John E. Cornell

Preoperative Pulmonary Risk Stratification for Noncardiothoracic Surgery: Systematic Review for the American College of Physicians

Postoperative pulmonary complications contribute importantly to the risk for surgery and anesthesia. The most important and morbid postoperative pulmonary complications are atelectasis, pneumonia, respiratory failure, and exacerbation of underlying chronic lung disease. Since the publication of the first cardiac risk index in 1977 (1), clinicians have been aware of the importance of, and the risk factors for, cardiac complications. Clinicians who care for patients in the perioperative period may be surprised to learn that postoperative pulmonary complications are equally prevalent and contribute similarly to morbidity, mortality, and length of stay. For example, in a large retrospective cohort study of 8930 patients undergoing hip fracture repair, 1737 (19%) patients had postoperative medical complications (2). Serious pulmonary complications occurred in 229 (2.6%) patients and serious cardiac complications occurred in 178 (2.0%) patients. Similarly, in a study of 2964 patients undergoing elective noncardiac surgery, postoperative pulmonary and cardiac complications occurred in 53 patients and 64 patients, respectively (3). Rates of postoperative cardiac and pulmonary complications are similar in other large cohort studies of patients undergoing noncardiac surgery (4-6). Pulmonary complications may also be more likely than cardiac complications to predict long-term mortality after surgery. For example, among postoperative complications in a recent study of patients older than 70 years of age who were undergoing noncardiac surgery, only pulmonary and renal complications predicted long-term mortality (7). In another report of patients undergoing esophagectomy for cancer, postoperative pneumonia was second only to tumor stage in predicting long-term survival after surgery and predicted long-term mortality to a greater degree than postoperative cardiac, renal, or hepatic complications (8). Office and hospital consultation for patients preparing for surgery is an important activity for internists. While guidelines and consensus statements for perioperative cardiac evaluation have been published (9, 10), no similar guideline is available to assist in perioperative pulmonary evaluation. The quality and number of studies that estimate perioperative pulmonary risk have increased in the past 2 decades, and this is no longer a neglected area of inquiry. We prepared this 2-part systematic review 1) to guide clinicians on clinical and laboratory predictors of perioperative pulmonary risk before noncardiothoracic surgery and 2) to evaluate the efficacy of strategies to reduce the risk for postoperative pulmonary complications (11). Risk factors for postoperative venous thromboembolism differ substantially from those for postoperative pulmonary complications, and they are not the subject of our review. Methods Literature Search and Selection Criteria The Appendix contains a detailed description of our methodology. We performed a MEDLINE search to identify relevant publications from 1 January 1980 through 30 June 2005. We used the following Medical Subject Heading (MeSH) terms and specified that they be the articles primary focus: intraoperative complications, postoperative complications, preoperative care, intraoperative care, and postoperative care, plus the text term perioperative complications in the title or abstract. We identified additional MeSH and text terms by a review of the MEDLINE indexing for the retrieved articles. These included terms for pulmonary, respiratory, or cardiopulmonary diseases, conditions, or complications and terms for oxygenation and chest roentgenography. We performed additional searches specific to preoperative chest radiography and preoperative spirometry. We identified additional references by reviewing bibliographies of retrieved studies. We included only English-language publications and excluded publication types without primary data (that is, letters, editorials, case reports, conference proceedings, and narrative reviews). We excluded 1) studies with fewer than 25 participants per study group; 2) studies that used only administrative data (for example, International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM] codes) or lacked explicit criteria or definitions for pulmonary complications; 3) studies from developing countries (because of potential differences in respiratory and intensive care technology); 4) studies of ambulatory surgery; 5) studies of physiologic (for example, lung volumes and flow, oximetry) rather than clinical outcomes; 6) studies of gastric pH manipulation; 7) studies of complications unique to a particular type of surgery (for example, upper airway obstruction after uvulectomy); 8) studies of cardiopulmonary or pediatric surgery; and 9) studies of organ transplantation surgery (because of profoundly immunosuppressive drugs). Of 16959 citations identified by the search, 