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Biomedical subjects

J Nordin

Publications and source records attributed to J Nordin.

At least 19 recordsLinked to original sources
PubMed2005

Influence of clinical outcome and outcome period definitions on estimates of absolute clinical and economic benefits of influenza vaccination in community dwelling elderly persons.

Studies assessing the clinical and economic benefits of vaccination in the elderly have used different clinical outcomes (e.g. hospitalizations for pneumonia or influenza versus hospitalizations for respiratory and cardiovascular causes) and different outcome periods (e.g. peak versus total influenza season) on which to base estimates of clinical effectiveness and cost effectiveness. We explored the implications of these varying approaches by comparing two health economic analysis models of influenza vaccination of community-dwelling elderly persons. We developed computerized models using clinical data from 3 large US HMOs for the 1998-1999 and 1999-2000 influenza seasons. The primary health economic model used a broad definition of clinical events and outcome period and included hospitalizations for all respiratory and cardiovascular events that occurred during the entire influenza season. The alternative model used more restrictive definitions and included pneumonia or influenza hospitalizations occurring during the peak influenza season. The results of Monte Carlo simulation showed that, with the more inclusive primary model, influenza vaccination resulted in net medical care cost savings due to fewer respiratory or cardiovascular hospitalizations of Dollars 71/person vaccinated (5th-95th percentile Dollars 32-118) and net savings of Dollars 809/year of life saved (5th-95th percentile Dollars 331-1450). In contrast, the alternate model found costs of Dollars 3.50/person vaccinated (5th-95th percentile Dollars -11 to 5) and net costs of Dollars 91/year of life saved (5th-95th percentile Dollars -309 to 126). Our findings confirm that influenza vaccination of the elderly is most likely cost saving and supports policies and programs that advocate routine immunization of all persons 65 and older. They also highlight how different outcome definitions can influence the results of health economic analyses.

Aged↗
PubMed2005

Ambulatory-care diagnoses as potential indicators of outbreaks of gastrointestinal illness--Minnesota.

INTRODUCTION: Syndromic surveillance's capability to augment existing surveillance for community-acquired gastrointestinal disease is unknown. OBJECTIVE: The objective of this study was to evaluate the capability of a syndromic surveillance system to detect outbreaks of gastrointestinal disease. METHODS: A retrospective analysis was conducted comparing ambulatory care data from a health plan with a set of 110 gastrointestinal-disease outbreaks identified by the Minnesota Department of Health during 2001-02. Unusual clusters of illness (i.e., signals) in the health-plan data were identified by analyzing daily counts of gastrointestinal illness using an adjusted space-time scan statistic. Concordance was defined as < or =5 km between outbreak and signal and the signal occurring within 1 week of the outbreak. RESULTS: During 104 weeks, the number of signals was roughly what would have been expected by chance, suggesting that the modeling did a good job of estimating the expected counts of illness and that false alarms would not have occurred much more often than the number predicted at the various thresholds. During the same period, the health department identified 110 eligible gastrointestinal outbreaks. Apparent associations of the three statistically most unusual concordant signals with outbreaks of viral or bacterial gastrointestinal illness were ruled out by the health department on the basis of detailed knowledge of the circumstances and low numbers of affected persons seeking medical care. CONCLUSION: No previously known gastrointestinal outbreaks were identified by this surveillance system. However, relatively few recognized outbreaks resulted in patients seeking medical care, and the sensitivity of this system to detect outbreaks of real significance to public health remains to be determined. Prospective evaluation probably will be required to understand the usefulness of syndromic surveillance systems to enhance existing disease surveillance.

Ambulatory Care↗
PubMed2004

National Bioterrorism Syndromic Surveillance Demonstration Program.

