Gail Berkenblit

Meta-analysis: Glycosylated hemoglobin and cardiovascular disease in diabetes mellitus

Context The relationship between glycosylated hemoglobin and cardiovascular disease in diabetic persons is less clear than its relationship with microvascular disease. Contribution This meta-analysis of 13 observational studies estimates that, for every 1-percentage point increase in glycosylated hemoglobin, the relative risk for any cardiovascular disease event is 1.18 for patients with type 2 diabetes mellitus and 1.15 for patients with type 1 diabetes mellitus. Cautions Although this analysis suggests that improvements in glycosylated hemoglobin level might translate into reductions in cardiovascular events, confirmation from randomized trials is necessary. The Editors Persons with diabetes mellitus are at an increased risk for cardiovascular disease; they have more than a 2-fold increased risk for cardiovascular death compared with persons without diabetes (1-3). Cardiovascular death accounts for more than 75% of all deaths among persons with diabetes mellitus (3, 4). Because this excess risk is only partially explained by traditional risk factors, such as obesity, dyslipidemia, and hypertension, diabetes is often considered an independent risk factor for cardiovascular disease. A strong body of evidence links chronic hyperglycemia to microvascular complications, such as retinopathy, neuropathy, and nephropathy, in persons with diabetes (5-10). In randomized clinical trials, improving glycemic control substantially reduces the incidence of microvascular disease in persons with diabetes (5, 6, 11). However, few randomized trials have specifically been designed to examine the influence of glycemic control on macrovascular complications, such as coronary heart disease, stroke, and peripheral arterial disease. Results from clinical trials that collected information on cardiovascular outcomes have been equivocal. In interpreting recent clinical trial data in a position statement, the American Diabetes Association stated that the role of hyperglycemia in cardiovascular complications is still unclear (12). Fasting blood glucose levels in diabetic and nondiabetic persons have been linked to an excess risk for cardiovascular disease (13-15); this link suggests an association between glycemic control and cardiovascular risk. A meta-regression analysis that combined data from more than 95 000 persons without diagnosed diabetes found a graded relationship between fasting and postprandial blood glucose levels and subsequent risk for a cardiovascular event (15). An important clinical question is whether improving long-term glycemic control in persons with diabetes reduces the risk for cardiovascular disease events. Glycosylated hemoglobin reflects long-term glycemic control and is a more accurate and stable measure than fasting blood glucose levels (16). It tracks well over time in persons with diabetes and has less measurement error than fasting blood glucose (17-20). Glycosylated hemoglobin is at the center of the clinical management of hyperglycemia in persons with diabetes. However, clinical guidelines for glycosylated hemoglobin levels are based on cut-points relevant for the prevention of microvascular complications (21). The relationship between glycosylated hemoglobin and cardiovascular disease, the most deadly complication of diabetes mellitus, has not been adequately characterized. We performed a systematic review to characterize the risk relation between long-term glycemic control, as measured by glycosylated hemoglobin, and cardiovascular end points (peripheral arterial disease, coronary heart disease, and cerebrovascular disease) in persons with type 1 and type 2 diabetes mellitus. Methods Study Design We systematically reviewed prospective cohort studies of glycosylated hemoglobin and cardiovascular disease in persons with diabetes mellitus. This study was part of a larger project commissioned by the Agency for Healthcare Research and Quality, which was conducted by the Johns Hopkins Evidenced-based Practice Center (22). Study Selection We searched the MEDLINE database for articles published in English from 1966 to July 2003 by using Medical Subject Heading terms and text words related to cardiovascular disease (coronary heart disease, peripheral arterial disease, or cerebrovascular disease), diabetes mellitus, glycemic control, and glycosylated hemoglobin (the Appendix contains the full text of the search string). We reviewed all abstracts obtained from our search for relevance. We manually reviewed bibliographies and review articles for additional citations and obtained the full text of all potentially relevant articles. We also queried experts to identify any additional studies. Our prespecified inclusion criteria were as follows: 1) prospective cohort studies that examined the cardiovascular outcomes of interest (peripheral arterial disease, coronary heart disease, and stroke) and 2) studies that reported a measure of glycosylated hemoglobin and that were conducted in samples that included persons with type 1 or type 2 diabetes. Persons described as having insulin-dependent diabetes mellitus or younger- or juvenile-onset diabetes were classified as having type 1 diabetes. Individuals described as having noninsulin-dependent diabetes mellitus or older-onset diabetes were classified as having type 2 diabetes. We excluded studies if they 1) had no original data, 2) did not address persons with diabetes, 3) involved nonprospective studies (for example, cross-sectional and retrospective casecontrol studies), 4) had less than 1 year of follow-up, 5) assessed the effect of glycemic control on cardiovascular outcomes after admission to a hospital or after surgery, and 6) involved only patients receiving dialysis or transplants. We excluded 1 additional study (23) in which the outcome was self-reported and the authors did not use standard definitions for classifying cardiovascular outcomes. When several, sequentially published studies were performed in the same sample, the publication with the longest follow-up was selected for inclusion in our analysis. For multiple studies of the same sample with equivalent follow-up, the most recent publication was selected. Data Abstraction Two investigators independently reviewed each article that met the selection criteria and abstracted the data by using standardized data abstraction forms. Discrepancies were resolved by consensus. Data abstracted were age, percentage of male and female study participants, sample size, outcome or outcomes, duration of follow-up, method of measuring glycosylated hemoglobin, main results, statistical methods, number of study participants included in the final analysis, and variables included in the adjusted model or models. For each prospective cohort study that met our inclusion criteria, we abstracted adjusted effect estimates (odds ratios, relative risks, or relative hazards) for the association between cardiovascular risk (based on incident events during follow-up) and baseline or updated mean glycosylated hemoglobin values. Standard errors for the estimates were abstracted or derived by using data reported in the manuscript. The cardiovascular disease end points, defined a priori, were fatal and nonfatal coronary heart disease (myocardial infarction, angina, and ischemic heart disease); cerebrovascular disease (fatal and nonfatal stroke); peripheral arterial disease (lower-extremity peripheral arterial disease, amputation, and claudication); and a combined cardiovascular disease outcome that included studies of coronary heart disease and stroke (but not peripheral arterial disease). We conducted separate analyses for each cardiovascular end point and for samples of persons with type 1 and type 2 diabetes. Studies using a combined outcome that included both coronary heart disease and stroke (24-26) were excluded from the pooled effect estimates for stroke alone and coronary heart disease alone but were included in the combined coronary heart disease and stroke subgroup. Statistical Analysis We conducted separate meta-analyses of the prospective cohort studies for study samples of persons with type 1 and type 2 diabetes and for the different cardiovascular outcomes. Most studies reported glycosylated hemoglobin as percentage hemoglobin A1c or its equivalent, although some studies (27-32) measured hemoglobin A1 and 1 study (33) measured total glycosylated hemoglobin. Although the American Diabetes Association advises that all measurements of glycosylated hemoglobin be reported as percentage hemoglobin A1c or its equivalent (16), there are direct linear relationships between glycosylated hemoglobin subfractions (34); therefore, we did not consider the measured subfraction to be an important source of heterogeneity across studies. For 4 studies (27, 30-32) that reported relative risk estimates for participants in the highest tertile of glycosylated hemoglobin compared with participants in the 2 lowest tertiles, we assumed a normal distribution for glycosylated hemoglobin values and used the reported mean and SD to estimate the 33rd and 83rd percentiles of glycosylated hemoglobin (corresponding to the midpoints of the 2 lowest and the highest tertiles, respectively). Then, we divided the log relative risk by the difference of these 2 values to estimate the effect of a 1-unit change in glycosylated hemoglobin (35). For the study (36) that reported a dichotomous relative risk estimate (it compared glycosylated hemoglobin above and below the median), we used the same method to estimate the effect of a 1-unit change in glycosylated hemoglobin but calculated the 25th and 75th percentiles and divided the log relative risk by the difference of these 2 values. One study (29) did not report relative risks or odds ratios but reported the mean and SD of glycosylated hemoglobin in persons with and without cardiovascular disease events. In this case, we estimated the odds ratio and its 95% CI on the basis of a linear discriminant function model. This m

