David H. Wesorick

Effect of Perioperative Statins on Death, Myocardial Infarction, Atrial Fibrillation, and Length of Stay A Systematic Review and Meta-analysis

OBJECTIVE To assess the influence of perioperative statin treatment on the risk of death, myocardial infarction, atrial fibrillation, and hospital and intensive care unit length of stay in statin-naive patients undergoing cardiac or noncardiac surgery. DATA SOURCES MEDLINE via PubMed, EMBASE, Biosis, and the Cochrane Central Register of Controlled Trials via Ovid. Additional studies were identified through hand searches of bibliographies, trial Web sites, and clinical experts. Randomized controlled trials reporting the effect of perioperative statins in statin-naive patients undergoing cardiac and noncardiac surgery were included. STUDY SELECTION Two investigators independently selected eligible studies from original research published in any language studying the effects of statin use on perioperative outcomes of interest. DATA EXTRACTION Two investigators performed independent article abstraction and quality assessment. DATA SYNTHESIS Fifteen randomized controlled studies involving 2292 patients met the eligibility criteria. Random-effects meta-analyses of unadjusted and adjusted data were performed according to the method described by DerSimonian and Laird. Perioperative statin treatment decreased the risk of atrial fibrillation in patients undergoing cardiac surgery (relative risk [RR], 0.56; 95% CI, 0.45 to 0.69; number needed to treat [NNT], 6). In cardiac and noncardiac surgery, perioperative statin treatment reduced the risk of myocardial infarction (RR, 0.53; 95% CI, 0.38 to 0.74; NNT, 23) but not the risk of death (RR, 0.62; 95% CI, 0.34 to 1.14). Statin treatment reduced mean length of hospital stay (standardized mean difference, -0.32; 95% CI, -0.53 to -0.11) but had no effect on length of intensive care unit stay (standardized mean difference, -0.08; 95% CI, -0.25 to 0.10). CONCLUSIONS Perioperative statin treatment in statin-naive patients reduces atrial fibrillation, myocardial infarction, and duration of hospital stay. Wider use of statins to improve cardiac outcomes in patients undergoing high-risk procedures seems warranted.

Safety and Efficacy of Sitagliptin Therapy for the Inpatient Management of General Medicine and Surgery Patients With Type 2 Diabetes: A pilot, randomized, controlled study

OBJECTIVE This study investigated the safety and efficacy of sitagliptin (Januvia) for the inpatient management of type 2 diabetes (T2D) in general medicine and surgery patients. RESEARCH DESIGN AND METHODS In this pilot, multicenter, open-label, randomized study, patients (n = 90) with a known history of T2D treated with diet, oral antidiabetic agents, or low total daily dose of insulin (≤0.4 units/kg/day) were randomized to receive sitagliptin alone or in combination with glargine insulin (glargine) or to a basal bolus insulin regimen (glargine and lispro) plus supplemental (correction) doses of lispro. Major study outcomes included differences in daily blood glucose (BG), frequency of treatment failures (defined as three or more consecutive BG >240 mg/dL or a mean daily BG >240 mg/dL), and hypoglycemia between groups. RESULTS Glycemic control improved similarly in all treatment groups. There were no differences in the mean daily BG after the 1st day of treatment (P = 0.23), number of readings within a BG target of 70 and 140 mg/dL (P = 0.53), number of BG readings >200 mg/dL (P = 0.23), and number of treatment failures (P > 0.99). The total daily insulin dose and number of insulin injections were significantly less in the sitagliptin groups compared with the basal bolus group (both P < 0.001). There were no differences in length of hospital stay (P = 0.78) or in the number of hypoglycemic events between groups (P = 0.86). CONCLUSIONS Results of this pilot indicate that treatment with sitagliptin alone or in combination with basal insulin is safe and effective for the management of hyperglycemia in general medicine and surgery patients with T2D.

