David I Buckley

C-reactive protein as a risk factor for coronary heart disease: a systematic review and meta-analyses for the U.S. Preventive Services Task Force.

In the United States, cardiovascular disease accounts for nearly 40% of all deaths each year (1). The factors that make up the Framingham risk score (age, sex, blood pressure, serum total cholesterol or low-density lipoprotein cholesterol level, high-density lipoprotein cholesterol level, cigarette smoking, and diabetes) account for most of the excess risk for incident coronary heart disease (CHD) (2, 3). However, these factors do not explain all of the excess risk (4, 5), and approximately 40% of CHD deaths occur in persons with cholesterol levels that are lower than the population average (6). Several lines of evidence (7, 8) have implicated chronic inflammation in CHD, and inflammatory markers have received much attention as new or emerging risk factors that could account for some of the unexplained variability in CHD risk. C-reactive protein (CRP) is a sensitive, nonspecific systemic marker of inflammation (9). Although it is unknown whether CRP is involved in CHD pathogenesis (10, 11), elevated serum CRP levels are associated with traditional cardiovascular risk factors and obesity (12, 13). In 2002, an expert panel recommended against routine use of CRP in risk assessment for primary prevention of CHD but supported CRP measurement in persons with a 10-year CHD risk of 10% to 20%. It noted that the benefits of this strategy remain uncertain and recommended further research into the implications of using CRP in risk categorization for therapeutic risk reduction in patients (14). The potential clinical benefit of new risk factors for refining global risk assessment is thought to be greatest for persons who are classified as intermediate-risk when stratified by using conventional risk factors (15). In the Framingham risk scoring system, intermediate-risk persons are those with a 10% to 20% risk for coronary death or nonfatal myocardial infarction (hard CHD events) over 10 years. Further stratification by using new markers might reclassify some intermediate-risk persons as low-risk (10-year risk<10%) and others as high-risk (10-year risk >20%). This would permit more aggressive risk reduction therapy in persons reclassified as high-risk and may consequently reduce incident CHD events (16). Several previous meta-analyses (1719) have assessed the possible independent predictive ability of CRP level for incident CHD risk. In 1998, a meta-analysis of 5 long-term, population-based prospective cohort studies and 2 cohorts of patients with preexisting CHD (17) calculated a risk ratio for coronary events of 1.7 (95% CI, 1.4 to 2.1) for CRP levels in the top tertile versus the bottom tertile. An update of this meta-analysis in 2000 (18) included 7 additional studies. The combined risk ratio for the 11 population-based prospective cohort studies of persons without preexisting CHD was 2.0 (CI, 1.6 to 2.5). Another update in 2004 (19) included 11 new studies as well as the 11 previous cohorts. The combined odds ratio for all 22 studies was 1.58 (CI, 1.48 to 1.69). These 3 meta-analyses, however, lacked a systematic assessment of the characteristics and quality of study design and execution. In particular, they did not systematically assess the degree of adjustment for standard measures of CHD risk (such as the Framingham risk score). Although the first 2 meta-analyses reported the degree of adjustment for potential confounders in each of the included studies, they did not specify how many or which standard coronary risk factors were adjusted for. Furthermore, these meta-analyses did not use the degree of adjustment as a basis for quality rating or inclusion. The most recent meta-analysis (19) did not rate quality or degree of adjustment for potential confounders. In addition, because the investigators used broad inclusion criteria, the studies in these meta-analyses do not necessarily represent the intermediate-risk population. We conducted a systematic review and meta-analyses of epidemiologic studies to help the U.S. Preventive Services Task Force (USPSTF) determine whether CRP level should be incorporated into guidelines for coronary and cardiovascular risk assessment in primary care. Our review addresses the question of whether elevated CRP levels are independently predictive of incident CHD events, specifically among intermediate-risk persons. Our approach incorporated elements previously used by the USPSTF (20) and several domains of the approach developed by the Grading of Recommendations, Assessment, Development, and Evaluation workgroup (21). Methods Data Sources and Searches We searched MEDLINE for original epidemiologic studies published between 1966 and November 2007. Our search strategy included the terms cardiovascular diseases, C-reactive protein, inflammation, and biological markers and was limited to articles published in English. We obtained additional articles from recent systematic reviews; reference lists of pertinent