Kristine M Schmit

The Effect of Increasing Age on the Risk of Surgical Site Infection

BACKGROUND An increasing number of older persons undergo surgery, but the relationship between increasing age and risk of surgical site infection (SSI) has not been established. The objective of the present study was to determine the relationship between increasing age and risk of SSI. METHODS The present cohort study included patients who underwent surgery between February 1991 and July 2002. Patients >17 years of age were divided randomly into derivation and validation cohorts. The study was conducted at 11 hospitals. SSIs were prospectively identified by use of Centers for Disease Control and Prevention criteria. RESULTS The study included 144,485 consecutive surgical patients and 1684 SSIs (rate of SSI, 1.2%). There were 72,139 procedures and 873 SSIs in the derivation cohort. Adjusted analyses revealed a significant relationship between age and risk of SSI (P=.006). Risk of SSI increased by 1.1%/year between ages 17 and 65 years (P=.002). At age >/=65 years, risk of SSI decreased by 1.2% for each additional year (P=.008). There were 72,334 procedures and 811 SSIs in the validation cohort. The relationship between age and risk of SSI was similar in the validation cohort. CONCLUSIONS Increasing age independently predicted an increased risk of SSI until age 65 years. At ages >/=65 years, increasing age independently predicted a decreased risk of SSI.

Comparative effectiveness of endovascular and surgical revascularization for patients with peripheral artery disease and critical limb ischemia

BACKGROUND For patients with critical limb ischemia (CLI), the optimal treatment to enhance limb preservation, prevent death, and improve functional status is unknown. We performed a systematic review and meta-analysis to assess the comparative effectiveness of endovascular revascularization and surgical revascularization in patients with CLI. METHODS We systematically searched PubMed, Embase, and the Cochrane Database of Systematic Reviews for relevant English-language studies published from January 1995 to August 2012. Two investigators screened each abstract and full-text article for inclusion, abstracted the data, and performed quality ratings and evidence grading. Random-effects models were used to compute summary estimates of effects, with endovascular treatment as the control group. RESULTS We identified a total of 23 studies, including 1 randomized controlled trial, which reported no difference in amputation-free survival at 3 years (odds ratio [OR] 1.22, 95% CI 0.84-1.77) and all-cause mortality (OR 1.07, 0.73-1.56) between the 2 treatments. Meta-analysis of the observational studies showed a statistically nonsignificant reduction in all-cause mortality at 6 months (11 studies, OR 0.85, 0.57-1.27) and amputation-free survival at 1 year (2 studies, OR 0.76, 0.48-1.21) in patients treated with endovascular revascularization. There was no difference in overall death, amputation, or amputation-free survival at ≥2 years. CONCLUSIONS The currently available literature suggests that there is no difference in clinical outcomes for patients with CLI treated with endovascular or surgical revascularization. There is a paucity of high-quality data available to guide clinical decision making, especially as it pertains to patient subgroups or anatomical considerations.

Comparative Effectiveness and Safety of Drug Therapy for Pulmonary Arterial Hypertension: A Systematic Review and Meta-analysis

BACKGROUND Current treatments for pulmonary arterial hypertension (PAH) have been shown to improve dyspnea, 6-min walk distance (6MWD), and pulmonary hemodynamics, but few studies were designed to compare treatment regimens or assess the impact of treatment on mortality. METHODS We conducted a systematic review to evaluate the comparative effectiveness and safety of monotherapy or combination therapy for PAH using endothelin receptor antagonists, phosphodiesterase inhibitors, or prostanoids. We searched English-language publications of comparative studies that reported intermediate or long-term outcomes associated with drug therapy for PAH. Two investigators abstracted data and rated study quality and applicability. RESULTS We identified 28 randomized controlled trials involving 3,613 patients. We found no studies that randomized treatment-naive patients to monotherapy vs combination therapy. There was insufficient statistical power to detect a mortality difference associated with treatment. All drug classes demonstrated increases in 6MWD when compared with placebo, and combination therapy showed improved 6MWD compared with monotherapy. For hospitalization, the OR was lower in patients taking endothelin receptor antagonists or phosphodiesterase-5 inhibitors compared with placebo (OR, 0.34 and 0.48, respectively). CONCLUSIONS Although no studies were powered to detect a mortality reduction, monotherapy was associated with improved 6MWD and reduced hospitalization rates. Our findings also suggest an improvement in 6MWD when a second drug is added to monotherapy.