Subcutaneous insulin order sets and protocols: Effective design and implementation strategies†‡

6 Yale Diabetes Center, Yale New Haven Hospital, New Haven, Connecticut. I npatient glycemic control and hypoglycemia are issues with well deserved increased attention in recent years. Prominent guidelines and technical reviews have been published, and a recent, randomized controlled trial demonstrated the superiority of basal bolus insulin regimens compared to sliding-scale regimens. Effective glycemic control for inpatients has remained elusive in most medical centers. Recent reports detail clinical inertia and the continued widespread use of sliding-scale subcutaneous insulin regimens, as opposed to the anticipatory, physiologic ‘‘basal-nutrition-correction dose’’ insulin regimens endorsed by these reviews. Inpatient glycemic control faces a number of barriers, including fears of inducing hypoglycemia, uneven knowledge and training among staff, and competing institutional and patient priorities. These barriers occur in the background of an inherently complex inpatient environment that poses unique challenges in maintaining safe glycemic control. Patients frequently move across a variety of care teams and geographic locations during a single inpatient stay, giving rise to multiple opportunities for failed communication, incomplete handoffs, and inconsistent treatment. In addition, insulin requirements may change dramatically due to variations in the stress of illness, exposure tomedications that effect glucose levels, and varied forms of nutritional intake with frequent interruption. Although insulin is recognized as one of the medications most likely to be associated with adverse events in the hospital, many hospitals do not have protocols or order sets in place to standardize its use. A ‘‘Call to Action’’ consensus conference, hosted by the American Association of Clinical Endocrinologists (AACE) and the American Diabetes Association (ADA), brought together many thought leaders and organizations, including representation from the Society of Hospital Medicine (SHM), to address these barriers and to outline components necessary for successful implementation of a program to improve inpatient glycemic control in the face of these difficulties. Institutional insulin management protocols and standardized insulin order sets (supported by appropriate educational efforts) were identified as key interventions. It may be tempting to quickly deploy a generic insulin order set in an effort to improve care. This often results in mediocre results, due to inadequate incorporation of standardization and guidance into the order set and other documentation tools, and uneven use of the order set. The SHM Glycemic Control Task Force (GCTF) recommends the following steps for developing and implementing successful No honoraria were paid to any authors for time and expertise spent on the writing of this article.

Management of Diabetes and Hyperglycemia in the Hospital: A Practical Guide to Subcutaneous Insulin Use in the Non-Critically Ill, Adult Patient

5 MedStar Diabetes Institute, Washington, DC. R ecently, there has been a heightened interest in improving the quality and safety of the management of diabetes and hyperglycemia in the hospital. While observational data strongly suggests an association of hyperglycemia with morbidity and mortality in adults on general medicine and surgery units, clinical research has not yet defined the best practices for managing hyperglycemia in the hospital outside the intensive care unit (ICU). As a result, many physicians do not have a well-formulated approach to managing hyperglycemia in the noncritically ill hospital patient, and the use of insulin therapy to attain targeted blood glucose (BG) control is often subject to practice variability, leading to suboptimal glycemic outcomes. Practical ‘‘guidelines’’ for the management of this common clinical problem have been formulated by experts in the field, based on understanding of the physiology of glucose and insulin dynamics, the characteristics of currently available insulin preparations, and clinical experience. In 2004, in Clement et al., the American Diabetes Association published a technical review promoting the use of physiologic (‘‘basal-nutritional-correction dose’’) insulin regimens in the hospital to achieve targeted glycemic outcomes. This approach has been disseminated via review articles, and more recently, a randomized, controlled trial demonstrated that hospitalized type 2 diabetes patients experienced better glycemic control when treated with a physiologic insulin regimen than when treated with sliding-scale insulin alone. The Society of Hospital Medicine has assembled a Glycemic Control Task Force, which is charged with providing physicians and hospitals with practical tools to improve the safety and efficacy of diabetes management in the hospital. One product of this work is an educational module that serves as a tutorial on the best practice for the management of diabetes and hyperglycemia in the noncritically ill hospital patient. This article is based on that module, and provides a practical summary of the key concepts that will allow clinicians to confidently employ physiologic insulin regimens when caring for their hospital patients. Case: Ms. X is a 56-year-old obese woman with type 2 diabetes mellitus who is admitted for treatment of an infected diabetes-related foot ulcer. The patient will be allowed to eat dinner in a couple of hours, but the surgeons have requested that she be kept ‘‘nothing by mouth’’ (NPO) after midnight for surgical debridement in the morning. Her current weight is 100 kg, and her No honoraria were paid to any authors for time and expertise spent on the writing of this article.

