Nananda F. Col

Estimating Hip Fracture Morbidity, Mortality and Costs

OBJECTIVES:  To estimate lifetime morbidity, mortality, and costs from hip fracture incorporating the effect of deficits in activities of daily living.

Meta-analysis of Vascular and Neoplastic Events Associated with Tamoxifen

OBJECTIVE: Tamoxifen reduces the risk of developing breast cancer but also affects the risks of certain vascular and neoplastic events. Our purpose was to estimate the effects of tamoxifen on potentially life-threatening vascular and neoplastic outcomes.DESIGN: Random effects meta-analysis of published randomized controlled trials.PATIENTS: Participants in all trials in which a treatment arm that included tamoxifen was compared to a similar control arm. Breast cancer risk reduction and treatment trials were included.INTERVENTIONS: Tamoxifen at variable dose and duration.MEASUREMENTS AND MAIN RESULTS: Thirty-two trials (52,929 patients) reported one or more outcomes of interest. Tamoxifen was associated with significantly increased risks of endometrial cancer (relative risk [RR] 2.70; 95% CI, 1.94 to 3.75), gastrointestinal cancers (RR 1.31; 95% CI, 1.01 to 1.69), strokes (RR 1.49; 95% CI, 1.16 to 1.90), and pulmonary emboli (RR 1.88; 95% CI, 1.77 to 3.01). Tamoxifen had no effect on secondary malignancies other than endometrial and gastrointestinal cancers (RR 0.96; 95% CI, 0.81 to 1.13). In contrast, tamoxifen significantly decreased myocardial infarction deaths (RR 0.62; 95% CI, 0.41 to 0.93) and was associated with a statistically insignificant decrease in myocardial infarction incidence (RR 0.90; 95% CI, 0.66 to 1.23). Postmenopausal women had greater risk increases for neoplastic outcomes.CONCLUSIONS: This meta-analysis of randomized trials found tamoxifen use to be significantly associated with several neoplastic and vascular outcomes. Consideration of tamoxifen use requires balance of potential benefits and risks.

American society of clinical oncology clinical practice guideline update on the use of pharmacologic interventions including tamoxifen, raloxifene, and aromatase inhibition for breast cancer risk reduction.

PURPOSE To update the 2002 American Society of Clinical Oncology guideline on pharmacologic interventions for breast cancer (BC) risk reduction. METHODS A literature search identified relevant randomized trials published since 2002. Primary outcome of interest was BC incidence (invasive and noninvasive). Secondary outcomes included BC mortality, adverse events, and net health benefits. An expert panel reviewed the literature and developed updated consensus guidelines. Results Seventeen articles met inclusion criteria. In premenopausal women, tamoxifen for 5 years reduces the risk of BC for at least 10 years, particularly estrogen receptor (ER) -positive invasive tumors. Women < or = 50 years of age experience fewer serious side effects. Vascular and vasomotor events do not persist post-treatment across all ages. In postmenopausal women, raloxifene and tamoxifen reduce the risk of ER-positive invasive BC with equal efficacy. Raloxifene is associated with a lower risk of thromboembolic disease, benign uterine conditions, and cataracts than tamoxifen in postmenopausal women. No evidence exists establishing whether a reduction in BC risk from either agent translates into reduced BC mortality. Recommendations In women at increased risk for BC, tamoxifen (20 mg/d for 5 years) may be offered to reduce the risk of invasive ER-positive BC, with benefits for at least 10 years. In postmenopausal women, raloxifene (60 mg/d for 5 years) may also be considered. Use of aromatase inhibitors, fenretinide, or other selective estrogen receptor modulators to lower BC risk is not recommended outside of a clinical trial. Discussion of risks and benefits of preventive agents by health providers is critical to patient decision making.

National Institutes of Health State-of-the-Science Conference: role of active surveillance in the management of men with localized prostate cancer.

