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Antibiotic guidelines and antibiotic use in adult bacterial meningitis in The Netherlands.

In The Netherlands, national guidelines for the treatment of adult patients with bacterial meningitis were introduced in October 1997. In 1998 we began a prospective, nationwide study to evaluate the compliance with these consensus-based guidelines. In addition, we evaluated whether the recommended initial treatment provides adequate microbiological coverage. From October 1998 to January 2000, 365 adults with bacterial meningitis were identified using information from The Netherlands Reference Laboratory for Bacterial Meningitis; 263 patients were classified into four categories depending on patient's age and underlying health status. In the first category, patients 16-60 years without risk factors, Neisseria meningitidis was the most common pathogen (53%); 62 of 127 patients (49%) received treatment in compliance with the guidelines. In the second and third categories, patients >60 years without risk factors and those with risk factors independently of age, Streptococcus pneumoniae caused 61% and 58% of cases, respectively. Compliance in these categories was about 17%. Overall, 33% of patients received treatment in compliance with the guidelines. The microbiological coverage of patients treated in compliance and not in compliance with the guidelines was 98% and 93%, respectively. In conclusion, 1 year after national consensus-based guidelines for the initial treatment of adult patient with bacterial meningitis were introduced in The Netherlands, only one-third of Dutch physicians were adhering to the guidelines. The microbiological coverage for the patients who were treated in compliance with the guidelines was almost complete (98%).

Adolescent↗

European best practice guidelines for the management of anaemia in patients with chronic renal failure.

Best practice guidelines recommend management strategies and attempt to set standards for optimal patient care. The momentum towards formulating guidelines comes not only from health care professionals, but also from health care management organizations, who need some way of measuring the quality of the services they purchase. The European Best Practice Guidelines for the Management of Anaemia in Patients with Chronic Renal Failure have been drawn up by a Working Party including representatives of the European Renal Association/European Dialysis and Transplantation Association (ERA-EDTA) and the national nephrology societies of a cross-section of European countries. The guidelines draw on the National Kidney Foundation-Dialysis Outcomes Quality Initiative (NKF-DOQI) Clinical Best Practice Guidelines for the Treatment of Anemia in Chronic Renal Failure, but reflect European clinical practice and experience. They include additional publications, and new analysis and interpretation of the evidence base. Topics covered in the European guidelines include diagnosis of the anaemia of chronic renal failure, indications for starting treatment with epoetin, recommended minimum target haemoglobin concentrations, epoetin dosage and route of administration, assessing and optimizing iron stores, causes and management of epoetin resistance, and possible adverse effects of epoetin treatment. The guidelines are not intended to be prescriptive but rather to provide clinical guidance based on the best available evidence. The evidence supporting each guideline is graded, so that physicians may judge its reliability.

Anemia↗

Impact of a worker's compensation practice guideline on lumbar spine fusion in Washington State.

OBJECTIVES: In the face of escalating medical costs for injured workers, the Washington State Department of Labor and Industries (L&I), which pays for most workers' compensation costs in the state, established guidelines for elective lumbar fusion as part of its inpatient utilization review program. The guidelines were tied to reimbursement strictures. The authors attempt to assess the effects of these guidelines, which were introduced in November 1988, upon subsequent L&I fusion procedures. METHODS: Discharge data from the Comprehensive Hospital Abstract Reporting System and algorithms using International Classification of Diseases, Version 9, Clinical Modification diagnosis and procedure codes were used to identify lumbar surgical cases. Population estimates were from the 1990 US Census Bureau. RESULTS: During the period of years 1987 through 1992, the lumbar fusion rate for the state showed a 26% decline compared with a 3% decrease for all lumbar operations. After November 1988, when the guidelines went into effect, the state fusion rate declined 33%, whereas rates for nonfusion operations essentially were unchanged. The sharpest decline corresponded in time to implementation of the guidelines. Prior to the initiation of L&I guidelines, the proportion of fusions among L&I patients was higher than among non-L&I patients. The opposite was true by the end of 1992, and the L&I proportion decreased more rapidly than the non-L&I proportion. Time series analysis revealed that both the decline in Washington state lumbar fusion rates and the decline in the proportion of lumbar fusion among L&I patients were statistically significant. CONCLUSIONS: The data suggest that the L&I lumbar fusion surgery criteria and reimbursement standards implemented in 1988 contributed to a decline in rates of performing that procedure. The utilization review aspect of the guidelines as well as the process of involving surgeons in the preparation and dissemination of guidelines also may have been contributory.

