Testing for pulmonary embolism often differs from that recommended by evidence-based guidelines.
To assess the effectiveness of a handheld clinical decision-support system to improve the diagnostic work-up of suspected pulmonary embolism among patients in the emergency department.
Cluster randomized trial. Assignment was by random-number table, providers were not blinded, and outcome assessment was automated. (ClinicalTrials.gov registration number: NCT00188032)
20 emergency departments in France.
1103 and 1768 consecutive outpatients with suspected pulmonary embolism.
After a preintervention period involving 20 centers and 1103 patients, in which providers grew accustomed to inputting clinical data into handheld devices and investigators assessed baseline testing, emergency departments were randomly assigned to activation of a decision-support system on the devices (10 centers, 753 patients) or posters and pocket cards that showed validated diagnostic strategies (10 centers, 1015 patients).
Appropriateness of diagnostic work-up, defined as any sequence of tests that yielded a posttest probability less than 5% or greater than 85% (primary outcome) or as strict adherence to guideline recommendations (secondary outcome); number of tests per patient (secondary outcome).
The proportion of patients who received appropriate diagnostic work-ups was greater during the trial than in the preintervention period in both groups, but the increase was greater in the computer-based guidelines group (adjusted mean difference in increase, 19.3 percentage points favoring computer-based guidelines [95% CI, 2.9 to 35.6 percentage points]; P = 0.023). Among patients with appropriate work-ups, those in the computer-based guidelines group received slightly fewer tests than did patients in the paper guidelines group (mean tests per patient, 1.76 [SD, 0.98] vs. 2.25 [SD, 1.04]; P < 0.001).
The study was not designed to show a difference in the clinical outcomes of patients during follow-up.
A handheld decision-support system improved diagnostic decision making for patients with suspected pulmonary embolism in the emergency department.
French National Hospital Clinical Research Project.
Fewer than 40% of persons with hypertension in the United States have adequate blood pressure (BP) control.
To compare 2 self-management interventions for improving BP control among hypertensive patients.
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)
2 university-affiliated primary care clinics.
636 hypertensive patients.
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.
The primary outcome was BP control at 6-month intervals over 24 months.
475 patients (75%) completed the 24-month BP follow-up. 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 mm Hg) for the behavioral intervention group, –0.6 mm Hg (CI, –3.6 to 2.3 mm Hg) for the BP monitoring group, and –3.9 mm Hg (CI, –6.9 to –0.9 mm Hg) for the combined intervention group; patterns were similar for diastolic BP.
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.
Combined home BP monitoring and tailored behavioral telephone intervention improved BP control, systolic BP, and diastolic BP at 24 months relative to usual care.
National Heart, Lung, and Blood Institute; Pfizer Foundation Health Communication Initiative; and the American Heart Association.
Adherence to short-term continuous positive airway pressure (CPAP) may predict long-term use. Unfortunately, initial CPAP intolerance may lead to poor adherence or abandonment of therapy.
To determine whether a short course of eszopiclone at the onset of therapy improves long-term CPAP adherence more than placebo in adults with obstructive sleep apnea.
Parallel randomized, placebo-controlled trial from March 2007 to December 2008. Randomization, maintained and concealed centrally by pharmacy personnel, was computer-generated using fixed blocks of 10. Referring physicians, investigators, and patients were blinded to the treatment assignment until after the final data were collected. (ClinicalTrials.gov registration number: NCT00612157)
Academic sleep disorder center.
160 adults (mean age, 45.7 years [SD, 7.3]; mean apnea–hypopnea index, 36.9 events/h [SD, 23]) with newly diagnosed obstructive sleep apnea initiating CPAP.
Eszopiclone, 3 mg (n = 76), or matching placebo (n = 78) for the first 14 nights of CPAP.
Use of CPAP was measured weekly for 24 weeks. Adherence to CPAP (primary outcome) and the rate of CPAP discontinuation and improvements in symptoms (secondary outcomes) were compared. Follow-up at 1, 3, and 6 months was completed by 150, 136, and 120 patients, respectively.
Patients in the eszopiclone group used CPAP for 20.8% more nights (95% CI, 7.2% to 34.4%; P = 0.003), 1.3 more hours per night for all nights (CI, 0.4 to 2.2 hours; P = 0.005), and 1.1 more hours per night of CPAP use (CI, 0.2 to 2.1 hours; P = 0.019). The hazard ratio for discontinuation of CPAP was 1.90 (CI, 1.1 to 3.4; P = 0.033) times higher in the placebo group. Side effects were reported in 7.1% of patients and did not differ between groups.
