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Biomedical subjects

B Friedman

Publications and source records attributed to B Friedman.

At least 19 recordsLinked to original sources
PubMed2001

Potentially inappropriate medication use in the community-dwelling elderly: findings from the 1996 Medical Expenditure Panel Survey.

CONTEXT: Inappropriate medication use is a major patient safety concern, especially for the elderly population. Using explicit criteria, prior studies have found that 23.5% and 17.5% of the US community-dwelling elderly population used at least 1 of 20 potentially inappropriate medications in 1987 and 1992, respectively. OBJECTIVES: To determine the prevalence of potentially inappropriate medication use in community-dwelling elderly persons in 1996, to assess trends over 10 years, categorize inappropriate medication use according to explicit criteria, and to examine risk factors for inappropriate medication use. DESIGN, SETTING, AND PARTICIPANTS: Respondents aged 65 years or older (n = 2455) to the 1996 Medical Expenditure Panel Survey, a nationally representative survey of the US noninstitutionalized population were included. A 7-member expert panel was convened to categorize inappropriate medications. MAIN OUTCOME MEASURE: Prevalence of use of 33 potentially inappropriate medications. RESULTS: In 1996, 21.3% (95% confidence interval [CI], 19.5%-23.1%) of community-dwelling elderly patients in the United States received at least 1 of 33 potentially inappropriate medications. Using the expert panel's classifications, about 2.6% of elderly patients (95% CI, 2.0%-3.2%) used at least 1 of the 11 medications that should always be avoided by elderly patients; 9.1% (95% CI, 7.9%-10.3%) used at least 1 of the 8 that would rarely be appropriate; and 13.3% (95% CI, 11.7%-14.9%) used at least 1 of the 14 medications that have some indications but are often misused. Use of some inappropriate medications declined between 1987 and 1996. Persons with poor health and more prescriptions had a significantly higher risk of inappropriate medication use. CONCLUSIONS: Overall inappropriate medication use in elderly patients remains a serious problem. Despite challenges in using explicit criteria for assessing inappropriate medications for elderly patients, such criteria can be applied to population-based surveys to identify opportunities to improve quality of care and patient safety. Enhancements of existing data sources to include dosage, duration, and indication may augment national improvement and monitoring efforts.

Aged↗
PubMed2001

Selective loss of sphingosine 1-phosphate signaling with no obvious phenotypic abnormality in mice lacking its G protein-coupled receptor, LP(B3)/EDG-3.

Sphingosine 1-phosphate (S1P) exerts diverse physiological actions by activating its cognate G protein-coupled receptors. Five S1P receptors have been identified in mammals: LP(B1)/EDG-1, LP(B2)/H218/AGR16/EDG-5, LP(B3)/EDG-3, LP(B4)/NRG-1/EDG-8, and LP(C1)/EDG-6. One of these receptors, LP(B1), has recently been shown to be essential for mouse embryonic development. Here we disrupted the lp(B3) gene in mice, resulting in the complete absence of lp(B3) gene, transcript, and LP(B3) protein. LP(B3)-null mice were viable and fertile and developed normally with no obvious phenotypic abnormality. We prepared mouse embryonic fibroblast (MEF) cells to examine effects of LP(B3) deletion on S1P-induced signal transduction pathways. Wild-type MEF cells expressed lp(B1), lp(B2), and lp(B3) but neither lp(B4) nor lp(C1), and they were highly responsive to S1P in phospholipase C (PLC) activation, adenylyl cyclase inhibition, and Rho activation. Identically prepared LP(B3)-null MEF cells showed significant decreases in PLC activation, slight decreases in adenylyl cyclase inhibition, and no change in Rho activation. Retrovirus-mediated rescue of the LP(B3) receptor in LP(B3)-null MEF cells restored S1P-dependent PLC activation and adenylyl cyclase inhibition. These results indicate a nonessential role for LP(B3) in normal development of mouse but show nonredundant cellular signaling mediated by a single type of S1P receptor.

Adenylyl Cyclase Inhibitors↗
PubMed2001

Preventable illness and out-of-area travel of children in New York counties.

