Second international guidelines for the diagnosis and management of hereditary hemorrhagic telangiectasia

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease with an estimated prevalence of 1 in 5000 that is characterized by the presence of vascular malformations (VMs). These result in chronic bleeding, acute hemorrhage, and complications from shunting through VMs. The goal of the Second International HHT Guidelines process was to develop evidence-based consensus guidelines for the management and prevention of HHT-related symptoms and complications. The guidelines were developed using the AGREE II (Appraisal of Guidelines for Research and Evaluation II) framework and GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. The guidelines expert panel included expert physicians (clinical and genetic) in HHT from 15 countries, guidelines methodologists, health care workers, health care administrators, patient advocacy representatives, and persons with HHT. During the preconference process, the expert panel generated clinically relevant questions in 6 priority topic areas. A systematic literature search was done in June 2019, and articles meeting a priori criteria were included to generate evidence tables, which were used as the basis for recommendation development. The expert panel subsequently convened during a guidelines conference to conduct a structured consensus process, during which recommendations reaching at least 80% consensus were discussed and approved. The expert panel generated and approved 6 new recommendations for each of the following 6 priority topic areas: epistaxis, gastrointestinal bleeding, anemia and iron deficiency, liver VMs, pediatric care, and pregnancy and delivery (36 total). The recommendations highlight new evidence in existing topics from the first International HHT Guidelines and provide guidance in 3 new areas: anemia, pediatrics, and pregnancy and delivery. These recommendations should facilitate implementation of key components of HHT care into clinical practice.

International guidelines for the diagnosis and management of hereditary haemorrhagic telangiectasia.

BACKGROUND: HHT is an autosomal dominant disease with an estimated prevalence of at least 1/5000 which can frequently be complicated by the presence of clinically significant arteriovenous malformations in the brain, lung, gastrointestinal tract and liver. HHT is under-diagnosed and families may be unaware of the available screening and treatment, leading to unnecessary stroke and life-threatening hemorrhage in children and adults. OBJECTIVE: The goal of this international HHT guidelines process was to develop evidence-informed consensus guidelines regarding the diagnosis of HHT and the prevention of HHT-related complications and treatment of symptomatic disease. METHODS: The overall guidelines process was developed using the AGREE framework, using a systematic search strategy and literature retrieval with incorporation of expert evidence in a structured consensus process where published literature was lacking. The Guidelines Working Group included experts (clinical and genetic) from eleven countries, in all aspects of HHT, guidelines methodologists, health care workers, health care administrators, HHT clinic staff, medical trainees, patient advocacy representatives and patients with HHT. The Working Group determined clinically relevant questions during the pre-conference process. The literature search was conducted using the OVID MEDLINE database, from 1966 to October 2006. The Working Group subsequently convened at the Guidelines Conference to partake in a structured consensus process using the evidence tables generated from the systematic searches. RESULTS: The outcome of the conference was the generation of 33 recommendations for the diagnosis and management of HHT, with at least 80% agreement amongst the expert panel for 30 of the 33 recommendations.

Is foundry work a risk for cardiovascular disease? A systematic review.

UNLABELLED: Aims Foundry work has been associated with an increased risk of adverse cardiovascular events. The objective of this review was systematically and qualitatively to review the published literature to determine whether foundry work is significantly associated with cardiac disease. METHODS: MEDLINE and Cochrane databases were systematically searched to identify relevant English-language publications between 1966 and October 2002. Articles were rated as 'good', 'fair' or 'poor', using published quality review criteria. Additionally, variables suggesting causality were extracted. A qualitative summation of the literature was presented for two scenarios: all studies, or using only studies rated 'fair' and above. RESULTS: Fourteen studies were analysed. Four were found to be of 'fair' quality, the remainder 'poor'. No 'good' quality studies were found. Nine studies show increased cardiac mortality among foundry worker groups and four studies also show a decreased risk. When only 'fair' quality studies are taken into consideration, two support increased risk of cardiac disease, one supports a protective effect of foundry work on cardiac disease and one revealed both increased and decreased risk for different cardiac outcomes. CONCLUSIONS: The exploration of foundry workers' risks of cardiac events reveals conflicting findings, which can only be partly attributed to confounders. Further prospective research to establish the independent contribution of foundry work to cardiac disease is needed.

