Joy Melnikow

Ultrasonography versus Computed Tomography for Suspected Nephrolithiasis

BACKGROUND There is a lack of consensus about whether the initial imaging method for patients with suspected nephrolithiasis should be computed tomography (CT) or ultrasonography. METHODS In this multicenter, pragmatic, comparative effectiveness trial, we randomly assigned patients 18 to 76 years of age who presented to the emergency department with suspected nephrolithiasis to undergo initial diagnostic ultrasonography performed by an emergency physician (point-of-care ultrasonography), ultrasonography performed by a radiologist (radiology ultrasonography), or abdominal CT. Subsequent management, including additional imaging, was at the discretion of the physician. We compared the three groups with respect to the 30-day incidence of high-risk diagnoses with complications that could be related to missed or delayed diagnosis and the 6-month cumulative radiation exposure. Secondary outcomes were serious adverse events, related serious adverse events (deemed attributable to study participation), pain (assessed on an 11-point visual-analogue scale, with higher scores indicating more severe pain), return emergency department visits, hospitalizations, and diagnostic accuracy. RESULTS A total of 2759 patients underwent randomization: 908 to point-of-care ultrasonography, 893 to radiology ultrasonography, and 958 to CT. The incidence of high-risk diagnoses with complications in the first 30 days was low (0.4%) and did not vary according to imaging method. The mean 6-month cumulative radiation exposure was significantly lower in the ultrasonography groups than in the CT group (P<0.001). Serious adverse events occurred in 12.4% of the patients assigned to point-of-care ultrasonography, 10.8% of those assigned to radiology ultrasonography, and 11.2% of those assigned to CT (P=0.50). Related adverse events were infrequent (incidence, 0.4%) and similar across groups. By 7 days, the average pain score was 2.0 in each group (P=0.84). Return emergency department visits, hospitalizations, and diagnostic accuracy did not differ significantly among the groups. CONCLUSIONS Initial ultrasonography was associated with lower cumulative radiation exposure than initial CT, without significant differences in high-risk diagnoses with complications, serious adverse events, pain scores, return emergency department visits, or hospitalizations. (Funded by the Agency for Healthcare Research and Quality.).

Patient compliance and medical research. Issues in methodology

Compliance with medication and medical appointments is presumed to have a critical influence on outcomes of medical interventions. However, compliance may not always be easily defined or accurately measured. No single method of measuring compliance with appointments or medication is applicable in all settings. The apparent effects of compliance on outcome may be both direct and indirect; research is needed to define more clearly how these effects may be mediated. Identifying effective methods of enhancing compliance requires accurate methods of measuring compliance. In addition, the effectiveness of interventions may decay over time, and differences in effectiveness in acute versus long-term settings have not been well studied. Researchers conducting clinical trials of medical interventions must evaluate compliance in the population studied and consider the potential impact of noncompliance on trial results and their generalizability. In some trial designs, data may best be analyzed by considering compliance a dependent or an outcome variable. Under appropriate circumstances, compliance may be considered an independent variable. Readers of the medical literature should consider how compliance was measured and analyzed when interpreting the results of clinical trials. Table 4 suggests criteria for critical appraisal of compliance-related issues in reports of clinical trials.

Cervical Intraepithelial Neoplasia Outcomes After Treatment: Long-term Follow-up From the British Columbia Cohort Study

BACKGROUND Information on the long-term risk of cervical intraepithelial neoplasia (CIN) recurrence among women treated for CIN is limited yet critical for evidence-based surveillance recommendations. METHODS We retrospectively identified 37,142 women treated for CIN 1, 2, or 3 from January 1, 1986, through December 31, 2000 (CIN cohort), from the British Columbia Cancer Agency cytology database and linked their records with cancer registry and vital statistics data. Treatment included cryotherapy, loop electrosurgical excision procedure, cone biopsy, and laser vaporization or excision. A comparison cohort contained 71,213 women with normal cytology and no previous CIN diagnosis. Follow-up continued through December 31, 2004. Among women in both cohorts under active surveillance, we compared rates of CIN 2 or 3 (CIN 2/3) and cervical cancer. Cumulative incidence rates of CIN 2/3 and 95% confidence intervals (CIs) were estimated by a life table approach by using annual rates. Cumulative rates of invasive cancer were examined by the person-years method. RESULTS Overall observed cumulative rates of CIN 2/3 in the first 6 years after treatment were 14.0% (95% CI = 13.84% to 14.15%) for women originally treated for CIN 3, 9.3% (95% CI = 9.09% to 9.42%) for CIN 2, and 5.6% (95% CI = 4.91% to 5.21%) for CIN 1. Annual rates of CIN 2/3 were less than 1% after 6 years. Initial diagnosis, age, and treatment type were associated with a diagnosis of CIN 2/3 after treatment, with 6-year adjusted rates for women aged 40-49 years ranging from 2.6% (95% CI = 1.9% to 3.4%) for treatment of CIN 1 with the loop electrosurgical excision procedure to 34.0% (95% CI = 30.9% to 37.1%) for treatment of CIN 3 with cryotherapy. Overall incidence of invasive cancer (per 100,000 woman-years) was higher in the CIN cohort (37 invasive cancers, 95% CI = 30.6 to 42.5 cancers) than in the comparison cohort (six cancers, 95% CI = 4.3 to 7.7 cancers). Cryotherapy, compared with other treatments, was associated with the highest rate of subsequent disease (adjusted odds ratio for invasive cancer = 2.98, 95% CI = 2.09 to 4.60). CONCLUSION Risk of CIN 2/3 after treatment was associated with initial CIN grade, treatment type, and age. Long-term risk of invasive cancer remained higher among women treated for CIN, particularly those treated with cryotherapy.