1223 citations were duplicates and 14793 citations were not relevant by title and abstract review (Figure). Of the remaining 943 potentially relevant citations, we excluded 626 citations after review of the full publication and abstracted 145 citations in detail. Figure 1. Flow chart for article selection process. Assessing Study Quality We used the U.S. Preventive Services Task Force (USPSTF) criteria for assigning hierarchy of research design, grading a studys internal validity as our basis for assessing study quality, and assigning summary strength of recommendations for each risk factor and laboratory test (12). Statistical Analysis Our literature search yielded primarily unadjusted estimates for most laboratory factors of interest. Limited multivariable, adjusted studies were available for serum albumin level less than 30 g/L and elevated blood urea nitrogen level. However, rather than attempt to compute potentially biased summary estimates, we provided narrative descriptions of the pattern of results for these potential risk factors. The eligible multivariable risk factor studies varied considerably in the number and type of competing risks and confounders included in the analyses. Extensive use of prescreening methods and variable selection algorithms often limited reporting to the subset of risk factors that were determined to be statistically significant in a given sample. The result is a subtle form of publication bias, which we verified by examination of the funnel plots and trim-and-fill estimates for each risk factor. We extracted odds ratios from each study, along with their respective SEs, 95% confidence limits, or both. We used the I 2 statistic (13) and the Cochran Q statistic (14) to assess study heterogeneity. We also recomputed pooled estimates with and without studies that produced extreme results. An I 2 statistic of 50% or more indicates substantial heterogeneity among study estimates. We used the DerSimonianLaird method to compute random-effects estimates when the set of studies was heterogeneous (15). In cases where 3 or more studies contributed estimates for a risk factor, we used the trim-and-fill method to adjust pooled estimates of a risk factors effect on postoperative pulmonary complications for publication bias (16). Trim-and-fill estimates check the sensitivity of pooled estimates to potential publication bias (17). We used meta-analysis procedures available in Stata software, version 8 (Stata Corp., College Station, Texas), to conduct these analyses (18). Role of the Funding Source The Veterans Evidence-based Research, Dissemination, and Implementation Center (VERDICT) (Veterans Affairs Health Services Research and Development, HFP 98-002) provided the research librarian and administrative support for the study. The funding source had no role in the design, conduct, or reporting of the study or in the decision to submit the manuscript for publication. Results Eighty-three publications provided univariate data on clinical predictors of postoperative pulmonary complications. Appendix Table 1 summarizes the characteristics of these studies (2, 3, 19-99). Seventy-three (88.0%) publications were cohort studies; 3 (3.6%) were randomized, controlled trials; 2 (2.4%) were casecontrol studies; and the remaining 5 (6.0%) were case-series studies. Slightly less than half (45.8%) of the cohort studies used a prospective design. Ten studies were of good quality, 18 studies were of fair quality, and 55 studies were of poor quality. Eligible studies included 11851 postoperative pulmonary complication events among 173500 patients. Appendix Table 1. Study Characteristics of Univariate Studies of Clinical Risk Factors Twenty-seven studies reporting multivariable analyses (10960 postoperative pulmonary complication events among 324648 patients) met our inclusion criteria (Appendix Table 2) (100-126). These studies form the principal basis of our review. Most studies (96%) were prospective cohort studies, and only 1 report was a casecontrol study. The 3 largest studies (118, 120, 123) used subsets of patients from the Veterans Affairs National Surgical Quality Improvement Project (NSQIP) (127). These 3 studies accounted for 89.8% of all patients included in the multivariable studies and 82.3% of the observed postoperative pulmonary complications. The crude postoperative pulmonary complication rate among the cohort studies was 3.4%. Appendix Table 2. Study Characteristics of Multivariate Studies of Clinical Predictors The studies were heterogeneous with respect to study objectives, study samples, and criteria for defining a postoperative pulmonary complication. Seventeen of the 27 (63.0%) studies aimed to identify potential risk factors for postoperative pulmonary complications. The objective in 3 studies was to develop a risk index for postoperative pulmonary complications (113, 118, 120). The remaining studies focused on high-risk subgroups, such as patients undergoing aortic surgery (104, 125), patients with smoking histories (114), elderly patients