National Institutes of Health (NIH) Consensus and State-of-the-Science Statements are prepared by independent panels of health professionals and public representatives on the basis of 1) the results of a systematic literature review prepared under contract with the Agency for Healthcare Research and Quality, 2) presentations by investigators working in areas relevant to the conference questions during a 2-day public session, 3) questions and statements from conference attendees during open discussion periods that are part of the public session, and 4) closed deliberations by the panel during the remainder of the second day and morning of the third. This statement is an independent report of the panel and is not a policy statement of NIH or the U.S. government. The statement reflects the panel’s assessment of medical knowledge available at the time the statement was written. Thus, it provides a “snapshot in time” of the state of knowledge on the conference topic. When reading the statement, keep in mind that new knowledge is inevitably accumulating through medical research. The following statement is an abridged version of the panel’s report, which is available in full at http://consensus.nih.gov/2011/prostatefinalstatement.htmNational Institutes of Health (NIH) Consensus and Stateof-the-Science Statements are prepared by independent panels of health professionals and public representatives on the basis of 1) the results of a systematic literature review prepared under contract with the Agency for Healthcare Research and Quality, 2) presentations by investigators working in areas relevant to the conference questions during a 2-day public session, 3) questions and statements from conference attendees during open discussion periods that are part of the public session, and 4) closed deliberations by the panel during the remainder of the second day and morning of the third. This statement is an independent report of the panel and is not a policy statement of NIH or the U.S. government. The statement reflects the panel’s assessment of medical knowledge available at the time the statement was written. Thus, it provides a “snapshot in time” of the state of knowledge on the conference topic. When reading the statement, keep in mind that new knowledge is inevitably accumulating through medical research. The following statement is an abridged version of the panel’s report, which is available in full at http: //consensus.nih.gov/2011/prostatefinalstatement.htm In 2011, more than 240 000 men are projected to receive a diagnosis of prostate cancer and 33 000 are projected to die of this condition. More than 2.5 million men in the United States are long-term survivors of prostate cancer. Men with a strong family history of prostate cancer and African American men are at increased risk for prostate cancer. Most cases of prostate cancer are localized at diagnosis and detected as a result of screening with prostatespecific antigen (PSA) testing. Most of these screendetected cases of cancer are low risk and are unlikely to cause death. The natural history of prostate cancer has changed dramatically in the past 3 decades because of PSA screening. Although most cases of prostate cancer are slowgrowing and unlikely to spread, most men receive immediate treatment with surgery or radiation. These therapeutic strategies are associated with shortand long-term complications, including impotence and urinary incontinence. Only a few men choose observational strategies, thereby delaying the initiation of curative therapy or avoiding it completely. Given the high prevalence of low-risk prostate cancer, the roles of active surveillance and other observational strategies as alternatives to immediate treatment need to be clarified. The National Cancer Institute, the Centers for Disease Control and Prevention, and the NIH Office of Medical Applications of Research convened a State-of-the-Science Conference on 5 to 7 December 2011 to assess the available scientific evidence about active surveillance for men with localized prostate cancer. The conference, which addressed 5 key questions, was informed by a formal evidence report commissioned through the Agency for Healthcare Research and Quality, data presented by speakers, and input from attendees.

Use of Pharmacologic Interventions for Breast Cancer Risk Reduction: American Society of Clinical Oncology Clinical Practice Guideline

PURPOSE To update the 2009 American Society of Clinical Oncology guideline on pharmacologic interventions for breast cancer (BC) risk reduction. METHODS A systematic review of randomized controlled trials and meta-analyses published from June 2007 through June 2012 was completed using MEDLINE and Cochrane Collaboration Library. Primary outcome of interest was BC incidence (invasive and noninvasive). Secondary outcomes included BC mortality, adverse events, and net health benefits. Guideline recommendations were revised based on an Update Committees review of the literature. RESULTS Nineteen articles met the selection criteria. Six chemoprevention agents were identified: tamoxifen, raloxifene, arzoxifene, lasofoxifene, exemestane, and anastrozole. RECOMMENDATIONS In women at increased risk of BC age ≥ 35 years, tamoxifen (20 mg per day for 5 years) should be discussed as an option to reduce the risk of estrogen receptor (ER) -positive BC. In postmenopausal women, raloxifene (60 mg per day for 5 years) and exemestane (25 mg per day for 5 years) should also be discussed as options for BC risk reduction. Those at increased BC risk are defined as individuals with a 5-year projected absolute risk of BC ≥ 1.66% (based on the National Cancer Institute BC Risk Assessment Tool or an equivalent measure) or women diagnosed with lobular carcinoma in situ. Use of other selective ER modulators or other aromatase inhibitors to lower BC risk is not recommended outside of a clinical trial. Health care providers are encouraged to discuss the option of chemoprevention among women at increased BC risk. The discussion should include the specific risks and benefits associated with each chemopreventive agent.

