematischen Reviews.

Background: The Federal Joint Committee (Gemeinsamer Bundesausschuss) assigns the highest evidence level of Ia to systematic reviews of randomized controlled trials in evaluating the benefit of therapeutic interventions. Contradictory results among randomized and non-randomized studies may not always be caused by the study design. Methods: The objective of the study was to identify statements in systematic or non-systematic reviews about the choice of study designs in systematic reviews. Another objective was to develop an algorithm to facilitate the choice of appropriate study designs in systematic reviews. Results: The inclusion of non-randomized in addition to randomized study designs was supported by 85% of the 42 identified articles. A strong reason was the need to evaluate the possible treatment-associated harm. The developed algorithm included the 4 decision points of length of follow-up, frequency of events, outcomes, and study designs. Conclusions: If the benefit and the harm of a therapeutic intervention is planned to be evaluated, then often multiple study designs are required to be included. The algorithm provides guidance on which study designs should be considered for inclusion in systematic reviews.

Measurement properties of patient-reported outcome measures used in rehabilitation of adults with chronic musculoskeletal pain: A mapping review.

BACKGROUND: Choosing measurement tools for diagnostic, prognostic, or evaluative purposes in a chronic musculoskeletal pain (CMP) population is challenging for rehabilitation practice. Implementation of measurement tools for clinical practice is impaired by gaps in knowledge about measurement properties. OBJECTIVE: Identifying evidence about the measurement properties of tools frequently used in Dutch pain rehabilitation practice. METHODS: A mapping review was conducted of eligible studies that investigated reliability, validity, or responsiveness, and interpretability, as defined by the COSMIN taxonomy, of original versions or Dutch translations of predefined Patient-Reported Outcome Measures (PROMs) in a CMP population. MEDLINE, PsycINFO, EMBASE, and CINAHL were searched in March 2021. Results were visually mapped. RESULTS: Thirty-five studies were included. The results show many knowledge gaps in both original and translated versions. In general, aspects of validity were most frequently reported. The Pain Disability Index, Pain Catastrophizing Scale, and the 12-Item Short Form Health Survey were the most studied measurement tools. No results were found for the Checklist Individual Strength, Illness Perception Questionnaire, and Utrecht Coping List. CONCLUSION: Little evidence of the measurement properties of PROMs used in rehabilitation of patients with CMP in the Netherlands was found. PROMs need to be used and interpreted with caution in daily practice.

5% lidocaine-medicated plaster vs other relevant interventions and placebo for post-herpetic neuralgia (PHN): a systematic review.

Several pharmacological treatments are used to manage post-herpetic neuralgia (PHN). The use of topical analgesics, such as 5% lidocaine-medicated plaster (5% LMP), may be preferable to systemic treatments in that they are formulated to produce a local pain relieving effect with minimal systemic absorption. However, direct head-to-head comparisons are relatively few, and a rigorous assessment of the relative efficacy and safety of the various treatment options is lacking. The objective of this study was to compare 5% LMP for the relief of PHN with other relevant interventions and placebo. Six databases were searched up to May 2010. Quantitative methods for data synthesis were used, and a network meta-analysis was conducted. Twenty unique studies (32 publications) were included. Placebo-controlled studies showed 5% LMP to be effective in providing pain relief and reducing allodynia while adverse event rates were generally low. A comparison between 5% LMP and pregabalin indicated the non-inferiority of 5% LMP for pain reduction and showed greater improvement of quality of life for 5% LMP. Adverse events (AE) were significantly fewer with 5% LMP. In the network meta-analysis, only 5% LMP and gabapentin were associated with a greater change in pain from baseline than placebo [-15.50 (95% CI -18.85 to -12.16) and -7.56 (95% CI -12.52 to -2.59) respectively]. 5% LMP was shown to be more effective than capsaicin [-16.45 (95% CI -20.04 to -12.86)], gabapentin [-7.95 (95% CI -13.29 to -2.61)] and pregabalin [-13.45 (95% CI -19.19 to -7.71)]. For pain relief, two comparators were more effective than placebo [mean pain relief, gabapentin: 32.77 (95% CI 15.57-49.97); 5% LMP: 26.77 (95% CI 9.11-44.43)]. 5% LMP was shown to be comparable to gabapentin [-6.00 (95% CI -25.32-13.32)]. The results suggest that 5% LMP and gabapentin have similar effects on pain relief and that 5% LMP is more effective than capsaicin and pregabalin (change in pain from baseline). Topical agents, such as 5% LMP, are associated with fewer and less clinically significant AE than is the case for systemic agents. However, small numbers, and limited size and quality of included studies should be taken into account. Further studies are needed.