Supervised vs unsupervised exercise for intermittent claudication: A systematic review and meta-analysis.

BACKGROUND Supervised exercise (SE) is widely accepted as an effective therapy for intermittent claudication (IC), but its use is limited by cost. Unsupervised exercise (UE) represents a less costly alternative. We assessed the comparative effectiveness of SE vs UE in patients with IC. METHODS AND RESULTS We searched PubMed, EMBASE, and the Cochrane Database of Systematic Reviews and identified 27 unique studies (24 randomized controlled trials, 4 observational studies) that evaluated the comparative effectiveness of SE vs UE in 2074 patients with IC. Compared with UE, SE was associated with a moderate improvement in maximal walking distance at 6 months (effect size 0.77, 95% CI 0.36-1.17, P < .001) and 12 months (effect size 0.56, 95% CI 0.34-0.77, P < .001). Supervised exercise also improved claudication distance to a moderate extent compared with UE at 6 months (effect size 0.63, 95% CI 0.40-0.85, P < .001) and 12 months (effect size 0.41, 95% CI 0.18-0.65, P = .001). There was no difference in the Short Form-36 quality of life at 6 months (effect size -0.05, 95% CI -0.50 to 0.41, P = .84) or walking impairment questionnaire distance (effect size 0.24, 95% CI -0.03 to 0.50, P = .08) or speed (effect size 0.26, 95% CI -0.06 to 0.59, P = .11). CONCLUSIONS In claudication patients, SE is more effective than UE at improving maximal walking and claudication distances, yet there is no difference in general quality of life or patient-reported community-based walking. Further studies are needed to investigate the relationship between functional gain and disease-specific quality of life.

Evaluating Cough Assessment Tools: A Systematic Review

BACKGROUND Little is known about the comparative validity, reliability, or responsiveness of instruments for assessing cough frequency or impact, where the term impact encompasses both cough severity and the impact of cough on health-related quality of life. METHODS We conducted a systematic review to evaluate instruments that assess cough frequency or impact in adults, adolescents, and children with acute or chronic cough. RESULTS Seventy-eight studies were included, of which eight were randomized controlled trials and 70 were observational studies. In all age groups, audio and video electronic recording devices had good reliability compared with other methods of assessing cough frequency but had variable correlation with other cough assessments, such as visual analog scale scores, quality-of-life questionnaires, cough diaries, and tussigenic challenges. Among adult and adolescent patients, the Leicester Cough Questionnaire (LCQ) and the Cough-Specific Quality-of-Life Questionnaire (CQLQ) were valid and reliable, showing high intraclass and test-retest correlations. Among children, the Parent Cough-Specific Quality of Life Questionnaire and Pediatric Cough Questionnaire were valid and reliable. CONCLUSIONS Electronic recording devices can be valid assessments of cough frequency. The LCQ and CQLQ for adults and the Parent Cough-Specific Quality of Life questionnaire for children are valid instruments for assessing cough impact. There is limited but insufficient evidence to determine the reliability or concurrent validity of the different types of cough diaries or visual analog scale scores. There are also limited data to support the responsiveness of recording devices. There is good responsiveness data for the LCQ and CQLQ, but more evidence is needed.