Patients had severe obstructive sleep apnea treated at a specialized sleep center with frequent follow-up; results may not be generalizable to different settings. Patients' tolerance to CPAP and their reasons for discontinuation were not assessed.
Compared with placebo, a short course of eszopiclone during the first 2 weeks of CPAP improved adherence and led to fewer patients discontinuing therapy.
Sepracor.
Despite convincing evidence that lowering blood pressure decreases cardiovascular morbidity and mortality, the hypertension burden remains high and control rates are poor in developing countries.
To assess the effectiveness of 2 community-based interventions on blood pressure in hypertensive adults.
Cluster randomized, 2 x 2 factorial, controlled trial. (ClinicalTrials.gov registration number: NCT00327574)
12 randomly selected communities in Karachi, Pakistan.
1341 patients 40 years or older with hypertension (systolic blood pressure ≥140 mm Hg, diastolic blood pressure ≥90 mm Hg, or already receiving treatment).
Reduction in systolic blood pressure from baseline to end of follow-up at 2 years.
Family-based home health education (HHE) from lay health workers every 3 months and annual training of general practitioners (GPs) in hypertension management.
The age, sex, and baseline blood pressure–adjusted decrease in systolic blood pressure was significantly greater in the HHE and GP group (10.8 mm Hg [95% CI, 8.9 to 12.8 mm Hg]) than in the GP-only, HHE-only, or no intervention groups (5.8 mm Hg [CI, 3.9 to 7.7 mm Hg] in each; P < 0.001). The interaction between the main effects of GP training and HHE on the primary outcome approached significance (interaction P = 0.004 in intention-to-treat analysis and P = 0.044 in per-protocol analysis).
Follow-up blood pressure measurements were missing for 22% of patients. No mechanism was detected by which interventions lowered blood pressure.
Family-based HHE delivered by trained lay health workers, coupled with educating GPs on hypertension, can lead to significant blood pressure reductions among patients with hypertension in Pakistan. Both strategies in combination may be feasible for upscaling within the existing health care systems of Indo-Asian countries.
Wellcome Trust.
Cervical cancer screening guidelines were substantially revised in 2002 and 2003. Little information is available about primary care physicians' current Papanicolaou (Pap) test screening practices, including initiation, frequency, and stopping.
To assess current Pap test screening practices in the United States.
Cross-sectional survey.
Nationally representative sample of physicians during 2006 to 2007.
1212 primary care physicians.
The survey included questions about physician and practice characteristics and recommendations for Pap screening presented as clinical vignettes describing women by age and by sexual and screening histories. A composite measure—guideline-consistent recommendations—was created by using responses to vignettes in which major guidelines were uniform.
Most physicians reported providing Pap tests to their eligible patients (91.0% [95% CI, 89.0% to 92.6%]). Among Pap test providers (n = 1114), screening practices, including number of tests ordered or performed, use of patient reminder systems, and cytology method used, varied by physician specialty (P < 0.001). Although most Pap test providers reported that screening guidelines were very influential in their clinical practice, few had guideline-consistent recommendations for starting and stopping Pap screening across multiple vignettes (22.3% [CI, 19.9% to 25.0%]). Guideline-consistent recommendations varied by specialty (obstetrics/gynecology, 16.4%; internal medicine, 27.5%; and family or general practice, 21.1%). Compared with obstetricians/gynecologists, internal medicine specialists and family or general practice specialists were more likely to have guideline-consistent screening recommendations (odds ratio, 1.98 [CI, 1.22 to 3.23] and 1.45 [CI, 0.99 to 2.13], respectively) in multivariate analysis.
Physician self-report may reflect idealized rather than actual practice.
Primary care physicians' recommendations for Pap test screening are not consistent with screening guidelines, reflecting overuse of screening. Implementation of effective interventions that focus on potentially modifiable physician and practice factors is needed to improve screening practice.
National Cancer Institute, Centers for Disease Control and Prevention, and Agency for Healthcare Research and Quality.
Long-term control or remission of rheumatoid arthritis (RA) may be possible with very early treatment. However, no optimal first therapeutic strategy has been determined.
To assess the potential cost-effectiveness of major therapeutic strategies for very early RA.
Decision analytic model with probabilistic sensitivity analyses.
Published data, the National Data Bank for Rheumatic Diseases, and actual 2007 hospital costs.
U.S. adults with very early RA (symptom duration ≤3 months).
Lifetime.
Health care provider and societal.