Efficacy of sitagliptin for the hospital management of general medicine and surgery patients with type 2 diabetes (Sita-Hospital): a multicentre, prospective, open-label, non-inferiority randomised trial

BACKGROUND The role of incretin-based drugs in the treatment of patients with type 2 diabetes admitted to hospital has not been extensively assessed. In this study, we compared the safety and efficacy of a dipeptidyl peptidase-4 inhibitor (sitagliptin) plus basal insulin with a basal-bolus insulin regimen for the management of patients with type 2 diabetes in general medicine and surgery in hospitals. METHODS We did a multicentre, prospective, open-label, non-inferiority randomised clinical trial (Sita-Hospital) in five hospitals in the USA, enrolling patients aged 18-80 years with type 2 diabetes and a random blood glucose concentration of 7·8-22·2 mmol/L who were being treated with diet or oral antidiabetic drugs or had a total daily insulin dose of 0·6 units per kg or less, admitted to general medicine and surgery services. We randomly assigned patients (1:1) to receive either sitagliptin plus basal glargine once daily (the sitagliptin-basal group) or a basal-bolus regimen with glargine once daily and rapid-acting insulin lispro or aspart before meals (the basal-bolus group) during the hospital stay. All other antidiabetic drugs were discontinued on admission. The randomisation was achieved by computer-generated tables with block stratification according to randomisation blood glucose concentrations (ie, higher or lower than 11·1 mmol/L). The primary endpoint of the trial was non-inferiority in mean differences between groups in their daily blood glucose concentrations during the first 10 days of therapy (point-of-care measurements; non-inferiority was deemed a difference <1 mmol/L). The safety endpoints included hypoglycaemia and uncontrolled hyperglycaemia leading to treatment failure. All participants who received at least one dose of study drug were included in the analysis. This study is registered with ClinicalTrials.gov, number NCT01845831. FINDINGS Between Aug 23, 2013, and July 27, 2015, we recruited 279 patients, and randomly assigned 277 to treatment; 138 to sitagliptin-basal and 139 to basal-bolus. The length of stay in hospital was similar for both groups (median 4 days [IQR 3-8] vs 4 [3-8] days, p=0·54). The mean daily blood glucose concentration in the sitagliptin-basal group (9·5 mmol/L [SD 2·7]) was not inferior to that in the basal-bolus group 9·4 mmol/L [2·7]) with a mean blood glucose difference of 0·1 mmol/L (95% CI -0·6 to 0·7). No deaths occurred in this trial. Treatment failure occurred in 22 patients (16%) in the sitagliptin-basal group versus 26 (19%) in the basal-bolus group (p=0·54). Hypoglycaemia occurred in 13 patients (9%) in the sitagliptin-basal group and in 17 (12%) in the basal-bolus group (p=0·45). No differences in hospital complications were noted between groups. Seven patients (5%) developed acute kidney injury in the sitagliptin-basal group and six (4%) in the basal-bolus group. One patient (0·7%) developed acute pancreatitis (in the basal-bolus group). INTERPRETATION The trial met the non-inferiority threshold for the primary endpoint, because there was no significant difference between groups in mean daily blood glucose concentrations. Treatment with sitagliptin plus basal insulin is as effective and safe as, and a convenient alternative to, the labour-intensive basal-bolus insulin regimen for the management of hyperglycaemia in patients with type 2 diabetes admitted to general medicine and surgery services in hospital in the non-intensive-care setting. FUNDING Merck.