The National Bioterrorism Syndromic Surveillance Demonstration Program identifies new cases of illness from electronic ambulatory patient records. Its goals are to use data from health plans and practice groups to detect localized outbreaks and to facilitate rapid public health follow-up. Data are extracted nightly on patient encounters occurring during the previous 24 hours. Visits or calls with diagnostic codes corresponding to syndromes of interest are counted; repeat encounters are excluded. Daily counts of syndromes by zip code are sent to a central data repository, where they are statistically analyzed for unusual clustering by using a model-adjusted SaTScan approach. The results and raw data are displayed on a restricted website. Patient-level information stays at the originating health-care organization unless required by public health authorities. If a cluster surpasses a threshold of statistical aberration chosen by the corresponding public health department, an electronic alert can be sent to that department. The health department might then call a clinical responder, who has electronic access to records of cases contributing to clusters. The system is flexible, allowing for changes in participating organizations, syndrome definitions, and alert thresholds. It is transparent to clinicians and has been accepted by the health-care organizations that provide the data. The system's data are usable by local and national health agencies. Its software is compatible with commonly used systems and software and is mostly open-source. Ongoing activities include evaluating the system's ability to detect naturally occurring outbreaks and simulated terrorism events, automating and testing alerts and response capability, and evaluating alternative data sources.

Ambulatory Care↗
PubMed2001

Influenza vaccine effectiveness in preventing hospitalizations and deaths in persons 65 years or older in Minnesota, New York, and Oregon: data from 3 health plans.

This study developed methods and determined the impact of influenza vaccination on elderly persons in 3 large health plans: Kaiser Permanente Northwest, HealthPartners, and Oxford Health Plans. Data for the 1996-1997 and 1997-1998 seasons were extracted from administrative databases. Subjects were health plan members > or = 65 years old. Comorbid conditions collected from the preceding year were used for risk adjustment with logistic regression. The virus-vaccine match was excellent for year 1 and fair for year 2. Both years, during peak and total periods, vaccination reduced all causes of death and hospitalization for pneumonia and influenza: hospitalizations were reduced by 19%-20% and 18%-24% for years 1 and 2, respectively, and deaths were reduced by 60%-61% and 35%-39% for the same periods. These results show that all elderly persons should be immunized annually for influenza. The methods used in this study are an efficient cost-effective way to study vaccine impact and similar questions.

Age Factors↗
PubMed2001

Population-based incidence of pertussis among adolescents and adults, Minnesota, 1995-1996.

To estimate the incidence of pertussis, a prospective study was done among members of a managed care organization in Minneapolis/St. Paul, Minnesota. Of 212 patients 10-49 years old enrolled from January 1995 through December 1996, 8 were found to be culture positive, 10 were found to be positive by polymerase chain reaction assay, 13 had a > or =2-fold increase in IgG or IgA to pertussis toxin (PT), and 18 had IgG to PT in a single serum specimen > or =3 SD above the mean of an age-matched control group. At least 1 positive laboratory test result for pertussis infection was found in 27 (13%) patients, among whom the duration of cough illness was a median of 42 days (range, 27-66 days). On the basis of any positive laboratory result, the estimated annual incidence of pertussis was 507 cases per 100,000 person-years (95% confidence interval, 307-706 cases). Bordetella pertussis infection may be a more common cause of cough illness among adolescents and adults than was recognized previously.

Adolescent↗
PubMed2000

Pharmacokinetics and safety of single oral doses of sirolimus (rapamycin) in healthy male volunteers.

A phase I study was conducted to determine the pharmacokinetics, safety, and tolerability of sirolimus, a new immunosuppressive drug, in 45 healthy men between 19 and 36 years of age. Nine subjects in each group were randomly assigned to receive single oral doses of either sirolimus (n = 6) or placebo (n = 3) in group I (0.3 mg/m2), group II (1 mg/m2), group III (3 mg/m2), group IV (5 mg/m2) and group V (8 mg/m2). No serious adverse events occurred during the study. Twenty-eight of the 45 volunteers (62%) reported an adverse event; 19 of 30 (63%) were in the sirolimus group and 9 of 15 (60%) were in the placebo group (ns). Asthenia was the most common adverse event, occurring in 7 of 30 (23%) in the sirolimus group compared with 6 of 15 (40%) in the placebo group (ns). Absorption occurred within 1 hour in all volunteers. Whole blood peak concentration and area under the concentration-time curve increased proportionally with dose. Mean (+/- SD) whole blood terminal disposition half-life (t1/2), apparent oral dose clearance (Cl/F), and volume of distribution (Vss/F) were 82 +/- 12 hours, 278 +/- 117 mL/h x kg and 23 +/- 10 L/kg, respectively. Distribution of sirolimus into formed blood elements was extensive, with a mean whole blood-to-plasma ratio of 36. Single oral doses of sirolimus (0.3 to 8 mg/m2) solution were well tolerated in healthy male volunteers.