A systematic review of newer pharmacotherapies for depression in adults: evidence report summary.

Depressive disorders, including major depression and dysthymia, are serious disabling illnesses. Approximately one in five persons is affected by a mood disorder at some point (1, 2). The attendant economic costs to society and personal burden to patients and families are enormous. In the United States, the estimated costs of treating depression and the costs incurred by lost productivity exceeded

Strategies to reduce postoperative pulmonary complications after noncardiothoracic surgery: Systematic review for the American College of Physicians

44 billion in 1990 (3). The personal burden of depression includes higher mortality and impairment in multiple areas of functioning. The World Health Organization estimates that major depression is now the fourth most important cause worldwide of loss in disability-adjusted life-years and will be the second most important cause by 2020 (4, 5). In the late 1980s, the U.S. Department of Health and Human Services sponsored the development of standard treatment guidelines for major depression (6, 7). Since publication of the guidelines, widely publicized emphasis on recognizing and treating depression and development of many new pharmacotherapies have contributed to explosive growth in antidepressant prescribing and increasing pharmacy costs for health plans. Newer antidepressants and readily available herbal remedies have led to wider but sometimes confusing choices for clinicians. The purpose of this paper is to help clinicians make informed choices about antidepressants and herbal therapies for the treatment of depression. Because previous reviews have conclusively demonstrated the efficacy of older antidepressants, this paper focuses on 29 newer antidepressants and 3 herbal remedies (6, 8-11). Older antidepressants and psychosocial therapies are considered only when they are compared directly with a newer antidepressant. Our goal was to summarize data on the efficacy of newer antidepressants and herbal treatments compared with placebo, older antidepressants, and each other for a broad spectrum of depressive disorders. 1.0 Methods English-language and non-English-language literature was identified by using the Cochrane Collaboration Depression, Anxiety and Neurosis Groups specialized registry of 8451 clinical trial articles and from references of pertinent meta-analyses and consultation with experts (1, 6-8, 10, 12-54). The specialized registry contained trials addressing depression identified from multiple sources, including electronic databases, such as MEDLINE, EMBASE, PsychLIT, LILACS, Psyndex, SIGLE, CINAHL, Biological Abstracts, and The Cochrane Library; hand searches of 69 psychiatry-related journals; and contacts with 30 pharmaceutical companies. Sources were searched from 1980 to January 1998 to capture literature relevant to newly released antidepressants. The terms depression, depressive disorder, or dysthymic disorder were combined with a list of 32 specific newer antidepressants and herbal treatments to yield 1277 relevant records. The newer antidepressants are selective serotonin reuptake inhibitors (SSRIs); serotonin and noradrenaline reuptake inhibitors; selective norepinephrine reuptake inhibitors; reversible inhibitors of monoamine oxidase; 5-hydroxy-tryptophan (5-HT2) receptor antagonists; 5-HT1a receptor agonists; -aminobutyric acid (GABA) mimetics; dopamine reuptake inhibitors and antagonists; and herbal remedies, such as hypericum (Table 1). Randomized, controlled trials that were at least 6 weeks in duration; compared a newer antidepressant with another antidepressant (newer or older), placebo, or psychosocial intervention; involved participants with depressive disorders; and had a clinical outcome were reviewed. Two or more independent reviewers identified 315 such trials. Table 1. Classification and Dosage Range of Antidepressants Two persons independently abstracted data from each trial. Data were synthesized descriptively, with attention to participant and diagnostic descriptors; study design, including randomization method and blinding; intervention characteristics; and clinical outcomes. When the studies were conceptually homogenous, quantitative analyses were done by using an empirical Bayes random-effects estimator method. Conceptual homogeneity required similar trial design, comparison of similar drug classes, diagnostic homogeneity, and adequate numbers of trials to justify pooling. Statistical heterogeneity was evaluated by using the chi-square test for homogeneity and Galbraith plots to identify outliers. When statistical heterogeneity was identified, outlier studies were reviewed to identify possible reasons for heterogeneity and studies were reanalyzed without the outliers. Primary outcomes were symptomatic response rate, total discontinuation rates (dropouts), and rates of discontinuation because of adverse events. Secondary outcomes were health-related quality-of-life, functional status, and suicide. Response rates were defined as a 50% or greater