American Society of Clinical Oncology Technology Assessment of Pharmacologic Interventions for Breast Cancer Risk Reduction Including Tamoxifen, Raloxifene, and Aromatase Inhibition

OBJECTIVE To update an evidence-based technology assessment of chemoprevention strategies for breast cancer risk reduction. POTENTIAL INTERVENTIONS: Tamoxifen, raloxifene, aromatase inhibition, and fenretinide. OUTCOMES Outcomes of interest include breast cancer incidence, breast cancer-specific survival, overall survival, and net health benefit. EVIDENCE A comprehensive, formal literature review was conducted for relevant topics. Testimony was collected from invited experts and interested parties. The American Society of Clinical Oncology (ASCO) prescribed technology assessment procedure was followed. VALUES More weight was given to published randomized trials. BENEFITS/HARMS: A womans decision regarding breast cancer risk reduction strategies is complex and will depend on the importance and weight attributed to information regarding both cancer- and noncancer-related risks and benefits. CONCLUSIONS For women with a defined 5-year projected breast cancer risk of > or= 1.66%, tamoxifen (at 20 mg/d for 5 years) may be offered to reduce their risk. Risk/benefit models suggest that greatest clinical benefit with least side effects is derived from use of tamoxifen in younger (premenopausal) women (who are less likely to have thromboembolic sequelae and uterine cancer), women without a uterus, and women at higher breast cancer risk. Data do not as yet suggest that tamoxifen provides an overall health benefit or increases survival. In all circumstances, tamoxifen use should be discussed as part of an informed decision-making process with careful consideration of individually calculated risks and benefits. Use of tamoxifen combined with hormone replacement therapy or use of raloxifene, any aromatase inhibitor or inactivator, or fenretinide to lower the risk of developing breast cancer is not recommended outside of a clinical trial setting. This technology assessment represents an ongoing process and recommendations will be updated in a timely matter. VALIDATION The conclusions were endorsed by the ASCO Health Services Research Committee and the ASCO Board of Directors.

Duration of vasomotor symptoms in middle-aged women: a longitudinal study.

Objective: Vasomotor symptoms adversely affect the quality of life and functional status of most women during the menopausal transition, but little is known about how long these symptoms last. The most effective treatment, hormone therapy (HT), carries risks and benefits that depend on the timing and duration of use. In this study we sought to estimate the duration of vasomotor symptoms in a longitudinal study. Methods: We reanalyzed primary data from 438 women in the longitudinal cohort of the population-based Melbourne Womens Midlife Health Project. Two hundred and five women who had completed 13 years of follow-up were included in the analyses. The onset and cessation of vasomotor symptoms were reported, stratifying analyses according to ever use of HT. Symptom duration was calculated as the time between the first and last bothersome hot flush reported. Results: The mean (SD) duration of bothersome menopausal symptoms for women who completed 13 years of follow-up and who never used HT was estimated to be 5.2 (3.8) years (median, 4 years). If women who used HT were included, the mean (SD) duration was 5.5 (4.0) years (median, 4 years). The estimated duration of symptoms varied according to the duration of longitudinal follow-up, with a mean estimate of 3.4 years (median, 3 years) when only 8 years of follow-up data were analyzed. The only factor associated with duration of hot flushes was regular exercise-more exercise was associated with shorter symptom duration. Conclusions: The average duration of vasomotor symptoms in this sample is more than 5 years, substantially longer than had been previously reported.

Gender differences and factors associated with the receipt of thrombolytic therapy in patients with acute myocardial infarction: A community-wide perspective

