Ulcerative Colitis: Epidemiology,Diagnosis, and Management

Ulcerative colitis is a chronic idiopathic inflammatory bowel disease characterized by continuous mucosal inflammation that starts in the rectum and extends proximally. Typical presenting symptoms include bloody diarrhea, abdominal pain, urgency, and tenesmus. In some cases, extraintestinal manifestations may be present as well. In the right clinical setting, the diagnosis of ulcerative colitis is based primarily on endoscopy, which typically reveals evidence of continuous colonic inflammation, with confirmatory biopsy specimens having signs of chronic colitis. The goals of therapy are to induce and maintain remission, decrease the risk of complications, and improve quality of life. Treatment is determined on the basis of the severity of symptoms and is classically a step-up approach. 5-Aminosalycilates are the mainstay of treatment for mild to moderate disease. Patients with failed 5-aminosalycilate therapy or who present with more moderate to severe disease are typically treated with corticosteroids followed by transition to a steroid-sparing agent with a thiopurine, anti–tumor necrosis factor agent, or adhesion molecule inhibitor. Despite medical therapies, approximately 15% of patients still require proctocolectomy. In addition, given the potential risks of complications from the disease itself and the medications used to treat the disease, primary care physicians play a key role in optimizing the preventive care to reduce the risk of complications.     

Contemporary Strategies in the Diagnosis and Management of Heart Failure

Heart failure (HF) is an important public health problem, and strategies are needed to improve outcomes and decrease health care resource utilization and costs. Its prevalence has increased as the population ages, and HF continues to be associated with a high mortality rate and frequent need for hospitalization. The total cost of care for patients with HF was $30.7 billion in 2012, and it is estimated to more than double to $69.8 billion by 2030. Given this reality, there has been recent investigation into ways of identifying and preventing HF in patients at risk (stage A HF) and those with cardiac structural and functional abnormalities but no clinical HF symptoms (stage B). For patients who have symptoms of HF (stage C), there has been important research into the most effective ways to decongest patients hospitalized with acute decompensated HF and prevent future hospital readmissions. Successful strategies to treat patients with HF and preserved ejection fraction, which has increased in prevalence, continue to be sought. We are in the midst of a rapid evolution in our ability to care for patients with end-stage HF (stage D) because of the introduction of and improvements in mechanical circulatory support. Left ventricular assist devices used as destination therapy offer an important therapeutic option to patients who do not qualify for heart transplant because of advanced age or excessive comorbidity. This review provides a thorough update on contemporary strategies in the diagnosis and management of HF by stage (A to D) that have emerged during the past several years.     

Breast Density and Breast Cancer Risk: A Practical Review

New legislation in several states requiring breast density notification in all mammogram reports has increased awareness of breast density. Estimates indicate that up to 50% of women undergoing mammography will have high breast density; thus, with increased attention and high prevalence of increased breast density, it is crucial that primary care clinicians understand the implications of dense breasts and are able to provide appropriate counseling. This review provides an overview of breast density, specifically by defining breast density, exploring the association between breast density and breast cancer risk, both from masking and as an independent risk factor, and reviewing supplemental screening options as part of a larger framework for counseling patients with dense breasts.     

Evaluation and Management of Patients With Heart Disease and Cancer: Cardio-Oncology

The care for patients with cancer has advanced greatly over the past decades. A combination of earlier cancer diagnosis and greater use of traditional and new systemic treatments has decreased cancer-related mortality. Effective cancer therapies, however, can result in short- and long-term comorbidities that can decrease the net clinical gain by affecting quality of life and survival. In particular, cardiovascular complications of cancer treatments can have a profound effect on the health of patients with cancer and are more common among those with recognized or unrecognized underlying cardiovascular diseases. A new discipline termed cardio-oncology has thus evolved to address the cardiovascular needs of patients with cancer and optimize their care in a multidisciplinary approach. This review provides a brief introduction and background on this emerging field and then focuses on its practical aspects including cardiovascular risk assessment and prevention before cancer treatment, cardiovascular surveillance and therapy during cancer treatment, and cardiovascular monitoring and management after cancer therapy. The content of this review is based on a literature search of PubMed between January 1, 1960, and February 1, 2014, using the search terms cancer, cardiomyopathy, cardiotoxicity, cardio-oncology, chemotherapy, heart failure, and radiation.     