“We’ll Do this Together”: The Role of the First Person Plural in Fostering Partnership in Patient-physician Relationships

BackgroundPartnership is integral to therapeutic relationships, yet few studies have examined partnership-fostering communication behaviors in the clinic setting. We conducted this study to better understand how statements in which physicians use the first person plural might foster partnership between patient and provider.MethodsWe audio-recorded encounters between 45 HIV providers and 418 patients in the Enhancing Communication and HIV Outcomes (ECHO) Study. We used the Roter Interaction Analysis System (RIAS) to code for statements made by the physician that used the first person plural to refer to themselves and their patient. Using multiple logistic regression, we examined the associations between the occurrence of one or more first person plural statements with patient ratings of provider communication. To better understand the meaning of first person plural statements, we conducted a qualitative analysis.Main ResultsProviders were mostly white (69%) and Asian (24%); 57% were female. Patients were black (60%), white (25%), and Hispanic (15%); 33% were female. One or more first person plural statements occurred in 92/418 (22%) of encounters. In adjusted analyses, encounters with first person plural statements were associated with younger patient age (OR 0.97, 95% CI 0.94–0.99), higher patient depression scores (highest tertile compared to lowest tertile: OR 1.89, 95% CI 1.01–3.51), the patient not being on anti-retroviral therapy (OR 0.53, 95% CI 0.29–0.93), and older provider age (OR 1.05, 95% CI 1.00–1.09). After adjustment, patients were less likely to highly rate their provider’s communication style if first person plural statements were used (AOR 0.57, 95% CI 0.33–0.96). There were 167 first person plural statements made by physicians in the 418 encounters. Qualitative analysis revealed that many first person plural features had at least one negative feature such as being overtly persuasive (“That’s going to be our goal”), indirect (“What can we do to improve your diet?”), or ambiguous (“Let’s see what we can do”), although there were also positive statements that involved patients in the health-care process, contributed to a mutual understanding, and addressed the patients’ goals.ConclusionsContrary to our hypotheses, use of first person plural was not associated with higher ratings of provider communication, probably because some of these statements were overtly persuasive, indirect, or ambiguous. Physicians should become aware of benefits and pitfalls of using the first person plural with patients. Further research is needed to determine the most effective methods through which providers can build alliances with patients.