studies, reviews, editorials, and Web sites; and consultations with experts. Study Selection We included studies that published original data relevant to measuring the increased risk for incident CHD associated with elevated CRP level. We only considered prospective cohort studies (including those based on a cohort within a randomized trial), casecohort studies, and nested casecontrol studies. We only included studies that had a follow-up of 2 years or more, reported the outcomes of coronary death and nonfatal myocardial infarction, and adjusted for a minimum of 5 of the 7 risk factors used in the Framingham risk score. We excluded studies in which no participants were likely to be classified as intermediate-risk by using the Framingham risk score and those conducted exclusively in patients with previously diagnosed coronary disease, coronary disease equivalents (such as diabetes), or medical conditions that may cause premature CHD. We included studies in which some patients had cardiovascular disease at baseline only if the studies adjusted for prevalent disease in their analysis. The full systematic evidence report (22) provides a more detailed description of our study methods. Data Extraction and Quality Assessment One investigator reviewed the relevant articles and recorded overlap with the studies included in previous meta-analyses. For our meta-analyses, when multiple articles were published from a single cohort, we included the findings from the analysis with the highest applicability to the study question and the highest validity, on the basis of our quality ratings. In general, we selected cohort studies over nested casecontrol studies, good-quality studies over fair-quality studies, studies that adjusted for more Framingham risk variables, studies with longer follow-up, and studies that most closely addressed our principal question. We used standardized forms to abstract data on study design, population, size, CRP measurement, Framingham risk factor measurement, length of follow-up, outcomes, and data analysis. For each study, we recorded how many Framingham risk factors and other confounding factors were included in the model; whether the investigators reported model fit measures, discrimination measures, or model calibration statistics separately for models with and without CRP; and whether the study assessed the degree to which persons were reclassified on the basis of CRP level, overall or in the intermediate-risk group. Two investigators used the USPSTF criteria (20) to independently assess the quality of each study as good, fair, or poor. These criteria are specific to the study design (cohort or nested casecontrol) and include such items as appropriate assembly or ascertainment of the cohort or the case patients and control participants, reliability and equal application of measurements, response or follow-up rate, and appropriate adjustment for confounding. Because we sought to evaluate the predictive ability of CRP independent of the Framingham risk factors, we required that a study adjust for all 7 of the Framingham variables to receive a quality rating of good, even if the study otherwise had high internal validity. We resolved disagreements regarding quality by discussion, further review, and adjudication by a third reviewer (if necessary). Data Synthesis and Analysis The ideal approach to assessing the clinical effect of expanding the Framingham risk score has been debated extensively. Most previous research on the effect of a new risk factor has focused on the c-statistic, a measure of discrimination. The c-statistic, however, may be a poor indicator of the effect of using CRP level to further stratify persons classified as intermediate-risk by the Framingham risk score. For this reason, recent literature (2326) has emphasized that studies should examine how well assessing CRP level improves risk prediction and further risk stratification among persons initially classified as intermediate-risk. Most studies provided an overall estimate of the risk associated with high CRP levels, after adjustment for other risk factors, but did not provide specific evidence about the intermediate-risk group. For these studies, we conducted 2 meta-analyses to obtain pooled adjusted risk ratios for the association of hard CHD events and CRP level. The first included all studies that were fair-quality or better, adjusted for at least 5 Framingham risk factors, included at least some participants who were likely to be at intermediate risk, and estimated the risk for CHD associated with CRP level after adjusting for confounders. Because including studies that had methodological flaws or assessed fewer Framingham risk factors could have led to overestimation of the pooled risk ratio, we conducted a second meta-analysis that was restricted to good-quality studies, all of which adjusted for all Framingham risk factors. Because different studies reported ratios for different cutoff levels (including tertiles, quartiles, or quintiles), or as an increase in risk for a given unit of increas

