Drug-Induced Liver Injury

Drug hepatoxicity can be nonidiosyncratic (predictable), as in the case of acetaminophen, or idiosyncratic (unpredictable). This review article focuses primarily on idiosyncratic drug-induced liver injury (DILI). New epidemiologic data suggest that approximately 20 new cases of DILI per 100,000 persons occur each year. Idiosyncratic DILI accounts for 11% of the cases of acute liver failure in the United States. Risk factors for DILI include medication dose, drug lipophilicity, and extent of hepatic metabolism. There is mixed evidence to support the role of host factors such as age, sex, and chronic liver disease in the development of DILI. For specific drugs, a genetic predisposition appears to be a risk factor for DILI. Suspected cases of idiosyncratic DILI should be categorized as hepatitic, cholestatic, or mixed on the basis of the degree/ratio of abnormalities in the alanine aminotransferase and alkaline phosphatase. A careful evaluation for other causes of liver disease should be performed, though a liver biopsy is rarely needed. There is evidence that some patients with DILI may actually have hepatitis E and this diagnosis should be considered. Amoxicillin/clavulanate isoniazid, and nonsteroidal anti-inflammatory drugs are among the most common causes of DILI. Drug discontinuation or dechallenge should lead to an improvement in liver biochemistries in most patients, though a bilirubin value of more than 3 g/dL is associated with mortality of at least 10%. New biomarkers for DILI using proteomics and micro RNA appear promising but require further study. New studies on drugs with potential for causing DILI are reviewed herein, including tumor necrosis factor-alpha antagonists, fluoroquinolones, tyrosine kinase inhibitors, statins, and supplements. PubMed was used with search terms of drug induced liver injury OR DILI with filter settings of “English language” and “humans” and custom date range of “January 1, 2000.” The authors also manually searched bibliographies from key references and included seminal references before the year 2000.     

Alcohol and Cardiovascular Health: The Dose Makes the Poison…or the Remedy

Habitual light to moderate alcohol intake (up to 1 drink per day for women and 1 or 2 drinks per day for men) is associated with decreased risks for total mortality, coronary artery disease, diabetes mellitus, congestive heart failure, and stroke. However, higher levels of alcohol consumption are associated with increased cardiovascular risk. Indeed, behind only smoking and obesity, excessive alcohol consumption is the third leading cause of premature death in the United States. Heavy alcohol use (1) is one of the most common causes of reversible hypertension, (2) accounts for about one-third of all cases of nonischemic dilated cardiomyopathy, (3) is a frequent cause of atrial fibrillation, and (4) markedly increases risks of stroke—both ischemic and hemorrhagic. The risk-to-benefit ratio of drinking appears higher in younger individuals, who also have higher rates of excessive or binge drinking and more frequently have adverse consequences of acute intoxication (for example, accidents, violence, and social strife). In fact, among males aged 15 to 59 years, alcohol abuse is the leading risk factor for premature death. Of the various drinking patterns, daily low- to moderate-dose alcohol intake, ideally red wine before or during the evening meal, is associated with the strongest reduction in adverse cardiovascular outcomes. Health care professionals should not recommend alcohol to nondrinkers because of the paucity of randomized outcome data and the potential for problem drinking even among individuals at apparently low risk. The findings in this review were based on a literature search of PubMed for the 15-year period 1997 through 2012 using the search terms alcohol, ethanol, cardiovascular disease, coronary artery disease, heart failure, hypertension, stroke, and mortality. Studies were considered if they were deemed to be of high quality, objective, and methodologically sound.     