3 management strategies were compared: a symptomatic or "pyramid" strategy with initial nonsteroidal anti-inflammatory drugs, patient education, pain management, and low-dose glucocorticoids, and disease-modifying antirheumatic drugs (DMARDs) at 1 year for nonresponders; early DMARD therapy with methotrexate; and early therapy with biologics and methotrexate.
Cost per quality-adjusted life-year (QALY) gained.
By reducing the progression of joint erosions and subsequent functional disability, both early intervention strategies increase quality-adjusted life more than the pyramid strategy and save long-term costs. When the cost of very early intervention is factored in, the cost-effectiveness ratio of the early DMARD strategy is $4849 per QALY (95% CI, $0 to $16 354 per QALY) compared with the pyramid strategy, whereas the benefits gained through the early biologic strategy come at a substantial incremental cost. The early DMARD strategy maximizes the effectiveness of early DMARDs and reserves the use of biologics for patients with more treatment-resistant disease of longer duration, for which the incremental benefit of biologics is greater.
The early biologic strategy becomes more cost-effective if drug prices are reduced, risk for death is permanently lowered through biologic therapy, patients experience drug-free remission, responders can be selected before therapy initiation, or effective alternative antirheumatic agents are available for patients for whom several biologics have failed.
Data on the long-term effect of very early therapeutic interventions on the natural progression in disability and joint erosions are limited. The study considered only tumor necrosis factor inhibitors and not the newer biologics.
According to the most objective measures of RA progression, very early intervention with conventional DMARDs is cost-effective. The cost-effectiveness of very early intervention with biologics remains uncertain.
Objective: To determine whether long-term ICS therapy, with and without LABAs, reduces inflammation and improves pulmonary function in COPD.
Design: Randomized, placebo-controlled trial. (ClinicalTrials.gov registration number: NCT00158847)
Setting: 2 university medical centers in The Netherlands.
Patients: 114 steroid-naive current or former smokers with moderate to severe COPD.
Measurements: Cell counts in bronchial biopsies and sputum (primary outcome); methacholine responsiveness at baseline, 6, and 30 months; and clinical outcomes every 3 months.
Intervention: Random assignment by minimization method to receive fluticasone propionate, 500 µg twice daily, for 6 months (n = 31) or 30 months (n = 26); fluticasone, 500 µg twice daily, and salmeterol, 50 µg twice daily, for 30 months (single inhaler; n = 28); or placebo twice daily (n = 29).
Results: 101 patients were greater than 70% adherent to therapy. Fluticasone therapy decreased counts of mucosal CD3+ cells (–55% [95% CI, –74% to –22%]; P = 0.004), CD4+ cells (–78% [CI, –88% to 60%]; P < 0.001), CD8+ cells (–57% [CI, –77% to –18%]; P = 0.010), and mast cells (–38% [CI, –60% to –2%]; P = 0.039) and reduced hyperresponsiveness (P = 0.036) versus placebo at 6 months, with effects maintained after 30 months. Fluticasone therapy for 30 months reduced mast cell count and increased eosinophil count and percentage of intact epithelium, with accompanying reductions in sputum neutrophil, macrophage, and lymphocyte counts and improvements in FEV1 decline, dyspnea, and quality of life. Reductions in inflammatory cells correlated with clinical improvements. Discontinuing fluticasone therapy at 6 months increased counts of CD3+ cells (120% [CI, 24% to 289%]; P = 0.007), mast cells (218% [CI, 99% to 407%]; P < 0.001), and plasma cells (118% [CI, 9% to 336%]; P = 0.028) and worsened clinical outcome. Adding salmeterol improved FEV1 level.
Limitations: The study was not designed to evaluate clinical outcomes. Measurement of primary outcome was not available for 24% of patients at 30 months.
Conclusion: ICS therapy decreases inflammation and can attenuate decline in lung function in steroid-naive patients with moderate to severe COPD. Adding LABAs does not enhance these effects.
Primary Funding Source: Netherlands Organization for Scientific Research, Netherlands Asthma Foundation, GlaxoSmithKline of The Netherlands, University Medical Center Groningen, and Leiden University Medical Center.
]]>Objective: To assess the relationship between BMD and fracture and all common single-nucleotide polymorphisms (SNPs) in previously proposed osteoporosis candidate genes.
Design: Large-scale meta-analysis of genome-wide association data.
Setting: 5 international, multicenter, population-based studies.
Participants: Data on BMD were obtained from 19 195 participants (14 277 women) from 5 populations of European origin. Data on fracture were obtained from a prospective cohort (n = 5974) from the Netherlands.