Periodontal disease and coronary heart disease incidence: a systematic review and meta-analysis.

BACKGROUNDPeriodontal disease is common among adults in the US and is a potential source of chronic inflammation. Recent data have suggested an important role for chronic inflammation in the development of coronary heart disease (CHD).OBJECTIVETo aid the United States Preventive Services Task Force (USPSTF) in evaluating whether periodontal disease is an independent novel risk factor for incident CHD.METHODSStudies were identified by searching Medline (1966 through March 2008) and reviewing prior systematic reviews, reference lists, and consulting experts. Prospective cohort studies that assessed periodontal disease, Framingham risk factors, and coronary heart disease incidence in the general adult population without known CHD were reviewed and quality rated using criteria developed by the USPSTF. Meta-analysis of good and fair quality studies was conducted to determine summary estimates of the risk of CHD events associated with various categories of periodontal disease.RESULTSWe identified seven articles of good or fair quality from seven cohorts. Several studies found periodontal disease to be independently associated with increased risk of CHD. Summary relative risk estimates for different categories of periodontal disease (including periodontitis, tooth loss, gingivitis, and bone loss) ranged from 1.24 (95% CI 1.01–1.51) to 1.34 (95% CI 1.10–1.63). Risk estimates were similar in subgroup analyses by gender, outcome, study quality, and method of periodontal disease assessment.CONCLUSIONPeriodontal disease is a risk factor or marker for CHD that is independent of traditional CHD risk factors, including socioeconomic status. Further research in this important area of public health is warranted.

Duration of symptoms of respiratory tract infections in children: systematic review.

Objective To determine the expected duration of symptoms of common respiratory tract infections in children in primary and emergency care. Design Systematic review of existing literature to determine durations of symptoms of earache, sore throat, cough (including acute cough, bronchiolitis, and croup), and common cold in children. Data sources PubMed, DARE, and CINAHL (all to July 2012). Eligibility criteria for selecting studies Randomised controlled trials or observational studies of children with acute respiratory tract infections in primary care or emergency settings in high income countries who received either a control treatment or a placebo or over-the-counter treatment. Study quality was assessed with the Cochrane risk of bias framework for randomised controlled trials, and the critical appraisal skills programme framework for observational studies. Main outcome measures Individual study data and, when possible, pooled daily mean proportions and 95% confidence intervals for symptom duration. Symptom duration (in days) at which each symptom had resolved in 50% and 90% of children. Results Of 22 182 identified references, 23 trials and 25 observational studies met inclusion criteria. Study populations varied in age and duration of symptoms before study onset. In 90% of children, earache was resolved by seven to eight days, sore throat between two and seven days, croup by two days, bronchiolitis by 21 days, acute cough by 25 days, common cold by 15 days, and non-specific respiratory tract infections symptoms by 16 days. Conclusions The durations of earache and common colds are considerably longer than current guidance given to parents in the United Kingdom and the United States; for other symptoms such as sore throat, acute cough, bronchiolitis, and croup the current guidance is consistent with our findings. Updating current guidelines with new evidence will help support parents and clinicians in evidence based decision making for children with respiratory tract infections.

Interventions to influence consulting and antibiotic use for acute respiratory tract infections in children: a systematic review and meta-analysis.

Background Respiratory tract infections (RTIs) are common in children and generally self-limiting, yet often result in consultations to primary care. Frequent consultations divert resources from care for potentially more serious conditions and increase the opportunity for antibiotic overuse. Overuse of antibiotics is associated with adverse effects and antimicrobial resistance, and has been shown to influence how patients seek care in ensuing illness episodes. Methodology/Principal Findings We conducted a systematic review and meta-analysis to assess the effectiveness of interventions directed towards parents or caregivers which were designed to influence consulting and antibiotic use for respiratory tract infections (RTIs) in children in primary care. Main outcomes were parental consulting rate, parental knowledge, and proportion of children subsequently consuming antibiotics. Of 5,714 references, 23 studies (representing 20 interventions) met inclusion criteria. Materials designed to engage children in addition to parents were effective in modifying parental knowledge and behaviour, resulting in reductions in consulting rates ranging from 13 to 40%. Providing parents with delayed prescriptions significantly decreased reported antibiotic use (Risk Ratio (RR) 0.46 (0.40, 0.54); moreover, a delayed or no prescribing approach did not diminish parental satisfaction. Conclusions In order to be most effective, interventions to influence parental consulting and antibiotic use should: engage children, occur prior to an illness episode, employ delayed prescribing, and provide guidance on specific symptoms. These results support the wider implementation of interventions to reduce inappropriate antibiotic use in children.