Female Athlete Triad and Its Components: Toward Improved Screening and Management

As female athletic participation has increased, the positive effects of exercise on health have become evident. However, with this growth in sports activity, a set of health problems unique to the female athlete has emerged. The female athlete triad as first described in 1992 by the American College of Sports Medicine consisted of disordered eating, amenorrhea, and osteoporosis; the definition was updated in 2007 to include a spectrum of dysfunction related to energy availability, menstrual function, and bone mineral density. For this review, a comprehensive search of databases—MEDLINE In-Process & Other Non-Indexed Citations, MEDLINE, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, and Scopus, from earliest inclusive dates to January 2013—was conducted by an experienced librarian with input from the authors. Controlled vocabulary supplemented with keywords such as female athlete triad, amenorrhea, oligomenorrhea, fracture, osteopenia, osteoporosis, bone disease, anorexia, bulimia, disordered eating, low energy availability was used to search for articles on female athlete triad. Articles addressing the prevalence, screening, and management of the female athlete triad were selected for inclusion in the review. This article reviews the current definitions of the triad components, epidemiology, pathophysiology, and recommended screening and management guidelines. The lack of efficacy of current screening of athletes is highlighted. Low energy availablity, from either dietary restriction or increased expenditure, plays a pivotal role in development of the triad. Athletes involved in “lean sports” (those that emphasize weight categories or aesthetics, such as ballet, gymnastics, or endurance running) are at highest risk. Treatment is centered on restoring energy availability to reverse adverse changes in the metabolic milieu. Prevention and early recognition of triad disorders are crucial to ensure timely intervention. Caregivers and physicians of female athletes must remain vigilant in education, recognition, and treatment of athletes at risk.     

Erdheim-Chester Disease: Characteristics and Management

Erdheim-Chester disease is a rare CD68⁺, CD1a⁻ non-Langerhans cell histiocytosis with multiorgan involvement. The etiology of Erdheim-Chester disease is unclear; there are no known associated infectious or hereditary genetic abnormalities. However, somatic BRAF mutations have recently been identified in these patients. Historically, the literature regarding the management of Erdheim-Chester disease consisted of case reports and small case series with anecdotal therapeutic responses to agents including, but not limited to, cytotoxic chemotherapy, bone marrow transplantation, cladribine, corticosteroids, IFN-α, the BCR-ABL/KIT inhibitor imatinib mesylate, the IL-1 receptor antagonist anakinra, the TNF-inhibitor infliximab, and recently the BRAF inhibitor vemurafenib. We performed a search of the literature using PubMed with the terms Erdheim Chester disease, without date limitations, including case reports, case series, original articles, and previous review articles. In the absence of large-scale studies, experience-based management prevails. The present review details our approach to the management of patients with Erdheim-Chester disease.     

Willis-Ekbom Disease Foundation Revised Consensus Statement on the Management of Restless Legs Syndrome

Restless legs syndrome (RLS)/Willis-Ekbom disease (WED) is a common disorder, occurring at least twice a week and causing at least moderate distress in 1.5% to 2.7% of the population. It is important for primary care physicians to be familiar with this disorder and its management. Much has changed in its management since our previous algorithm was published in 2004, including the availability of several new drugs. This revised algorithm was written by members of the Medical Advisory Board of the Willis-Ekbom Disease Syndrome Foundation based on scientific evidence and expert opinion. It considers the management of RLS/WED under intermittent RLS/WED, chronic persistent RLS/WED, and refractory RLS/WED. Nonpharmacological approaches, including mental alerting activities, avoiding substances or medications that may exacerbate RLS, and the role of iron supplementation, are outlined. Chronic persistent RLS/WED should be treated with either a nonergot dopamine agonist or a calcium channel α-2-δ ligand. We discuss the available drugs, the factors determining which to use, and their adverse effects. We define refractory RLS/WED and describe management approaches, including combination therapy and the use of high-potency opioids.     

Isometric Exercise Training for Blood Pressure Management: A Systematic Review and Meta-analysis