Effects of an Educational Program and a Standardized Insulin Order Form on Glycemic Outcomes in Non-Critically Ill Hospitalized Patients

BACKGROUND The optimal approach to managing hyperglycemia in noncritically ill hospital patients is unclear. OBJECTIVE To investigate the effects of targeted quality improvement interventions on insulin prescribing and glycemic control. DESIGN A cohort study comparing an intervention group (IG) to a concurrent control group (CCG) and an historic control group (HCG). SETTING University of Michigan Hospital. PATIENTS Hyperglycemic, noncritically ill hospital patients treated with insulin. INTERVENTION Physician and nurse education and a standardized insulin order form based on the principles of physiologic insulin use. MEASUREMENTS Glycemic control and insulin prescribing patterns. RESULTS Patients in the IG were more likely to be treated with a combination of scheduled basal and nutritional insulin than in the other groups. In the final adjusted regression model, patients in the IG were more likely to be in the target glucose range (odds ratio [OR], 1.72; P = 0.01) and less likely to be severely hyperglycemic (OR, 0.65; P < 0.01) when compared to those in the CCG. Patients in the IG were also less likely to experience hypoglycemia than those in the CCG (P = 0.06) or the HCG (P = 0.01). Over 80% of all patient-days for all groups contained glucose readings outside of the target range. CONCLUSIONS Standardized interventions encouraging the physiologic use of subcutaneous insulin can lead to significant improvements in glycemic control and patient safety in hospitalized patients. However, the observed improvements are modest, and poor metabolic control remains common, despite these interventions. Additional research is needed to determine the best strategy for safely achieving metabolic control in these patients.

Perioperative Medicine for the Hospitalized Patient

Given the increasing complexity of hospitalized patients and the increasing specialization among surgeons, there is greater reliance on hospitalists for preoperative assessment. Several institutions have developed surgery/medicine comanagement teams that jointly care for patients in the perioperative setting. Despite a growing body of evidence, it is important to recognize there are many gaps in the perioperative literature. This has led to considerable dependence on consensus statements and expert opinion when evaluating patients perioperatively. This review focuses on the preoperative cardiovascular and pulmonary evaluation of the hospitalized patient: the two systems responsible for the greatest morbidity and mortality. Prevention of postoperative venous thromboembolism and management of perioperative hyperglycemia are also discussed.

Annals for Hospitalists Inpatient Notes - Clinical Pearls—A Young Man With Lung Cancer and Diarrhea