Fetal umbilical artery Doppler to predict compromise of fetal/neonatal wellbeing in a high-risk population: systematic review and bivariate meta-analysis.

OBJECTIVE: We investigated the accuracy of fetal umbilical artery Doppler to predict the risk of compromise of fetal/neonatal wellbeing in a high-risk population. METHODS: Searches in MEDLINE, Embase, The Cochrane Library and Medion (from inception to March 2009) were carried out, together with hand searching of relevant journals, reference list checking of included articles and contact with experts. Criteria for selection were observational studies with umbilical artery Doppler used in a high-risk pregnant population with an outcome measure for compromise of fetal/neonatal wellbeing. Data on study design, quality and results were extracted to construct 2 × 2 tables. Bivariate meta-analysis was performed. Likelihood ratios (LRs) were used as the summary measure of accuracy. RESULTS: One-hundred and four studies met the selection criteria (19 191 fetuses). In a high-risk population, umbilical artery Doppler predicted small-for-gestational age with a pooled LR+ of 3.76 (2.96, 4.76) and pooled LR- of 0.52 (0.45, 0.61), and compromise of fetal/neonatal wellbeing with a pooled LR+ of 3.41 (2.68, 4.34) and pooled LR- of 0.55 (0.48, 0.62). In this group it was also possible to predict, with accuracy, intrauterine death (pooled LR+ = 4.37 (0.88, 21.8); pooled LR- = 0.25 (0.07, 0.91)) and acidosis (pooled LR+ = 2.75 (1.48, 5.11); pooled LR- = 0.58 (0.36, 0.94)). CONCLUSIONS: In a high-risk population, fetal umbilical artery Doppler is a moderately useful test with which to predict mortality and risk of compromise.

[Epidemiology of chronic non-malignant pain in Germany]. / Epidemiologie von nicht tumorbedingten chronischen Schmerzen in Deutschland.

BACKGROUND: Although chronic pain is a common health problem, epidemiological data are rare. The aim of this study is to present information on chronic, non-malignant pain in Germany. METHODS: In order to identify relevant studies on chronic pain (> 3 months) a total of 7 databases were searched in the timeframe from 1995 to 2009. Representative, recent, comprehensive and valid studies were selected. RESULTS: The prevalence of chronic pain in Germany is estimated to be 17% and varies according to the underlying cause of the disease. Neck, shoulder and back pain are the most common forms. Chronic pain has a direct impact on quality of life (QoL), days off work and costs. A variety of drugs and non-drug treatments are used. However, treatment is often inadequate with 13-51% of the patients receiving insufficient pain therapy. CONCLUSIONS: Chronic pain is a common problem which influences the QoL of patients resulting in high costs for the health system. Treatment is often inadequate. More research is needed to close knowledge gaps. The transfer of research results into clinical practice should be improved.

Ethical issues in engineering models: an operations researcher's reflections.

This article starts with an overview of the author's personal involvement--as an Operations Research consultant--in several engineering case-studies that may raise ethical questions; e.g., case-studies on nuclear waste, water management, sustainable ecology, military tactics, and animal welfare. All these case studies employ computer simulation models. In general, models are meant to solve practical problems, which may have ethical implications for the various stakeholders; namely, the modelers, the clients, and the public at large. The article further presents an overview of codes of ethics in a variety of disciples. It discusses the role of mathematical models, focusing on the validation of these models' assumptions. Documentation of these model assumptions needs special attention. Some ethical norms and values may be quantified through the model's multiple performance measures, which might be optimized. The uncertainty about the validity of the model leads to risk or uncertainty analysis and to a search for robust models. Ethical questions may be pressing in military models, including war games. However, computer games and the related experimental economics may also provide a special tool to study ethical issues. Finally, the article briefly discusses whistleblowing. Its many references to publications and websites enable further study of ethical issues in modeling.

Living systematic reviews in rehabilitation science can improve evidence-based healthcare.