Development and Validation of a Risk Calculator for Predicting Postoperative Pneumonia

ObjectiveTo identify preoperative factors associated with an increased risk of postoperative pneumonia and subsequently develop and validate a risk calculator.Patients and MethodsThe American College of Surgeons’ National Surgical Quality Improvement Program, a multicenter, prospective data set (2007-2008) was used. Univariate and multivariate logistic regression analyses were performed. The 2007 data set (N=211,410) served as the training set, and the 2008 data set (N=257,385) served as the validation set.ResultsIn the training set, 3825 patients (1.8%) experienced postoperative pneumonia. Patients who experienced postoperative pneumonia had a significantly higher 30-day mortality (17.0% vs 1.5%; P<.001). On multivariate logistic regression analysis, 7 preoperative predictors of postoperative pneumonia were identified: age, American Society of Anesthesiologists class, chronic obstructive pulmonary disease, dependent functional status, preoperative sepsis, smoking before operation, and type of operation. The risk model based on the training data set was subsequently validated on the validation data set, with model performance being very similar (C statistic: 0.860 and 0.855, respectively). The high C statistic indicates excellent predictive performance. The risk model was used to develop an interactive risk calculator.ConclusionPreoperative variables associated with an increased risk of postoperative pneumonia include age, American Society of Anesthesiologists class, chronic obstructive pulmonary disease, dependent functional status, preoperative sepsis, smoking before operation, and type of operation. The validated risk calculator provides a risk estimate for postoperative pneumonia and is anticipated to aid in surgical decision making and informed patient consent.     

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.     

Comparative Efficacy of Biologic Therapy in Biologic-Naïve Patients With Crohn Disease: A Systematic Review and Network Meta-analysis

ObjectiveTo study the comparative efficacy of biologic therapy in the management of biologic-naïve patients with Crohn disease (CD).Patients and MethodsWe conducted a systematic review of randomized controlled trials published from January 1, 1985, through September 30, 2013, comparing biologic agents (infliximab [IFX], adalimumab [ADA], certolizumab pegol, natalizumab, vedolizumab, and ustekinumab) with each other or placebo for inducing and maintaining clinical remission in adults with moderate to severe CD. To increase comparability across trials, we focused on a subset of biologic-naïve patients for the induction end point and on responders to induction therapy for the maintenance end point. We followed a Bayesian network meta-analysis approach.ResultsWe identified 17 randomized controlled trials of good methodological quality comparing 6 biologic agents with placebo, with no direct comparison of biologic agents. In network meta-analysis, we observed that IFX (relative risk [RR], 6.11; 95% credible interval [CrI], 2.49-18.29) and ADA (RR, 2.98; 95% CrI, 1.12-8.18), but not certolizumab pegol (RR, 1.48; 95% CrI, 0.76-2.93), natalizumab (RR, 1.36; 95% CrI, 0.69-2.86), vedolizumab (RR, 1.40; 95% CrI, 0.63-3.28), and ustekinumab (RR, 0.61; 95% CrI, 0.15-2.49), were more likely to induce remission than placebo. Similar results were observed for maintenance of remission. Infliximab had the highest probability of being ranked as the most efficacious agent for induction (86%) and ADA for maintenance of remission (48%).ConclusionOn the basis of network meta-analysis, IFX may be most efficacious agent for inducing remission in CD in biologic-naïve patients. In the absence of head-to-head treatment comparison, the confidence in these estimates is low. Future comparative efficacy studies are warranted.     

Comparative Effectiveness of Telaprevir-Based Triple Therapy in Patients With Chronic Hepatitis C

ObjectiveTo examine the effectiveness and tolerability of triple therapy with pegylated interferon (p-IFN), ribavirin (RBV), and telaprevir in patients with chronic hepatitis C receiving treatment in an academic practice setting and in a more clinically diverse population compared with patients receiving treatment in phase 3 trials.Patients and MethodsA prospective database of all patients with viral hepatitis undergoing antiviral therapy from January 1, 2006, to July 1, 2012, was queried to identify treatment-naive and -experienced patients with chronic hepatitis C receiving dual and triple therapies. On-treatment response categories included rapid virologic response, extended rapid virologic response, early virologic response, and sustained virologic response. These patients were compared with matched controls, namely, patients who underwent dual therapy with p-IFN and RBV. Matching was performed for age, cirrhosis status, and prior treatment.ResultsThere were 55 patients who received triple therapy and met the eligibility criteria, consisting of treatment-naive (n=35) and -experienced patients (n=20: those with relapse, 9; those with nonresponse, 9; and those who terminated the treatment early, 2). Rapid virologic response was achieved in 41% of the patients, extended rapid virologic response in 41%, and early virologic response in 75%. Sustained virologic response was observed in 51% (18/35) of treatment-naive patients, 67% (6/9) of the patients with prior nonresponse, and 56% (5/9) of those with prior relapse. Corresponding results after dual therapy were 37% (23/62), 11% (2/18), and 27% (3/11), respectively. The mean decrease in the hemoglobin level at weeks 4, 8, and 24 of triple therapy was 2.8, 3.8, and 3.2 mg/dL compared with 2.4, 2.6, and 2.4 mg/dL with dual therapy (to convert mg/dL to mmol/L, multiply values by 0.0259).ConclusionTelaprevir-based triple therapy in clinical practice is considerably more effective than dual therapy with p-IFN and RBV despite the significant degree of anemia that complicated therapy, requiring RBV dose reduction and erythropoietin support.     

