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Biomedical subjects

R Platt

Publications and source records attributed to R Platt.

At least 73 records · Page 4Linked to original sources

Simplified surveillance for nosocomial bloodstream infections.

OBJECTIVE: To compare a surveillance definition of noso comial bloodstream infections requiring only microbiology data to the Centers for Disease Control and Prevention's (CDC) current definition. SETTING: Six teaching hospitals. METHODS: We classified a representative sample of 73 positive blood cultures from six hospitals growing common skin contaminant isolates using a definition for bacteremia requiring only microbiology data and the CDC definition for primary bloodstream infection (National Nosocomial Infections Surveillance [NNIS] System review method). The classifications assigned during routine prospective surveillance also were noted, and the time required to classify isolates by the two methods was compared. RESULTS: Among 65 blood cultures growing common skin contaminant isolates obtained from adults, the agreement rate between the microbiology data method and the NNIS review method was 91%. Agreement was significantly poorer for the eight blood cultures growing common skin contaminant isolates obtained from pediatric patients. The microbiology data method requires approximately 20 minutes less time per isolate than does routine surveillance. CONCLUSIONS: A definition based on microbiology data alone yields the same result as the CDC's definition in the large majority of instances. It is more resource-efficient than the CDC's current definition.

Adult↗

Approximate hierarchical modelling of discrete data in epidemiology.

Hierarchical models are used in epidemiology to estimate and analyse multiple, related relative risks. Examples include meta-analyses of series of 2 x 2 tables and mapping of spatially correlated disease rates. Empirical transform and penalized quasilikelihood procedures, both of which may be implemented using standard programs for mixed model analysis, provide satisfactory approximate inferences for these problems when cell frequencies are large. Simulation studies show that, in certain situations involving small cell frequencies, penalized quasilikelihood provides satisfactory estimates of variance components and regression coefficients whereas the empirical transform approach does not.

BCG Vaccine↗

Antibiotic prophylaxis in clean surgery: does it work? Should it be used if it does?

Perioperative antibiotic prophylaxis has been demonstrated to prevent postoperative wound infection after clean surgery in a majority of clinical trials with sufficient power to identify a 50% reduction in risk. The low risk of infection after many clean procedures requires studies of more than 1,000 procedures (sometimes many more) to detect such reductions reliably. This is a serious obstacle to performing conclusive tests of efficacy, and it all but precludes use of conventional clinical trials to identify optimal regimens. Regimens that have been shown to be effective have usually been those with efficacy against Staphylococcus aureus and other pathogens that may be carried in the nares or on the skin. In addition, relatively long half-life in the serum and low cost are important considerations. Cefazolin is a good prophylaxis agent for many clean surgical procedures, although special characteristics of the procedure, increased likelihood of antimicrobial resistance, or antibiotic utilization concerns may make other agents more suitable in specific situations The decision to use perioperative antibiotic prophylaxis for clean surgical procedures depends not only on its efficacy, but also on the cost of preventing infection. Few cost-benefit analyses have been performed, especially for procedures in which prophylaxis has been least used. To perform such analyses, it will be necessary to acquire information that is currently lacking for many procedures. This includes the risk and cost of postoperative infection, adverse reactions to the prophylaxis agent, and increased antimicrobial resistance; in addition, detailed information is needed on infection-associated costs of medical care, lost productivity, and the value that the infected person places on avoiding infection. For many procedures, timely use of an appropriate antibiotic is the single most effective infection prevention method that can be implemented and monitored on a broad scale. These features make it amenable to adoption as a subject of continuous quality improvement activities. To accomplish this, it is necessary to articulate standards of care clearly so that systems to support the intended goal can be developed. Both the standards and the support systems can be tailored to specific surgical situations and to the values of providers and patients.

Antibiotic Prophylaxis↗

Epidemiology of sepsis syndrome in 8 academic medical centers.

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 sepsis 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.

Adult↗

The sequelae of herpes zoster.