Administration, Oral↗
PubMed2000

[Acute compartment syndrome in the thigh: 3 cases].

We report three cases of compartment syndrome in the thigh related to drug intoxications. Compartment syndrome is an uncommon condition often diagnosed late as it may occur in unconscious patients. The typical clinical presentation begins with pain of the lower limb refractory to major antagesics. The condition then progresses with sensoromotor involvement of the sciatic nerve. Rapid onset of acute renal failure in the setting of a crush syndrome may be life-threatening with a long-term risk of major sensoromotor sequelae. Surgical treatment with aponeurotomy is required rapidly to limit sequelae.

Acute Kidney Injury↗
PubMed1999

A comparison of costs of universal versus targeted lead screening for young children.

The purposes of this study were to compare universal blood lead screening for young children versus targeting by a risk assessment questionnaire and to examine the cost implications of each approach. Costs reflect the total number of blood tests required and cost of specimen collection, handling, and testing per elevated case. The setting included the metropolitan areas of Minneapolis and St. Paul, Minnesota. Children (N=9603) from 17 community organizations had blood tests. In addition, each child's parent or guardian completed a questionnaire assessing potential risk for lead poisoning. Four different screening approaches are presented. Each screening approach is presented with associated costs of overall screening and cost per child identified at blood levels of >/=10 microg/dl (N=1140) and >/=15 microg/dl (N=317). Based on the screening strategy selected and an estimate of $17 per blood test, total screening costs ranged from $91,596 to $165,945. The cost per child identified with elevated lead levels ranged from $361 to $523 at >/=15 and $105 to $146 at >/=10. Nine to 13% of children would not have been detected by policies other than universal screening. A geographically based approach was able to detect 90% of children with elevated blood levels at two-thirds the cost of universal screening. Blood tests would be taken for all children living within city limits. Those residing elsewhere would be tested only if answers to questionnaire items pertaining to age of housing, prior history of lead poisoning, or eating paint chips indicated risk. The new CDC guidelines suggest that screening be based on an assessment of housing, population demographics, and community risk and resources. This paper presents such an assessment.

Child↗
PubMed1998

Comparison of the Adsorption of o-Phthalate on Boehmite (gamma-AlOOH), Aged gamma-Al2O3, and Goethite (alpha-FeOOH).

This work is concerned with the adsorption of o-phthalate (1,2-benzenedicarboxylate) at the water-metal (hydr)oxide interface. Previously published infrared spectroscopic, potentiometric, and adsorption data characterizing the boehmite (gamma-AlOOH) system are compared with new data collected for o-phthalate adsorption on aged gamma-Al2O3 and goethite (alpha-FeOOH). The study focuses on identifying bonding mechanisms, stoichiometries, and stabilities of the formed complexes, and comparing these among the three systems. Furthermore, the effects of ionic strength and composition of the ionic medium are investigated. The infrared spectroscopic data provided direct, molecular-level evidence for the existence of two dominating surface complexes on all three solids. One was shown to be a deprotonated outer-sphere species and the other was an inner-sphere surface complex. The inner-sphere complexes on the three solids were structurally related, and they were tentatively assigned to a mononuclear, chelating structure involving both carboxylate groups. The outer-sphere complexes were shown to increase in relative importance at high pH and low ionic strengths, while low pH and high ionic strengths favored the inner-sphere complexes. The information gained from the infrared spectroscopic investigations was used as qualitative input in the formulation of the surface complexation models. New models, based on the extended constant capacitance approach, were presented for the o-phthalate/aged gamma-Al2O3 and o-phthalate/goethite systems. Copyright 1998 Academic Press.

Journal Article↗
PubMed1998

High-performance liquid chromatography-mass spectrometry for the quantification of nortriptyline and 10-hydroxynortriptyline in plasma.

A highly sensitive and selective method for the quantification of nortriptyline and its major 10-hydroxy metabolite in plasma is described. The method is based on liquid-liquid extraction in combination with acid dehydration of the 10-hydroxy metabolite to the less polar 10,11-dehydronortriptyline. Deuterium labelled internal standards ([2H4]NT and [2H3]10-OH-NT) were used and the compounds were separated by reversed-phase HPLC and detected using atmospheric pressure chemical ionisation and mass spectrometry. The limit of quantification was 0.8 ng/ml for both compounds. A 1-ml volume of plasma was used for analysis in the concentration range 0.8-32 ng/ml. The within- and between-day coefficients of variation were 11% in the low, 1.6 ng/ml range, and 7% at 8 ng ml/ml. Using this method it was possible to quantify plasma concentrations for 168 h following a single oral dose of 25 mg of nortriptyline with good accuracy and precision.