Human Immunodeficiency Virus: What Primary Care Clinicians Need to Know

Human immunodeficiency virus (HIV) has evolved from an illness that consistently led to death to a chronic disease that can be medically managed. Primary care clinicians can provide beneficial care to the individual patient and potentially decrease the transmission of HIV to others through appropriate HIV screening and recognition of clinical clues to both chronic and acute HIV. Most patients who take combination antiretroviral therapy experience immune reconstitution and resume normal lives. These patients benefit from the care of an experienced primary care clinician in addition to a clinician with HIV expertise. Primary care clinicians have expertise providing preventive care, including counseling regarding healthier lifestyle choices and managing cardiovascular risk factors, osteoporosis, hypertension, and diabetes, all of which have become increasingly important for individuals with HIV as they age. This article reviews the many important roles of primary care clinicians with regard to the HIV epidemic and care of patients with HIV.     

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.     

The Increasing Incidence of Young-Onset Colorectal Cancer: A Call to Action

In the United States, colorectal cancer (CRC) is the third most common and second most lethal cancer. More than one-tenth of CRC cases (11% of colon cancers and 18% of rectal cancers) have a young onset (ie, occurring in individuals younger than 50 years). The CRC incidence and mortality rates are decreasing among all age groups older than 50 years, yet increasing in younger individuals for whom screening use is limited and key symptoms may go unrecognized. Familial syndromes account for approximately 20% of young-onset CRCs, and the remainder are typically microsatellite stable cancers, which are more commonly diploid than similar tumors in older individuals. Young-onset CRCs are more likely to occur in the distal colon or rectum, be poorly differentiated, have mucinous and signet ring features, and present at advanced stages. Yet, stage-specific survival in patients with young-onset CRC is comparable to that of patients with later-onset cancer. Primary care physicians have an important opportunity to identify high-risk young individuals for screening and to promptly evaluate CRC symptoms. Risk modification, targeted screening, and prophylactic surgery may benefit individuals with a predisposing hereditary syndrome or condition (eg, inflammatory bowel disease) or a family history of CRC or advanced adenomatous polyps. When apparently average-risk young adults present with CRC-like symptoms (eg, unexplained persistent rectal bleeding, anemia, and abdominal pain), endoscopic work-ups can expedite diagnosis. Early screening in high-risk individuals and thorough diagnostic work-ups in symptomatic young adults may improve young-onset CRC trends.     