Adult↗

Evaluating an integrated approach to clinical quality improvement: clinical guidelines, quality measurement, and supportive system design.

BACKGROUND: Implementing clinical practice guidelines to change patient outcomes presents a challenge. Studies of single interventions focused on changing provider behavior demonstrate modest effects, suggesting that effective guideline implementation requires a multifaceted approach. Traditional biomedical research designs are not well suited to evaluating systems interventions. OBJECTIVES: RAND and the Army Medical Department collaborated to develop and evaluate a system for implementing guidelines and documenting their effects on patient care. RESEARCH DESIGN: The evaluation design blended quality improvement, case study, and epidemiologic methods. A formative evaluation of implementation process and an outcome evaluation of patient impact were combined. SUBJECTS: Guidelines were implemented in 3 successive demonstrations targeting low back pain, asthma, and diabetes. This paper reports on the first wave of 4 facilities implementing a low back pain guideline. METHODS: Organizational climate and culture, motivation, leadership commitment, and resources were assessed. Selected indicators of processes and outcomes of care were compared before, during, and after guideline implementation at the demonstration facilities and at comparison facilities. Logistic regression analysis was used to test for guideline effects on patient care. RESULTS: Process evaluation documented varied approaches to quality improvement across sites. Outcome evaluation revealed a significant downward trend in the percentage of acute low back pain patients referred to physical therapy or chiropractic care (10.7% to 7.2%) at demonstration sites and no such trend at control sites. CONCLUSIONS: Preliminary results suggest the power of this design to stimulate improvements in guideline implementation while retaining the power to evaluate rigorously effects on patient care.

Adolescent↗

Guideline attribute and implementation preferences among physicians in multiple health systems.

OBJECTIVES: Although practice guidelines are effective in assisting providers with clinical decision making, ineffective implementation strategies often prevent their use in practice. This study aimed to understand physician preferences for guideline format, placement, content, evidence, and learning strategies in different clinical environments. SUBJECTS AND METHODS: Semistructured telephone interviews were conducted with 500 randomly selected physicians from 4 major US health systems who were involved in the treatment of patients with acute myocardial infarction or pediatric asthma. Paired sample t tests and Tukey's method of comparisons determined the relative ranking of physicians' guideline implementation preferences. RESULTS: Physicians preferred guidelines located on the front of the patient chart, in palm pilots, or in progress notes and presented as flow charts/flow diagrams, algorithms, or preprinted orders that contain strategies to minimize readmits/encourage self-management and immediate treatment flows. Discussions with colleagues and continuing medical education are the most effective strategies for encouraging guideline use, and randomized controlled trials remain the most persuasive medical evidence. CONCLUSIONS: Health care organizations must align guideline implementation efforts with physician preferences to encourage utilization. The results of this study reveal systematic physician preferences for guideline implementation that can be applied to clinical settings to encourage guideline use by physicians.

Asthma↗

The effect of a materials-based intervention on knowledge of risk-based clinical prevention screening guidelines.

The release of the U.S. Preventive Services Task Force guidelines (GUIDELINES) introduces an opportunity to modify patient expectations about the timing of routine examinations. This randomized, controlled study examines the effect of a materials-based educational intervention on knowledge and beliefs about risk-based preventive screening guidelines. The study was conducted in a large multi-specialty group practice participating in a network model HMO in the upper midwest with over 250,000 members. Subjects were selected from patients of a primary care clinic in a suburban section of a major metropolitan area. A 48-page prevention guidebook based on the GUIDELINES was distributed to a randomly assigned treatment group of 200 patients enrolled in an HMO. A 22-item questionnaire on preventive health services that measured respondents' age-adjusted risks and knowledge of risk-based screening guidelines was sent to both experimental and control groups. A 69% response rate was achieved. chi 2 analysis and t-tests showed that the treatment group was significantly more accurate in identifying recommended GUIDELINES for colon examinations (digital rectal, stool occult, sigmoidoscopy), blood pressure, and Pap tests. No significant differences related to identifying GUIDELINES for mammograms and clinical breast examinations were found between the groups. Communications about new screening guidelines can yield positive but selective changes in knowledge and beliefs about appropriate screening intervals.

Communication↗

Impact of guidelines to alter antitetanus prophylaxis practices and reduce costs in the emergency department.