Chromatography, High Pressure Liquid↗
PubMed1998

10-Hydroxylation of nortriptyline in white persons with 0, 1, 2, 3, and 13 functional CYP2D6 genes.

OBJECTIVE: To investigate the disposition and effects of nortriptyline and its major metabolite 10-hydroxy-nortriptyline line in panels of white subjects with different CYP2D6 genotypes, including those with duplicated and multiduplicated CYP2D6*2 genes and to evaluate the contribution of the number of functional C gamma P2D6 alleles to the metabolism of nortriptyline, used here as a model drug for CYP2D6 substrates. METHODS: Oral single doses of 25 to 50 mg nortriptyline were given to five poor metabolizers of debrisoquin (INN; debrisoquine) with no functional CYP2D6 gene, five extensive metabolizers with one functional CY2D6 gene, five extensive metabolizers with two functional CYP2D6 genes, five ultrarapid metabolizers with duplicated CYP2D6*2 genes, and one ultrarapid metabolizer with 13 copies of the CYP2D6*2 gene. Plasma kinetics of nortriptyline and 10-hydroxynortriptyline were analyzed. Anticholinergic effects (inhibition of salivation and accommodation disturbances), sedation, blood pressure, and effect on supine and erect pulse rate were measured. RESULTS: There was a clear relation between the C gamma P2D6 genotype and the plasma kinetics of nortriptyline and 10-hydroxynortriptyline. The proportion between the apparent oral clearances of nortriptyline in the groups with 0, 1, 2, 3, and 13 functional genes was 1:1:4:5:17. The proportions between AUC(nortriptyline) to AUC(10-hydroxynortriptyline) ratios in the groups with 0, 1, 2, 3, and 13 functional genes were 36:25:10:4:1. Oral plasma clearance of nortriptyline and AUC(nortriptyline) to AUC(10-hydroxynortriptyline) ratio both correlated significantly with the debrisoquin metabolic ratio (rS = -0.89, p = 0.0001; rS = 0.92, p = 0.0001). Although ultrarapid metabolizer subjects were given double the nortriptyline dose (50 mg), inhibition of salivation was not more pronounced compared with the other genotype groups given 25 mg nortriptyline. CONCLUSION: The results of this study show the quantitative importance of the CYP2D6 genotype, especially the presence of multiple functional CYP2D6 genes for the pharmacokinetics of nortriptyline and 10-hydroxynortriptyline. Genotyping of subjects with multiple copies of functional genes may be of great value for differentiating ultrarapid metabolizers from patients who do not comply with the prescription and for assuring adequate drug choice and dosage for these patients.

Analysis of Variance↗
PubMed1998

Lead levels in high-risk and low-risk young children in the Minneapolis-St Paul metropolitan area.

OBJECTIVES: To determine distribution of lead levels among children in a low-risk area; to validate a prescreening questionnaire; and to determine if universal lead screening is necessary in children in this area. DESIGN: Blood lead levels and questionnaires were obtained on eligible patients. Data were analyzed using stepwise regression analysis. SETTING: Community clinics and a health maintenance organization (HMO) in the Minneapolis-St Paul metropolitan area. PATIENTS: A total of 9603 children at well-child visits, age 6 months to 6 years at community clinics, and 6 months to 3 years at the HMO. OUTCOME MEASURES: Whole blood lead levels (WBLs) and questionnaires. RESULTS: The total sample rate of WBLs at >/=10 microg/dL was 12%, at >/=15 microg/dL was 31/2%, and at >/=20 microg/dL was 1.2%. At both 10 microg/dL and 15 microg/dL, the non-HMO group was at higher risk. For both groups, risk factors included living in the central cities, and living in housing built before 1950. For the non-HMO group a history of the child eating paint chips, or the child or a sibling having previous lead poisoning were also risk factors. CONCLUSIONS: Not all children need lead screening. Children living in the central cities, or with the risk factors of living in housing built before 1950 or a previous history of lead poisoning should be screened.