Although systematic reviews are considered as central components in evidence-based practice, they currently face an important challenge to keep up with the exponential publication rate of clinical trials. After initial publication, only a minority of the systematic reviews are updated, and it often takes multiple years before these results become accessible. Consequently, many systematic reviews are not up to date, thereby increasing the time-gap between research findings and clinical practice. A potential solution is offered by a living systematic reviews approach. These types of studies are characterized by a workflow of continuous updates which decreases the time it takes to disseminate new findings. Although living systematic reviews are specifically designed to continuously synthesize new evidence in rapidly emerging topics, they have also considerable potential in slower developing domains, such as rehabilitation science. In this commentary, we outline the rationale and required steps to transition a regular systematic review into a living systematic review. We also propose a workflow that is designed for rehabilitation science.

Systematic review of aromatase inhibitors in the first-line treatment for hormone sensitive advanced or metastatic breast cancer.

To undertake a systematic review of three first-line treatments (letrozole, anastrozole and exemestane) for hormone sensitive advanced or metastatic breast cancer (MBC) in post-menopausal women. We searched six databases from inception up to January 2009 for relevant trials regardless of language or publication status. Randomised controlled clinical trials assessing the safety and efficacy of first-line AIs for post-menopausal women with hormone receptor-positive (HR+, i.e. ER+ and/or PgR+) with or without ErbB2 (HER2)-positive MBC, who have not received prior therapy for advanced or metastatic disease were included. Where meta-analysis using direct or indirect comparisons was considered unsuitable for some or all of the data, we employed a narrative synthesis method. Four studies (25 papers) met the inclusion criteria. From the available evidence, it was possible to directly compare the three AIs with tamoxifen. In addition, by using a network meta-analysis it was possible to compare the three AIs with each other. Based on direct evidence, letrozole seemed to be significantly better than tamoxifen in terms of time-to-progression (TTP) (HR = 0.70 (95% CI: 0.60, 0.82)), objective response rate (RR = 0.65 (95% CI: 0.52, 0.82)) and quality-adjusted time without symptoms or toxicity (Q-Twist difference = 1.5; P < 0.001). Exemestane seemed significantly superior to tamoxifen in terms of objective response rate (RR = 0.68 (95% CI: 0.53, 0.89)). Anastrozole seemed significantly superior to tamoxifen in terms of TTP in one trial (HR = 1.42 (95% CI: 1.15, NR)), but not in the other (HR = 1.01 (95% CI: 0.87, NR)). In terms of adverse events, no significant differences were found between letrozole and tamoxifen. Tamoxifen was associated with significantly more serious adverse events in comparison with exemestane (OR = 0.61 (95% CI: 0.38, 0.97)); while exemestane was associated with significantly more arthralgia in comparison with tamoxifen (OR = 2.33 (95% CI: 1.07, 5.11)). Anastrozole was associated with significantly more total adverse events (OR = 1.04 (95% CI: 1.00, 1.09)) and hot flushes (OR = 1.39 (95% CI: 1.03, 1.89)) in comparison with tamoxifen in one trial; however, the other trial showed no significant differences in adverse events between anastrozole and tamoxifen. The indirect comparison of AIs with each other in women with post-menopausal, hormone sensitive advanced or MBC showed that letrozole and exemestane were better in terms of objective response rate than anastrozole; while the more clinically relevant outcomes overall survival (OS) and progression-free survival (PFS) showed no significant differences between AIs. OS and PFS showed no significant differences between AIs and hence based on these results a class effect for all AIs is possible. However, these results are based on indirect comparisons and a network analysis for which the basic assumptions of homogeneity, similarity and consistency were not fulfilled. Therefore, despite the fact that these are the best available data, the results need to be interpreted with appropriate caution. Head-to-head comparisons between letrozole, anastrozole and exemestane in the first-line MBC setting are warranted.

The development of a cryptoglandular Anal Fistula Core Outcome Set (AFCOS): an international Delphi study protocol.