The objective of this study was to assess the impact of an intervention to modify antitetanus prophylaxis of open wounds. This prospective, before-and-after study was conducted in an emergency department of a large metropolitan hospital. Consecutive patients with open wounds were managed according to the World Health Organization (WHO) guidelines before an intervention, then according to new guidelines afterwards. Locally developed guidelines were introduced and backed up by a teaching program, with emphasis on reducing unwarranted human tetanus immunoglobulins and costs. Serum tetanus antitoxins level was measured in postintervention patients mainly to verify the soundness of the intervention, eventually to complete patients' protection during follow-up, and to derive more reliable recommendations for the future. Main outcome measures included the number of treatments conforming to each set of guidelines, the rate of tetanus immunoglobulin prescriptions, and the cost of each strategy. Two groups of 389 and 459 patients were included. Treatment conforming to guidelines increased from 60% to 79%, undertreatment decreased from 31% to 19%, and overtreatment decreased from 9% to 2% (P < 0.001). Tetanus immunoglobulin prescriptions decreased from 23% to 1% (P < 0.001). On the basis of antitoxins level, 60% of 367 postintervention patients were correctly treated, 29% were overtreated, and 11% were undertreated. Nevertheless, with the WHO guidelines, only 49% would have been correctly treated, 39% would have been overtreated (29% with immunoglobulins), and 12% would have been undertreated (P < 0.001). Costs decreased from $32 to $24 per patient. New guidelines resulted in improved tetanus prophylaxis at reduced costs in an emergency department. Because they rely on immunization history, however, guidelines currently in use are misleading. More reliable recommendations, including a test for tetanus antibody status in some cases, are needed.

Adult↗

Chronic obstructive pulmonary disease international guidelines.

Although chronic obstructive pulmonary disease (COPD) has a public health importance similar to asthma, it has received less attention. The first guideline on the management of COPD was released in 1987 by the American Thoracic Society. In 1992 the Canadian Thoracic Society released its guidelines. In 1995 the European Respiratory Society and the Thoracic Society of Australia and New Zealand released their guidelines and the American Thoracic Society updated and expand its COPD guidelines. All these documents were followed in 1997 by the guidelines developed by the British Thoracic Society. These COPD guidelines show many similarities but also have some interesting differences. The aim of this paper is to review these similarities and discrepancies. Like all guidelines, COPD guidelines suffer from the limited amount of evidence-based medicine supporting them, a limitation that, however, provides a strong stimulus for further research.

Female↗

Guidelines for nutritional support in intensive care unit patients: a critical analysis.

PURPOSE OF REVIEW: Guidelines are supposed to be helpful in clinical practice. Guidelines are also supposed to rest upon the evidence that there is. In the field of clinical nutrition the problem is that many clinical trials are not conclusive because they are underpowered and sometimes have an inferior design. RECENT FINDINGS: The publication of the Canadian guidelines one year ago initiated a lively debate. The Canadian guidelines used meta-analysis as a tool to review the literature. This resulted in both a sound evaluation of studies as well as some controversial recommendations. The Canadian guidelines are here put in a perspective in which the older type of guidelines are compared, and some of the points of recommendation are scrutinized. SUMMARY: What all guidelines agree upon is the shortage of solid knowledge, the conviction that complications related to nutritional therapy in the intensive care unit are not acceptable, and that enteral nutrition is preferable if it can be given without risk. Beyond that, many controversies remain and the need for high quality prospective studies must be emphasized. In addition, such studies must address the clinically important questions that the guidelines try to answer.

Critical Illness↗

Impact of self-reported familiarity with guidelines for cystic fibrosis carrier screening.

OBJECTIVE: To assess the impact of self-reported familiarity with published guidelines on knowledge, implementation, and opinions of obstetrician-gynecologists regarding carrier screening for cystic fibrosis. METHODS: A questionnaire pertaining to cystic fibrosis screening guidelines was mailed to 1,165 members of the American College of Obstetricians and Gynecologists. RESULTS: Sixty-four percent of questionnaires were returned. Statistical analyses were limited to the 632 respondents whose primary medical specialty was gynecology (GynOnly) or obstetrics and gynecology (ObGyns). More ObGyns had thoroughly read or skimmed the guidelines (67.1%) than had GynOnlys (41.6%). Correctly responding to basic questions regarding cystic fibrosis was associated with having read the guidelines, although responding to a more complex question was not. Familiarity with the guidelines was associated with correctly identifying the recommendations for offering screening, with practice implementation of cystic fibrosis screening, and with self-ratings of qualifications and training to offer screening and to provide counseling. In contrast, familiarity with the guidelines was not associated with ObGyn's opinion that burden of disease is likely to be influential in patient acceptance of screening. Physicians who had thoroughly read the guidelines were more likely to disagree that the cystic fibrosis screening test is too inaccurate to risk influencing reproductive decision making (thoroughly read = 79% disagree, skimmed = 69%, not read = 58%, not heard of it = 50%). CONCLUSION: There was a strong association between self-reported familiarity with the American College of Obstetricians and Gynecologists/American College of Medical Genetics guidelines and physicians' knowledge, implementation, and ratings of training for offering cystic fibrosis carrier screening.