improvement in symptoms as assessed by a depression symptoms rating scale or a rating of much or very much improved as assessed by a global assessment method. Response rates were computed by using a modified intention-to-treat approach. This approach computes response rates as the number of patients who stay in treatment and get better divided by the total number of randomly assigned patients. The modified intention-to-treat analysis produces an estimate of treatment effect that is conservative because it assumes that all persons who drop out of the study early receive no benefit. A sensitivity analysis was based on an end point method. In this method, the denominator for the risk ratio was the number of participants who completed follow-up or whose last observation was carried forward. Funnel plots with the Beggs rank-order correlation test and the Egger regression approach were used to estimate the possibility of publication bias whenever a quantitative meta-analysis was performed (54). Publication bias is the tendency of published studies to have different results (usually positive findings) from studies rejected from publication or never submitted for review (usually negative findings). More detailed methods and updates through September 1998 are available in the report on which this manuscript is based (55, 56). This study was funded by the Agency for Healthcare Research and Quality, which specified certain aspects of the study, such as a technical advisory panel and the report format. 2.0 Data Synthesis 2.1 Literature on Newer Antidepressants Three hundred fifteen randomized trials evaluated newer pharmacotherapies for depression. Because some trials had multiple treatment arms, the 315 trials yielded 355 pairwise comparisons. More than 90% of the trials focused on major depression (Table 2). Nine studies focused on dysthymia, a chronic mood disorder characterized by depressed mood for at least 2 years accompanied by two or more vegetative or psychological symptoms. Three studies each examined mixed-anxiety depression and subsyndromal depression, a less symptomatic, acute depression that causes less impairment in social or occupational functioning than major depression. Forty-four trials involved participants with heterogeneous groups of depressive disorders. Most studies (n =206) compared newer and older antidepressants. Serotonin reuptake inhibitors have been the most widely tested; 60 comparisons have been made with placebo, 123 with older antidepressants, and 36 with an SSRI or other newer agent. Table 2. Treatment Trials of Newer Antidepressants and Herbal Remedies More than 90% of the included trials were of short duration (6 to 8 weeks). Among trials reporting visit frequency, patients were seen weekly (62%), every other week (23%), monthly (5%), or on a schedule that varied over time. Trial reporting was often incomplete. Fewer than one third of studies described study settings, few studies described the nature and content of clinical interactions between providers and patients, and fewer than 10% described ethnic background or socioeconomic status of the participants. Of studies that described the study setting, 77 were based in mental health specialty practices and 27 were exclusively in primary care settings. Most studies reported whether recruitment involved inpatient or outpatient settings, and most (160 studies) were based in outpatient practices. Secondary outcomes (health-related quality-of-life, functional status, and suicide) were reported too infrequently for analysis. More than 90% of the randomized trials used double-blinded methods, but fewer than 5% reported whether blinding was successful. Few studies described the method of randomization or allocation and concealment. Approximately 30% of studies had relatively low dropout rates ( 20%), and approximately 20% reported dropout rates exceeding 40%. Analysis of adverse events was complicated by variability in data collection, including voluntary reporting, generic questioning, and standardized scales that may differ and affect the reliability of the overall estimates. 2.2 Major Depression: Newer Antidepressants for Initial Treatment The lifetime risk for major depressive disorder ranges from 10% to 25% for women and 5% to 12% for men, with a point prevalence rate of 5% to 9% for women and 2% to 3% for men (2, 6, 57). It affects persons of all ages, ethnicities, and socioeconomic circumstances. Major depression is characterized by at least 2 weeks of depressed mood or loss of interest or pleasure in nearly all activities (58). The person must experience at least four additional symptoms drawn from a list of vegetative (for example, loss of appetite) and psychological (for example, difficulty concentrating or making decisions) symptoms. In addition, the symptoms must cause clinically significant distress or impairment in social, occupational, or other areas of functioning. In the trials that we reviewed, the average severity of depression was moderate to moderately severe, as measured by a standard symptom rating scale (mean score, 24 [range, 14 to 32], stand