ObjectiveTo conduct a systematic review and meta-analysis quantifying the effects of isometric resistance training on the change in systolic blood pressure(SBP), diastolic blood pressure (DBP), and mean arterial pressure in subclinical populations and to examine whether the magnitude of change in SBP and DBP was different with respect to blood pressure classification.Patients and MethodsWe conducted a systematic review and meta-analysis of randomized controlled trials lasting 4 or more weeks that investigated the effects of isometric exercise on blood pressure in healthy adults (aged ≥18 years) and were published in a peer-reviewed journal. PubMed, CINAHL, and the Cochrane Central Register of Controlled Trials were searched for trials reported between January 1, 1966, and July 31, 2013. We included 9 randomized trials, 6 of which studied normotensive participants and 3 that studied hypertensive patients, that included a total of 223 participants (127 who underwent exercise training and 96 controls).ResultsThe following reductions were observed after isometric exercise training: SBP—mean difference (MD), −6.77 mm Hg (95% CI, −7.93 to −5.62 mm Hg; P<.001); DBP—MD, −3.96 mm Hg (95% CI, −4.80 to −3.12 mm Hg; P<.001); and mean arterial pressure—MD, −3.94 mm Hg (95% CI, −4.73 to −3.16 mm Hg; P<.001). A slight reduction in resting heart rate was also observed (MD, −0.79 beats/min; 95% CI, −1.23 to −0.36 beats/min; P=.003).ConclusionIsometric resistance training lowers SBP, DBP, and mean arterial pressure. The magnitude of effect is larger than that previously reported in dynamic aerobic or resistance training. Our data suggest that this form of training has the potential to produce significant and clinically meaningful blood pressure reductions and could serve as an adjunctive exercise modality.     

Prostate Cancer Ki-67 (MIB-1) Expression,Perineural Invasion,and Gleason Score as Biopsy-Based Predictors of Prostate Cancer Mortality: The Mayo Model

ObjectiveTo determine the role of cellular proliferation and other biopsy-based features in the prediction of prostate cancer mortality.Patients and MethodsBetween 1993 and 2012, our institution has performed quantitation of prostate cancer DNA ploidy and Ki-67 (MIB-1) on most prostate cancer needle biopsy specimens. The outcomes of 451 consecutive patients with biopsy-proven cancer treated by radical prostatectomy between January 24, 1995, and December 29, 1998, without neoadjuvant hormonal therapy were assessed. Clinical and biopsy information obtained before radical prostatectomy was placed in multivariate Cox proportional hazards regression models to predict local or systemic progression and cancer-specific death. Predictive ability was evaluated using a concordance index.ResultsWith a median follow-up of 12.9 years, 46 patients experienced local or systemic progression, and 18 patients died of prostate cancer. On multivariate analysis, the biopsy features of Ki-67 expression, perineural invasion, and Gleason score were associated with local or systemic progression. Ki-67 expression, perineural invasion, and Gleason score were associated with cancer-specific death with a concordance index of 0.892. After adjusting for perineural invasion and Gleason score, each 1% increase in Ki-67 expression was associated with a 12% increased risk of cancer-specific death (P<.001). Ki-67 expression alone was a strong predictor of cancer-specific outcomes and improved the predictive ability of currently used algorithms.ConclusionThis study documents that long-term prostate cancer outcomes are best estimated with a combination of Gleason score, perineural invasion, and Ki-67 expression. Given its low cost, rapid assessment, and strong predictive power, we believe that adding Ki-67 expression to perineural invasion and Gleason score at biopsy should be considered a standard by which all new biomarkers are compared before introducing them into clinical practice.     

Nonsteroidal Anti-inflammatory Drugs,Proton Pump Inhibitors,and Gastrointestinal Injury: Contrasting Interactions in the Stomach and Small Intestine

Nonsteroidal anti-inflammatory drugs (NSAIDs) and proton pump inhibitors (PPIs) are among the most frequently prescribed groups of drugs worldwide. The use of NSAIDs is associated with a high number of significant adverse effects. Recently, the safety of PPIs has also been challenged. Capsule endoscopy studies reveal that even low-dose NSAIDs are responsible for gut mucosal injury and numerous clinical adverse effects, for example, bleeding and anemia, that might be difficult to diagnose. The frequent use of PPIs can exacerbate NSAID-induced small intestinal injury by altering intestinal microbiota. Thus, the use of PPI is considered to be an independent risk factor associated with NSAID-associated enteropathy. In this review, we discuss this important clinical problem and review relevant aspects of epidemiology, pathophysiology, and management. We also present the hypothesis that even minor and subclinical injury to the intestinal mucosa can result in significant, though delayed, metabolic consequences, which may seriously affect the health of an individual. PubMed was searched using the following key words (each key word alone and in combination): gut microbiota, microbiome, non-steroidal anti inflammatory drugs, proton pump inhibitors, enteropathy, probiotic, antibiotic, mucosal injury, enteroscopy, and capsule endoscopy. Google engine search was also carried out to identify additional relevant articles. Both original and review articles published in English were reviewed.     

Severe Sepsis and Septic Shock: Clinical Overview and Update on Management

Sepsis is among the oldest themes in medicine; however, despite modern advances, it remains a leading cause of death in the United States. Every clinician should be able to recognize the signs and symptoms of sepsis, along with early management strategies, to expeditiously provide appropriate care and decrease resultant morbidity and mortality. This review addresses the definitions, pathogenesis, clinical manifestations, management, and outcomes of patients with sepsis, severe sepsis, and septic shock.     