The long-distance travellers could be important to any cost-benefit assessment of policies to increase or improve local resources. This study examines the out-of-area hospital admission pattern for patients with Ambulatory Care Sensitive (ACS) conditions, also known as preventable conditions. The availability of local resources play a significant role for hospitalization for these conditions. Despite a growing literature investigating hospital choice, little is known about the effects of resource availabilities in local areas and patient characteristics prompting people to seek care at a longer distance from home for these conditions. Based on hospital discharge data for New York residents (children) admitted to hospitals in New York, Pennsylvania, New Jersey or Connecticut in 1994, the study uses logistic regression to predict travel out of the local area for ACS admission. The actual distance between residence and hospital is a highly skewed and problematic measure, but the crossing of county boundaries is a related and very useful dichotomous measure of distant hospitalization. The study finds a strong association of types of insurance and availability of primary care with episodes of hospitalization for children outside the area of residence, after controlling for severity of illness and several other patient and county characteristics.

Ambulatory Care↗
PubMed2001

Burns due to exposure to steam.

Injuries due to accidental contact with steam are occasionally encountered. They can be quite severe, especially when associated respiratory problems are present. Thirteen patients with burns resulting from exposure to steam were admitted to the Joseph M. Still Burn Center during a 2-year period. All injuries were employment related. Twelve burns resulted from the rupture of pipes carrying steam. One additional case was due to a cooking accident. There were 12 males and one female. Burn size ranged from 1 to 57% (mean 26.2%). Age ranged from 26 to 53 years (mean 33). Seven had inhalation injuries with blistering and slough of bronchial mucosa. The hospital stay ranged from 2 to 41 days. One patient died of respiratory problems. From one to five operations were required by the survivors; two required later reconstructive surgery. Closer supervision of industrial plants in which pipes carrying steam are present may have prevented some of these accidents.

Accidents, Occupational↗
PubMed2001

Advance directives in skilled nursing facility residents transferred to emergency departments.

OBJECTIVE: Ten years have passed since Congress enacted the Patient Self-Determination Act to promote the use of advance directives (ADs). This study was performed to determine the frequency, type, demographic distribution, and utility of ADs that accompany residents of skilled nursing facilities (SNFs) transferred to emergency departments (EDs). METHODS: This was an observational, cross-sectional cohort of SNF residents, transferred to two urban, academic EDs. Chart review and physician interviews were conducted on consecutive patients arriving during 12-hour data collection shifts. RESULTS: Among 715 patients entered, 315 [44%, 95% confidence interval (95% CI) = 40% to 48%] had an AD. Advance directives were significantly more prevalent among white (50%) than African American (34%) or Hispanic (39%) patients (p < 0.001), and varied from 0% to 94% among SNFs. Of the 315 patients with ADs, do-not-resuscitate (DNR) orders were the most prevalent (65%, 95% CI = 58% to 69%). Although 75% (95% CI = 69% to 81%) of the DNR orders addressed cardiopulmonary resuscitation (CPR), only 12% (95% CI = 8% to 16%) addressed intubation. Among 39 patients who required intubation or CPR, 44% had ADs, 82% (95% CI = 57% to 96%) of which were deemed useful. CONCLUSIONS: Despite a decade of legislation promoting their use, ADs are lacking in most SNF residents transferred to EDs for evaluation and in most settings in which a clinical indication exists for intubation or CPR. Variation in their prevalence appears to be associated with both ethnicity and SNF origin. Although about three-fourths of DNR ADs addressed CPR, only about one in ten offered guidance regarding intubation. When available, ADs are used in most instances to guide emergency care.

Advance Directives↗
PubMed2001

Health insurance, primary care, and preventable hospitalization of children in a large state.