The Effectiveness of Depression Care Management on Diabetes-Related Outcomes in Older Patients

Postoperative pulmonary complications are as common as cardiac complications for patients undergoing noncardiothoracic surgery (1-6). Further, these complications have similar mortality rates and length of stay after elective abdominal surgery or hip fracture repair (1, 2). In an accompanying systematic review (7), we identify patient, procedure, and laboratory risk factors for postoperative pulmonary complications. Our current systematic review synthesizes the evidence on preventive strategies and focuses on atelectasis, pneumonia, and respiratory failure. While we have written the review primarily for internists, this field crosses specialty disciplines. Methods Literature Search and Selection Criteria We performed a systematic MEDLINE English-language literature search from 1 January 1980 to 30 June 2005. The search strategy and inclusion and exclusion criteria are described in the accompanying review of risk factors and in further detail in its Appendix (7). The search strategy used 1) the Medical Subject Heading (MeSH) terms preoperative care, intraoperative care, postoperative care, intraoperative complications, and postoperative complications as a focus of the article; 2) the MeSH text term perioperative complications as a text term in the title or abstract; and 3) additional MeSH and text terms for pulmonary, respiratory, or cardiopulmonary conditions, complications, or care. In addition, we performed additional focused searches for preoperative chest radiography and spirometry, laparoscopic versus open major abdominal operations, general versus spinal or epidural anesthesia, intraoperative neuromuscular blockade, postoperative pain management, and postoperative lung expansion techniques. Eligible studies were randomized, controlled trials; systematic reviews; or meta-analyses. We excluded studies with less than 25 participants per group; studies from developing countries (because of potential differences in respiratory and intensive care technology); studies that used physiologic (for example, lung volumes and flow, oximetry) rather than clinical outcome measures; studies of gastric pH manipulation; studies of complications that are unique to the surgery (for example, upper airway obstruction after uvulectomy); studies of cardiopulmonary, pediatric, or organ transplantation surgery (because of profoundly immunosuppressive drugs); and studies that used only administrative data to identify postoperative complications (for example, International Classification of Diseases, Ninth Revision, Clinical Modification [ICD-9-CM], codes) because of recent evidence that administrative data have poor validity for postoperative complications (8, 9). Assessment of Study Quality We used the Quality of Reporting of Meta-analyses (QUOROM) statement for reporting meta-analyses and the U.S. Preventive Services Task Force criteria for hierarchy of research design to assess internal validity and study quality (good, fair, or poor) and to make conclusions about strength of the evidence (10, 11). Statistical Analysis We used simple means and chi-square tests to calculate CIs and P values when they were not provided in publications. We did not perform quantitative pooling because multiple meta-analyses were beyond the scope of a broad review of multiple potential interventions. We report pooled results from previous meta-analyses when applicable. Role of the Funding Source The Veterans Evidence-based Research, Dissemination, and Implementation Center (VERDICT) (Veterans Affairs Health Services Research and Development, HFP 98-002) provided the research librarian and administrative support for the study. The funding source had no role in the design, conduct, or reporting of the study or in the decision to submit the manuscript for publication. Results The search and inclusion criteria identified 20 randomized clinical trials and 11 systematic reviews or meta-analyses (12-42). Figure 1 in the accompanying review (7) of risk factors for postoperative pulmonary complications details the search results. Appendix Tables 1, 2, 3, 4, 5, 6, and 7 provide detailed characteristics of the eligible randomized trials and systematic reviews. Appendix Table 1. Abstracted Data for Eligible Randomized Trials Appendix Table 2. Abstracted Data for Eligible Randomized Trials, Continued Appendix Table 3. Abstracted Data for Eligible Randomized Trials, Continued Appendix Table 4. Abstracted Data for Eligible Randomized Trials, Continued Appendix Table 5. Abstracted Data for Eligible Randomized Trials, Continued Appendix Table 6. Abstracted Data for Eligible Systematic Reviews and Meta-Analyses Appendix Table 7. Abstracted Data for Eligible Systematic Reviews and Meta-Analyses, Continued Preoperative Smoking Cessation In the only trial of preoperative smoking cessation (12), 108 older, relatively healthy men undergoing hip or knee replacement were randomly assigned to usual care or weekly meetings with