Lipoprotein(a), Cardiovascular Disease,and Contemporary Management

Elevated lipoprotein(a) (Lp[a]) is a causal genetic risk factor for cardiovascular disease. To determine if current evidence supports both screening and treatment for elevated Lp(a) in high-risk patients, an English-language search of PubMed and MEDLINE was conducted. In population studies, there is a continuous association between Lp(a) concentrations and cardiovascular risk, with synergistic effects when low-density lipoprotein (LDL) is also elevated. Candidates for Lp(a) screening include patients with a personal or family history of premature cardiovascular disease, familial hypercholesterolemia, recurrent cardiovascular events, or inadequate LDL cholesterol (LDL-C) responses to statins. Given the comparative strength of clinical evidence, reducing LDL-C to the lowest attainable value with a high-potency statin should be the primary focus of lipid-modifying therapies. If the Lp(a) level is 30 mg/dL or higher in a patient who has the aforementioned characteristics plus residual LDL-C elevations (≥70-100 mg/dL) despite maximum-potency statins or combination statin therapy, the clinician may consider adding niacin (up to 2 g/d). If, after these interventions, the patient has progressive coronary heart disease (CHD) or LDL-C levels of 160-200 mg/dL or higher, LDL apheresis should be contemplated. Although Lp(a) is a major causal risk factor for CHD, no currently available controlled studies have suggested that lowering it through either pharmacotherapy or LDL apheresis specifically and significantly reduces coronary risk. Further research is needed to (1) optimize management in order to reduce CHD risk associated with elevated Lp(a) and (2) determine what other intermediate- or high-risk groups might benefit from Lp(a) screening.     

Relationship of Body Mass Index With Total Mortality,Cardiovascular Mortality,and Myocardial Infarction After Coronary Revascularization: Evidence From a Meta-analysis

ObjectiveTo investigate the relationship of body mass index (BMI) with total mortality, cardiovascular (CV) mortality, and myocardial infarction (MI) after coronary revascularization procedures (coronary artery bypass grafting [CABG] and percutaneous coronary intervention [PCI]).Patients and MethodsSystematic search of studies was conducted using PubMed, CINAHL, Cochran CENTRAL, Scopus, and the Web of Science databases. We identified studies reporting the rate of MI, CV mortality, and total mortality among coronary artery disease patients' postcoronary revascularization procedures in various BMI categories: less than 20 (underweight), 20-24.9 (normal reference), 25-29.9 (overweight), 30-34.9 (obese), and 35 or more (severely obese). Event rates were compared using a random effects model assuming interstudy heterogeneity.ResultsA total of 36 studies (12 CABG; 26 PCI) were selected for final analyses. The risk of total mortality (relative risk [RR], 2.59; 95% CI, 2.09-3.21), CV mortality (RR, 2.67; 95% CI, 1.63-4.39), and MI (RR, 1.79; 95% CI, 1.28-2.50) was highest among patients with low BMI at the end of a mean follow-up period of 1.7 years. The risk of CV mortality was lowest among overweight patients (RR, 0.81; 95% CI, 0.68-0.95). Increasing degree of adiposity as assessed by BMI had a neutral effect on the risk of MI for overweight (RR, 0.92; 95% CI, 0.84-1.01), obese (RR, 0.99; 95% CI, 0.85-1.15), and severely obese (RR, 0.93; 95% CI, 0.78-1.11) patients.ConclusionAfter coronary artery disease revascularization procedures (PCI and CABG), the risk of total mortality, CV mortality, and MI was highest among underweight patients as defined by low BMI and CV mortality was lowest among overweight patients.     

Comparison of the Quality of Patient Referrals From Physicians,Physician Assistants,and Nurse Practitioners