BACKGROUND: The last 40 years was a period during which the incidence of herpes zoster appears to have increased substantially. OBJECTIVE: To determine whether the risk of complications of herpes zoster has changed during the last 40 years. METHODS: The automated medical records of a health maintenance organization were screened for diagnosis codes suggesting herpes zoster and potentially complicated cases of zoster. The predictive value of a herpes zoster diagnosis was calculated from sampling full-text records. Records of all patients with codes suggesting complications were reviewed in full. RESULTS: Of 859 individuals with herpes zoster who met the eligibility criteria, 101 were identified who experienced at least 1 complication, corresponding to a 60-day risk of 12%. Corrected for the sensitivity of the complication-finding strategy, the risk estimate was 14%. Risk increased markedly with age, with those older than 64 years having more than 6 times the risk of complications of those younger than 25 years (odds ratio, 8.3; 95% confidence interval, 2.5-29.3). Trigeminal distribution of rash and the presence of certain conditions associated with immune compromise appeared to increase risk. CONCLUSIONS: The apparent increase in the incidence of herpes zoster was not accompanied by a change in the risk of specific or overall complications in a population-based sample. Advanced age and other conditions associated with waning cellular immunity may confer an increased risk of experiencing a complicated course of herpes zoster.

Adolescent↗

Risk factors for postherpetic neuralgia.

BACKGROUND: The risk factors for postherpetic neuralgia (PHN), the most common complication of herpes zoster, have not been well established. OBJECTIVE: To elucidate the risk factors for PHN. METHODS: Automated medical, claims, and pharmacy records of a health maintenance organization were used to identify cases of PHN and obtain data on risk factors. A case-base design was used to assess the impact of various patient, disease, and treatment factors on the prevalence of PHN 1 and 2 months after developing zoster. RESULTS: There were 821 cases of herpes zoster that met all eligibility criteria. The prevalence of PHN more than 30 days after onset of zoster was 8.0% (95% confidence interval [CI], 6.3%-10.1%) and 4.5% (95% CI, 3.2%-6.2%) after 60 days. Compared with patients younger than 50 years, individuals aged 50 years or older had a 14.7-fold higher prevalence (95% CI, 6.8-32.0) 30 days and a 27.4-fold higher prevalence (95% CI, 8.8-85.4) 60 days after developing zoster. Prodromal sensory symptoms and certain conditions associated with compromised immunity were also associated with PHN. Systemic corticosteroids before zoster and treatment of zoster with acyclovir or corticosteroids did not significantly affect the prevalence of PHN. CONCLUSIONS: Increased age and prodromal symptoms are associated with higher prevalence of PHN 1 and 2 months after onset of zoster. Overall, systemic acyclovir appears not to confer any protection against PHN, although benefit among elderly patients cannot be excluded.

Acyclovir↗

Inhaled steroids and the risk of hospitalization for asthma.

OBJECTIVE: To determine if anti-inflammatory treatment for asthma reduces the risk of asthma hospitalization. DESIGN: Retrospective cohort study. SETTING: A health maintenance organization (HMO) in eastern Massachusetts. PARTICIPANTS: Members of the HMO who were identified during the period October 1991 through September 1994 as having a diagnosis of asthma using a computerized medical record system. MAIN OUTCOME: Hospitalization for asthma. RESULTS: Of the 16941 eligible persons, 742 (4.4%) were hospitalized for asthma. The overall relative risk (RR) of hospitalization among those who received inhaled steroids was 0.5 (95% confidence interval [CI], 0.4-0.6) after adjustment for beta-agonist dispensing. Additional adjustment for age, race, other asthma medications, and amount and type of ambulatory care for asthma did not substantially affect the inverse relationship between use of inhaled steroids and hospitalization. Cromolyn was similarly associated with reduced risk, especially among children (RR,0.8; 95% CI, 0.7-0.9). In contrast, increasing beta-agonist use was associated with increasing hospitalization risk even after adjustment for other factors and medications. The steroid-associated protection was most marked among individuals who received the largest amount of beta-agonist. CONCLUSIONS: Inhaled steroids and, to a lesser extent, cromolyn confer significant protection against exacerbations of asthma leading to hospitalization. These results support the use of inhaled steroids by individuals who require more than occasional beta-agonist use to control asthma symptoms.

Administration, Inhalation↗

Cytokine response modifier A (CrmA) inhibits ceramide formation in response to tumor necrosis factor (TNF)-alpha: CrmA and Bcl-2 target distinct components in the apoptotic pathway.

Proteases are now firmly established as major regulators of the "execution" phase of apoptosis. Here, we examine the role of proteases and their relationship to ceramide, a proposed mediator of apoptosis, in the tumor necrosis factor-alpha (TNF-alpha)-induced pathway of cell death. Ceramide induced activation of prICE, the protease that cleaves the death substrate poly(ADP-ribose) polymerase. Bcl-2 inhibited ceramide-induced death, but not ceramide generation. In contrast, Cytokine response modifier A (CrmA), a potent inhibitor of Interleukin-1 beta converting enzyme and related proteases, inhibited ceramide generation and prevented TNF-alpha-induced death. Exogenous ceramide could overcome the CrmA block to cell death, but not the Bcl-2 block. CrmA, however, did not inhibit the activation of nuclear factor (NF)-kappa B by TNF-alpha, demonstrating that other signaling functions of TNF-alpha remain intact and that ceramide does not play a role in the activation of NF-kappa B. These studies support a distinct role for proteases in the signaling/activation phase of apoptosis acting upstream of ceramide formation.