OBJECTIVES: To analyze variations in the admission rate to hospitals of children with ambulatory care-sensitive (ACS) conditions and to test the relationship of ACS admission rates to insurance coverage, health maintenance organization (HMO) enrollment, availability of primary care, severity of illness, distance to hospital, and a number of other factors. STUDY DESIGN: Hypotheses were derived from basic considerations about demand and use of primary care and preventive services and then were tested with a weighted linear regression model of the ACS admission rate for children residing in each county. PATIENTS AND METHODS: The principal data were all hospital discharges for New York resident children admitted to hospitals in New York, Pennsylvania, New Jersey, or Connecticut in 1994. The data and methodology were noteworthy for including out-of-area hospital admissions. RESULTS: There was a substantial negative association of the ACS rate with private HMO coverage. There also were sizable negative effects of the availability of primary care services in physician offices and the distance traveled. Large differences related to racial and ethnic composition of the population were found independent of other determinants. There was a positive association with the proportion of all admissions (admissions for all conditions) covered by Medicaid or self-pay. Severity of illness and use of emergency departments were controlled. There was no independent effect of a location in New York City. CONCLUSIONS: The results are consistent with smaller-scale studies suggesting that improved health insurance for children could reduce hospital admissions. Contracting with HMOs also appears to be beneficial. Independently, programs to increase the availability of primary and preventive services could substantially reduce ACS admissions.

Ambulatory Care↗
PubMed2001

Vancomycin-resistant organisms on a burn unit.

The incidence of infections due to vancomycin-resistant organisms has significantly increased during the past several years. This is important because vancomycin has been the drug of choice for treatment of infections due to methicillin-resistant Staphylococcus aureus (MRSA). Enterococci resistant to vancomycin are now emerging, and MRSA organisms with intermediate resistance to vancomycin have been identified in some centers. Cross transfer of resistance will eventually lead to the widespread development of organisms that are more difficult to eradicate. In our burn unit, we have encountered six patients (five with burns, one with necrotizing fasciitis) who had wound infections with vancomycin-resistant enterococci. Four patients died, and two recovered after prolonged hospital stays. Attempts to limit development of vancomycin-resistant enterococci are important.

Adult↗
PubMed2000

Recombinant human antithrombin III improves survival and attenuates inflammatory responses in baboons lethally challenged with Escherichia coli.

Plasma-derived antithrombin III (ATIII) prevents the lethal effects of Escherichia coli infusion in baboons, but the mechanisms behind this effect are not clear. In the present study, we evaluated the effects of recombinant human ATIII (rhATIII) on the clinical course and the inflammatory cytokine and coagulation responses in baboons challenged with lethal dose of E coli. Animals in the treatment group (n = 5) received high doses of rhATIII starting 1 hour before an E coli challenge. Those in the control group were administered saline. Survival was significantly improved in the treatment group (P =.002). Both groups had similar hemodynamic responses to E coli challenge but different coagulation and inflammatory responses. The rhATIII group had an accelerated increase of thrombin-ATIII complexes and significantly less fibrinogen consumption compared to controls. In addition, the rhATIII group had much less severe thrombotic pathology on autopsy and virtually no fibrinolytic response to E coli challenge. Furthermore, the rhATIII group had a significantly attenuated inflammatory response as evidenced by marked reduction of the release of various cytokines. We conclude that the early administration of high doses of rhATIII improves the outcome in baboons lethally challenged with E coli, probably due to the combined anticoagulation and anti-inflammatory effects of this therapy. (Blood. 2000;95:1117-1123)

Animals↗
PubMed2000

Identification of an intronic regulatory element in the human protein C (PROC) gene.

Regulatory DNA elements responsible for human protein C (PROC) gene expression have previously been identified in the upstream promoter region and first (untranslated) exon of the gene. Here we show that an additional sequence element located more than 500 bp downstream of the core promoter within intron 1 further enhances PROC promoter-driven reporter gene expression in human hepatoma cells. In common with core promoter constructs used in previous studies, the activity of this 3'-extended regulatory region is diminished by a naturally occurring promoter mutation. However, in contrast to constructs lacking intronic sequence, the promoter/intron regulatory region is repressed rather than activated by the transcription factor HNF-1. Using both conventional alignment procedures and complexity analysis to study the human and canine PROC sequences, we identified two conserved intronic regions, which were tested for their involvement in gene regulation. High-level gene expression from the intron-coupled promoter was dependent upon the integrity of a 142 bp sequence element, a duplicate copy of which is located in an upstream region of the PROC gene that possesses enhancer activity. These findings emphasise the potential importance of intragenic sequences for gene regulation and serve to illustrate that the results of PROC promoter/reporter gene experiments are critically dependent upon the sequence context. The identification of such intragenic elements is relevant to the analysis of human genetic disease since it will facilitate the detection and functional evaluation of regulatory mutations and polymorphisms.