In spite of national interest in gender differences in the presentation and management of chronic disease, limited information is available about possible gender differences in the receipt of thrombolytic therapy after acute myocardial infarction (AMI). As part of an ongoing community-based study of AMI, we examined gender differences in the receipt of thrombolytic therapy among 2885 patients with confirmed AMI. The study sample consisted of 1680 males and 1205 females with validated AMI who were admitted to 16 hospitals in the Worcester, Massachusetts, metropolitan area in four study periods between 1986 and 1991. During the years under study, 24.4% of men and 14.4% of women received thrombolytic therapy. Increases over time in the use of thrombolytic therapy were seen in both men (13.9% in 1986; 31.6% in 1991) and women (3.2% in 1986; and 19.0% in 1991). After controlling for a variety of factors that might affect use of thrombolytic agents, younger age, absence of a history of either congestive heart failure or stroke, and experiencing a Q-wave AMI were associated with receipt of thrombolytic therapy in both men and women; having an anterior AMI also was associated with use of thrombolytic agents in men. Women without as compared with those with a history of angina pectoris were significantly more likely to receive thrombolytics. Men who had Medicare insurance were significantly less likely to receive thrombolytics than were men with other types of health insurance. When this analysis was restricted to patients who were seen in area-wide hospitals within 6 hours of the onset of symptoms suggestive of AMI, similar factors were associated with the receipt of thrombolytic agents in men and women. The results of this community-wide study suggest a marked increase over the 5-year study period in the use of thrombolytic therapy in both men and women, with a greater relative increase observed in women. A relatively similar profile of patients likely to receive thrombolytic therapy was seen in both men and women.

Clarifying Values: An updated review

BackgroundConsensus guidelines have recommended that decision aids include a process for helping patients clarify their values. We sought to examine the theoretical and empirical evidence related to the use of values clarification methods in patient decision aids.MethodsBuilding on the International Patient Decision Aid Standards (IPDAS) Collaboration’s 2005 review of values clarification methods in decision aids, we convened a multi-disciplinary expert group to examine key definitions, decision-making process theories, and empirical evidence about the effects of values clarification methods in decision aids. To summarize the current state of theory and evidence about the role of values clarification methods in decision aids, we undertook a process of evidence review and summary.ResultsValues clarification methods (VCMs) are best defined as methods to help patients think about the desirability of options or attributes of options within a specific decision context, in order to identify which option he/she prefers. Several decision making process theories were identified that can inform the design of values clarification methods, but no single “best” practice for how such methods should be constructed was determined. Our evidence review found that existing VCMs were used for a variety of different decisions, rarely referenced underlying theory for their design, but generally were well described in regard to their development process. Listing the pros and cons of a decision was the most common method used. The 13 trials that compared decision support with or without VCMs reached mixed results: some found that VCMs improved some decision-making processes, while others found no effect.ConclusionsValues clarification methods may improve decision-making processes and potentially more distal outcomes. However, the small number of evaluations of VCMs and, where evaluations exist, the heterogeneity in outcome measures makes it difficult to determine their overall effectiveness or the specific characteristics that increase effectiveness.

Factors associated with treatment of women with osteoporosis or osteopenia from a national survey

BackgroundHealth outcomes could be improved if women at high risk for osteoporotic fracture were matched to effective treatment. This study determined the extent to which treatment for osteoporosis/osteopenia corresponded to the presence of specific risk factors for osteoporotic fracture.MethodsThis retrospective analysis of the United States 2007 National Health and Wellness Survey included women age ≥ 40 years who reported having a diagnosis of osteoporosis (69% of 3276) or osteopenia (31% of 3276). Patients were stratified by whether they were or were not taking prescription treatment for osteoporosis/osteopenia. Using 34 patient characteristics as covariates, logistic regression was used to determine factors associated with treatment.ResultsCurrent prescription treatment was reported by 1800 of 3276 (54.9%) women with osteoporosis/osteopenia. The following factors were associated with receiving prescription treatment: patient-reported diagnosis of osteoporosis (versus osteopenia); previous bone mineral density test; ≥ 2 fractures since age 50; older age; lower body mass index; better physical functioning; postmenopausal status; family history of osteoporosis; fewer comorbidities; prescription insurance coverage; higher total prescription count; higher ratio of prescription costs to monthly income; higher income; single status; previous visit to a rheumatologist or gynecologist; and 1 or 2 outpatient visits to healthcare provider (vs. none) in the prior 6 months. Glucocorticoid, tobacco, and daily alcohol use were risk factors for fracture that were not associated with treatment.ConclusionsThere is a mismatch between those women who could benefit from treatment for osteoporosis and those who are actually treated. For example, self-reported use of glucocorticoids, tobacco, and alcohol were not associated with prescription treatment of osteoporosis. Other clinical and socioeconomic factors were associated with treatment (e.g. prescription drug coverage and higher income) or not (e.g. comorbid osteoarthritis and anxiety) and could be opportunities to improve care.