Attitude of Health Personnel↗

Factors impeding the implementation of cardiovascular prevention guidelines: findings from a survey conducted by the European Society of Cardiology.

BACKGROUND: Cardiovascular disease mortality remains high in Europe and many patients have elevated risk factors, despite evidence-based targets and treatment guidelines. This survey examined barriers to implementing cardiovascular risk reduction guidelines. DESIGN: We conducted a semi-structured market research survey of physicians. METHODS: The survey was conducted in six European countries among cardiologists and primary care physicians. In total, 67 questions were used: 35 had multiple choice answers (prompted) and 32 allowed any answer (unprompted). Respondents were working full-time in patient care (>or=3 years experience) and were in a position to initiate cardiovascular drug treatment. RESULTS: Of the 220 respondents (155 primary care physicians, 65 cardiologists), most (85%) based assessment of cardiovascular risk on all risk factors, reflecting a global approach to risk, rather than considering risk factors individually. A majority (62%) used subjective assessments for establishing global risk rather than guidelines or risk calculators. The most common unprompted barrier to guideline implementation was patient compliance (36%) and a lack of time (23%), and when prompted, the most important was government health policy (40%). The most common unprompted suggestion for improving implementation were financial opportunities (24%) and clear and easy to use guidelines (23%), while when prompted the most important change required was the development of simpler guidelines (46%). CONCLUSIONS: Although a majority of physicians are aware of the need to look at a combination of cardiovascular disease risk factors, less than half use guidelines or risk calculators to determine total risk. It is recommended that guidelines need to be simpler and easier to use and supplemented with (patient friendly) risk calculators.

Cardiovascular Diseases↗

Pressure ulcers: guideline development and economic modelling.

AIM: This paper presents the development process for clinical guidelines on the use of pressure-relieving devices (beds, mattresses and overlays), with emphasis on incorporating economic evidence. BACKGROUND: Previous UK guidelines on the use of pressure-relieving devices to prevent pressure ulcers have not considered whether any recommendations made are cost effective. The routine inclusion of cost effectiveness evidence in guidelines is a recent policy development, and there has been little research into its potential role in the guideline process. METHODS: We systematically reviewed the literature to assess both the clinical and cost effectiveness of pressure-relieving devices for prevention of pressure ulcers. Where there was sufficient evidence on the comparative clinical effectiveness between alternative devices, economic modelling was undertaken to assess comparative cost effectiveness. A guideline development group (comprising both clinicians and patient representatives) reviewed all the available evidence to formulate clinical practice guidelines and recommendations for further research. RESULTS: Studies showed that caring for people vulnerable to developing pressure ulcers on high-specification foam mattresses compared with standard hospital mattresses significantly reduced their risk of developing a pressure ulcer. Cost effectiveness modelling indicated that, because of savings accruing through treating fewer pressure ulcers, high-specification foam mattresses are likely to cost less overall and are more effective. The resulting clinical practice guideline was uncompromising on the use of high-specification foam mattresses as the minimum provision in patients vulnerable to pressure ulcers. Significant weaknesses were identified in both the quality and availability of evidence for most of the other pressure relieving devices considered. CONCLUSIONS: Cost effectiveness assessment was an integral part of the guideline development process. It clarified the shortcomings of some of the clinical effectiveness evidence and helped in formulating pragmatic clinical practice recommendations.

Bedding and Linens↗

Developing a tool to appraise fetal monitoring guidelines for women at low obstetric risk.

AIM: The aim of this paper is to report the development and use of a tool to appraise guidelines for fetal heart rate monitoring and discuss the findings generated in the appraisal process. BACKGROUND: Expert guidance on the appropriate method of monitoring the fetal heart in labour has been available for some time. However, practices not based on evidence were continuing routinely in the United Kingdom. METHODS: We produced an 18-item tool for the appraisal of guidelines. Heads of Midwifery Services were asked to send the guideline currently in use. Twenty-four out of 28 responded, and sent 32 guidelines. Pairs of multidisciplinary reviewers appraised each guideline. RESULTS: A prevalidated generic appraisal instrument was not found to be appropriate for intrapartum fetal monitoring guidelines. When using our own specifically-developed appraisal tool for assessing the quality of fetal monitoring guidelines, only 11 reviewer pairs showed 'good' or 'moderate' agreement in their scores. CONCLUSIONS: Generically-validated guidelines may not be sufficiently discriminatory for specialized areas of practice such as intrapartum fetal monitoring.