Efficacy and Tolerability of Treatments for Chronic Cough: A Systematic Review and Meta-analysis

BACKGROUND Understanding the comparative effectiveness of treatments for patients with unexplained or refractory cough is important to increase awareness of proven therapies and their potential adverse effects in this unique population. METHODS We performed a literature search for English-language studies published up to June 2012 that compared symptomatic therapies for chronic cough. Two investigators screened each abstract and full-text article for inclusion, abstracted data, and rated quality. Meta-analysis with random-effects models was used to summarize effects of treatments. RESULTS We identified 49 studies (3,067 patients) comprising 68 therapeutic comparisons. Of the studied agents, opioid and certain nonopioid and nonanesthetic antitussives had demonstrated efficacy for chronic cough in adults. Compared with placebo, effect sizes (standardized mean differences for cough severity and rate ratios for cough frequency) for opioids were 0.55 (95% CI, 0.38-0.72; P < .0001) and 0.57 (95% CI, 0.36-0.91; P = .0260), respectively. For dextromethorphan, effect sizes were 0.37 (95% CI, 0.19-0.56; P = .0008) and 0.40 (95% CI, 0.18-0.85; P = .0248), respectively. The overall strength of evidence was limited by inconsistency and imprecision of results and by small numbers of direct comparisons. Nonpharmacologic therapies and the management of cough in children were infrequently studied. CONCLUSIONS Although evidence is limited, opioid and certain nonopioid and nonanesthetic antitussives demonstrated efficacy for treating chronic cough in adults. There is a need for further studies in patients with unexplained or refractory cough as well as for more systematic study designs, assessment of patient-centered outcomes, and reporting.

Original ResearchSigns and Symptoms of Chest DiseasesEfficacy and Tolerability of Treatments for Chronic Cough: A Systematic Review and Meta-analysis

BACKGROUND Understanding the comparative effectiveness of treatments for patients with unexplained or refractory cough is important to increase awareness of proven therapies and their potential adverse effects in this unique population. METHODS We performed a literature search for English-language studies published up to June 2012 that compared symptomatic therapies for chronic cough. Two investigators screened each abstract and full-text article for inclusion, abstracted data, and rated quality. Meta-analysis with random-effects models was used to summarize effects of treatments. RESULTS We identified 49 studies (3,067 patients) comprising 68 therapeutic comparisons. Of the studied agents, opioid and certain nonopioid and nonanesthetic antitussives had demonstrated efficacy for chronic cough in adults. Compared with placebo, effect sizes (standardized mean differences for cough severity and rate ratios for cough frequency) for opioids were 0.55 (95% CI, 0.38-0.72; P < .0001) and 0.57 (95% CI, 0.36-0.91; P = .0260), respectively. For dextromethorphan, effect sizes were 0.37 (95% CI, 0.19-0.56; P = .0008) and 0.40 (95% CI, 0.18-0.85; P = .0248), respectively. The overall strength of evidence was limited by inconsistency and imprecision of results and by small numbers of direct comparisons. Nonpharmacologic therapies and the management of cough in children were infrequently studied. CONCLUSIONS Although evidence is limited, opioid and certain nonopioid and nonanesthetic antitussives demonstrated efficacy for treating chronic cough in adults. There is a need for further studies in patients with unexplained or refractory cough as well as for more systematic study designs, assessment of patient-centered outcomes, and reporting.

Prioritization of patient-centered comparative effectiveness research for osteoarthritis.