PURPOSE: Cryptoglandular anal fistula is a disorder with an incidence of around 1 per 5,000 people per year in European countries. Many studies have been conducted to evaluate the effectiveness of interventions for anal fistula. However, there is considerable heterogeneity in the outcomes assessed and reported in these studies. This limits research quality and complicates evidence synthesis. A solution for heterogeneity in outcome reporting is the development of a Core Outcome Set (COS). This paper describes the protocol for the development of a European COS for Anal Fistula (AFCOS). METHODS: The first step will be a systematic review of the literature to identify potential outcomes that may be included in the COS. Patient interviews will be conducted in The United Kingdom and The Netherlands to ensure that both clinician-important and patient-important outcomes are captured. The outcomes will be categorized using the COMET taxonomy and taken forward to a Delphi consensus exercise. In up to three web-based Delphi surveys the outcomes will be prioritized by patients, clinicians (surgeons, gastroenterologists, and radiologists), and (clinical) researchers. The responses will be summarized and reported anonymously in subsequent round(s) facilitating convergence to a consensus opinion. The final COS will be decided during a face-to-face consensus meeting with patients, clinicians, and (clinical) researchers. DISCUSSION: This study protocol describes the development of a European COS for anal fistula to improve research quality, evidence synthesis, and patient care.

Quality of randomised trials in COPD.

Randomised trials can provide high-level evidence to inform treatment decisions. Since their quality in respiratory medicine is largely unknown, we assessed the quality of a large set of chronic obstructive pulmonary disease (COPD) trials. As a marker of trial quality, we assessed the procedure and concealment of random allocation, and the conduct of an intention-to-treat-analysis in 344 randomised trials published between 1957 and 2006. We used ordered logistic regression to assess the association between trial quality and type of intervention, type of journal, journal impact factor and year of publication. 257 (75%) trials assessed pharmacological and 87 (25%) assessed nonpharmacological interventions. The generation of appropriate randomisation was reported in 27.0% of the trials, concealment of random allocation in 11.6% and an intention-to-treat analysis in 21.8% of trials. Significantly higher quality was found in trials on nonpharmacological interventions (OR 2.49, 95% CI 1.56-3.99), and in trials published in general medical journals (versus specialised journals; OR 2.25, 95% CI 1.30-3.90) and after 2000 (versus 1957-2000; OR 2.28, 95% CI 1.45-3.58). The association of quality with a high impact factor was of borderline significance (p = 0.06). The quality of many COPD trials is low but tends to become better since the adoption of the CONSORT (Consolidated Standards of Reporting Trials) statement.

Smoking cessation interventions in COPD: a network meta-analysis of randomised trials.

The aim of this study was to rank order the effectiveness of smoking cessation interventions for chronic obstructive pulmonary disease (COPD) patients. We searched 10 databases to identify randomised trials of smoking cessation counselling (SCC) with or without pharmacotherapy or nicotine replacement therapy (NRT). We conducted a network meta-analysis using logistic regression analyses to assess the comparative effectiveness of smoking cessation interventions while preserving randomisation of each trial. The analysis of 7,372 COPD patients from six out of eight identified trials showed that SCC in combination with NRT had the greatest effect on prolonged abstinence rates versus usual care (OR 5.08, p<0.0001) versus SCC alone (2.80, p = 0.001) and versus SCC combined with an antidepressant (1.53, p = 0.28). The second most effective intervention was SCC combined with an antidepressant (3.32, p = 0.002) versus SCC alone (1.83, p = 0.007), with no difference between antidepressants. SCC alone was of borderline superiority compared with usual care (1.81, p = 0.07). A small body of evidence suggests that SCC combined with NRT is more effective than other combinations and single smoking cessation treatments in COPD, but substantially more research is needed for this most important COPD treatment.

Predicting foot ulcers in patients with diabetes: a systematic review and meta-analysis.

Clinical guidelines recommend that all patients with diabetes should be screened annually to establish their risk of foot ulceration. The aim of this systematic review was to quantify the predictive value of diagnostic tests, physical signs and elements from the patient's history in relation to diabetic foot ulcers. Observational studies were identified from: electronic databases (MEDLINE, EMBASE and CINAHL); bibliographies of studies meeting the inclusion criteria; review articles and clinical guidelines; direct contact with authors. Published reports of cohort and case-control studies were considered for inclusion. Pooled estimates were calculated from absolute numbers as weighted mean differences, standard mean differences or odds ratios. Adjusted odds ratios from published reports were also extracted. We identified five case-control and 11 cohort studies. The incidence of foot ulcers ranged from 8% to 17% in the cohort studies, with varying lengths of follow-up. Diagnostic tests and physical signs that detect peripheral neuropathy (biothesiometry, monofilaments and absent ankle reflexes), and those that detect excessive plantar pressure (peak plantar pressure and joint deformity) were all significantly associated with future diabetic foot ulceration. However, there was a paucity of evidence concerning the predictive value of symptoms and signs. Further research is needed to establish the independent factors associated with diabetic foot ulceration, particularly elements from a patient's history and physical examination.