Apoptosis↗

Erythromycin prolongs the QTc interval among patients with pneumonia.

Erythromycin is commonly used to treat simple community-acquired pneumonia. We measured the prolongation in QT(c) intervals in EKGs associated with intravenous erythromycin administration among patients hospitalized for simple pneumonia (DRGs 89 and 90). We reviewed the medical records of 50 patients who received at least 5 days of intravenous erythromycin, and found 15 with readable paired EKGs, at least one taken during the period of erythromycin administration and at least one other obtained when the patient had no erythromycin. The mean QT(c) interval in lead II for EKGs taken without erythromycin was 0.422 s and the average prolongation of the QT(c) interval associated with erythromycin administration was 0.046 s (P<0.01). The administration of erythromycin was thus associated with an increase in QT(c) intervals to a mean of 0.468 s, a value considered to be abnormally prolonged. We conclude that erythromycin prolongs the QT(c) interval among patients hospitalized with pneumonia in the same manner previously reported for healthy volunteers in an experimental setting. The magnitude of this erythromycin-induced QT(c) prolongation raises QT(c) intervals into the abnormal range. Although no patient in this small study suffered an adverse effect from the QT(c) prolongation, the magnitude of this effect is sufficiently large to raise clinical concerns.

Journal Article↗

Ibuprofen and skin and soft tissue superinfections in children with varicella.

PURPOSE: To investigate the possible association between ibuprofen use and dermatologic superinfections among children with recent varicella infection. METHODS: A retrospective cohort study of children in Harvard Pilgrim Health Care, a health maintenance organization in New England, was conducted. Outcomes and exposures of interest were identified from automated medical and pharmacy records. Exposure was defined by dispensing of ibuprofen before varicella to avoid potential confounding by indication. RESULTS: Between July 1, 1990 and September 30, 1994, 89 superinfections developed among 7,013 cases of varicella. The 30-day risk of superinfection was 7.2/10(3) cases (95% CI = 5.8-8.8/10(3) cases). Four of 169 children dispensed ibuprofen within 180 days of varicella developed superinfection. Relative to children without prior use, children with ibuprofen dispensed in the month prior to varicella were 3.1 times more likely to be diagnosed with a superinfection (95% CI = 0.1-19.7; P-value: 0.31). Restriction of outcomes to superinfections treated with systemic antibiotics increased the odds ratio to 5.1 (95% CI = 0.1-32.5; P-value: 0.22). CONCLUSIONS: The results of this study are consistent with a broad range of effects including no association and suggest that further study is needed.

Age Distribution↗

Predicting bacteremia in patients with sepsis syndrome. Academic Medical Center Consortium Sepsis Project Working Group.

The goal of this study was to develop and validate clinical prediction rules for bacteremia and subtypes of bacteremia in patients with sepsis syndrome. Thus, a prospective cohort study, including a stratified random sample of 1342 episodes of sepsis syndrome, was done in eight academic tertiary care hospitals. The derivation set included 881 episodes, and the validation set included 461. Main outcome measures were bacteremia caused by any organism, gram-negative rods, gram-positive cocci, and fungal bloodstream infection. The spread in probability between low- and high-risk groups in the derivation sets was from 14.5% to 60.6% for bacteremia of any type, from 9.8% to 32.8% for gram-positive bacteremia, from 5.3% to 41.9% for gram-negative bacteremia, and from 0.6% to 26.1% for fungemia. Because the model for gram-positive bacteremia performed poorly, a model predicting Staphylococcus aureus bacteremia was developed; it performed better, with a low- to high-risk spread of from 2.6% to 21.0%. The prediction models allow stratification of patients according to risk of bloodstream infections; their clinical utility remains to be demonstrated.

Adult↗

Assessment of asthma using automated and full-text medical records.