Osteoarthritis (OA) is a leading form of disability in the United States and can affect weight-bearing and nonweight-bearing joints (1, 2). It can manifest as a generalized condition affecting multiple joint groups or a localized condition affecting only 1 joint. In OA, structural and then symptomatic failure of 1 or more synovial joints occurs with loss and erosion of articular cartilage, subchondral bone alterations, meniscal degeneration, limited synovial inflammatory response, and bone and cartilage overgrowth (3). Physical and psychological factors influence the symptoms of pain and stiffness in the joints affected by OA (4). Diagnosing OA can be complex, usually requiring a complete clinical history, physical examination, laboratory testing, and radiographic studies to help confirm the suspected diagnosis. Approximately 27 million adults in the United States are living with OA of 1 or more joints (5), and this number is projected to increase steadily over the coming decades because of an aging population and an increasing prevalence of obesity (6). In the Framingham Heart Study cohort, the prevalence of symptomatic knee OA has increased by 4.1% among women and 6.0% among men over 20 years (7). Osteoarthritis exacts a tremendous toll on patients and society; it ranks third (behind depression and alcohol misuse) in years lost to disability in the United States (8). Health care costs of OA are highand are increasing. Between 1997 and 2009, the number of hospitalizations with a primary diagnosis of OA more than doubled to an estimated 921000 (5). Moreover, the health care costs of inpatient, outpatient, and pharmaceutical treatment have been estimated to be 50% greater than those for persons without the condition (9). Nonsurgical management options for OA include analgesics and anti-inflammatory drugs, weight management, exercise, and physical therapy or a combination of these strategies (such as medication plus exercise). When medication and exercise or physical therapy are not enough to decrease pain and improve quality of life, joint surgery is another option. Each management strategy has tradeoffs. For example, persons with OA are twice as likely as those without to develop peptic ulcers (relative risk, 2.49 [95% CI, 1.37 to 4.51]) and renal disease (relative risk, 2.10 [CI, 1.10 to 4.01]), which are probably associated with high use of anti-inflammatory medications (10). However, evidence is limited on the relative benefits and harms of therapies within each category (medication, physical therapy and exercise, weight loss, or surgery) and there are few direct comparisons of effectiveness, in terms of patient-centered outcomes, among categories or combinations of categories. Given the high prevalence of OA and the effect on functional status, productivity, and quality of life, optimizing treatments to stabilize symptoms, reduce pain, and maintain functional status should be a high priority. The aim of this project was to develop, in collaboration with diverse stakeholders, a prioritized research agenda about OA management that would reduce uncertainty about nonsurgical management options and optimize patient-centered outcomes. Methods The Appendix Figure shows our methods, which were previously detailed (11). We identified and appraised recently published systematic reviews; clinical practice guidelines; and documents on future research needs, including an Agency for Healthcare Research and Quality report identifying future research needs for physical therapy for knee OA (12). On the basis of recommended areas for future research from these sources, we developed a draft list of 31 possible evidence gaps. Appendix Figure. Overview of prioritization process. Adapted from reference 19. ESG = Evidence Synthesis Group; PCORI = Patient-Centered Outcomes Research Institute. We then engaged a group of 13 stakeholders that included clinical experts and researchers in OA treatment strategies; representatives from federal and nongovernmental funding agencies, relevant professional societies, and related consumer and patient advocacy groups; and health care decision makers and policymakers. The stakeholders provided input on the draft list of evidence gaps. We modified certain gaps and added others on the basis of their feedback and then constructed a relevant analytic framework (Figure). Using a forced-ranking prioritization method (13), stakeholders prioritized the list of possible evidence gaps via Web-based surveys. Figure. Analytic framework. Italicized text indicates top-tier gaps. ADLs = activities of daily living; FRN = future research need; OA = osteoarthritis. We then performed 2 database searches to identify recently published and ongoing studies relevant to the future research questions that stakeholders ranked in the top tier. Database queries included a search of PubMed between 16 December 2008 and 16 December 2013 and ClinicalTrials.gov on 16 December 2013. We categorized topic areas and key characteristics of the identified studies. Finally, senior Evidence Synthesis Group investigators proposed appropriate study designs to address the stakeholders highest-ranked priority research areas. (Tables 1 and 2 of the Supplement] show the stakeholder panel and search strategies.) Supplement. Supplementary Data for Prioritization of Research Addressing Osteoarthritis Role