Measurements: Systematic literature review using the Human Genome Epidemiology Navigator identified autosomal genes previously evaluated for association with osteoporosis. We explored the common SNPs arising from the haplotype map of the human genome (HapMap) across all these genes. BMD at the femoral neck and lumbar spine was measured by dual-energy x-ray absorptiometry. Fractures were defined as clinically apparent, site-specific, validated nonvertebral and vertebral low-energy fractures.
Results: 150 candidate genes were identified and 36 016 SNPs in these loci were assessed. SNPs from 9 gene loci (ESR1, LRP4, ITGA1, LRP5, SOST, SPP1, TNFRSF11A, TNFRSF11B, and TNFSF11) were associated with BMD at either site. For most genes, no SNP was statistically significant. For statistically significant SNPs (n = 241), effect sizes ranged from 0.04 to 0.18 SD per allele. SNPs from the LRP5, SOST, SPP1, and TNFRSF11A loci were significantly associated with fracture risk; odds ratios ranged from 1.13 to 1.43 per allele. These effects on fracture were partially independent of BMD at SPP1 and SOST.
Limitation: Only common polymorphisms in linkage disequilibrium with SNPs in HapMap could be assessed, and previously reported associations for SNPs in some candidate genes could not be excluded.
Conclusion: In this large-scale collaborative genome-wide meta-analysis, 9 of 150 candidate genes were associated with regulation of BMD, 4 of which also significantly affected risk for fracture. However, most candidate genes had no consistent association with BMD.
Primary Funding Source: European Union, Netherlands Organisation for Scientific Research, Research Institute for Diseases in the Elderly, Netherlands Genomics Initiative, Wellcome Trust, National Institutes of Health, deCODE Genetics, and Canadian Institutes of Health Research.
]]>Objective: To assess the health and economic outcomes of HPV vaccination in older U.S. women.
Design: Cost-effectiveness analysis with an empirically calibrated model.
Data Sources: Published literature.
Target Population: U.S. women aged 35 to 45 years.
Time Horizon: Lifetime.
Perspective: Societal.
Intervention: HPV vaccination added to screening strategies that differ by test (cytology or HPV DNA testing), frequency, and start age versus screening alone.
Outcome Measures: Incremental cost-effectiveness ratios (2006 U.S. dollars per quality-adjusted life-year [QALY] gained).
Results of Base-Case Analysis: In the context of annual or biennial screening, HPV vaccination of women aged 35 to 45 years ranged from $116 950 to $272 350 per QALY for cytology with HPV DNA testing for triage of equivocal results and from $193 690 to $381 590 per QALY for combined cytology and HPV DNA testing, depending on age and screening frequency.
Results of Sensitivity Analysis: The probability of HPV vaccination being cost-effective for women aged 35 to 45 years was 0% with annual or biennial screening and less than 5% with triennial screening, at thresholds considered good value for money.
Limitation: The natural history of the disease and the efficacy of the vaccine in older women are uncertain.
Conclusion: Given currently available information, the effectiveness of HPV vaccination for women older than 30 years who are screened seems to be small. Compared with current screening that uses sensitive HPV DNA testing, HPV vaccination is associated with less attractive cost-effectiveness ratios in this population than those for other, well-accepted interventions in the United States.
Primary Funding Source: National Cancer Institute, Centers for Disease Control and Prevention, and the American Cancer Society.
]]>Objective: To investigate whether hand hygiene and use of facemasks prevents household transmission of influenza.
Design: Cluster randomized, controlled trial. Randomization was computer generated; allocation was concealed from treating physicians and clinics and implemented by study nurses at the time of the initial household visit. Participants and personnel administering the interventions were not blinded to group assignment. (ClinicalTrials.gov registration number: NCT00425893)
Setting: Households in Hong Kong.
Patients: 407 people presenting to outpatient clinics with influenza-like illness who were positive for influenza A or B virus by rapid testing (index patients) and 794 household members (contacts) in 259 households.
Intervention: Lifestyle education (control) (134 households), hand hygiene (136 households), or surgical facemasks plus hand hygiene (137 households) for all household members.
Measurements: Influenza virus infection in contacts, as confirmed by reverse-transcription polymerase chain reaction (RT-PCR) or diagnosed clinically after 7 days.