Urinary biomarkers for diagnosis of bladder cancer: A systematic review and meta-analysis

Bladder cancer is the fourth most commonly diagnosed cancer in U.S. men and the 10th most commonly diagnosed cancer in U.S. women (1). Standard methods for diagnosis of bladder cancer involve cytologic evaluation of urine, imaging tests, and cystoscopy (2, 3). Because cystoscopy is uncomfortable and costly, alternative diagnostic methods have been sought. Urine-based biomarkers have been developed as potential alternatives or adjuncts to standard tests for the initial diagnosis of bladder cancer or identification of recurrent disease (4). Six urinary biomarkers have been approved by the U.S. Food and Drug Administration (FDA) for diagnosis or surveillance of bladder cancer: quantitative nuclear matrix protein 22 (NMP22) (Alere NMP22 [Alere]), qualitative NMP22 (BladderChek [Alere]), qualitative bladder tumor antigen (BTA) (BTA stat [Polymedco]), quantitative BTA (BTA TRAK [Polymedco]), fluorescence in situ hybridization (FISH) (UroVysion [Abbott Molecular]), and fluorescent immunohistochemistry (ImmunoCyt [Scimedx]). The qualitative NMP22 and BTA tests can be performed as point-of-care tests, and the others are performed in a laboratory. One additional test, Cxbladder (Pacific Edge Diagnostics USA), is a laboratory-developed test that does not require FDA approval. Other biomarkers have been developed but are not FDA-approved. The purpose of this study was to systematically review the evidence on the comparative accuracy of urinary biomarkers for diagnosis of bladder cancer. It was done as part of a larger review (5) on the evaluation and treatment of nonmuscle-invasive bladder cancer that was nominated to the Agency for Healthcare Research and Quality (AHRQ) by the American Urological Association for use in updating its guidelines. Methods Detailed methods and data for this review, including the analytic framework, key questions, search strategies, inclusion criteria, study data extraction, and quality ratings, are available in the full report (5). The protocol was developed using a standardized process (6) with input from experts and the public and is registered in the PROSPERO database (7). This article focuses on the accuracy of urinary biomarkers for initial diagnosis of bladder cancer or for diagnosis of recurrent disease, including any variance in diagnostic accuracy based on tumor characteristics, patient characteristics, or the nature of presenting signs or symptoms. Data Sources and Searches A research librarian searched multiple electronic databases, including Ovid MEDLINE (January 1990 through June 2015), the Cochrane Central Register of Controlled Trials, and the Cochrane Database of Systematic Reviews (through June 2015). We also reviewed reference lists and searched ClinicalTrials.gov. Study Selection Two investigators independently reviewed abstracts and full-text articles against prespecified eligibility criteria. We included cross-sectional and cohort studies on the diagnostic accuracy of urinary biomarkers in adults who had signs or symptoms of bladder cancer or were undergoing surveillance for recurrent disease after treatment. We focused on urinary biomarkers approved by the FDA for the diagnosis of bladder cancer (quantitative or qualitative NMP22, qualitative or quantitative BTA, FISH, and ImmunoCyt) or classified by the FDA as a laboratory-developed test (Cxbladder). We excluded studies that used a casecontrol design; studies that did not evaluate the diagnostic accuracy of biomarkers against standard diagnostic methods (cystoscopy and histopathology); and studies on the accuracy of biomarkers for screening in assessing prognosis, guiding therapy, or monitoring response to treatment. Data Extraction and Quality Assessment One investigator extracted details about the setting, tests evaluated, definition of a positive test result, study design, reference standard, inclusion criteria, population characteristics, proportion found to have bladder cancer, bladder cancer stage and grade, results, and funding sources. We constructed 22 tables with the number of true-positive, false-positive, true-negative, and false-negative results from published sample sizes, prevalence, sensitivity, and specificity. A second investigator verified extractions for accuracy. Two investigators independently assessed the risk of bias for each study as low, moderate, or high using criteria adapted from QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies 2) (8). Discrepancies were resolved through discussion and consensus. Data Synthesis and Analysis We performed meta-analyses for sensitivity and specificity using a bivariate logistic mixed-effects model (9) with SAS, version 10.0 (SAS Institute) (10). We assumed random effects with a bivariate normal distribution and measured statistical heterogeneity with the random-effects variance (2). When few studies were available for an analysis, we used the moment estimates of correlation between sensitivity and specificity