The patient is a 30-year-old man with metastatic nonsmall cell lung cancer who presents with diarrhea. The cancer was diagnosed 7 months prior to admission (PTA), with metastases to the brain, liver, and bone. He has been treated with radiation therapy to the brain and the right iliac wing. He also received 6 doses of pembrolizumab (last dose 6 weeks PTA). Reevaluation about 1 month PTA found disease progression, so the treatment regimen was switched to osimertinib. The patient has been receiving this treatment on a daily basis for the past 3 weeks. For the past 2 weeks, he has had diarrhea several times per day that intermittently contains dark blood. On the day of admission, he felt lightheaded, developed a new fever, and presented to the emergency department. He reported no exposure to people with gastrointestinal illness or new animals, travel, antibiotic use, or consumption of uncooked foods or unsafe water. On initial evaluation, the patients heart rate was 122 beats per minute, blood pressure was 100/54 mm Hg, respiratory rate was 22 breaths per minute, and temperature was 38.3 C. Vital signs normalized with administration of fluids and broad-spectrum antibiotics, and he was admitted to the hospital for further care. Relevant laboratory studies included a leukocyte count of 5300/L and a hemoglobin level of 14.8 g/dL. Stool was negative for Clostridium difficile, and a gastrointestinal polymerase chain reaction panel (including studies for Shigella, Shiga-like toxin-producing Escherichia coli, and enteroinvasive E coli) was also negative. The diarrhea admixed with dark blood persisted over the next 48 hours, and the patient was referred for colonoscopy. Endoscopic evaluation found an area of severely altered, atrophic, congested, erythematous, friable, and hemorrhagic mucosa in the rectum, sigmoid colon, and descending colon. Biopsies were taken. The patients oncologist suspected that these findings were related to the cancer therapy. How might this presentation be related to the patients cancer treatment? Clinical Pearls 1. Osimertinib, an epidermal growth factor receptor tyrosine kinase inhibitor, commonly causes diarrhea (1). However, diarrhea caused by this agent is almost always mild (grade 1 to 2) and only rarely treatment-limiting. In this case, the fever and blood suggested another cause of the symptoms. 2. Pembrolizumab is one of the drugs in a class of agents referred to as immune checkpoint inhibitors (ICPis) (2). These medications enhance antitumor immunity by blocking the effects of negative regulators (so-called checkpoints) on host T cells. Other ICPis include ipilimumab, nivolumab, atezolizumab, darvalumab, and avelumab. 3. ICPis are associated with a diverse side effect profile called immune-related adverse events (irAEs) (2). These side effects can involve almost any organ system and can present with symptoms ranging in severity from mild to life-threatening. Examples include rash, colitis, hepatitis, endocrinopathies (e.g., hypo- and hyperthyroidism, primary adrenal failure, and hypophysitis), pneumonitis, nephritis, inflammatory arthritis, myositis, myocarditis, pericarditis, and a range of neurologic and hematologic syndromes. 4. Immune-related colitis is one of the most common irAEs. In this case, the patients colitis was believed to be caused by prior use of pembrolizumab, even though the medication had been discontinued weeks before the symptoms developed. Immune-related colitis can occur anywhere from 1 to 32 weeks after initiation of therapy, sometimes long after the ICPi has been discontinued (3). In this case, the diarrhea was intermittently bloody, but immune-related colitis can also present with nonbloody diarrhea. The pathology of immune-related colitis has not been well described. So far, there are no histologic features that seem to be pathognomonic for the condition (3). Overall, the histologic findings of immune-related colitis appear to be nonspecific, overlapping with other causes of colitis. In this case, the histology was indistinguishable from naturally occurring ulcerative colitis, emphasizing the importance of the clinical history in making an accurate diagnosis. 5. Treatment of irAEs includes discontinuation of the offending medications and judicious use of immunosuppressant medications, including corticosteroids (2, 4). Given the relative novelty of ICPis, there is little evidence to guide treatment of the side effects, and most contemporary recommendations are based on expert opinion. It is generally believed that mild symptoms can simply be monitored and may not require discontinuation of the drug; however, more severe symptoms usually do require discontinuation as well as corticosteroid therapy. Although the optimal corticosteroid regimen is not well established, 1 to 2 mg of prednisone/kg of body weight per day is typically recommended. More severe disease, or disease that is refractory to corticosteroids, has been treated with infliximab in some cases. It seems that irAEs usually resolve with treatment. 6. When patients receiving active cancer therapy are hospitalized, communication between the hospital team and the patients oncologist is critical. This is especially true for patients being treated with novel medications or those that are associated with complex side effects. In this case, only the patients oncologist suspected the diagnosis of pembrolizumab-associated immune-related colitis. As hospitalists continue to learn about these medications, it will be important to maintain open communication with the managing oncologists when these patients require hospital admission. Resolution The osimertinib therapy was withheld, and the patient was prescribed 1.5 mg/kg of body weight per day of intravenous methylprednisolone, which was later converted to oral prednisone. The patient improved rapidly, with only 1 to 2 nonbloody bowel movements per day at the time of discharge from the hospital. Summary When patients receiving cancer therapies are admitted to the hospital with acute illness, hospitalists should consider the possibility that the problem may be iatrogenic. Communication with the patients oncologist can be very helpful in recognizing the admission problem as a side effect of treatment. As the use of ICPis expands, hospitalists will need to become familiar with the wide range of associated irAEs.