Mild Cognitive Impairment and Mild Dementia: A Clinical Perspective

Mild cognitive impairment and mild dementia are common problems in the elderly. Primary care physicians are the first point of contact for most patients with these disorders and should be familiar with their diagnosis, prognosis, and management. Both mild cognitive impairment and mild dementia are characterized by objective evidence of cognitive impairment. The main distinctions between mild cognitive impairment and mild dementia are that in the latter, more than one cognitive domain is invariably involved and substantial interference with daily life is evident. The diagnosis of mild cognitive impairment and mild dementia is based mainly on the history and cognitive examination. The prognosis for mild cognitive impairment and mild dementia is an important motivation for diagnosis because in both, there is a heightened risk for further cognitive decline. The etiology of mild cognitive impairment and mild dementia can often be established through the clinical examination, although imaging and other laboratory tests may also contribute. Although Alzheimer disease is the most common cause of both, cerebrovascular disease and Lewy body disease make important contributions. Pharmacological treatments are of modest value in mild dementia due to Alzheimer disease, and there are no approved pharmacological treatments for mild cognitive impairment of any etiology. Nonetheless, new-onset cognitive impairment is a worrisome symptom to patients and families that demands answers and advice. If a patient is having difficulties managing medications, finances, or transportation independently, diagnosis and intervention are necessary to ensure the health and safety of the patient.     

Advances in Regenerative Orthopedics

Orthopedic injuries are common and a source of much misery and economic stress. Several relevant tissues, such as cartilage, meniscus, and intra-articular ligaments, do not heal. And even bone, which normally regenerates spontaneously, can fail to mend. The regeneration of orthopedic tissues requires 4 key components: cells, morphogenetic signals, scaffolds, and an appropriate mechanical environment. Although differentiated cells from the tissue in question can be used, most cellular research focuses on the use of mesenchymal stem cells. These can be retrieved from many different tissues, and one unresolved question is the degree to which the origin of the cells matters. Embryonic and induced pluripotent stem cells are also under investigation. Morphogenetic signals are most frequently supplied by individual recombinant growth factors or native mixtures provided by, for example, platelet-rich plasma; mesenchymal stem cells are also a rich source of trophic factors. Obstacles to the sustained delivery of individual growth factors can be addressed by gene transfer or smart scaffolds, but we still lack detailed, necessary information on which delivery profiles are needed. Scaffolds may be based on natural products, synthetic materials, or devitalized extracellular matrix. Strategies to combine these components to regenerate tissue can follow traditional tissue engineering practices, but these are costly, cumbersome, and not well suited to treating large numbers of individuals. More expeditious approaches make full use of intrinsic biological processes in vivo to avoid the need for ex vivo expansion of autologous cells and multiple procedures. Clinical translation remains a bottleneck.     

Physical Activity and Dietary Behavior in US Adults and Their Combined Influence on Health

ObjectiveTo examine the association between objectively measured physical activity and dietary behavior and their combined effect on health.Patients and MethodsData for this study were obtained from the 2003-2006 National Health and Nutrition Examination Survey cycles. The data were evaluated between September 9, 2012, and August 14, 2013. As part of the national survey, participants wore an accelerometer for 4 or more days to assess physical activity, blood samples were obtained to assess various biological markers, and interviews were conducted to assess dietary behavior. We selected a sample of 5211 participants and categorized them into 4 groups: (1) healthy diet and active, (2) unhealthy diet and active, (3) healthy diet and inactive, and (4) unhealthy diet and inactive.ResultsA total of 16.5% of participants (weighted proportions) were classified as consuming a healthy diet and being sufficiently active. After adjustments, participants were 32% more likely to consume a healthy diet if they met physical activity guidelines. For nearly all biomarkers, those who consumed a healthy diet and were sufficiently active had the most favorable biomarker levels. Compared with those who consumed a healthy diet and were active, participants who consumed an unhealthy diet and were inactive were 2.4 times more likely to have metabolic syndrome.ConclusionOur findings indicate a relationship between objectively measured physical activity and dietary behavior and that participating in regular physical activity and eating a healthy diet are associated with better health outcomes when compared with diet or physical activity alone.     

Sudden Cardiac Death From the Perspective of Coronary Artery Disease

Sudden cardiac death accounts for approximately 50% of all deaths attributed to cardiovascular disease in the United States. It is most commonly associated with coronary artery disease and can be its initial manifestation or may occur in the period after an acute myocardial infarction. Decreasing the rate of sudden cardiac death requires the identification and treatment of at-risk patients through evidence-based pharmacotherapy and interventional strategies aimed at primary and secondary prevention. For this review, we searched PubMed for potentially relevant articles published from January 1, 1970, through March 1, 2014, using the following key search terms: sudden cardiac death, ischemic heart disease, coronary artery disease, myocardial infarction, and cardiac arrest. Searches were enhanced by scanning bibliographies of identified articles, and those deemed relevant were selected for full-text review. This review outlines various mechanisms for sudden cardiac death in the setting of coronary artery disease, describes risk factors for sudden cardiac death, explores the management of cardiac arrest, and outlines optimal practice for the monitoring and treatment of patients after an acute ST-segment elevation myocardial infarction to decrease the risk of sudden death.     