Automated medical records systems are used to study clinical outcomes and quality of care, but this requires accurate disease identification and assessment of severity. We sought to determine the reliability of identifying asthmatics through automated medical and pharmacy records, and the adequacy of such data for severity assessment. All adult health maintenance organization (HMO) members who received at least one asthma drug and an asthma diagnosis between April 1988 and September 1991 were identified. Records of a random sample were reviewed to validate the diagnosis and extract clinical information. Asthma drugs were dispensed to 15,491 individuals; 7583 (49%) also received an asthma diagnosis. Asthma drug use was three times greater for persons with diagnosed asthma compared to those with no diagnosis. Record review revealed that a coded asthma diagnosis had a positive predictive value of 86%. Nearly 4000 ambulatory encounters were reviewed, 10% of which were for asthma; the median number of encounters was two. Asthma symptoms were mentioned in 9% of all encounters; wheezing was most common. Peak flow and spirometry were measured in 4% and 1% of encounters, respectively. Records from recipients of asthma drugs who lacked an asthma diagnosis showed that 79% did not have asthma. Automated medical and pharmacy records from an HMO were relatively accurate when used to identify individuals with asthma. Similarly, most asthma drug recipients who lacked a coded diagnosis of asthma did not have asthma. However, conventional full-text records usually do not contain sufficient information to assess asthma severity, limiting the utility of such records for research and quality improvement.

Adult↗

Discontinuations of antihyperlipidemic drug therapy: assessment by means of automated databases.

Discontinuations of drugs used in the treatment of chronic conditions such as hyperlipidemia often signal adverse drug effects or therapeutic ineffectiveness. Discontinuations of antihyperlipidemic drug therapy among 2369 patients were evaluated using the computerized files and written medical records of two health maintenance organizations (HMOs) in Massachusetts for the period 1988 to 1990. Three methods were assessed for the identification of potential discontinuations of drug therapy using the automated databases. Overall, 75% of discontinuations flagged by the automated databases were confirmed in the medical charts. (1) In new users, 618 of the 635 (97%) drugs identified as drug switches by the computerized HMO pharmacy files were confirmed as discontinuations by the medical charts. (2) Of 620 eligible HMO members 332 (54%) identified with greater than 6 months between the last refill for an antihyperlipidemic drug and the end of the study stopped the drug therapy according to the medical chart. (3) Of 219 eligible drug therapies flagged with an 'inactive' or with an 'omit' status in the clinical encounter files 198 (90%) were discontinued according to the medical chart. This study demonstrates the utility of clinical automated databases to facilitate the study of drug discontinuations in primary care settings, reducing the cost and the amount of time required for the evaluation.

Journal Article↗

The incidence of depression in new users of beta-blockers and selected antihypertensives.

We studied the occurrence of depression in new users of propranolol (n = 704), other beta-blockers (n = 587), angiotensin-converting enzyme inhibitors (n = 976), calcium channel blockers (n = 742), and diuretics (n = 773) in the Harvard Community Health Plan population. The period of the study was from April 1988 to June 1991. All study subjects were followed for new or newly recurrent depression for up to 6 months after receiving their first study prescription. Case status was confirmed by blinded medical record review. We found 10 cases of depression that met DSM-III-R criteria ("major depression") and an additional 18 cases that had one or more symptoms consistent with depression ("minor depression"). Rates of major depression in users of beta-blockers and users of non-beta-blocker study drugs were 5.8 per 1000 person-years of exposure and 9.6 per 1000 person-years, respectively. None of the cases of major depression was propranolol associated. Rates of major or minor depression (combined) in users of beta-blockers and users of non-beta-blockers were 20.2 per 1000 person-years and 25.2 per 1000 person-years, respectively. The age- and sex-adjusted relative risk of major or minor depression associated with the use of beta-blockers compared to non-beta-blockers was 0.8 (95% CI, 0.3-1.9). The relative risk associated with propranolol compared to non-beta-blockers was also 0.8 (95% CI, 0.1-2.7). Therefore, depression occurred no more frequently in beta-blocker users than in other members of the study base.

Adrenergic beta-Antagonists↗

Surgical site infections occurring after hospital discharge.

Although surgical site infections (SSIs) occurring after hospital discharge cause substantial morbidity, their epidemiology is not well understood, and methods for routine postdischarge surveillance have not been validated. Inpatient and outpatient surveillance followed 5572 nonobstetric procedures among members of a health maintenance organization with extensive automated records. Records were screened for coded diagnoses, tests, and prescriptions and, if positive, were reviewed by reading full text. Questionnaires regarding the occurrence of an SSI were sent to the same patients and their surgeons. One hundred thirty-two SSIs were documented, of which 84% occurred after hospital discharge and 63% were managed outside the surgical facility. Postdischarge SSIs led to an average of 4.6 additional ambulatory encounters. Patient and surgeon questionnaires had a sensitivity of 28% and 15%, respectively. These data suggest that most SSIs occur after discharge and are not detectable by conventional surveillance. Nonetheless, they cause substantial resource utilization.