Annals for Hospitalists: Celebrating the One-Year Anniversary of an Easier Way for Hospitalists to Access Annals

Annals of Internal Medicine publishes many important articles on a range of topics, so how does a busy hospitalist quickly identify hospitalist-relevant material? One year ago, Annals launched Annals for Hospitalists. This feature highlights hospitalist-relevant content and brings perspectives from leaders in the field to clinicians, policymakers, and researchers. To date, more than 112000 people are registered to receive, the e-mail alerts. Annals for Hospitalists identifies relevant articles and provides brief summaries of these articles, tailored to a hospitalists perspective. Over the past year, Annals for Hospitalists has summarized more than 45 Annals articles, including original research, guidelines, and editorials. Hospitalists who read Annals for Hospitalists know that it guides them to the articles that are likely to inform and change practicearticles like the meta-analysis that demonstrated the benefits of using an age-adjusted D-dimer level to rule out pulmonary embolism (1), or the Ideas and Opinions piece that warned clinicians of the high variability among the many D-dimer assays (2). Annals for Hospitalists also summarized the first double-blind, randomized controlled trial of fecal microbiota transplantation for recurrent Clostridium difficle infection (3), as well as a systematic review that challenged conventional thinking about early feeding in patients with acute pancreatitis (4). Without Annals for Hospitalists, some hospitalists might have missed key articles, such as how the HEART score can improve triage of patients with chest pain (5), or that high-sensitivity troponin testing may change the way we rule out myocardial infarction (6). Last year, Annals for Hospitalists also highlighted more than 30 ACP Journal Club summaries of topics judged to be of interest to hospitalists. Thus, hospitalists no longer need to skim the full table of contents of every Annals issueAnnals for Hospitalists does this for them, and delivers exactly what they need, right to their e-mail. The crown jewel of Annals for Hospitalists is the Inpatient Notes feature. These commentaries are written by thought leaders in the field on issues germane to hospital medicine. For example, Wachters article on the pitfalls and promises of electronic health records helped us to better contextualize the nuances of the health information technology revolution (7). Similarly, Vaughn and Flanders asserted that antibiotic stewardship is not necessarily an infectious disease or pharmacist issue, but a hospitalist one (8). In their Inpatient Note, they ask hospitalists to be mindful of the potential harms associated with overtesting for infections and overtreating with antibiotics. Patel and Saints reflection on hand hygiene encouraged us to think outside the box to enhance patient safety, linking the history of French wine to that of infection prevention (9). Hosamani and Vergheses discussion of rituals taught us new ways to focus on what is truly important in our daily work (10). Inpatient Notes provides readers with insights and views into issues that they might otherwise not fully appreciate or understand. Given the successes of its first year, whats next for Annals for Hospitalists? Going forward, we will open up Inpatient Notes to unsolicited submissions from hospitalists worldwide. To this end, we have created a Web page that allows potential authors to propose an Inpatient Note. Each proposal will be reviewed by Annals for Hospitalists editors, and only the best and most relevant information will be published. Through this mechanism, we hope to attract a broader group of authors and ideas and allow experts and thought leaders from around the world to disseminate their unique knowledge and perspective to the hospitalist community. Interested authors should access this link: https://forms.acponline.org/webform/submit-your-proposal-author-inpatient-notes-commentary. Readers can also sign up for Annals for Hospitalists e-mail alerts here: http://go.annals.org/alerts, and visit the Annals for Hospitalists Web page here: http://annals.org/aim/annals-for-hospitalists. Annals of Internal Medicine publishes high-impact literature, along with insightful, expert commentaries and the renowned ACP Journal Club feature. Now, Annals for Hospitalists and Inpatient Notes bring some of the most intriguing ideas in the field of hospital medicine into the Annals realm. We thank those hospitalists who have made Annals for Hospitalists a success so far, and we extend an invitation to those who have not yet discovered its benefits.

Painful losses: Painful Losses

David H. Wesorick, MD*1, Daniel J. Brotman, MD, SFHM, FACP, Craig Jaffe, MD, Aaron Berg, MD, May P. Chan, MD, Nathan Houchens, MD, FACP Division of General Medicine, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan; Hospitalist Program, Johns Hopkins Hospital, Baltimore, Maryland; Division of Metabolism, Endocrinology & Diabetes, Department of Internal Medicine, VA Ann Arbor Healthcare System, University of Michigan, Ann Arbor, Michigan; Department of Pathology, University of Michigan, Ann Arbor, Michigan; Division of General Medicine, Department of Internal Medicine, VA Ann Arbor Healthcare System, University of Michigan, Ann Arbor, Michigan.