Corticosteroid therapy for patients with acute exacerbations of chronic obstructive pulmonary disease: a systematic review.

OBJECTIVE: To determine whether systemic corticosteroids are of benefit to patients with acute exacerbations of chronic obstructive pulmonary disease (COPD). METHODS: An English-language search of MEDLINE (1966 to February 2002) and the Cochrane Library and a bibliographic review was performed to identify published clinical trials of systemic corticosteroid administration in acute exacerbations of COPD. All relevant English-language, randomized, placebo-controlled clinical trials were considered. Trials investigating the adverse effects of systemic steroids were also retrieved. Studies were assigned a quality rating according to explicit criteria. Clinically relevant end points, such as treatment failure and duration of hospital stay, were considered preferentially. To compare outcomes across all qualifying studies, we considered the difference in spirometric measures between treatment and placebo groups. Potential confounding factors and bias relating to patient selection, treatment protocols, and outcome measurement were considered independently for each study. RESULTS: Among the 8 studies that met all criteria, 5 found that significant improvement in forced expiratory volume in 1 second (>20%) was associated with steroid administration. Two studies found improvement in clinically relevant outcomes. One published study and 2 study abstracts did not find significant improvement in spirometric measures with corticosteroid administration. CONCLUSION: Short courses of systemic corticosteroids in acute exacerbations of COPD have been shown to improve spirometric outcomes (good-quality evidence) and clinical outcomes (good-quality evidence).

Controlling blood glucose levels in patients with type 2 diabetes mellitus. An evidence-based policy statement by the American Academy of Family Physicians and American Diabetes Association.

OBJECTIVE: To review evidence about the benefit of intensive glycemic control for patients with type 2 diabetes and to develop practice recommendations. PARTICIPANTS: A 9-member panel composed of family physicians, general internists, endocrinologists, and a practice guidelines methodologist was assembled by the American Academy of Family Physicians, the American Diabetes Association, and the American College of Physicians. EVIDENCE: Admissible evidence included published randomized controlled trials and observational studies regarding the effects of glycemic control on microvascular and macrovascular complications and on adverse effects. We followed systematic search and data abstraction procedures. Greater weight was given to clinical trials and to evidence about health outcomes. CONSENSUS PROCESS: Interpretations of evidence and approval of documents were finalized by unanimous vote, with recommendations linked to evidence and not expert opinion. The full report was prepared by the chair and 2 panel members, representing each of the 3 organizations. The initial draft underwent external review by 14 diabetologists and family physicians and changes consistent with the evidence were incorporated. CONCLUSIONS: The evidence demonstrates that the risk of microvascular and neuropathic complications is reduced by lowering glucose concentrations. Whether glycemic control affects macrovascular outcomes is less clear. The potential benefits of glycemic control must be balanced against factors that either preempt benefits (eg, limited life expectancy, comorbid disease) or increase risk (eg, severe hypoglycemia). The magnitude of benefit is a function of individual clinical variables (eg, baseline glycated hemoglobin level, presence of preexisting microvascular disease). Appropriate targets for treatment should be determined by considering these factors, patients' risk profiles, and personal preferences.

Breast cancer patients' attitudes about rationing postlumpectomy radiation therapy: applicability of trade-off methods to policy-making.

PURPOSE: Along with evidence, clinical policies must take patients' values into account. Particularly where evidence is limited and where assumptions of utility-maximizing behavior may not be valid, new methods such as trade-off techniques (TOTs), which allow elicitation of patients' treatment alternatives, might be useful in policy formulation. We used TOTs to assess breast cancer patients' attitudes toward two clinical policies designed to ration adjuvant postlumpectomy breast radiation therapy. METHODS: Cross-sectional interviews were performed in a tertiary cancer center. A total of 102 patients were presented with information about the side effects and benefits associated with two hypothetical decisions: (1) willingness to receive treatment elsewhere to shorten the wait for radiation therapy, and (2) foregoing radiation therapy in the face of small marginal benefits. For each scenario, a TOT was used to identify the maximal acceptable wait time (MAWT) for therapy and the benefit threshold at which the patient would forego therapy. Associations of clinical and demographic factors with these decisions were determined by regression analysis. RESULTS: Patients would be willing to wait, on average, 7 weeks before wanting to leave their city for radiation therapy, less than the 13-week delay our patients actually faced. Older patients were less willing to wait (P = .013); 46% of patients would not give up radiation therapy, even in the face of no stated benefit. Willingness to give up radiation therapy was predicted by willingness to accept delay (odds ratio [OR], 1.84; 95% confidence interval [CI], 1.05 to 3.37) and being employed (OR, 2.61; 95% CI, 1.08 to 6.54). Patients with larger tumors were less willing to give up radiation therapy (OR, 0.57; 95% CI, 0.31 to 0.97). CONCLUSION: Even in difficult decisions such as rationing postlumpectomy breast cancer radiation therapy, TOTs can inform policy formulation by indicating the distributions of patients' preferences.