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.     

My Treatment Approach to Chronic Hepatitis C Virus

The treatment of chronic hepatitis C virus (HCV) is evolving rapidly. In 2014, the standard of care and new backbone of HCV treatment is the polymerase inhibitor sofosbuvir (SOF). Our treatment approach in patients with HCV genotype 1 is 12 weeks of SOF, peginterferon (PEGINF), and ribavirin (RBV). In patients with cirrhosis or extrahepatic manifestations of HCV who cannot tolerate PEGINF, we use 12 weeks of SOF and simeprevir. The latter is less costly and more effective than SOF and RBV for 24 weeks. Our treatment approach in all patients with genotype 2 is SOF and RBV for 12 weeks. Hepatitis C virus genotype 3 is now the most costly and difficult to cure. Our approach to treatment-naive patients with genotype 3 is SOF and RBV for 24 weeks. In patients who have previously undergone PEGINF and RBV treatment, we use PEGINF, SOF, and RBV for 12 weeks, which is equally if not more effective and less costly than SOF and RBV for 24 weeks. Patients with cirrhosis who cannot tolerate PEGINF should be treated for 24 weeks with SOF and RBV, although the sustained virologic response is suboptimal.     

Cellular Therapy for Liver Disease

Regenerative medicine is energizing and empowering basic science and has the potential to dramatically transform health care in the future. Given the remarkable intrinsic regenerative properties of the liver, as well as widespread adoption of regenerative strategies for liver disease (eg, liver transplant, partial hepatectomy, living donor transplant), hepatology has always been at the forefront of clinical regenerative medicine. However, an expanding pool of patients awaiting liver transplant, a limited pool of donor organs, and finite applicability of the current surgical approaches have created a need for more refined and widely available regenerative medicine strategies. Although cell-based therapies have been used extensively for hematologic malignant diseases and other conditions, the potential application of cellular therapy for acute and chronic liver diseases has only more recently been explored. New understanding of the mechanisms of liver regeneration and repair, including activation of local stem/progenitor cells and contributions from circulating bone marrow–derived stem cells, provide the theoretical underpinnings for the rational use of cell-based therapies in clinical trials. In this review, we dissect the scientific rationale for various modalities of cell therapy for liver diseases being explored in animal models and review those tested in human clinical trials. We also attempt to clarify some of the important ongoing questions that need to be addressed in order to bring these powerful therapies to clinical translation. Discussions will cover transplant of hepatocytes and liver stem/progenitor cells as well as infusion or stimulation of bone marrow–derived stem cells. We also highlight tremendous scientific advances on the horizon, including the potential use of induced pluripotent stem cells and their derivatives as individualized regenerative therapy for liver disease.     

Activity-Based Therapy for Recovery of Walking in Chronic Spinal Cord Injury: Results From a Secondary Analysis to Determine Responsiveness to Therapy

