Richard Platt

Bio: Richard Platt is an academic researcher from Harvard University. The author has contributed to research in topics: Population & Health care. The author has an hindex of 94, co-authored 422 publications receiving 32051 citations. Previous affiliations of Richard Platt include Center for Drug Evaluation and Research & Boston Children's Hospital.

Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs.

Abstract: Context Lipid-lowering agents are widely prescribed in the United States. Reliable estimates of rhabdomyolysis risk with various lipid-lowering agents are not available. Objective To estimate the incidence of rhabdomyolysis in patients treated with different statins and fibrates, alone and in combination, in the ambulatory setting. Design, setting, and patients Drug-specific inception cohorts of statin and fibrate users were established using claims data from 11 managed care health plans across the United States. Patients with at least 180 days of prior health plan enrollment were entered into the cohorts between January 1, 1998, and June 30, 2001. Person-time was classified as monotherapy or combined statin-fibrate therapy. Main outcome measure Incidence rates of rhabdomyolysis per 10,000 person-years of treatment, number needed to treat, and relative risk of rhabdomyolysis. Results In 252,460 patients treated with lipid-lowering agents, 24 cases of hospitalized rhabdomyolysis occurred during treatment. Average incidence per 10,000 person-years for monotherapy with atorvastatin, pravastatin, or simvastatin was 0.44 (95% confidence interval [CI], 0.20-0.84); for cerivastatin, 5.34 (95% CI, 1.46-13.68); and for fibrate, 2.82 (95% CI, 0.58-8.24). By comparison, the incidence during unexposed person-time was 0 (95% CI, 0-0.48; P = .056). The incidence increased to 5.98 (95% CI, 0.72-216.0) for combined therapy of atorvastatin, pravastatin, or simvastatin with a fibrate, and to 1035 (95% CI, 389-2117) for combined cerivastatin-fibrate use. Per year of therapy, the number needed to treat to observe 1 case of rhabdomyolysis was 22,727 for statin monotherapy, 484 for older patients with diabetes mellitus who were treated with both a statin and fibrate, and ranged from 9.7 to 12.7 for patients who were treated with cerivastatin plus fibrate. Conclusions Rhabdomyolysis risk was similar and low for monotherapy with atorvastatin, pravastatin, and simvastatin; combined statin-fibrate use increased risk, especially in older patients with diabetes mellitus. Cerivastatin combined with fibrate conferred a risk of approximately 1 in 10 treated patients per year.

The Incidence of Herpes Zoster

Abstract: Background: There are few population-based studies of the natural history and epidemiology of herpes zoster. Although a relatively common cause of morbidity, especially among the elderly, contemporary estimates of herpes zoster incidence are lacking. Herein we describe a population-based investigation of incident and recurrent herpes zoster from 1990 through 1992 in a health maintenance organization. Methods: The health maintenance organization's automated medical records contain clinical and administrative information about care rendered to patients in ambulatory settings, emergency departments, and hospitals. Cases of herpes zoster were ascertained by screening the medical record for coded diagnoses. The predictive value of a herpes zoster diagnosis code was determined by review of a sample of patient records. Records from all patients with potential recurrences were also reviewed. Results: The overall incidence, based on 1075 cases in 500 408 person-years, was 215 per 100 000 person-years (95% confidence interval, 192 to 240 per 100 000) and did not vary by gender. Although the rate increased sharply with age, approximately 5% of the cases occurred among children younger than 15 years. Infection with human immunodeficiency virus was documented in 5% of the persons with incident herpes zoster and cancer in 6%. Four persons had confirmed recurrences of herpes zoster (744 per 100 000 person-years; 95% confidence interval, 203 to 1907); three of these persons were infected with the human immunodeficiency virus. Conclusions: The recorded incidence of herpes zoster was 64% higher than that reported 30 years ago; the age-standardized rate was more than twofold higher. Immunosuppressive conditions had little impact on overall incidence, although they were strongly associated with early recurrences. (Arch Intern Med. 1995;155:1605-1609)

Reducing antibiotic use in children: a randomized trial in 12 practices.

Abstract: Objective. To test whether an educational outreach intervention for families and physicians, based on the Centers for Disease Control and Prevention (CDC) principles of judicious antibiotic use, decreases antimicrobial drug prescribing for children younger than 6 years old. Setting. Twelve practices affiliated with 2 managed care organizations (MCOs) in eastern Massachusetts and northwest Washington State. Patients. All enrolled children younger than 6 years old. Methods. Practices stratified by MCO and size were randomized to intervention or control groups. The intervention included 2 meetings of the practice with a physician peer leader, using CDC-endorsed summaries of judicious prescribing recommendations; feedback on previous prescribing rates were also provided. Parents were mailed a CDC brochure on antibiotic use, and supporting materials were displayed in waiting rooms. Automated enrollment, ambulatory visit, and pharmacy claims were used to determine rates of antibiotic courses dispensed (antibiotics/person-year) during baseline (1996–1997) and intervention (1997–1998) years. The primary analysis (for children 3 to Results. The practices cared for 14 468 and 13 460 children in the 2 study years, respectively; 8815 children contributed data in both years. Sixty-two percent of antibiotic courses were dispensed for otitis media, 6.5% for pharyngitis, 6.3% for sinusitis, and 9.2% for colds and bronchitis. Antibiotic dispensing for children 3 to Conclusions. A limited simultaneous educational outreach intervention for parents and providers reduced antibiotic use among children in primary care practices, even in the setting of substantial secular trends toward decreased prescribing. Future efforts to promote judicious prescribing should continue to build on growing public awareness of antibiotic overuse.