Evidence-Based Medicine↗

Evaluating national guidelines for prevention of cardiovascular disease in primary care.

INTRODUCTION: National guidelines for prevention of cardiovascular disease make different recommendations in relation to screening and treating patients with aspirin, antihypertensive treatment and statins. The resource cost and health implications of these differences are quantified in this paper. DATA SOURCES: Guidelines were obtained from Australia, New Zealand, Canada, UK and USA. Effectiveness data were obtained from published sources, costs and a model population of 2000 patients from US sources. METHOD: The resource costs and health effects of screening and treating a standard population of 2000 persons were determined for each of the five national guidelines. Costs and effects were calculated over a 5-year time horizon and cost-effectiveness determined cost per cardiovascular event prevented. RESULTS: Cost per cardiovascular event prevented is lowest in older patients and very high under 35. The New Zealand guidelines are more cost-effective of the national guidelines, however, they would be more effective if they incorporated US recommendations on the use of aspirin. Further antihypertensive treatment is the least cost-effective of the interventions considered. DISCUSSION: Cardiovascular disease prevention guidelines should focus on older rather than younger patients. Treatment eligibility should be informed more by risk than by individual risk factor status. Guidelines should put greater emphasis on the use of aspirin and initial antihypertensive treatment than on achieving blood pressure targets. CONCLUSION: In order to justify their recommendations guidelines should quantify the resource implications in relation to the health benefits.

Adolescent↗

Primary care nurses using guidelines in Thailand: a randomized controlled trial.

BACKGROUND: Nurses run primary health centres in Thailand. We examined whether clinical guidelines improved the quality of the care they provide. METHODS: Eighteen nurse-led health centres randomized to (a) guidelines, receiving a training workshop plus educational outreach visit, with guidelines for children (acute respiratory tract infection and diarrhoea) and adults (diazepam prescribing and diabetes management) or (b) usual care. Outcomes were changes at 6 months in antibiotic use, diazepam prescribing, drug costs per patient, and a composite process index for diabetes care. RESULTS: Baseline prescribing was high for antibiotics (37% of all attendees), and no difference between intervention and control sites was detected at follow-up for this variable. In children (0-5 years old), antibiotics were widely used for acute respiratory tract infection (34%), and fell with guidelines (intervention: 42% at baseline to 27% at follow-up; control: 27-30%, P=0.022), with an associated fall in drug costs per patient. Antibiotics were widely prescribed for diarrhoea in children (91%), but no change was detected with guidelines. In adults, diazepam prescribing at baseline was high (17%), and fell in the guidelines group (intervention: 17-10%; control 21-18%; P=0.029). Diabetes care was generally good, and changed little with guidelines. CONCLUSION: Staff at primary health centres over-prescribe antibiotics in children and tranquilizer in adults. Clinical guidelines implemented with workshops and educational outreach visits improved some but not all aspects of prescribing in the short-term.

Acute Disease↗

Management guidelines for Helicobacter pylori infection: utilization by paediatric gastroenterologists in Australasia.

OBJECTIVE: Although there are published guidelines representing the consensus of several large groups, it is unclear whether these are used by practitioners in the management of Helicobacter pylori infection in children and if the guidelines are relevant to particular regions of the world. The aim of this study was to answer these questions in regard to the Australasian region. METHODS: An email-based questionnaire was circulated to Australasian paediatric gastroenterologists to ascertain aspects of practice related to H. pylori infection in children and to review practitioner awareness and use of the guidelines. RESULTS: Twenty-five (78%) of 32 questionnaires were completed. Current practice reported by the respondents followed the principles of the published guidelines. However, only 15 gastroenterologists were aware of the guidelines: a number of these practitioners were uncomfortable adapting the published guidelines to their local situation. CONCLUSIONS: Although widely distributed in the paediatric gastroenterology literature, guidelines for management of H. pylori infection may not be utilized fully by individual practitioners. As these guidelines are updated, based upon current developments in the understanding of H. pylori disease, attempts should be made to ensure that such documents are widely distributed to practitioners and that they reflect regional variations in disease patterns.