Treatment outcomes for squamous intraepithelial lesions

Objective: To assess the effectiveness of cone biopsy, cryotherapy, laser ablation and the loop electrosurgical procedure in the treatment of squamous intraepithelial lesions. Method: Systematic review of randomized controlled trials in subjects who underwent treatment of low‐ and high‐grade squamous intraepithelial lesions with these modalities. Main outcome measures included the following: percent resolution and persistence of a lesion and notable complications for each procedure. Result: Pooled rates of resolution for low‐grade, high‐grade, or combined squamous intraepithelial lesions were similar across the different treatment modalities (range 85.2–94.7%), with substantial overlap among the 95% confidence intervals. Significant hemorrhage occurred most frequently in subjects who received cone biopsy (4.6%) (95% CI: 2.15, 6.99), followed by laser ablation (1.75%) (95% CI: 0.70, 2.81), and LEEP (1.35%) (95% CI: 0.24, 2.47). No hemorrhages were reported among subjects who received cryotherapy. Study sample sizes were relatively small. There were no reported cases of progression to invasive cancer, but duration of follow‐up (median follow‐up time for all eligible studies=12 months) was not sufficient to evaluate long‐term outcomes. Conclusions: There were no substantive differences in outcomes regarding persistence and resolution in the treatment of squamous intraepithelial lesions for subjects receiving cone biopsy, cryotherapy, laser ablation, or LEEP.

Comparing the Use of Physician Time and Health Care Resources Among Patients Speaking English, Spanish, and Russian

BACKGROUND AND OBJECTIVES The number of US residents with limited English proficiency (LEP) is 14 million and rising. The goal of this study was to estimate the effects of LEP on physician time and resource use. DESIGN This was a prospective, observational study. SETTING AND SUBJECTS The study included 285 Medicaid patients speaking English (n = 112), Spanish (n = 62), or Russian (n = 111) visiting the General Medicine and Family Practice Clinics at the UC Davis Medical Center in 1996-1997 (participation rate, 85%). Bilingual research assistants administered patient questionnaires, abstracted the medical record, and conducted detailed time and motion studies. MAIN OUTCOME MEASURES We used seemingly unrelated regression models to evaluate the effect of language on visit time, controlling for patient demographics and health status, physician specialty, visit type, and resident involvement in care. We also estimated the effect of LEP on cross-sectional utilization of health care resources and adherence to follow-up with referral and testing appointments. RESULTS The 3 language groups differed significantly by age, education, and reason for visit but not gender, number of active medical conditions, physical functioning, or mental health. Physician visit time averaged 38+/-20 minutes (mean+/-SD). Compared with English-speaking patients and after multivariate adjustment, Spanish and Russian speakers averaged 9.1 and 5.6 additional minutes of physician time, respectively (P <0.05). The language effect was confined largely to follow-up visits with resident physicians (house staff). Compared with English speakers, Russian speakers had more referrals (P = 0.003) and Spanish speakers were less likely to follow-up with recommended laboratory studies (P = 0.031). CONCLUSIONS In these academic primary care clinics, some groups of patients using interpreters required more physician time than those proficient in English Additional reimbursement may be needed to ensure continued access and high-quality care for this special population.

Preferences of Women Evaluating Risks of Tamoxifen (POWER) study of preferences for tamoxifen for breast cancer risk reduction.

The objective of this study was to understand the attitudes and preferences of risk‐eligible women regarding use of tamoxifen for breast cancer risk reduction.