A systematic review of duplex ultrasound, magnetic resonance angiography and computed tomography angiography for the diagnosis and assessment of symptomatic, lower limb peripheral arterial disease.

OBJECTIVES: To determine the diagnostic accuracy and cost-effectiveness of duplex ultrasound (DUS), magnetic resonance angiography (MRA), and computed tomography angiography (CTA), as alternatives to contrast angiography (CA), for the assessment of lower limb peripheral arterial disease (PAD). DATA SOURCES: Ten electronic databases were searched in April 2004, with an update in May 2005. Six key journals and bibliographies of included studies were also searched and experts in the field were consulted. REVIEW METHODS: Data extraction and quality assessment were performed in duplicate. Data were analysed according to test type and diagnostic threshold. For the economic analysis, a decision tree was developed and a probabilistic sensitivity analysis performed to incorporate statistical uncertainty into the cost-effectiveness analysis. RESULTS: A total of 113 studies met the inclusion criteria (including six economic evaluations). For the detection of stenosis greater than 50% in the whole leg, contrast-enhanced (CE) MRA (14 studies) had the highest diagnostic accuracy, with sensitivity ranging from 92 to 99.5% and specificity from 64 to 99%. Two-dimensional (2D) time-of-flight (TOF) MRA (11 studies) was less accurate, with sensitivity ranging from 79 to 94% and specificity from 74 to 92%. 2D phase-contrast (PC) MRA (one study) had a sensitivity of 98% and specificity of 74%. CTA (seven studies) also appeared slightly inferior to CE MRA, with a sensitivity ranging from 89 to 99% and specificity from 83 to 97%, but better than DUS (28 studies), which had a sensitivity ranging from 80 to 98% and specificity from 89 to 99%. There was some indication that CE MRA and DUS were more accurate for detecting stenoses/occlusions above the knee than below the knee or in the pedal artery. The four studies of patient attitudes strongly suggested that patients preferred CE MRA to CA. CA was considered the most uncomfortable test, followed by CE MRA, with CTA being the least uncomfortable. Half of the patients (from a sample who did not suffer from claustrophobia and had no metallic implants) expressed no preference between undergoing TOF MRA or DUS; most of those who did express a preference favoured TOF MRA. In the 55 studies identified for adverse events, MRA was associated with the highest reported proportion. However, the most severe adverse events were more common in patients undergoing CA; although these were rare for both tests. The economic evaluation showed DUS dominated the other alternatives when the whole leg was assessed, by presenting higher effectiveness at a lower cost per quality-adjusted life-year (QALY; i.e. 13,646 pounds per QALY). When the assessment was limited to a section of the leg, either above the knee or below the knee, 2D TOF MRA was the most cost-effective preoperative diagnostic strategy. The incremental cost per QALY for below-the-knee comparisons was equal to 37,024 pounds when 2D TOF MRA was compared with DUS. For above-the-knee comparisons, 2D TOF MRA presented the lowest cost and slightly lower effectiveness compared with CE MRA, with a cost per QALY equal to 13,442 pounds. CONCLUSIONS: The results of the review suggest that CE MRA has a better overall diagnostic accuracy than CTA or DUS, and that CE MRA is generally preferred by patients over CA. Where available, CE MRA may be a viable alternative to CA. The only controlled trial suggested that the results of DUS were comparable to those of CA, in terms of surgical planning and outcome. This finding conflicts with the results of diagnostic accuracy studies, which reported poor estimates of accuracy for DUS in comparison with CA. There was insufficient evidence to evaluate the usefulness of CTA for the assessment of PAD, particularly newer techniques. The results of the economic modelling suggest that for PAD patients for whom the whole leg is evaluated by a preoperative diagnostic test, DUS dominates the other alternatives by presenting higher effectiveness at a lower cost per QALY. However, when the analysis of stenosis is limited to a section of the leg, either above the knee or below the knee, 2D TOF MRA appears to be the most cost-effective preoperative diagnostic strategy. Further research is needed into a number of areas including the relative clinical effectiveness of the available imaging tests, in terms of surgical planning and postoperative outcome.

Diagnostic accuracy of faecal occult blood tests used in screening for colorectal cancer: a systematic review.