a nurse for advice about smoking cessation and nicotine withdrawal plus individualized nicotine replacement for 6 to 8 weeks before surgery until 10 days after surgery. The mean age of the men was 65 years, and 95% were American Society of Anesthesiologists (ASA) physical status class I or II. Of 56 patients in the intervention group, 36 stopped smoking and 14 reduced smoking before surgery. Overall complications rates were lower in the intervention group (18% vs. 52%; P< 0.001), primarily due to fewer wound complications and urinary tract infections. The only pulmonary outcome, postoperative ventilator support, occurred in 1 patient in each group. Nonstatistically significant trends favored shorter mean hospital stay (11 days vs. 13 days; P= 0.41) and fewer cardiac complications (0% vs. 10%; P= 0.08) in the intervention group. Although the trial was of good quality, several factors limit its ability to demonstrate decreased risk for postoperative pulmonary complications. Pulmonary risk is inherently low with hip and knee replacement. Furthermore, the timing of smoking cessation seems important. A previous cohort study showed paradoxically higher postoperative pulmonary complication rates for smokers who stopped or reduced smoking within 2 months before noncardiothoracic surgery (43). Smoking cessation may increase short-term risk because of transiently increased mucus production due to improved mucociliary activity and reduced coughing due to less bronchial irritation. Anesthetic and Analgesic Techniques Anesthetics disrupt central regulation of breathing and result in uncoordinated neural messaging. Due to resulting hypoventilation plus positional dependence, regional atelectasis occurs shortly after induction. It persists postoperatively and is compounded by ongoing disruption of respiratory muscles, limited respiratory excursion due to pain, and disruption of neurally mediated diaphragmatic functions after manipulation of abdominal viscera (43). Neuromuscular Blockade One good-quality trial found no difference in rates of postoperative pulmonary complications between intermediate-acting (atracurium, vecuronium) and long-acting (pancuronium) neuromuscular blocking agents among 691 patients undergoing elective abdominal, gynecologic, or orthopedic surgery (13). However, the incidence of residual neuromuscular block was higher among patients receiving pancuronium (26% vs. 5%; P< 0.001). Patients with residual blockade after pancuronium were 3 times more likely to develop postoperative pulmonary complications than those without residual block (17% vs. 5%; P< 0.02). In contrast, among patients receiving intermediate-acting agents, postoperative pulmonary complication rates did not differ between those with (4%) and without (5%) prolonged blockade. Therefore, pancuronium may directly lead to higher rates of prolonged neuromuscular blockade and indirectly to increased pulmonary risk compared with shorter-acting agents. Anesthesia and Analgesia Neuraxial blockade (either spinal or epidural anesthesia) blocks a constellation of stress responses to surgery (neuroendocrine, cytokine, and pain threshold) and may improve recovery and prevent complications (44). Postoperative epidural analgesia may reduce respiratory muscle dysfunction and pain-related hypoventilation. The epidural approach involves either a single injection or an infusion and can be used for both intraoperative anesthesia and postoperative analgesia. Spinal anesthesia has a faster onset (5 to 10 minutes vs. 15 to 20 minutes), produces denser sensory and motor block, and is technically easier than epidural anesthesia. However, spinal anesthesia is administered only as a single injection because of practical constraints of indwelling intrathecal catheters. The possible benefit of neuraxial blockade has generated studies of general versus neuraxial blockade anesthesia, followed by trials comparing epidural analgesia to other modes of analgesic delivery (for example, oral, intramuscular, intravenous, patient-controlled analgesia) and, more recently, trials of combined epidural intraoperative anesthesia and epidural postoperative analgesia. Intraoperative General Anesthesia versus Neuraxial Blockade A recent good-quality meta-analysis combined 141 trials (n= 9559) comparing general anesthesia and neuraxial blockade in patients undergoing a variety of operations (32). The authors compared patients receiving neuraxial blockade (with or without concomitant general anesthesia) with those receiving only general anesthesia. Neuraxial blockade reduced overall mortality (2% vs. 3%; odds ratio, 0.70 [95% CI, 0.54 to 0.90]), pneumonia (3% vs. 5%; odds ratio, 0.61 [CI, 0.48 to 0.76]), and respiratory failure (0.5% vs. 0.8%; odds ratio, 0.41 [CI, 0.23 to 0.73]). In a subgroup analysis of trials of neuraxial blockade alone versus general anesthesia alone, results were similar (odds ratio, 0.63 [CI, 0.46 to 0.87] for pneumonia; odds ratio, 0.37 [CI, 0.11 to 1.21] for respiratory failure). Potential sources of bi