Supplemental Screening for Breast Cancer in Women With Dense Breasts: A Systematic Review for the U.S. Preventive Services Task Force

Dense breasts are defined by mammographic appearance. The American College of Radiologys (ACRs) Breast Imaging Reporting and Data System (BI-RADS) classifies breasts as almost entirely fatty (BI-RADS category a), scattered areas of fibroglandular density (category b), heterogeneously dense (category c), or extremely dense (category d). About 27.6 million (43%) women aged 40 to 74 years in the United States have dense breasts; most of these are classified as category c (1). Higher breast density is associated with decreased mammographic sensitivity and specificity and also with increased breast cancer risk. The relative hazard of breast cancer for women with dense breasts ranged from 1.50 (women aged 65 to 74 years) to 1.83 (women aged 40 to 49 years) in an analysis of 1169248 women enrolled in the Breast Cancer Surveillance Consortium (unpublished data). Increased breast density has been associated with hormone replacement therapy use, younger age, and lower body mass index (2). Data on breast density and race or ethnicity are limited. In the United States, Asian women have higher breast density (3) but lower than average incidence of breast cancer (4). Increased breast density is not associated with higher breast cancer mortality among women with dense breasts diagnosed with breast cancer, after adjustment for stage and mode of detection (5). Supplemental breast cancer screening with additional screening modalities has been proposed to improve the early detection of breast cancers. No clinical guidelines explicitly recommend use of supplemental breast cancer screening on women with dense breasts (69), but as of September 2015, 24 states had enacted legislation requiring that women be notified of breast density with their mammography results; 9 more states are considering mandatory notification (10) (Appendix Table 1). Most states require specific language distinguishing dense (BI-RADS c and d) from nondense breasts, and 4 states require that insurers cover subsequent examinations and tests for women with dense breasts (1114). Federal legislation requiring breast density notification is pending (15). Appendix Table 1. Breast Density Legislation in the United States This report summarizes a systematic review of current evidence on the reproducibility of BI-RADS breast density determinations and on test performance characteristics and outcomes of supplemental screening of women with dense breasts by using hand-held ultrasonography (HHUS), automated whole-breast ultrasonography (ABUS), breast magnetic resonance imaging (MRI), and digital breast tomosynthesis (DBT). Mandatory reporting laws frame notification of women as dense/nondense, so this review focused on this categorization. Methods The review protocol included an analytic framework with 4 key questions (KQs) (Appendix Figure 1). Detailed methods, including search strategies, detailed inclusion criteria, and excluded studies, are available in the full evidence report (16). Appendix Figure 1. Analytic framework. BI-RADS = Breast Imaging Reporting and Data System; DCIS = ductal carcinoma in-situ; KQ = key question; MRI = magnetic resonance imaging. Data Sources and Searches MEDLINE, PubMed, EMBASE, and the Cochrane Library were searched for relevant English-language studies published between January 2000 and July 2015. We reviewed reference lists from retrieved articles and references suggested by experts. Study Selection Two investigators independently reviewed abstracts and full-text articles for inclusion according to predetermined criteria (E.P.W. and J.H.T. for KQ 1, J.M. and J.J.F. for KQs 2 to 4). Included studies examining the reproducibility of BI-RADS breast density categorization focused on asymptomatic women aged 40 years or older undergoing digital or film mammography. Included studies on supplemental screening with HHUS, ABUS, MRI, or DBT reported outcomes for asymptomatic women with dense breasts aged 40 years and older. In studies that focused primarily on women at high risk for breast cancer (including those with preexisting breast cancer or high-risk breast lesions [such as ductal carcinoma in situ, atypical hyperplasia, and lobular carcinoma in situ], BRCA mutations, familial breast cancer syndromes, or previous chest-wall radiation) and studies that included women with nondense breasts, we analyzed the relevant subset when available in the publication or provided by the authors. A priori inclusion criteria limited studies on BI-RADS reproducibility to fair- or good-quality randomized, controlled trials; cohort studies; or test sets involving multiple blind readings by at least 3 readers. Studies on test performance characteristics and outcomes of supplemental screening modalities were limited to fair- or good-quality randomized, controlled trials; cohort studies; or diagnostic accuracy studies with reference standards applied to all participants. We examined sensitivity, specificity, positive predictive values (PPVs), negative predictive values (NPVs), and available clinical outcomes (including cancer detection rates, recall rates, and biopsy rates). We defined recall as the need for any additional diagnostic testing after supplemental screening, including imaging and biopsy. Data Extraction and Quality Assessment Two investigators (E.P.W. and J.H.T. for KQ 1, J.M. and J.J.F. for KQs 2 to 4) critically appraised all included studies independently using the U.S. Preventive Services Task Forces (USPSTFs) design-specific criteria (17), supplemented with the National Institute for Health and Clinical Excellence methodology checklists (18) and the Quality Appraisal Tool for Studies of Diagnostic Reliability (19). According to USPSTF criteria, a good-quality study generally met all prespecified criteria; fair-quality studies did not meet all criteria but had no important limitations. Poor-quality studies had important limitations that could invalidate results (inadequate or biased application of reference standard; population limited to very high-risk patients). Data Synthesis and Analysis When available or provided by the authors, results of supplemental screening for subgroups of women with dense breasts were extracted; we excluded those with other risk factors for breast cancer. We calculated the sensitivity and specificity of the supplemental breast screening tests for women with negative mammography results. Only cancers detected by the supplemental test after negative mammography results and cancers found at interval follow-up were included. Hence, the values reported represent the sensitivity and specificity for detection of additional cancer in women with negative mammography findings. Similarly, we defined cancer detection rates, recall rates, and biopsy rates to include only those cancer cases, recalls, and biopsies related to supplemental screening after negative results on mammography. Meta-analysis was not performed because there were few good-quality studies. Role of the Funding Source This research was funded by the Agency for Healthcare Research and Quality (AHRQ) under a contract to support the work of the USPSTF. The investigators worked with USPSTF members to develop and refine the scope, analytic frameworks, and KQs. AHRQ had no role in study selection, quality assessment, synthesis, or development of conclusions. AHRQ provided project oversight; reviewed the draft report; and distributed the draft for peer review, including to representatives of professional societies and federal agencies. AHRQ performed a final review of the manuscript to ensure that the analysis met methodological standards. The investigators are solely responsible for the content and the decision to submit the manuscript for publication. Results The literature search yielded 2067 unique citations; 128 full-text articles considered potentially relevant were reviewed to identify 24 unique studies meeting inclusion criteria (Appendix Figure 2). Table 1 (2043) provides the characteristics of included studies. No studies addressed the effect of supplemental screening (compared with women without supplemental screening) on breast cancer morbidity or mortality. Appendix Figure 2. Summary of evidence search and selection. KQ = key question. Table 1. Characteristics of Included Studies Accuracy and Reliability of BI-RADS Density Determination Absent a gold standard for breast density, studies could not evaluate the accuracy of BI-RADS density determinations. Five studies reported repeated assignment of categorical BI-RADS breast density classification by the same or different radiologists, altogether including more than 440000 women, almost all with data from 2 sequential screening mammograms. To reflect current U.S. practice, we included only studies based on the BI-RADS density categories. The 3 largest studies were set in the United States. Two used data from the Breast Cancer Surveillance Consortium (20, 22), and the third presented findings from community radiologists conducting repeated readings of a large screening test set (24). Two other small studies (not discussed here) were based on mammographic screening programs in Spain (21) and Italy (23). All United Statesbased studies reflected community practice by use of clinical readings from community screening programs or test set readings by practicing community radiologists without additional training. Overall, group prevalence of BI-RADS density ratings was similar across initial and subsequent examinations among community radiologists (Appendix Table 2), but there was greater disagreement at the individual level. On subsequent screening examinations, approximately 1 in 5 women (23%) was placed in a different BI-RADS density category (a, b, c, d) by the same radiologist, while approximately 1 in 3 was categorized differently when a different radiologist read the subsequent examination result (Table 2). Considering clinical interpretations that combine categories (dense representing those with BI-RAD