OBJECTIVE: To determine the accuracy of guaiac and immunochemical faecal occult blood tests (FOBTs) for the detection of colorectal cancer in an average-risk screening population. METHODS: Fifteen electronic databases, the internet, key journals and reference lists of included studies were searched. We included diagnostic accuracy studies that compared guaiac or immunochemical FOBTs with any reference standard, for the detection of colorectal cancer in an average-risk adult population, with sufficient data to construct a 2 x 2 table. RESULTS: Fifty-nine studies were included. Thirty-three evaluated guaiac FOBTs, 35 immunochemical FOBTs and one evaluated sequential FOBTs. Sensitivities for the detection of all neoplasms ranged from 6.2% (specificity 98.0%) to 83.3% (specificity 98.4%) for guaiac FOBTs, and 5.4% (specificity 98.5%) to 62.6% (specificity 94.3%) for immunochemical FOBTs. Specificity ranged from 65.0% (sensitivity 44.1%) to 99.0% (sensitivity 19.3%) for guaiac FOBTs, and 89.4% (sensitivity 30.3%) to 98.5% (sensitivity 5.4%) for immunochemical FOBTs. Diagnostic case-control studies generally reported higher sensitivities. Sensitivities were higher for the detection of CRC, and lower for adenomas, in both the diagnostic cohort and diagnostic case-control studies for both guaiac and immunochemical FOBTs. CONCLUSIONS: Immudia HemSp appeared to be the most accurate immunochemical FOBT, however, there was no clear evidence to suggest whether guaiac or immunochemical FOBTs performed better, either from direct or indirect comparisons. Poor reporting of data limited the scope of this review, and the use the Standards for Reporting of Diagnostic Accuracy guidelines is recommended for reporting future diagnostic accuracy studies.

Molindone for schizophrenia and severe mental illness.

BACKGROUND: Antipsychotic therapy is the mainstay of treatment for people with schizophrenia. In recent years new or atypical antipsychotics have been introduced. These are less likely to produce movement disorders and raise serum prolactin. Researchers have suggested that molindone should be classified as an atypical antipsychotic. OBJECTIVES: To determine the effects of molindone compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and related psychoses. SEARCH STRATEGY: For the original search we searched the following databases: Biological Abstracts (1980-1999), The Cochrane Library CENTRAL (Issue 1, 1999), The Cochrane Schizophrenia Group's Register (January 1999), CINAHL (1982-1999), EMBASE (1980-1999), MEDLINE (1966-1999), LILACS (1982-1999), PSYNDEX (1977-1999), and PsycLIT (1974-1999). We also searched pharmaceutical databases on the Dialog Corporation Datastar and Dialog and the references of all identified studies for further trials. Finally, we contacted the manufacturer of molindone and the authors of any relevant trials. For the update of this review, we searched The Cochrane Schizophrenia Group's Trials Register (August 2005). SELECTION CRITERIA: We included all randomised controlled trials that compared molindone to other treatments for schizophrenia and schizophrenia-like psychoses. DATA COLLECTION AND ANALYSIS: We extracted data independently and analysed on an intention to treat basis calculating, for binary data, the fixed effect relative risk (RR), their 95% confidence intervals (CI), and the number needed to treat or harm (NNT or NNH). We excluded data if loss to follow up was greater than 50%. MAIN RESULTS: We included fourteen studies. Duration ranged from very short (10 days) studies of the intramuscular preparation, to trials lasting over three months. For measures of global assessment, available data do not justify any conclusions on the comparative efficacy of molindone and placebo. When compared to other typical antipsychotics we found no evidence of a difference in effectiveness (doctors' 4 RCTs n=150, RR 1.13, CI 0.69 to 1.86; nurses 4RCTs n=146, RR 1.23, CI 0.82 to 1.86). Molindone is no more or less likely than typical drugs to cause movement disorders, but it does cause significantly more weight loss (2RCTs n=60 RR 2.78, CI 1.10 to 6.99, NNH 5 CI 2 to 77). AUTHORS' CONCLUSIONS: The strength of the evidence relating to this compound is limited, owing to small sample size, poor study design, limited outcomes and incomplete reporting. Molindone may be an effective antipsychotic but its adverse effect profile does not differ significantly from that of typical antipsychotics (apart from the event of weight loss). Data from this review suggest, at present, there is no evidence to suggest that it may have an atypical profile.