A Randomized Trial of Physical Rehabilitation for Very Frail Nursing Home Residents

Context Many patients have both diabetes and depression. Some hypothesize that treating depression might improve diabetes outcomes. Contribution In this randomized trial, 12 months of depression care management for depressed patients with diabetes improved depression-related outcomes and increased the frequency of exercise. However, care management did not affect diet, diabetes medication adherence, glucose testing, or glycemic control. Cautions The study sample had reasonably good diabetes control at baseline. Whether patients with poorly controlled diabetes would benefit from depression care is not known. The Editors Major depression and dysthymic disorder affect 5% to 10% of older adults seen in primary care settings (1-3). Late-life depression is often chronic or recurrent (4-6) and is associated with substantial suffering, functional impairment, and diminished health-related quality of life (7). Diabetes mellitus affects 7.8% of all adults and almost 1 in 5 of those age 60 years and older (8). Individuals with diabetes mellitus have a 2-fold higher rate of major depression than those without diabetes (9, 10). Depression adversely affects the course of coexisting medical illness, contributing to increased symptom burden, functional impairment, and mortality (11, 12). For patients with diabetes mellitus, depression is associated with decreased glycemic control and increased number of micro- and macrovascular complications (13, 14). The mechanism of effect is not understood but may be related to depression-induced abnormalities in neuroendocrine and neurotransmitter function or decreased self-care behaviors (15-20). Integrating evidence-based depression care for persons with diabetes may improve both depression and diabetes outcomes. Three small randomized, controlled trials have studied the effect of treatment for depression on affective and glycemic outcomes in patients with depression and diabetes mellitus (21-23). These studies have consistently shown improvements in affective outcomes, but effects on glycemic control have been mixed. Primary care physicians are well positioned to provide integrated care for depression and diabetes mellitus but face many barriers. Controlled trials report that treatment for depression is efficacious in approximately 70% of persons who complete treatment compared with 30% of those who receive placebo (24). However, these results are difficult to replicate in routine primary care practice. Barriers to high-quality care include suboptimal recognition; inconsistent treatment with lack of close follow-up and monitoring; and organizational barriers, such as brief visits, poor integration with specialty mental health care, competing clinical priorities, and lack of decision support systems (25-27). Simple interventions, such as depression screening and physician education, have little impact on these barriers and patient outcomes (28-30). Treatment models that use a depression specialist working collaboratively with primary care physicians have shown clinically important improvement in patient outcomes (31-37). We recently reported robust effects of such a model for older adults with major depression or dysthymia (37). In this preplanned analysis, we evaluate the effects on affective and diabetes-specific outcomes. If effective care for depression also benefits adherence to self-care regimens, functional status, and other medical illness outcomes, it would add powerful quality-of-care and economic incentives for the dissemination and maintenance of these models. In addition, if effective care for depression improves self-care behaviors, it may also positively affect other chronic medical illnesses with important self-care components. For this prespecified subgroup analysis, we focused on older adults with clinical depression and coexisting diabetes mellitus. We hypothesized that the collaborative care intervention would improve affective symptoms, functional status, self-care behaviors, and glycemic control. In addition, we hypothesized that effects on glycemic control would be greatest for patients with baseline hemoglobin A1c values of 8.0% or greater. Methods The Improving MoodPromoting Access to Collaborative Treatment (IMPACT) study is a multisite randomized, controlled trial of a collaborative care intervention program for late-life depression in primary care (37, 38). Institutional review boards at participating sites approved study protocols, and all participants gave written informed consent. Patients Seven study sites representing 8 diverse health care organizations with a total of 18 primary care clinics in 5 states participated in the study. From July 1999 to August 2001, depressed older adults were recruited through referrals from primary care practitioners and other clinic staff or through systematic depression screening with a 2-item depression screener adapted from the Primary Care Evaluation of Mental Disorders (39). Of the 2190 patients referred to the study, 308 (14%) declined the initial eligibility screening or additional interviews, 54 (3%) had incomplete initial screenings, and 202 (9%) were ineligible because they were younger than 60 years of age or they did not plan to use the participating clinic over the coming 12 months. Of the 32908 patients approached for screening, 5246 (16%) declined the initial screening or follow-up interviews. A total of 1791 (5%) of the initial screenings were incomplete and 23233 (71%) of those screened were not eligible because they did not have one of the core depression symptoms (95%) or because of logistic reasons such as lack of transportation or access to a telephone (5%). The remaining 1626 (74%) of those referred and 2638 (8%) of those screened completed a computer-assisted structured clinical interview for Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV), to assess whether patients met research diagnostic criteria for major depression or dysthymia (40). Inclusion criteria were age 60 years or older, plans to use one of the participating clinics as the main source of general medical care in the coming year, and a diagnosis of current major depression or dysthymic disorder according to the structured clinical interview for DSM-IV. Otherwise eligible persons were excluded because of a current drinking problem (a score of 2 on the CAGE questionnaire) (41), a history of bipolar disorder or psychosis (38), ongoing treatment with a psychiatrist, or severe cognitive impairment defined by a score less than 3 on a 6-item cognitive screener (42). We identified 2102 eligible older adults with major depression or dysthymic disorder, of whom 1801 (86%) enrolled in the study. As part of the structured baseline interview, enrolled patients were asked Has a doctor or another health care worker diagnosed you with or treated you for high blood sugar or diabetes in the past 3 years? The 417 patients who endorsed this question are the focus of the diabetes-specific analyses. After the baseline interview, we randomly assigned participants to the IMPACT intervention or usual care. The randomization was stratified by recruitment method (screening or referral) and clinic. Randomization information was contained in a set of numbered, sealed envelopes for each stratum that were used sequentially for newly enrolled patients at each clinic (38). Diagnoses were communicated to enrolled patients and their primary care physicians. Intervention Patients in the intervention group received a 20-minute educational videotape and a booklet about late-life depression and were encouraged to have an initial visit with a depression care manager at the primary care clinic (43, 44). Care managers were nurses or psychologists who were trained for the study as a depression clinical specialist (38, 45). During the initial visit, the depression clinical specialist conducted a clinical and psychosocial history, reviewed the educational materials, and discussed patient preferences for depression treatment (antidepressant medications or psychotherapy). New patients and patients needing treatment plan adjustments were discussed with a supervising team psychiatrist and a liaison primary care physician during a weekly team meeting. The depression clinical specialist then worked with the patient and his or her regular primary care provider to establish a treatment plan according to an evidence-based treatment algorithm (38). The IMPACT algorithm suggested an initial choice of an antidepressant (usually a selective serotonin reuptake inhibitor) or a course of Problem-Solving Treatment in Primary Care (PST-PC), which consisted of 6 to 8 brief sessions of structured psychotherapy for depression, delivered by the depression clinical specialist in primary care (46-49). For patients who were already receiving antidepressant medications but who were still depressed, the recommendation for partial responders was to increase the dose or augment the antidepressant with a trial of PSTPC; the recommendation for nonresponders was to switch to a different medication or use a trial of PSTPC. Depression clinical specialists also encouraged patients to increase behavioral activation and referred them to additional health or social services, as clinically indicated. The intervention did not specifically address diabetes mellitus or other coexisting medical illnesses. As care managers, depression clinical specialists attempted to follow patients for up to 12 months; they monitored treatment response with the Primary Care Evaluation of Mental Disorders Patient Health Questionnaire (50) and a Web-based clinical information system (51). During the acute treatment phase, in-person or telephone follow-up contacts were suggested at least every other week. Patients who recovered from depression ( 50% reduction in the Patient Health Questionnaire score and <3 of 9 symptoms of major depression) were engaged in developing a relapse prevention plan and were then follo