ObjectiveTo gain insight into who is likely to benefit from activity-based therapy (ABT), as assessed by secondary analysis of data obtained from a clinical trial.DesignSecondary analysis of results from a randomized controlled trial with delayed treatment design.SettingOutpatient program in a private, nonprofit rehabilitation hospital.ParticipantsVolunteer sample of adults (N=38; 27 men; 11 women; age, 22–63y) with chronic (≥12mo postinjury), motor-incomplete (American Spinal Injury Association [ASIA] Impairment Scale [AIS] grade C or D) spinal cord injury (SCI).InterventionsA total of 9h/wk of ABT for 24 weeks including developmental sequencing; resistance training; repetitive, patterned motor activity; and task-specific locomotor training. Algorithms were used to guide group allocation, functional electrical stimulation utilization, and locomotor training progression.Main Outcome MeasuresWalking speed and endurance (10-meter walk test and 6-minute walk test) and functional ambulation (timed Up and Go test).ResultsThis secondary analysis identified likely responders to ABT on the basis of injury characteristics: AIS classification, time since injury, and initial walking ability. Training effects were the most clinically significant in AIS grade D participants with injuries <3 years in duration. This information, along with information about preliminary responsiveness to therapy (gains after 12wk), can help predict the degree of recovery likely from participation in an ABT program.ConclusionsABT has the potential to promote neurologic recovery and enhance walking ability in individuals with chronic, motor-incomplete SCI. However, not everyone with goals of walking recovery will benefit. Individuals with SCI should be advised of the time, effort, and resources required to undertake ABT. Practitioners are encouraged to use the findings from this trial to assist prospective participants in establishing realistic expectations for recovery.     

Prevalence of Multimorbidity in a Geographically Defined American Population: Patterns by Age,Sex, and Race/Ethnicity

ObjectiveTo describe the prevalence of multimorbidity involving 20 selected chronic conditions in a geographically defined US population, emphasizing age, sex, and racial/ethnic differences.Patients and MethodsUsing the Rochester Epidemiology Project records linkage system, we identified all residents of Olmsted County, Minnesota, on April 1, 2010, and electronically extracted the International Classification of Diseases, Ninth Revision codes associated with all health care visits made between April 1, 2005, and March 31, 2010 (5-year capture frame). Using these codes, we defined the 20 common chronic conditions recommended by the US Department of Health and Human Services. We counted only persons who received at least 2 codes for a given condition separated by more than 30 days, and we calculated the age-, sex-, and race/ethnicity-specific prevalence of multimorbidity.ResultsOf the 138,858 study participants, 52.4% were women (n=72,732) and 38.9% had 1 or more conditions (n=54,012), 22.6% had 2 or more conditions (n=31,444), and 4.9% had 5 or more conditions (n=6853). The prevalence of multimorbidity (≥2 conditions) increased steeply with older age and reached 77.3% at 65 years and older. However, the absolute number of people affected by multimorbidity was higher in those younger than 65 years. Although the prevalence of multimorbidity was similar in men and women overall, the most common dyads and triads of conditions varied by sex. Compared with white persons, the prevalence of multimorbidity was slightly higher in black persons and slightly lower in Asian persons.ConclusionMultimorbidity is common in the general population; it increases steeply with older age, has different patterns in men and women, and varies by race/ethnicity.     

Protective Role of Resting Heart Rate on All-Cause and Cardiovascular Disease Mortality

ObjectiveTo study the protective role of lower resting heart rate (RHR) in cardiovascular disease (CVD) and all-cause mortality.Patients and MethodsPatients (n=53,322) who received a baseline medical examination between January 1, 1974, and December 31, 2002, were recruited from the Cooper Clinic, Dallas, Texas. They completed a medical questionnaire and underwent clinical evaluation. Patients with CVD or cancer or who had less than 1 year of mortality follow-up were excluded from the study. Relative risks and 95% CIs for all-cause and CVD mortality across RHR categories were estimated using Cox proportional hazards models.ResultsHighest cardiorespiratory fitness with lower mortality was found in individuals with an RHR of less than 60 beats/min. Similarly, patients with a higher RHR (≥80 beats/min) were at greater risk for CVD and all-cause mortality compared with an RHR of less than 60 beats/min. This analysis was followed by stratification of the data by hypertension, where hypertensive individuals with high RHRs (≥80 beats/min) were found to be at greater risk for CVD and all-cause mortality compared with those with hypertension and lower RHRs (<60 beats/min). In addition, unfit individuals with high RHRs had the greatest risk of CVD and all-cause mortality. The unfit with low RHR group had a similar risk for CVD and all-cause mortality as the fit with high RHR group.ConclusionLower cardiorespiratory fitness levels and higher RHRs are linked to greater CVD and all-cause mortality.