Purpose: To assess the beneficial and adverse effects of collecting family history in primary care populations; how well family history predicts individual disease risk; and how accurately patients report it.

Data Sources: English-language studies in MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, and PsycINFO from 1995 to 2 March 2009.

Study Selection: Two independent reviewers selected studies that met question-specific eligibility criteria. These included controlled and uncontrolled intervention studies of systematic family history collection and uptake of preventive interventions or adverse effects, longitudinal and cross-sectional studies that examined family history and disease frequency, and studies in which reported family history was validated against relatives' true disease status.

Data Extraction: Information about study quality, setting, and findings was extracted by using standardized protocols.

Data Synthesis: Two uncontrolled studies provided insufficient evidence to assess whether querying about family history improves any outcomes. One randomized, controlled trial and 2 uncontrolled studies provided weak evidence that some patients experienced a reversible, short-term increase in anxiety associated with family history taking. In 41 studies, different family history definitions were associated with sensitivities of 0 to 0.51 and specificities of 0.66 to 1.00 for detection of disease risk, and 0 to 0.83 and 0.48 to 1.00, respectively, for detection of prevalent disease. Twenty-three studies suggested that absence of disease in relatives was more accurately reported than presence of disease and that reporting accuracy was higher for information related to first-degree relatives than more distant relatives.

Limitation: Few studies were designed to address the specific questions of interest.

Conclusion: Insufficient evidence evaluates how to collect family history information accurately in the primary care setting and the effects of taking family history on patient outcomes. Patients seem to correctly report the absence of disease in relatives more often than the presence of disease.

Primary Funding Source: Agency for Healthcare Research and Quality, U.S. Department of Health and Human Services (contract no. 290-02-0020).

Purpose: To compare benefits and harms of using angiotensin-converting enzyme (ACE) inhibitors, angiotensin II–receptor blockers (ARBs), or combination therapy in adults with stable ischemic heart disease and preserved ventricular function.

Data Sources: MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews (earliest date, July 2009) were searched without language restrictions.

Study Selection: Two independent investigators screened citations for trials of at least 6 months' duration that compared ACE inhibitors, ARBs, or combination therapy with placebo or active control and reported any of several clinical outcomes.

Data Extraction: Using standardized protocols, 2 independent investigators extracted information about study characteristics and rated the quality and strength of evidence. Disagreement was resolved by consensus.

Data Synthesis: 41 studies met eligibility criteria. Moderate- to high-strength evidence (7 trials; 32 559 participants) showed that ACE inhibitors reduce the relative risk (RR) for total mortality (RR, 0.87 [95% CI, 0.81 to 0.94]) and nonfatal myocardial infarction (RR, 0.83 [CI, 0.73 to 0.94]) but increase the risk for syncope (RR, 1.24 [CI, 1.02 to 1.52]) and cough (RR, 1.67 [CI, 1.22 to 2.29]) compared with placebo. Low-strength evidence (1 trial; 5926 participants) suggested that ARBs reduce the RR for the composite end point of cardiovascular mortality, nonfatal myocardial infarction, or stroke (RR, 0.88 [CI, 0.77 to 1.00]) but not for the individual components. Moderate-strength evidence (1 trial; 25 620 participants) showed similar effects on total mortality (RR, 1.07 [CI, 0.98 to 1.16]) and myocardial infarction (RR, 1.08 [CI, 0.94 to 1.23]) but an increased risk for discontinuations because of hypotension (P < 0.001) and syncope (P = 0.035) with combination therapy compared with ACE inhibitors alone.

Limitations: Many studies either did not assess or did not report harms in a systematic manner. Many studies did not adequately report benefits or harms by various patient subgroups.

Conclusion: Adding an ACE inhibitor to standard medical therapy improves outcomes, including mortality and myocardial infarctions, in some patients with stable ischemic heart disease and preserved ventricular function. Combination therapy seems no better than ACE inhibitor therapy alone and increases harms.

Primary Funding Source: University of Connecticut/Hartford Hospital Evidence-based Practice Center and the Agency for Healthcare Research and Quality.

Methods: Published literature on this topic was identified by using MEDLINE (1966 to May 2007), EMBASE (1980 to week 22 of 2007), Cochrane Central Register of Controlled Trials (second quarter of 2007), PsycINFO (1985 to June 2007), AMED (1985 to June 2007), and SCOPUS (2006). The literature search was updated by searching for articles in MEDLINE and EMBASE published between May 2007 and April 2009. Searches were limited to English-language publications. This guideline grades the evidence and recommendations by using the American College of Physicians' clinical practice guidelines grading system.