Fractional anisotropy of water diffusion in cerebral white matter across the lifespan

BACKGROUND Past studies suggest multidisciplinary interventions that include physical therapy (PT) can improve function of nursing home residents. This trial specifically evaluates effects of PT for frail long-stay nursing home residents. DESIGN Randomized, controlled trial. SETTING One academic nursing home and eight community nursing homes. PATIENTS A total of 194 elderly nursing home residents dependent in at least two activities of daily living residing in the nursing home for at least 3 months. INTERVENTIONS Patients were randomized to individually tailored one-on-one PT sessions or friendly visits (FVs) three times a week for 4 months. Physical therapy included range-of-motion, strength, balance, transfer, and mobility exercises. MAIN OUTCOME MEASURES Performance-based physical function assessed by the Physical Disability Index; self-perceived health status assessed with the Sickness Impact Profile; observer-reported activities of daily living; and falls. RESULTS Eighty-nine percent and 92% of PT and FV sessions, respectively, were attended; 5% and 9% of subjects dropped out in the PT group and FV group, respectively. Compared with the FV group, the PT group experienced no significant improvements in overall Physical Disability Index, Sickness Impact Profile, or activities of daily living scores. A 15.5% improvement in the mobility subscale of the Physical Disability Index was seen (95% confidence interval [CI], 6.4% to 24.7%); no benefits in range-of-motion, strength, or balance subscales were found. Compared with the FV group, the PT group used assistive devices for bed mobility tasks less often (P = .06) and were less likely to use assistive devices and wheelchairs for locomotion (P < .005). There were 79 falls in the PT group vs 60 falls in the FV group (P = .11). Charge for the 4-month PT program was

Inhibition of Pulmonary and Skeletal Metastasis by a Transforming Growth Factor-β Type I Receptor Kinase Inhibitor

1220 per subject (95% CI,

Random-Effects Meta-analysis of Inconsistent Effects: A Time for Change

412 to

Depression and Comorbid Illness in Elderly Primary Care Patients: Impact on Multiple Domains of Health Status and Well-being

1832). CONCLUSION This standardized physical therapy program provided modest mobility benefits for very frail long-stay nursing home residents with physical disability due to multiple comorbid conditions.

The in vivo Gene Expression Signature of Oxidative Stress

Determining the time of peak of cerebral maturation is vital for our understanding of when cerebral maturation ceases and the cerebral degeneration in healthy aging begins. We carefully mapped changes in fractional anisotropy (FA) of water diffusion for eleven major cerebral white matter tracts in a large group (831) of healthy human subjects aged 11-90. FA is a neuroimaging index of micro-structural white matter integrity, sensitive to age-related changes in cerebral myelin levels, measured using diffusion tensor imaging. The average FA values of cerebral white matter (WM) reached peak at the age 32 ± 6 years. FA measurements for all but one major cortical white matter tract (cortico-spinal) reached peaks between 23 and 39 years of age. The maturation rates, prior to age-of-peak were significantly correlated (r=0.74; p=0.01) with the rates of decline, past age-of-peak. Regional analysis of corpus callosum (CC) showed that thinly-myelinated, densely packed fibers in the genu, that connect pre-frontal areas, maturated later and showed higher decline in aging than the more thickly myelinated motor and sensory areas in the body and splenium of CC. Our findings can be summarized as: associative, cerebral WM tracts that reach their peak FA values later in life also show progressively higher age-related decline than earlier maturing motor and sensory tracts. These findings carry multiple and diverse implications for both theoretical studies of the neurobiology of maturation and aging and for the clinical studies of neuropsychiatric disorders.