in the bivariate model. We calculated positive and negative likelihood ratios (LRs) using the summarized sensitivity and specificity (11, 12). Because studies of a particular biomarker generally used the same definition for a positive test result, we did not plot summary receiver-operating characteristic curves (13). For head-to-head comparisons, we used the same bivariate logistic mixed-effects model, with an added indicator variable for the tests. We conducted analyses for each biomarker by using data from all patients and data stratified according to whether testing was performed for initial diagnosis (evaluation of symptoms) or diagnosis of recurrence (surveillance). We also performed analyses stratified by study design features (such as retrospective or prospective or use of a prespecified threshold to define a positive test result), risk of bias (overall and whether the study performed blinding to the results of the index test), the country in which the study was conducted, and tumor grade and stage (14). We assessed the strength of evidence (SOE) for each body of evidence as high, moderate, low, or insufficient based on aggregate study quality, precision, consistency, and directness. Role of the Funding Source This project was funded under contract HHSA290201200014I from the AHRQ, U.S. Department of Health and Human Services. AHRQ staff assisted in developing the scope and key questions. The AHRQ had no role in study selection, quality assessment, or synthesis. Results The literature flow diagram (Figure 1) summarizes the search and selection of articles. Database searches resulted in 4358 potentially relevant articles. After dual review of abstracts and titles, we selected 262 articles for full-text dual review and determined that 57 studies (in 60 publications) met our inclusion criteria (Appendix Table 1) (15-74). Nineteen studies evaluated quantitative NMP22, 4 evaluated qualitative NMP22, 23 evaluated qualitative BTA, 4 evaluated quantitative BTA, 10 evaluated FISH, 13 evaluated ImmunoCyt, and 1 evaluated Cxbladder. Sample sizes ranged from 26 to 3916, mean age ranged from 54 to 77 years, the proportion of male patients ranged from 57% to 88%, and the proportion diagnosed with bladder cancer ranged from 3% to 81%. Eight studies focused on diagnostic testing for signs and symptoms suggestive of bladder cancer, 16 focused on surveillance of previously treated bladder cancer, and 19 evaluated mixed populations. Forty-three studies were conducted in the United States or Europe. We rated 2 studies as having low risk of bias (20, 21), 3 as having high risk of bias (25, 62, 68), and the remainder as having medium risk of bias. Frequent methodological shortcomings were failure to report blinded interpretation of the reference standard, failure to report enrollment of a random or consecutive sample of patients, or failure to report predefined criteria for a positive test result. Figure 1. Summary of evidence search and selection. * Cochrane Central Register of Controlled Trials and Cochrane Database of Systematic Reviews. Includes prior reports, reference lists of relevant articles, and systematic reviews. Appendix Table 1. Biomarker Study Characteristics Appendix Table 1 Continued Appendix Table 1 Continued Appendix Table 1 Continued Quantitative NMP22 Sensitivity of quantitative NMP22 was 0.69 (95% CI, 0.62 to 0.75), and specificity was 0.77 (CI, 0.70 to 0.83) (19 studies), for a positive LR of 3.05 (CI, 2.28 to 4.10) and a negative LR of 0.40 (CI, 0.32 to 0.50) (Appendix Figure 1). Exclusion of 2 studies that used a cutoff other than >10 U/mL for a positive test result (18, 37) resulted in similar sensitivity and specificity. Diagnostic accuracy was similar for evaluation of symptoms and for surveillance. Excluding 1 study with high risk of bias (68) and restricting the analysis to prospective studies, those conducted in the United States or Europe, or those that used a prespecified threshold for a positive test result had little effect on pooled estimates. Restricting the analysis to 3 studies with blinded reference standard interpretation resulted in higher specificity (0.89 [CI, 0.78 to 0.95]) (15, 42, 58). Appendix Figure 1. Sensitivity and specificity of quantitative NMP22. NMP22 = nuclear matrix protein 22; TN = true-negative; TP = true-positive. Qualitative NMP22 Sensitivity of qualitative NMP22 was 0.58 (CI, 0.39 to 0.75), and specificity was 0.88 (CI, 0.78 to 0.94) (4 studies), for a positive LR of 4.89 (CI, 3.23 to 7.40) and a negative LR of 0.48 (CI, 0.33 to 0.71) (Appendix Figure 2) (20, 21, 23, 37). Restricting the analysis to 2 studies with low risk of bias resulted in similar estimates (sensitivity, 0.53 [CI, 0.29 to 0.75]; specificity, 0.87 [CI, 0.74 to 0.94]) (20, 21). Subgroup and sensitivity analyses were limited by small numbers of studies. Appendix Figure 2. Sensitivity and specificity of qualitative NMP22. NMP22 = nuclear matrix protein 22; TN = true-negative; TP = true-positive. Qualitative BTA Sensitivity of qualit