Cost-effectiveness of extending cervical cancer screening intervals among women with prior normal pap tests

OBJECTIVE: Annual cervical cancer screening in women with many prior normal Pap tests is common despite limited evidence on the cost-effectiveness of this strategy. We estimated the cost-effectiveness of screening women with 3 or more prior normal tests compared with screening those with no prior tests. METHODS: We used a validated cost-effectiveness model in conjunction with data on the prevalence of biopsy-proven cervical neoplasia in women enrolled in the Centers for Disease Control and Prevention National Breast and Cervical Cancer Early Detection Program. Women were grouped according to age at the final Program Pap test (aged < 30, 30–44, 45–59, and 60–65 years) and by screening history (0, 1, 2, and 3+ consecutive prior normal Program tests) to estimate cost per life-year and quality-adjusted life-year associated with annual, biennial, and triennial screening. RESULTS: For women aged 30–44 years with no prior tests, incremental cost-effectiveness ratios ranged from

Posttreatment human papillomavirus testing for recurrent cervical intraepithelial neoplasia: a systematic review

20,533 for screening triennially (compared with no further screening) to

Defining Risk of Prescription Opioid Overdose: Pharmacy Shopping and Overlapping Prescriptions Among Long-Term Opioid Users in Medicaid

331,837 for screening annually (compared with biennially) per life-year saved. Among same-aged women with 3 or more prior normal Program tests, incremental cost-effectiveness ratios for the same measures ranged from