ObjectiveTo compare the quality of referrals of patients with complex medical problems from nurse practitioners (NPs), physician assistants (PAs), and physicians to general internists.Patients and MethodsWe conducted a retrospective comparison study involving regional referrals to an academic medical center from January 1, 2009, through December 31, 2010. All 160 patients referred by NPs and PAs combined and a random sample of 160 patients referred by physicians were studied. Five experienced physicians blinded to the source of referral used a 7-item instrument to assess the quality of referrals. Internal consistency, interrater reliability, and dimensionality of item scores were determined. Differences between item scores for patients referred by physicians and those for patients referred by NPs and PAs combined were analyzed by using multivariate ordinal logistical regression adjusted for patient age, sex, distance of the referral source from Mayo Clinic, and Charlson Index.ResultsFactor analysis revealed a 1-dimensional measure of the quality of patient referrals. Interrater reliability (intraclass correlation coefficient for individual items: range, 0.77-0.93; overall, 0.92) and internal consistency for items combined (Cronbach α=0.75) were excellent. Referrals from physicians were scored higher (percentage of agree/strongly agree responses) than were referrals from NPs and PAs for each of the following items: referral question clearly articulated (86.3% vs 76.0%; P=.0007), clinical information provided (72.6% vs 54.1%; P=.003), documented understanding of the patient's pathophysiology (51.0% vs 30.3%; P<.0001), appropriate evaluation performed locally (60.3% vs 39.0%; P<.0001), appropriate management performed locally (53.5% vs 24.1%; P<.0001), and confidence returning patient to referring health care professional (67.8% vs 41.4%; P<.0001). Referrals from physicians were also less likely to be evaluated as having been unnecessary (30.1% vs 56.2%; P<.0001).ConclusionThe quality of referrals to an academic medical center was higher for physicians than for NPs and PAs regarding the clarity of the referral question, understanding of pathophysiology, and adequate prereferral evaluation and documentation.     

Bone Mass in Individuals With Chronic Spinal Cord Injury: Associations With Activity-Based Therapy,Neurologic and Functional Status,a Retrospective Study

ObjectiveTo describe the prevalence of osteoporosis and its association with functional electrical stimulation (FES) use in individuals with spinal cord injury (SCI)-related paralysis.DesignRetrospective cross-sectional evaluation.SettingClinic.ParticipantsConsecutive persons with SCI (N=364; 115 women, 249 men) aged between 18 and 80 years who underwent dual-energy x-ray absorptiometry (DXA) examinations.InterventionsNot applicable.Main Outcome MeasurePrevalence of osteoporosis defined as DXA T score ≤−2.5.ResultsThe prevalence of osteoporosis was 34.9% (n=127). Use of FES was associated with 31.2% prevalence of osteoporosis compared with 39.5% among persons not using FES. In multivariate adjusted logistic regression analysis, FES use was associated with 42% decreased odds of osteoporosis after adjusting for sex, age, body mass index, type and duration of injury, Lower Extremity Motor Scores, ambulation, previous bone fractures, and use of calcium, vitamin D, and anticonvulsant; (adjusted odds ratio [OR]=.58; 95% confidence interval [CI], .35–.99; P=.039). Duration of injury >1 year was associated with a 3-fold increase in odds of osteoporosis compared with individuals with injury <1 year; (adjusted OR=3.02; 95% CI, 1.60–5.68; P=.001).ConclusionsFES cycling ergometry may be associated with a decreased loss of bone mass after paralysis. Further prospective examination of the role of FES in preserving bone mass will improve our understanding of this association.     

Incidence of Leukocytoclastic Vasculitis, 1996 to 2010: A Population-Based Study in Olmsted County,Minnesota

ObjectiveTo determine the population-based incidence of leukocytoclastic vasculitis (LCV).Patients and MethodsThis is a retrospective population-based study of all Olmsted County, Minnesota, residents with a skin biopsy–proven diagnosis of LCV from January 1, 1996, through December 31, 2010.ResultsA total of 84 patients (mean age at diagnosis, 48.3 years) with newly diagnosed skin biopsy–proven LCV (43 women and 41 men) were identified. The incidence rate (age and sex adjusted to the 2000 US white population) was 4.5 per 100,000 person-years (95% CI, 3.5-5.4). The incidence of LCV increased significantly with age at diagnosis (P<.001) and did not differ between female and male patients. Subtypes of LCV were cutaneous small-vessel vasculitis (CSVV), 38 patients (45%); IgA vasculitis, 25 (30%); urticarial vasculitis, 10 (12%); cryoglobulinemic vasculitis, 3 (4%); and antineutrophil cytoplasmic antibody–associated vasculitis, 8 (10%). LCV was idiopathic in 29 of 38 patients with CSVV (76%) and 24 of 25 patients with IgA vasculitis (96%). Thirty-nine of 84 patients (46%) had systemic involvement, with the renal system most commonly involved (17 of 39 [44%]). Twenty-four of 80 patients (30%) with follow-up data available had recurrent disease. Compared with the Minnesota white population, observed survival in the incident LCV cohort was significantly poorer than expected (P<.001), including the subset of patients with idiopathic CSVV (P=.03).ConclusionThe incidence of LCV was higher than that reported in previously published studies. Idiopathic LCV was more common in our population-based cohort than that described previously. Overall survival was significantly poorer (P<.001) and should be explored further in future studies.