Base Sequence↗
PubMed2000

Deep laryngeal penetration as a predictor of aspiration.

Very little has been written about laryngeal penetration as a separate diagnostic event from aspiration. Laryngeal penetration has been described as an infrequent event in adult individuals without swallowing problems. This study describes the incidence of laryngeal penetration in 125 dysphagic children ranging in age from 7 days to 19 years who were seen over a 6-month period at The Children's Hospital in Denver, Colorado. Laryngeal penetration was identified in 60% of the study group, with 31% demonstrating deep laryngeal penetration. Of the children exhibiting deep laryngeal penetration, 85% aspirated, suggesting a strong correlation between these two events. It was noted that children exhibiting deep laryngeal penetration often began to aspirate further into their feedings. Use of extended feedings during videofluoroscopy is discussed as a diagnostic strategy in the presence of deep laryngeal penetration.

Adolescent↗
PubMed2000

Experience with pneumonia in acutely burned patients requiring ventilator support.

Acutely burned patients requiring ventilatory support who developed pneumonia while in the hospital were retrospectively reviewed. The Centers for Disease Control and Prevention (CDC) clinical criteria for pneumonia are based on clinical findings, radiographic findings, and culture data. During an 18-month period, 784 burn patients were admitted. Of these, 145 (18.5%) were placed on ventilators for at least 1 day. Fifty-three (36.6%) patients on ventilators developed acute pneumonia based on CDC criteria. Identification of causative organisms was based on positive cultures from blood or endotracheal aspiration within 3 days of the diagnosis of pneumonia. Thirty-nine patients were diagnosed as having inhalation injury. Forty-seven patients were placed on ventilators before or on the day of admission. Ages ranged from 2 to 82 years (mean, 39). Burn size ranged from 2 to 85 per cent (mean, 29.7%) of total body surface area. The total number of ventilator days was 1310 for the 53 patients, with a mean of 27.7 days. Ten patients had positive blood cultures during the period in which pneumonia was present. Thirty-one different organisms were recovered from blood or tracheal aspirates. The most commonly recovered organism was Pseudomonas aeruginosa. In 30 incidences, polymicrobial cultures were encountered. Initiation of appropriate antimicrobial therapy was begun on the basis of clinical impression and current burn unit experience and revised on the basis of the culture data. Of the 53 patients, 13 (25.5%) died, all while still on ventilators. The other 40 patients survived. Thirty-four were weaned off their ventilators, and 6 were transferred while still on ventilator support.

Adult↗
PubMed2000

Experience with the insertion of vena caval filters in acutely burned patients.

The use of inferior vena caval filters in patients at high risk of pulmonary emboli is a standard practice in many types of patients. The usefulness of such filters in acutely burned patients has yet to be established. Twenty inferior vena caval filters were inserted in burn patients. Five were inserted because of preexisting thromboembolic disease. Fifteen were placed prophylactically because of high-risk states, including prolonged immobilization, old age, bleeding problems, and obesity. There were no complications due to filter insertion. No postinsertion emboli were recognized. There were no cases of postinsertion thrombophlebitis. In this small series, the procedure appears to be effective and safe.

Acute Disease↗
PubMed1999

A comparison of the pharmacological properties of carbohydrate remodeled recombinant and placental-derived beta-glucocerebrosidase: implications for clinical efficacy in treatment of Gaucher disease.

The objective of these studies was to characterize the macrophage mannose receptor binding and pharmacological properties of carbohydrate remodeled human placental-derived and recombinant beta-glucocerebrosidase (pGCR and rGCR, respectively). These are similar but not identical molecules that were developed as enzyme replacement therapies for Gaucher disease. Both undergo oligosaccharide remodeling during purification to expose terminal mannose sugar residues. Competitive binding data indicated carbohydrate remodeling improved targeting to mannose receptors over native enzyme by two orders of magnitude. Mannose receptor dissociation constants (Kd) for pGCR and rGCR were each 13 nmol/L. At 37 degrees C, 95% of the total macrophage binding was mannose receptor specific. In vivo, pGCR and rGCR were cleared from circulation by a saturable pathway. The serum half-life (t1/2) was 3 minutes when less than saturable amounts were injected intravenously (IV) into mice. Twenty minutes postdose, beta-glucocerebrosidase activity increased over endogenous levels in all tissues examined. Fifty percent of the injected activity was recovered. Ninety-five percent of recovered activity was in the liver. Parenchymal cells (PC), Kupffer cells (KC), and liver endothelium cells (LEC) were responsible for 75%, 22%, and 3%, respectively, of the hepatocellular uptake of rGCR and for 76%, 11%, and 12%, respectively, of the hepatocellular uptake of pGCR. Both molecules had poor stability in LEC and relatively long terminal half-lives in PC (t1/2 = 2 days) and KC (t1/2 = 3 days).