Perioperative assessment and management of risk from coronary artery disease.

PURPOSE: To summarize available evidence on preoperative cardiac risk stratification so that the internist may 1) use clinical and electrocardiographic findings to stratify a patient's perioperative risk for myocardial infarction and death; 2) decide which tests provide useful additional risk-related information; and 3) understand the benefits, risks, and evidence surrounding the decision to undertake coronary revascularization before elective noncardiac surgery. DATA SOURCES: A MEDLINE search and review of the reference lists of identified articles. Sensitivities, specificities, and likelihood ratios for diagnostic tests were calculated, and a quality rating for study methods was applied. DATA EXTRACTION: Myocardial infarction and mortality were the major outcomes considered, and a quality rating for study methods was applied. DATA SYNTHESIS: Clinical and electrocardiographic findings, organized by multivariate prediction indices, accurately identify patients as having low, intermediate, or high risk for myocardial infarction or death. Pharmacologic stress imaging with thallium or echocardiography probably improves risk stratification for intermediate-risk patients having vascular surgery. These tests have not been shown to be effective prognostic indicators for patients having nonvascular surgery. No studies of angiography for risk prediction have been reported. Decision analyses and retrospective series suggest that the risks incurred by doing coronary angiography and revascularization before elective surgery outweigh the benefits. Prospective, controlled studies of coronary revascularization are lacking. Evidence from a randomized, controlled trial has shown a survival benefit with the perioperative use of beta-blockers in patients at risk for coronary artery disease. CONCLUSIONS: Evaluation of all surgical patients by use of clinical indices is recommended. Low-risk patients need no further evaluation before surgery. High-risk patients need optimal management of their high-risk problems, including (if appropriate) beta-blocker use, and may need to have their elective procedures canceled. Intermediate-risk patients probably benefit from further noninvasive stress testing, especially if they are having vascular surgery. Further clinical trials are needed for most areas of concern.

The rise of tamoxifen: temporal and geographical trends of tamoxifen use in Ontario.

PURPOSE: To describe the change in use of tamoxifen over time and across countries in Ontario. METHODS: Data from the Ontario Drug Benefit (ODB) plan, Census Canada, and the Ontario Cancer Registry (OCR) were combined and analysed to determine rates of tamoxifen use for females over 65 for each county and the province overall, by year. Rates were analyzed by repeated measures ANOVA to determine significance of changes over time. Consistency of tamoxifen use across counties was determined by the Spearman rank correlation coefficient, and overall variation between counties was described using three statistical techniques: Chi-square analysis, the extremal quotient (EQ), and the systematic component of variation (SCV). RESULTS: The number of one-month tamoxifen prescriptions per incident case of breast cancer rose significantly from 13.51 in 1985 to 20.54 in 1990 (p < 0.001) and to 34.06 in 1992 (p = 0.001). Viewed differently, the number of women over 65 receiving tamoxifen prescriptions per incident case of breast cancer changed from 1.91 in 1985 to 3.14 in 1990 to 4.54 in 1992. Statistically significant variation in the rate of tamoxifen prescribing was demonstrated between Ontario counties in all three years by Chi Squared analysis (p < 0.0001). Both the EQ and the SCV declined from 1985 to 1990, suggesting more uniform prescribing across the province. Little change in overall variation was seen between 1990 and 1992. All counties over time tended to prescribe generic preparations more often and shifted from 10 mg to 20 mg formulations. CONCLUSIONS: The significant increase in the rate of tamoxifen use and trend towards more uniform prescribing across Ontario between 1985 and 1990 coincided with the publication of two important documents outlining the benefits of tamoxifen in early breast cancer. Despite this trend, variation in tamoxifen use between counties remains. There has been little change in uniformity of prescribing since 1990.