Female↗

Synovial fluid interleukin-8 and neutrophil function in rheumatoid arthritis and seronegative polyarthritis.

The relationships between synovial fluid (SF) interleukin-8 (IL-8) and neutrophil turnover as measured by cytidine deaminase (CD), and SF metabolites were studied in 28 patients, 16 with rheumatoid arthritis (RA; median age and disease duration 62 and 14 yr, respectively) and 12 with seronegative polyarthritis (SNP; median age and disease duration 32 and 5 yr, respectively). Knee SF samples were aspirated using indwelling cannulae following a period of rest for 1 h. SF IL-8 levels (measured by an ELISA) were significantly elevated in RA compared to SNP (median 2.35 vs 0.22 ng/ml, P < 0.001), as were median levels of CD (55.8 vs 8.11 U/ml, P < 0.01), lactic acid (29.6 vs 16.6 mg/dl, P < 0.001), glucose (57.9 vs 84.5 mg/dl, P < 0.05) and the lactate to glucose ratio (0.85 vs 0.19, P < 0.001). Measures of disease activity, C-reactive protein, plasma viscosity and articular index were also elevated in RA compared to SNP (P < 0.05). SF IL-8 levels correlated strongly with CD, lactate, glucose and the lactate to glucose ratio when both disease groups were considered together (P < 0.001). These parameters also showed some association with the measures of disease activity (P < 0.05). All these associations were less marked when the individual disease groups were analysed separately. These results suggest that factors responsible for neutrophil accumulation and priming (probably IL-8) are present in SF, and these coincide with products of their activation (CD). The degree of neutrophil turnover is linked to the anaerobic metabolism of the synovial cavity.

Adult↗

Tissue impedance as a function of temperature and time.

Tissue impedance dependence on temperature has been measured for six tissue types. The information was gathered using an automated laboratory under computer control. This information is needed to be able to input these values into a computer model that predicts temperature distribution produced by delivery of radio frequency energy. Due to the thermal dose of time and temperature, tissue properties change and no published data are available that document this. Since there are no theoretical predictions, empirical data were measured to supply this information. Using an aluminum cylindrical cavity of volume 1.69 cm3, muscle, liver, brain, and fat tissue impedance were measured at 500 kHz over a range of temperatures. All tests began at room temperature where baseline measurements were made. The cylinder was then placed in a constant temperature water bath at between 30 and 90 degrees C. The tests were run for a period of 10 to 30 minutes. Temperature homogeneity was carefully studied throughout the volume of the cylinder. It was found that thermal equilibrium occurred within four minutes. Special care was taken with the tissue sample in regard to optimize moisture and freshness, and minimize fat content. Grain orientation was also taken into consideration depending on the test. For all tissue types, resistivity decreased initially as the sample temperature equilibrated with the bath temperature. For temperatures less than 75 degrees C, resistivity values remained approximately constant over time.

Adipose Tissue↗

Discontinuation of antihyperlipidemic drugs--do rates reported in clinical trials reflect rates in primary care settings?

BACKGROUND: Discontinuation rates for drugs used to treat chronic conditions may affect the success of therapy. However, the discontinuation rates reported in clinical trials may not reflect those in primary care settings. METHODS: We conducted a cohort study using computerized research files and medical records on 2369 new users of antihyperlipidemic therapy at two health maintenance organizations (HMOs) from 1988 through 1990. The rates of drug discontinuation in these primary care settings were compared with the rates reported in clinical trials published from 1975 through 1993, located with the Medline data base. RESULTS: In the HMOs, the one-year probability of drug discontinuation was 41 percent for bile acid sequestrants (95 percent confidence interval, 38 to 44 percent), 46 percent for niacin (95 percent confidence interval, 42 to 51 percent), 15 percent for lovastatin (95 percent confidence interval, 11 to 19 percent), and 37 percent for gemfibrozil (95 percent confidence interval, 31 to 43 percent). For the bile acid sequestrants, niacin, and gemfibrozil, the risks of discontinuation were substantially higher in the HMOs than in randomized clinical trials, in which the summary estimates of this risk were 31 percent, 4 percent, and 15 percent, respectively, for trials of one year or longer. The rates of discontinuation in open-label studies were similar to those in the HMOs. CONCLUSIONS: The discontinuation rates reported in randomized clinical trials may not reflect the rates actually observed in primary care settings. The effectiveness and tolerability of antihyperlipidemic medications should be studied further in populations that typically use the agents.

Adult↗