Targeted versus Universal Decolonization to Prevent ICU Infection

Abstract: A B S T R AC T BACKGROUND Both targeted decolonization and universal decolonization of patients in intensive care units (ICUs) are candidate strategies to prevent health care–associated infec tions, particularly those caused by methicillin-resistant Staphylococcus aureus (MRSA). METHODS We conducted a pragmatic, cluster-randomized trial. Hospitals were randomly assigned to one of three strategies, with all adult ICUs in a given hospital assigned to the same strategy. Group 1 implemented MRSA screening and isolation; group 2, targeted decolonization (i.e., screening, isolation, and decolonization of MRSA carriers); and group 3, universal decolonization (i.e., no screening, and decolonization of all patients). Proportional-hazards models were used to assess differences in infection reductions across the study groups, with clustering according to hospital. RESULTS

Epidemiology of sepsis syndrome in 8 academic medical centers.

Abstract: Context. —Sepsis syndrome is a leading cause of mortality in hospitalized patients. However, few studies have described the epidemiology of sepsis syndrome in a hospitalwide population. Objective. —To describe the epidemiology of sepsis syndrome in the tertiary care hospital setting. Design. —Prospective, multi-institutional, observational study including 5-month follow-up. Setting. —Eight academic tertiary care centers. Methods. —Each center monitored a weighted random sample of intensive care unit (ICU) patients, non-ICU patients who had blood cultures drawn, and all patients who received a novel therapeutic agent or who died in an emergency department or ICU. Sepsis syndrome was defined as the presence of either a positive blood culture or the combination of fever, tachypnea, tachycardia, clinically suspected infection, and any 1 of 7 confirmatory criteria. Estimates of total cases expected annually were extrapolated from the number of cases, the period of observation, and the sampling fraction. Results. —From January 4, 1993, to April 2, 1994, 12759 patients were monitored and 1342 episodes of sepsis syndrome were documented. The extrapolated, weighted estimate of hospitalwide incidence (mean±95% confidence limit) of sepsis syndrome was 2.0±0.16 cases per 100 admissions, or 2.8±0.17 per 1000 patient-days. The unadjusted attack rate for sepis syndrome between individual centers differed by as much as 3-fold, but after adjustment for institutional differences in organ transplant populations, variation from the expected number of cases was reduced to 2-fold and was not statistically significant overall. Patients in ICUs accounted for 59% of total extrapolated cases, non-ICU patients with positive blood cultures for 11%, and non-ICU patients with negative blood cultures for 30%. Septic shock was present at onset of sepsis syndrome in 25% of patients. Bloodstream infection was documented in 28%, with gram-positive organisms being the most frequent isolates. Mortality was 34% at 28 days and 45% at 5 months. Conclusions. —Sepsis syndrome is common in academic hospitals, although the overall rates vary considerably with the patient population. A substantial fraction of cases occur outside ICUs. An understanding of the hospitalwide epidemiology of sepsis syndrome is vital for rational planning and treatment of hospitalized patients with sepsis syndrome, especially as new and expensive therapeutic agents become available.

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

Abstract: Importance Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. Objective To evaluate and, as needed, update definitions for sepsis and septic shock. Process A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). Key Findings From Evidence Synthesis Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. Recommendations Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less. Conclusions and Relevance These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis.

Diagnosis and Management of the Metabolic Syndrome An American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement

Abstract: The metabolic syndrome has received increased attention in the past few years. This statement from the American Heart Association (AHA) and the National Heart, Lung, and Blood Institute (NHLBI) is intended to provide up-to-date guidance for professionals on the diagnosis and management of the metabolic syndrome in adults. The metabolic syndrome is a constellation of interrelated risk factors of metabolic origin— metabolic risk factors —that appear to directly promote the development of atherosclerotic cardiovascular disease (ASCVD).1 Patients with the metabolic syndrome also are at increased risk for developing type 2 diabetes mellitus. Another set of conditions, the underlying risk factors , give rise to the metabolic risk factors. In the past few years, several expert groups have attempted to set forth simple diagnostic criteria to be used in clinical practice to identify patients who manifest the multiple components of the metabolic syndrome. These criteria have varied somewhat in specific elements, but in general they include a combination of both underlying and metabolic risk factors. The most widely recognized of the metabolic risk factors are atherogenic dyslipidemia, elevated blood pressure, and elevated plasma glucose. Individuals with these characteristics commonly manifest a prothrombotic state and a pro-inflammatory state as well. Atherogenic dyslipidemia consists of an aggregation of lipoprotein abnormalities including elevated serum triglyceride and apolipoprotein B (apoB), increased small LDL particles, and a reduced level of HDL cholesterol (HDL-C). The metabolic syndrome is often referred to as if it were a discrete entity with a single cause. Available data suggest that it truly is a syndrome, ie, a grouping of ASCVD risk factors, but one that probably has more than one cause. Regardless of cause, the syndrome identifies individuals at an elevated risk for ASCVD. The magnitude of the increased risk can vary according to which components of the syndrome are …

Early Goal-Directed Therapy in the Treatment of Severe Sepsis and Septic Shock

Abstract: Background Goal-directed therapy has been used for severe sepsis and septic shock in the intensive care unit. This approach involves adjustments of cardiac preload, afterload, and contractility to balance oxygen delivery with oxygen demand. The purpose of this study was to evaluate the efficacy of early goal-directed therapy before admission to the intensive care unit. Methods We randomly assigned patients who arrived at an urban emergency department with severe sepsis or septic shock to receive either six hours of early goal-directed therapy or standard therapy (as a control) before admission to the intensive care unit. Clinicians who subsequently assumed the care of the patients were blinded to the treatment assignment. In-hospital mortality (the primary efficacy outcome), end points with respect to resuscitation, and Acute Physiology and Chronic Health Evaluation (APACHE II) scores were obtained serially for 72 hours and compared between the study groups. Results Of the 263 enrolled patients, 130 were ...