Anti-Bacterial Agents↗

Prognostic implications of clinical practice guidelines among hemodialysis patients.

Although the National Kidney Foundation (NKF) has published clinical practice guidelines for the management of risk factors for cardiovascular disease, these guidelines have not been tested rigorously for their effectiveness. We conducted an observational study among patients with end-stage kidney disease to examine the prognostic impact of threshold levels recommended by the NKF for blood pressure, hemoglobin, calcium-phosphate product, parathyroid hormone, low-density lipoprotein, and glycosylated hemoglobin. The study population (N = 197) was assembled from a previously completed randomized trial examining arteriovenous graft thrombosis. Cox proportional hazard analysis was used to calculate hazard ratios for the association of levels outside guideline recommended targets and death, adjusting for age, comorbidity, race, and albumin. The proportion of patients outside guideline targets ranged from 33% to 81%, and the impact of levels outside guideline targets on mortality varied substantially. Elevated calcium-phosphate product and glycosylated hemoglobin had harmful effects, with adjusted hazard ratios of 1.58 (95% CI 1.00-2.50; p = 0.050) and 2.21 (95% CI 0.99-4.97; p = 0.054), respectively. Nontarget levels for blood pressure, hemoglobin, and parathyroid hormone had little effect, with adjusted hazard ratios of 1.15 (95% CI 0.74-1.78; p = 0.542), 1.04 (95% CI 0.65-1.68; p = 0.866), and 0.90 (95% CI 0.50-1.61; p = 0.722), respectively. Elevated low-density lipoprotein had a paradoxically beneficial effect, with an adjusted hazard ratio of 0.48 (95% CI 0.23-1.00; p = 0.049). These results suggest that the prognostic impact of current threshold levels recommended by select NKF guidelines on mortality is variable. Accordingly, the development and implementation of clinical practice guidelines should be accompanied by corresponding efforts to confirm their impact on patient outcomes. Such efforts are essential for the improvement of guidelines and to inform health policy optimally.

Aged↗

Clinical performance of original and revised Bethesda guidelines for the identification of MSH2/MLH1 gene carriers in patients with newly diagnosed colorectal cancer: proposal of a new and simpler set of recommendations.

UNLABELLED: Identification of individuals who should undergo hereditary nonpolyposis colorectal cancer (HNPCC) genetic testing is a critical and difficult issue. For this purpose, the National Cancer Institute outlined a set of recommendations, the Bethesda guidelines, which have recently been revised. OBJECTIVE: To compare the clinical performance of original and revised Bethesda guidelines for the detection of MSH2/MLH1 gene carriers in patients with colorectal cancer. METHODS: A total of 1,222 patients with newly diagnosed colorectal cancer were included in the EPICOLON study, a prospective, multicenter, nationwide epidemiology survey aimed at establishing the incidence of HNPCC in Spain (JAMA 2005; 293:1986-1994). Performance characteristics of the original and revised Bethesda guidelines were assessed with respect to the presence of MSH2/MLH1 germline mutations. Logistic regression analysis was performed to establish the most effective strategy. RESULTS: Original or revised Bethesda guidelines were equivalent strategies in terms of sensitivity (100%vs 100%; ns), specificity (98.1%vs 97.9%; ns), and overall accuracy (98.1%vs 97.9%; ns), as well as positive (25.8%vs 24.2%) and negative predictive values (100%vs 100%). The most discriminating individual variables were criteria number 1 (i.e., fulfillment of the Amsterdam criteria; RR = 34.14; 95% CI = 6.85-170.16; p < 0.001) and number 2 (i.e., individuals with two HNPCC-related neoplasms; RR = 35.63; 95% CI = 4.83-262.6; p < 0.001) of the original guidelines, and criterion number 1 of the revised guidelines (i.e., colorectal cancer diagnosed under 50 yr of age; RR = 29.34; 95% CI = 3.81-225.96; p= 0.001). The aggregation of these three criteria was equivalent to both Bethesda guidelines in terms of sensitivity (100%) and negative predictive value (100%), but superior to the revised criteria regarding specificity (98.5%; p < 0.05), overall accuracy (98.5%; p < 0.05), and positive predictive value (30.8%). CONCLUSIONS: Original and revised Bethesda guidelines are equivalent, highly effective criteria for the identification of MSH2/MLH1 gene mutation carriers in patients with newly diagnosed colorectal cancer. A new set of recommendations, based on a combination of some of their individual criteria, may provide additional advantages in terms of effectiveness.

Adaptor Proteins, Signal Transducing↗