Recommendation 1: The American College of Physicians recommends that clinicians initiate therapy with a PDE-5 inhibitor in men who seek treatment for erectile dysfunction and who do not have a contraindication to PDE-5 inhibitor use (Grade: strong recommendation; high-quality evidence).

Recommendation 2: The American College of Physicians recommends that clinicians base the choice of a specific PDE-5 inhibitor on the individual preferences of men with erectile dysfunction, including ease of use, cost of medication, and adverse effects profile (Grade: weak recommendation; low-quality evidence).

Recommendation 3: The American College of Physicians does not recommend for or against routine use of hormonal blood tests or hormonal treatment in the management of patients with erectile dysfunction (Grade: insufficient evidence to determine net benefits and harms).

Purpose: To evaluate the efficacy and harms of oral phospho- diesterase-5 (PDE-5) inhibitors and hormonal treatments for ED and assess the effect of measuring serum hormone levels on treatment outcomes for ED.

Data Sources: English-language studies from MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, PsycINFO, AMED, and SCOPUS through April 2009. Trial reference lists also were scanned.

Study Selection: Randomized, controlled trials (RCTs) of oral PDE-5 inhibitors and hormonal treatment for ED, and observational studies reporting measurement of serum hormone levels, prevalence of hormonal abnormalities, or both in men with ED.

Data Extraction: Two independent reviewers abstracted data on study, participant, and treatment characteristics; efficacy and harms outcomes; and prevalence of hormonal abnormalities.

Data Synthesis: Data primarily from short-term trials (≤12 weeks) indicate that PDE-5 inhibitors were more effective than placebo in improving sexual intercourse success (69.0% vs. 35.0%). The proportion of men with improved erections was significantly greater among those treated with PDE-5 inhibitors (range, 67.0% to 89.0%) than with placebo (range, 27.0% to 35.0%). The PDE-5 inhibitors were associated with increased risk for any adverse events compared with placebo (for example, relative risk with sildenafil, 1.72 [95% CI, 1.53 to 1.93]). In 4 head-to-head RCTs comparing sildenafil, vardenafil, and tadalafil, improvement of ED and adverse events did not differ among treatments. Results from 15 RCTs evaluating hormonal treatment of ED were inconsistent on whether treatment improved outcomes. Evidence was insufficient regarding whether men with ED had a higher prevalence of hypogonadism than men without ED.

Limitations: Many RCTs were of low methodological and reporting quality, particularly those involving hormonal treatments or directly comparing different PDE-5 inhibitors. Most RCTs provided only short-term efficacy and harms data.

Conclusion: Oral PDE-5 inhibitors improved erectile functioning and had similar efficacy and safety profiles. Results on the efficacy of hormonal treatments and the value of hormone testing in men with ED were inconclusive.

Primary Funding Source: Agency for Healthcare Research and Quality.

Objective: To estimate the effectiveness and cost-effectiveness of pandemic influenza (H1N1) vaccination under different scenarios in October or November 2009.

Design: Compartmental epidemic model in conjunction with a Markov model of disease progression.

Data Sources: Literature and expert opinion.

Target Population: Residents of a major U.S. metropolitan city with a population of 8.3 million.

Time Horizon: Lifetime.

Perspective: Societal.

Interventions: Vaccination in mid-October or mid-November 2009.

Outcome Measures: Infections and deaths averted, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness.

Results of Base-Case Analysis: Assuming each primary infection causes 1.5 secondary infections, vaccinating 40% of the population in October or November would be cost-saving. Vaccination in October would avert 2051 deaths, gain 69 679 QALYs, and save $469 million compared with no vaccination; vaccination in November would avert 1468 deaths, gain 49 422 QALYs, and save $302 million.

Results of Sensitivity Analysis: Vaccination is even more cost-saving if longer incubation periods, lower rates of infectiousness, or increased implementation of nonpharmaceutical interventions delay time to the peak of the pandemic. Vaccination saves fewer lives and is less cost-effective if the epidemic peaks earlier than mid-October.

Limitations: The model assumed homogenous mixing of case-patients and contacts; heterogeneous mixing would result in faster initial spread, followed by slower spread. Additional costs and savings not included in the model would make vaccination more cost-saving.

Conclusion: Earlier vaccination against pandemic (H1N1) 2009 prevents more deaths and is more cost-saving. Complete population coverage is not necessary to reduce the viral reproductive rate sufficiently to help shorten the pandemic.

Primary Funding Source: Agency for Healthcare Research and Quality and National Institute on Drug Abuse.

Objective: To estimate the effectiveness and cost-effectiveness of alternative pandemic (H5N1) mitigation and response strategies.

Design: Compartmental epidemic model in conjunction with a Markov model of disease progression.

Data Sources: Literature and expert opinion.