Intravesical Therapy for the Treatment of Nonmuscle Invasive Bladder Cancer: A Systematic Review and Meta-Analysis

Purpose: We systematically review the benefits and harms of intravesical therapies for nonmuscle invasive bladder cancer. Materials and Methods: Systematic literature searches were performed of Ovid MEDLINE (January 1990 through February 2016), the Cochrane databases and reference lists. Randomized and quasi‐randomized trials of intravesical bacillus Calmette‐Guérin, mitomycin C, gemcitabine, thiotepa, valrubicin, doxorubicin, epirubicin and interferon vs transurethral bladder tumor resection alone, and head‐to‐head trials of intravesical therapies were selected. Data were pooled using a random effects model. Results: Overall 39 trials evaluated adjuvant intravesical therapy vs transurethral bladder tumor resection alone. Bacillus Calmette‐Guérin was associated with a decreased risk of bladder cancer recurrence (3 trials, RR 0.56, 95% CI 0.43–0.71) and progression (4 trials, RR 0.39, 95% CI 0.24–0.64) (strength of evidence low). Mitomycin C, doxorubicin, epirubicin and thiotepa were also associated with a decreased risk of recurrence, with no difference in risk of progression (strength of evidence low). There were 55 trials that compared one intravesical therapy agent against another. There were no differences between bacillus Calmette‐Guérin vs mitomycin C in recurrence risk (RR 0.95, 95% CI 0.81–1.11), but bacillus Calmette‐Guérin was associated with a decreased risk of recurrence in the subgroup of trials of maintenance regimens (RR 0.79, 95% CI 0.71–0.87, strength of evidence low). Bacillus Calmette‐Guérin was associated with a lower recurrence risk vs doxorubicin, epirubicin, interferon alpha‐2a, bacillus Calmette‐Guérin plus interferon alpha‐2b, and thiotepa (strength of evidence low to moderate). Bacillus Calmette‐Guérin was associated with higher rates of local and systemic adverse events than other intravesical agents (strength of evidence low). Head‐to‐head trials showed no clear differences between standard and lower doses of bacillus Calmette‐Guérin in recurrence, progression or mortality risk (strength of evidence low). Limited evidence suggested that bacillus Calmette‐Guérin maintenance regimens are associated with reduced recurrence risk vs no further intravesical therapy in responders to induction therapy (strength of evidence low). Conclusions: For nonmuscle invasive bladder cancer several intravesical therapies are associated with a decreased risk of recurrence vs transurethral bladder tumor resection alone. Bacillus Calmette‐Guérin is the only agent associated with a decreased progression risk vs transurethral bladder tumor resection alone, but may be associated with a higher risk of adverse events than other intravesical therapies, indicating trade‐offs between potential benefits and harms.

Influence of health insurance coverage on breast, cervical, and colorectal cancer screening in rural primary care settings.

The current study was performed to determine, in rural settings, the relation between the type and status of insurance coverage and being up‐to‐date for breast, cervical, and colorectal cancer screening.