Low grade Schwann cell neoplasms with leptomeningeal dissemination: clinicopathologic and autopsy findings.

Leptomeningeal dissemination of low-grade Schwann cell neoplasms is an exceptionally rare occurrence and has not been well documented in the literature. We encountered 2 cases of leptomeningeal dissemination of low-grade Schwann cell neoplasms. Patient 1 was a 63-year-old woman with neurofibromatosis type 1 and a progressive low-grade malignant peripheral nerve sheath tumor developing from a diffuse/plexiform orbital neurofibroma that arose in childhood. The neoplasm demonstrated local and leptomeningeal dissemination intracranially leading to the patients death. There was partial loss of H3K27 tri-methylation, p16 and collagen IV. Patient 2 was a 60-year-old man without neurofibromatosis type 1 who presented with cranial nerve symptoms and a disseminated neoplasm with a Schwann cell phenotype. The neoplasm stabilized after irradiation and chemotherapy, but the patient died of medical complications. Autopsy findings documented disseminated leptomeningeal disease in the intracranial and spinal compartment. H3K27M tri-methylation was preserved. The clinicopathologic and autopsy findings are studied and presented, and the literature is reviewed.

Update in HIV medicine for the generalist

This update examines and summarizes the most recent data on prevention, testing, and treatment of HIV infection for the general internist. Our aims were: (1) to describe the most recent data on HIV prevention; (2) to discuss the recommendations and emerging evidence for routine HIV screening, particularly in community-based settings; (3) to interpret the most recent data on initiation and selection of antiretroviral therapy; and (4) to facilitate the application of these findings to the clinical practice of the generalist. We performed a PUBMED search of from March 2008 through April 2010, using the Medial Subject Heading (MeSH) term “HIV,” limited to English language articles focusing on human subjects. Additionally, the authors each reviewed studies published between March 2008 and April 2010 in the major internal medicine and HIV journals. We also performed targeted searches using the search terms “HIV prevention” and “HIV testing.” Articles were included after review by consensus among a group of experts, all practicing HIV clinicians and researchers, if they met the following criteria: (1) offered novel findings in HIV prevention, HIV testing, or initiation of antiretroviral therapy; and (2) had the potential for direct clinical relevance to the practicing generalist. We narrowed down our selection by group consensus with the goal of presenting the eight to ten most relevant papers published since March 2008.

Update in HIV care.

This update in the care of individuals with HIV reviews key research publications from the past year relevant to General Internal Medicine practitioners. Specific topics that we have covered include new developments in the understanding of HIV transmission, risk behavior among injection drug users, baseline resistance testing, choice of initial treatment regimens, and controversies in treatment interruption. Our selection process was based on MEDLINE review of key journals by all authors and recommendations of experts in this field. The original MEDLINE review encompassed January 1, 2005 to March 1, 2006 and has been updated to Sepetember 1, 2006. Key phrases used in the search included “HIV,” “AIDS,” “heterosexuality,” “antiretroviral treatment (ART)/highly active antiretroviral therapy (HAART),” “drug resistance,” and “risk behaviors”.

Electronic Medical Systems

The use of EMRs is now widespread. The adoption of electronic medical records has changed the practice of clinical care and requires training of residents in effective use, while many faculty are still struggling to optimize theirs. The EMR allows the development of new note formats but also raises pitfalls of copy forwarding and note bloat. The EMR can be a useful tool or a distraction during patient-physician interaction, and best practices are evolving around exam room usage. The EMR also serves as a means of communication between the team and work flows around lab results, and patient communication must be established. Finally, the EMR can enhance population health and be a tool for panel management. This chapter focuses on teaching and evaluating resident practice in these skills.