Target Population: Residents of a U.S. metropolitan city with a population of 8.3 million.

Time Horizon: Lifetime.

Perspective: Societal.

Interventions: 3 scenarios: 1) vaccination and antiviral pharmacotherapy in quantities similar to those currently available in the U.S. stockpile (stockpiled strategy), 2) stockpiled strategy but with expanded distribution of antiviral agents (expanded prophylaxis strategy), and 3) stockpiled strategy but with adjuvanted vaccine (expanded vaccination strategy). All scenarios assumed standard nonpharmaceutical interventions.

Outcome Measures: Infections and deaths averted, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness.

Results of Base-Case Analysis: Expanded vaccination was the most effective and cost-effective of the 3 strategies, averting 68% of infections and deaths and gaining 404 030 QALYs at $10 844 per QALY gained relative to the stockpiled strategy.

Results of Sensitivity Analysis: Expanded vaccination remained incrementally cost-effective over a wide range of assumptions.

Limitations: The model assumed homogenous mixing of cases and contacts; heterogeneous mixing would result in faster initial spread, followed by slower spread. We did not model interventions for children or older adults; the model is not designed to target interventions to specific groups.

Conclusion: Expanded adjuvanted vaccination is an effective and cost-effective mitigation strategy for an influenza A (H5N1) pandemic. Expanded antiviral prophylaxis can help delay the pandemic while additional strategies are implemented.

Primary Funding Source: National Institutes of Health and Agency for Healthcare Research and Quality.

Objective: To compare Medicare spending for previously uninsured and insured adults by using Medicare claims data.

Design: We used longitudinal survey data and linked Medicare claims data to compare Medicare spending for beneficiaries age 65 to 74 years who were previously insured or previously uninsured before age 65 years. We used an inverse-probability-of-treatment weighting technique to adjust for fixed and time-varying sociodemographic and health characteristics before age 65 years. We also compared condition-specific hospitalizations and estimated their contribution to differences in Medicare spending.

Setting: Nationally representative Health and Retirement Study, 1992–2006.

Participants: 2951 continuously insured adults and 1616 adults who were continuously or intermittently uninsured before age 65 years.

Measurements: Mean adjusted annual Medicare spending (total and by type of service) and annual rates of condition-specific hospitalizations.

Results: Adjusted annual total Medicare spending was significantly higher for previously uninsured ($5796) than previously insured ($4773) adults (difference, $1023 [95% CI, $29 to $2016]; P = 0.044). Among relevant clinical subgroups, previously uninsured adults had higher adjusted annual hospitalization rates than previously insured adults for complications related to cardiovascular disease or diabetes (9.1% vs. 6.4%; P = 0.002) and for joint replacements (2.5% vs. 1.3%; P = 0.006). Differences in these hospitalizations accounted for 65.7% of the $644 difference in annual Medicare inpatient spending between all previously uninsured and insured adults.

Limitation: Unobserved confounders could have explained spending differences.

Conclusion: Costs of expanded coverage before age 65 years may be partially offset by subsequent reductions in Medicare spending after age 65 years, particularly for uninsured adults with cardiovascular disease, diabetes, or severe arthritis.

Primary Funding Source: The Commonwealth Fund.

Objective: To compare 2 self-management interventions for improving BP control among hypertensive patients.

Design: A 2 x 2 randomized trial, stratified by enrollment site and patient health literacy status, with 2-year follow-up. (ClinicalTrials.gov registration number: NCT00123058)

Setting: 2 university-affiliated primary care clinics.

Patients: 636 hypertensive patients.

Intervention: A centralized blinded and stratified randomization algorithm was used to randomly assign eligible patients to receive usual care, a behavioral intervention (bimonthly tailored nurse-administered telephone intervention targeting hypertension-related behaviors), home BP monitoring 3 times weekly, or the behavioral intervention plus home BP monitoring.

Measurements: The primary outcome was BP control at 6-month intervals over 24 months. 475 patients (75%) completed the 24-month BP follow-up.

Results: At 24 months, improvements in the proportion of patients with BP control relative to the usual care group were 4.3% (95% CI, –4.5% to 12.9%) in the behavioral intervention group, 7.6% (CI, –1.9% to 17.0%) in the home BP monitoring group, and 11.0% (CI, 1.9%, 19.8%) in the combined intervention group. Relative to usual care, the 24-month difference in systolic BP was 0.6 mm Hg (CI, –2.2 to 3.4) for the behavioral intervention group, –0.6 mm Hg (CI, –3.6 to 2.3) for the BP monitoring group, and –3.9 mm Hg (CI, –6.9 to –0.9) for the combined intervention group; patterns were similar patterns were for diastolic BP.