The Rural Older Adult Memory (ROAM) Study: A Practice-based Intervention to Improve Dementia Screening and Diagnosis

Introduction: The aim of the Rural Older Adult Memory (ROAM) pilot study was to evaluate the feasibility of screening and diagnosing dementia in patients aged 75 years or older in 6 rural primary care practices in a practice-based research network. Methods: Clinicians and medical assistants were trained in dementia screening using the ROAM protocol via distance learning methods. Medical assistants screened patients aged 75 years of age and older. For patients who screened positive, the clinician was alerted to the need for a dementia work-up. Outcomes included change in the proportion of patients who were screened and diagnosed with dementia or mild cognitive impairment, clinician confidence in diagnosing and managing dementia, and response to the intervention. Results: Results included a substantial increase in screening for dementia, a modest increase in the proportion of patients who were diagnosed with dementia or mild cognitive impairment, and improved clinician confidence in diagnosing dementia. Although clinicians and medical assistants found the ROAM protocol easy to implement, there was substantial variability in adherence to the protocol among the 6 practices. Conclusion: This study demonstrated the complex issues that must be addressed in implementing a dementia screening process in rural primary care. Further study is needed to develop effective strategies for overcoming the factors that impeded the full uptake of the protocol, including the logistic challenges in implementing practice change and clinicians’ attitudes toward dementia screening and diagnosis.

Treatment of muscle‐invasive bladder cancer: A systematic review

There is uncertainty regarding the use of bladder‐sparing alternatives to standard radical cystectomy, optimal lymph node dissection techniques, and optimal chemotherapeutic regimens. This study was conducted to systematically review the benefits and harms of bladder‐sparing therapies, lymph node dissection, and systemic chemotherapy for patients with clinically localized muscle‐invasive bladder cancer. Systematic literature searches of MEDLINE (from 1990 through October 2014), the Cochrane databases, reference lists, and the ClinicalTrials.gov Web site were performed. A total of 41 articles were selected for review. Bladder‐sparing therapies were found to be associated with worse survival compared with radical cystectomy, although the studies had serious methodological shortcomings, findings were inconsistent, and only a few studies evaluated currently recommended techniques. More extensive lymph node dissection might be more effective than less extensive dissection at improving survival and decreasing local disease recurrence, but there were methodological shortcomings and some inconsistency. Six randomized trials found cisplatin‐based combination neoadjuvant chemotherapy to be associated with a decreased mortality risk versus cystectomy alone. Four randomized trials found adjuvant chemotherapy to be associated with decreased mortality versus cystectomy alone, but none of these trials reported a statistically significant effect. There was insufficient evidence to determine optimal chemotherapeutic regimens. Cancer 2016;122:842–51.

Chronic opioid therapy and preventive services in rural primary care: an Oregon rural practice-based research network study.

PURPOSE For clinicians, using opioid therapy for chronic noncancer pain (CNCP) often gives rise to a conflict between treating their patients’ pain and fears of addiction, diversion of medication, or legal action. Consequent stresses on clinical encounters might adversely affect some elements of clinical care. We evaluated a possible association between chronic opioid therapy (COT) for CNCP and receipt of various preventive services. METHODS We conducted a retrospective cohort study in 7 primary care clinics within the Oregon Rural Practice-based Research Network (ORPRN). Using medical records of 704 patients, aged 35 to 85 years, seen during a 3-year period, we compared the receipt of 4 preventive services between patients on COT for CNCP and patients not on chronic opioid therapy (non-COT). We used multivariate log-binomial regression analyses to estimate the relative risk of receipt of each preventive service. RESULTS After adjustment for plausible confounders, we found that patients using COT had a statistically significantly lower relative risk (RR) of receipt of cervical cancer screening (RR = 0.60; 95% confidence interval [CI], 0.47–0.76) and colorectal cancer screening (RR = 0.42; 95% CI, 0.22–0.80) when compared with non-COT patients. The RR was reduced, without statistical significance, for lipid screening (RR = 0.77; 95% CI, 0.54–1.10), and not notably reduced for smoking cessation counseling (RR = 0.95; 95% CI, 0.78–1.15). CONCLUSIONS Patients using COT for CNCP were less likely to receive some preventive services. Research is needed to better understand barriers to and improved methods for providing preventive services for these patients.