Animals↗
PubMed1999

Tracking the State Children's Health Insurance Program with hospital data: national baselines, state variations, and some cautions.

State and federal agencies are concerned with the impact of the State Children's Health Insurance Program (CHIP) on the health care of enrolled children. As part of a broad program evaluation, and at relatively low cost, analysts can track data on hospital admissions for ambulatory care sensitive (ACS) conditions. This article uses hospital data for 19 states to calculate baseline ACS rates and to discuss trends and cross-state variations just prior to the start of the CHIPs. A few cautions and limitations are discussed. An unexpected result in the exploration was a substantial increase in the rate of ACS admissions for self-pay and Medicaid-enrolled children during the period of 1990-1995. During that same period, the admission rate for other insured children fell by more than a third. The comparisons across states are meant to be illustrative; they do reveal a relationship between the rate of asthma admissions and the proportion of self-pay plus Medicaid-enrolled cases.

Adolescent↗
PubMed1999

Nocturnal asthma: effect of salmeterol on quality of life and clinical outcomes.

OBJECTIVE: To evaluate the effect of salmeterol on asthma-specific quality of life in patients experiencing significant nocturnal symptoms. DESIGN: Randomized, double-blind, placebo-controlled, multicenter clinical trial. SETTING: Allergy/respiratory care clinics. PATIENTS: Nonsmokers > or = 12 years of age with nocturnal asthma symptoms on at least 6 of 14 days during screening and > or = 15% decrease in peak expiratory flow (PEF) from baseline on nocturnal awakening at least once during screening. INTERVENTIONS: Salmeterol, 42 microg, or placebo twice daily. Patients were allowed to continue theophylline, inhaled corticosteroids, and "as-needed" albuterol. MEASUREMENTS AND RESULTS: Outcome measures included Asthma Quality of Life Questionnaire (AQLQ) global and individual domain scores, FEV1, PEF, nighttime awakenings, asthma symptoms, and supplemental albuterol use. Mean change from baseline for the global and domain AQLQ scores was significantly greater (p < or = 0.005) with salmeterol compared with placebo. At week 12, salmeterol significantly (p < 0.001 compared with placebo) increased mean change from baseline in FEV1, morning and evening PEF, percentage of symptom-free days, percentage of nights with no awakenings due to asthma, and the percentage of days and nights with no supplemental albuterol use. Significant improvements in PEF were observed after treatment with salmeterol regardless of concomitant treatment with theophylline (p < 0.05). CONCLUSIONS: These results provide evidence that validates the role of salmeterol in improving quality of life in patients with moderate persistent asthma who exhibited nocturnal asthma symptoms and supports the efficacy of salmeterol compared with that of placebo (ie, "as-needed" albuterol).

Adolescent↗
PubMed1999

Does managed care affect the supply and use of ICU services?

This paper analyzes use of hospital intensive care units (ICUs) by adult patients who are under age 65 and not covered by Medicaid; it allows for variation in indicators of the patient's condition, severity of illness, type of admission, emergency status, and degree of constraint on the total hospital ICU supply. We use data for Massachusetts and Florida in 1992. In neither state is there a significant difference in ICU admission rates between managed care patients and other privately insured patients. In Massachusetts, we find that the length of stay in the ICU is somewhat less for managed care and uninsured patients than for other privately insured patients. In both states, a hospital's ratio of total annual supply of ICU services to expected demand has a strong effect. In Massachusetts, the differences across payer groups in length of stay disappear for hospitals where the total ICU supply is relatively constrained.

Adult↗