Limitation: Generalizability is limited because changes in medication use and diet were monitored only in intervention participants; 24-month outcome data were missing for 25% of participants, BP control was adequate at baseline in 73% of participants, and the study setting was an academic health center.

Conclusion: Combined home BP monitoring and tailored behavioral telephone intervention improved BP control, systolic BP, and diastolic BP at 24 months relative to usual care.

Primary Funding Source: National Heart, Lung, and Blood Institute; Pfizer Foundation Health Communication Initiative; and the American Heart Association.

Purpose: To summarize benefits and harms of tamoxifen citrate, raloxifene, and tibolone to reduce the risk for primary breast cancer.

Data Sources: MEDLINE and Cochrane databases from inception to January 2009, Web of Science, trial registries, and manufacturer information.

Study Selection: Predefined eligibility criteria were used to select articles. English-language reports of randomized, controlled trials (RCTs) for benefits and RCTs and observational studies for harms were included.

Data Extraction: Two reviewers assessed study data, quality, and applicability.

Data Synthesis: Seven placebo-controlled RCTs and 1 head-to-head trial provide results for main outcomes. Tamoxifen (risk ratio, 0.70 [95% CI, 0.59 to 0.82]; 4 trials), raloxifene (risk ratio, 0.44 [CI, 0.27 to 0.71]; 2 trials), and tibolone (risk ratio, 0.32 [CI, 0.13 to 0.80]; 1 trial) reduce risk for invasive breast cancer compared with placebo by 7 to 10/1000 women per year. Tamoxifen and raloxifene reduce estrogen receptor–positive breast cancer, but not estrogen receptor–negative breast cancer, noninvasive breast cancer, or mortality; all medications reduce fractures. Tamoxifen (risk ratio, 1.93 [CI, 1.41 to 2.64]; 4 trials) and raloxifene (risk ratio, 1.60 [CI, 1.15 to 2.23]; 2 trials) increase thromboembolic events by 4 to 7/1000 women per year; raloxifene causes fewer events than tamoxifen. Tamoxifen increases risk for endometrial cancer (risk ratio, 2.13 [CI, 1.36 to 3.32]; 3 trials) compared with placebo by 4/1000 women per year and causes cataracts compared with raloxifene. Tibolone causes strokes in older women.

Limitations: Biases, trial heterogeneity, and few head-to-head trials limit this review. Data are lacking on doses, duration, and timing of the medications; long-term effects; and nonwhite and premenopausal women.

Conclusion: Three medications reduce risk for primary breast cancer but increase risk for thromboembolic events (tamoxifen, raloxifene), endometrial cancer (tamoxifen), or stroke (tibolone).

Primary Funding Source: Agency for Healthcare Research and Quality.

Purpose: To compare the benefits and harms of high-dose statin monotherapy with those of combination therapy in adults at high risk for coronary disease.

Data Sources: English-language records from MEDLINE (1966–2009), EMBASE (1980–2009), and the Cochrane Library (third quarter of 2008).

Study Selection: A reviewer screened records, and a second reviewer verified selection of randomized, controlled trials in adult patients that compared combinations of statins and bile-acid sequestrants, fibrates, ezetimibe, niacin, or -3 fatty acids with statin monotherapy, as well as nonrandomized comparative studies that were longer than 24 weeks and reported clinical and harms outcomes.

Data Extraction: Data were abstracted for studies by using standardized forms, and study quality was rated with a standardized scale and strength of evidence by using the Grading of Recommendations Assessment, Development, and Evaluation approach.

Data Synthesis: 102 studies met eligibility criteria. The main analysis compared combination therapy with high-dose statin monotherapy in high-risk patients. Very-low-strength evidence showed that statin–ezetimibe (2 trials; n = 439) and statin–fibrate (1 trial; n = 166) combinations did not reduce mortality more than high-dose statin monotherapy. No trials compared the effect of combination therapy versus high-dose statin monotherapy on the incidence of myocardial infarction, stroke, or revascularization procedures. Two statin–ezetimibe trials (n = 295) demonstrated higher low-density lipoprotein cholesterol goal attainment with combination therapy (odds ratio, 7.21 [95% CI, 4.30 to 12.08]). Trials in lower-risk patients did not show a difference in mortality.

Limitations: Studies were generally short, focused on surrogate outcomes, and were heterogeneous in study sample risk for coronary disease. Few studies examined treatment combinations other than statin–ezetimibe.

Conclusion: Limited evidence suggests that combinations of lipid-lowering agents do not improve clinical outcomes more than high-dose statin monotherapy. Very-low-quality evidence favors statin–ezetimibe treatment for attainment of low-density lipoprotein cholesterol goals.

Primary Funding Source: Agency for Healthcare Research and Quality.