Results: Sixty (8%) contacts in the 259 households had RT-PCR–confirmed influenza virus infection in the 7 days after intervention. Hand hygiene with or without facemasks seemed to reduce influenza transmission, but the differences compared with the control group were not significant. In 154 households in which interventions were implemented within 36 hours of symptom onset in the index patient, transmission of RT-PCR–confirmed infection seemed reduced, an effect attributable to fewer infections among participants using facemasks plus hand hygiene (adjusted odds ratio, 0.33 [95% CI, 0.13 to 0.87]). Adherence to interventions varied.
Limitation: The delay from index patient symptom onset to intervention and variable adherence may have mitigated intervention effectiveness.
Conclusion: Hand hygiene and facemasks seemed to prevent household transmission of influenza virus when implemented within 36 hours of index patient symptom onset. These findings suggest that nonpharmaceutical interventions are important for mitigation of pandemic and interpandemic influenza.
Primary Funding Source: Centers for Disease Control and Prevention.
]]>Objective: To compare the effects of sleep restriction and alcohol on driving simulator performance in patients with OSA and age-matched control participants.
Design: Driving simulator assessments in 2 groups under 3 different conditions presented in random order.
Setting: Adelaide Institute for Sleep Health, Sleep Laboratory, Adelaide, Australia.
Participants: 38 untreated patients with OSA and 20 control participants.
Measurements: Steering deviation, crashes, and braking reaction time.
Intervention: Unrestricted sleep, sleep restricted to a maximum of 4 hours, and ingestion of an amount of 40% vodka calculated to achieve a blood alcohol level of 0.05 g/dL.
Results: Patients with OSA demonstrated increased steering deviation compared with control participants (mean, 50.5 cm [95% CI, 46.1 to 54.9 cm] in the OSA group and 38.4 cm [CI, 32.4 to 44.4 cm] in the control group; P < 0.01) and significantly greater steering deterioration over time (group by time interaction, P = 0.02). The increase in steering deviation after sleep restriction and alcohol was approximately 40% greater in patients with OSA than in control participants (group by condition interaction, P = 0.04). Patients with OSA crashed more frequently than control participants (1 vs. 24 participants; odds ratio [OR], 25.4; P = 0.03) and crashed more frequently after sleep restriction (OR, 4.0; P < 0.01) and alcohol consumption (OR, 2.3; P = 0.02) than after normal sleep. In patients with OSA, prolonged eye closure (>2 seconds) and microsleeps (> 2 seconds of theta activity on electroencephalography) were significant crash predictors (OR, 19.2 and 7.2, respectively; P < 0.01). Braking reaction time was slower after sleep restriction than after normal sleep (mean, 1.39 [SD, 0.06] seconds vs. 1.22 [SD, 0.04] seconds; P < 0.01) but not after alcohol consumption. No group differences were found.
Limitation: Simulated driving was assessed rather than on-road driving.
Conclusion: Patients with OSA are more vulnerable than healthy persons to the effects of alcohol consumption and sleep restriction on various driving performance variables.
Primary Funding Source: Australian National Health and Medical Research Council.
]]>Objective: To measure associations between structural capabilities of primary care practices and performance on commonly used quality measures.
Design: Cross-sectional analysis.
Setting: Massachusetts.
Participants: 412 primary care practices.
Measurements: During 2007, 1 physician from each participating primary care practice (median size, 4 physicians) was surveyed about structural capabilities of the practice (responses representing 308 practices were obtained). Data on practice structural capabilities were linked to multipayer performance data on 13 Healthcare Effectiveness Data and Information Set (HEDIS) process measures in 4 clinical areas: screening, diabetes, depression, and overuse.
Results: Frequently used multifunctional electronic health records were associated with higher performance on 5 HEDIS measures (3 in screening and 2 in diabetes), with statistically significant differences in performance ranging from 3.1 to 7.6 percentage points. Frequent meetings to discuss quality were associated with higher performance on 3 measures of diabetes care (differences ranging from 2.3 to 3.1 percentage points). Physician awareness of patient experience ratings was associated with higher performance on screening for breast cancer and cervical cancer (1.9 and 2.2 percentage points, respectively). No other structural capabilities were associated with performance on more than 1 measure. No capabilities were associated with performance on depression care or overuse.
Limitation: Structural capabilities of primary care practices were assessed by physician survey.
Conclusion: Among the investigated structural capabilities of primary care practices, electronic health records were associated with higher performance across multiple HEDIS measures. Overall, the modest magnitude and limited number of associations between structural capabilities and clinical performance suggest the importance of continuing to measure the processes and outcomes of care for patients.
Primary Funding Source: The Commonwealth Fund.
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