Child↗
PubMed1997

Liquid chromatography-tandem mass spectrometry applied to a study of the metabolism of pentamidine. Discussion of possibilities and problems.

Tandem mass spectrometry is usually employed to achieve rapid screening or structure elucidation. We have used liquid chromatography-tandem mass spectrometry in order to detect metabolites of the antiprotozoal drug pentamidine in urine. Samples of urine from rat and man were analysed both by direct injection and after solid-phase extraction. The present paper discusses advantages and disadvantages of using direct injection of urine samples, optimization of chromatographic conditions with regard to the performance of the mass spectrometer, automation and stability of the entire system.

Animals↗
PubMed1997

An S-mephenytoin cysteine conjugate identified in urine of extensive but not of poor metabolizers of S-mephenytoin.

A conjugate of S-mephenytoin excreted in urine of extensive but not of poor metabolizers of S-mephenytoin has previously been reported. This conjugate, which is easily hydrolysed back to S-mephenytoin, has now been isolated and identified in urine from one extensive metabolizer after a single dose of 100 mg racemic mephenytoin. High performance liquid chromatography purification, followed by gas chromatographic, mass spectrometric and amino acid analyses showed that the isolated compound is a cysteine conjugate of S-mephenytoin. The significant mass spectrometric ions have been confirmed in three additional extensive metabolizers of S-mephenytoin, but were not detectable in urine from three poor metabolizer subjects. The exact structure of the conjugate is unknown, but we suggest that an S-N bond between cysteine and S-mephenytoin is formed via an oxidative radical mechanism catalyzed by CYP2C19.

Chromatography, High Pressure Liquid↗
PubMed1996

Using continuous quality improvement tools to improve pediatric immunization rates.

BACKGROUND: In August 1992 the medical director of the 19 Group Health medical clinics (now part of HealthPartners) in Minnesota chartered a continuous quality improvement (CQI) team to improve the pediatric (two-year-old) immunization rates. THE TEAM'S WORK: The team created a process flow for the current immunization process, collected data on the process, determined the causes of late or missed immunizations, collected data on children not up-to-date with immunization, analyzed the data, acted on recommendations, and obtained buy-in. The chief reasons for the child's not being up-to-date on immunizations included missed opportunities (when the child is in the clinic receiving care, perhaps for an acute illness, and could have safely received the immunization but did not), no previous visits or chart, and parents instructed to have their child return at two years. INTERVENTION: Recommendations pertained to missed opportunities, record keeping, and enhanced patient and provider responsibility. For example, providers were given algorithms for catch-up of patients not on schedule or with incomplete immunizations. Another CQI team was launched to address and simplify the myriad locations in a medical record for recording information on immunizations. An automated vaccine administration record is now being piloted at two clinics. RESULTS: Immunizations have increased from a mean of 53.5% before the team started to meet to a mean of 86.5% for the most recent four quarters for which data are available. CONCLUSIONS: A problem is best addressed by the very people who will have to bring about the necessary changes for the desired improvements.

Algorithms↗
PubMed1995

Metabolism is an important route of pentamidine elimination in the rat: disposition of 14C-pentamidine and identification of metabolites in urine using liquid chromatography-tandem mass spectrometry.

This study assesses the contribution of metabolism for the disposition of pentamidine in the rat. With the use of 14C-labelled compound, the excretion of radioactivity in urine and faeces has been studied in four rats during 44 days after a single intravenous injection of the drug. The urinary and faecal excretion of the radioactivity were of equal importance; 22 +/- 2% (mean +/- S.D.) and 25 +/- 4% being detected in urine and faeces, respectively. The activity in organs and tissues at 44 days after drug administration was also measured and amounted to 21 +/- 5% of the administered dose. Using HPLC the proportion of metabolites in urine in relation to unchanged pentamidine increased with time after dose, being 76 +/- 15% (mean +/- S.D.) of the total excreted radioactivity on day 1 and 97 +/- 1% on day 6. HPLC--tandem mass spectometry was used for identification of metabolites in urine obtained from four rats given unlabelled pentamidine. Using synthetic reference compounds and the selective MS/MS mode four oxidized metabolites of pentamidine were identified either by direct injection into the system or by analyses of extracted urine. Thus, a substantial part of pentamidine is excreted as metabolites in urine.

Animals↗