of the Funding Source The Patient-Centered Outcomes Research Institute (PCORI) provided funding for this work. The funding source stipulated the topic for prioritization but did not participate in the literature search, determination of study eligibility criteria, data analysis or interpretation, or preparation or approval of the manuscript for publication. Staff from PCORI did review a draft version of the manuscript and provided suggestions to clarify language describing the process in selecting this topic for prioritization. Results Expansion of Evidence Gaps Through Stakeholder Engagement The stakeholder panel expanded the initial list of 31 evidence gaps to 48. The final list illustrated several common themes: Stakeholders stressed that future research should focus on engaging patients early in the disease process, helping patients navigate treatment options that optimize patient-centered outcomes (for example, negative affect, sleep, pain, and employment), and developing strategies that promote successful long-term engagement in nonsurgical treatment options. New questions suggested by the stakeholders addressed a wide range of evidence gaps related to the unique needs of subpopulations and the comparative effectiveness of diverse interventions. Stakeholders acknowledged that several patient groups received less attention than others and that it would be important to assess the comparative effectiveness of nonsurgical management strategies by sex, socioeconomic status, and prevalence and severity of comorbid conditions among adults and patients who had previously had surgical treatment of OA. Stakeholders stressed the progressive and chronic nature of OA and the importance of early detection and patient engagement. They also emphasized the importance of setting up patients for successthat is, that treatments should be tailored to patients abilities, insurance coverage, culture, and preferences. Stakeholders acknowledged that many current and ongoing studies focus on short-term outcomes and do not necessarily provide the needed information about long-term outcomes reflecting the chronic nature of the disease. They highlighted the importance of shared decision-making tools for not only exploring nonsurgical options but also discussing the optimal timing for transition to surgical interventions. They also stressed the incorporation of patient preferences for specific outcomes and their personal characteristics (and the effect of those characteristics on potential efficacy of treatment options) in such shared decision-making tools. Stakeholder Ranking of Future Research Needs The Appendix Table shows the 48 final potential research topics, the number of points each received, and the number of stakeholders who allotted points to each topic. The final ranking divides the possible evidence gaps into a top, middle, and lower tier on the basis of overall score. The top 12 future research needs (Table) prioritized by stakeholders were related to identifying key patient-centered outcomes; determining optimal duration, intensity, and frequency of interventions; examining the effect of socioeconomic differences on management strategies; determining the need for transition from nonsurgical to surgical interventions; promoting long-term behavior change; standardizing screening tools; evaluating biomechanical strategies; developing strategies to help patients engage in key self-management behaviors; promoting coordinated care in todays new health care delivery system; comparing methods for identifying and engaging patients early in the disease process; comparing safety and effectiveness of usual-care nonsurgical therapies; and identifying ways for setting patients up to succeed with nonsurgical management. Appendix Table. Final Ranking of Future Research Needs for Alternative Strategies for OA* Table. Top-Ranked Research Priorities and Recommended Study Designs or Suggested Analyses to Address Them Although the stakeholder group expanded the initial list to 48 potential future research needs, 18 of the final questions received no votes (5 questions) or 1 to 2 votes by at most 2 stakeholders (13 questions). Of the 12 questions ranked as highest priority, 2 were new questions that stakeholders suggested (questions focusing on the transition from nonsurgical to surgical interventions and on methods for setting patients up to succeed with nonsurgical management). The other 10 high-priority ranked questions were part of the original list of suggested future research needs. Of the 18 questions ranked low priority, 9 were from our original list and 9 were

Comparative Effectiveness Review of Antiplatelet Agents in Peripheral Artery Disease

Peripheral artery disease (PAD) was identified by the Institute of Medicine as one of the top 100 priorities for comparative effectiveness research because of the large population of patients affected with significant morbidity and mortality, the multiple potential treatment options, and the high

Comparative Effectiveness of Medical Therapy, Supervised Exercise, and Revascularization for Patients With Intermittent Claudication: A Network Meta‐analysis

There are limited data on the comparative effectiveness of medical therapy, supervised exercise, and revascularization to improve walking and quality of life in patients with intermittent claudication (IC).