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PubMed1996

Prior and current costs in capitated health plans: the effects of health status at enrollment.

We compared the prior and current costs of persons age 65 and older enrolling in a Social/Health Maintenance Organization in each of four sites with samples of persons using standard Medicare benefits in each site. Analyses were adjusted for individual health differences using case mix scores. Costs were examined in the year before S/HMO enrollment or prior to the sampling of a person using regular Medicare services as well as costs during the study. Costs during the study are analyzed using a two-stage procedure where first the propensity to enroll in a S/HMO is modeled and then costs derived from either Medicare sources or shadow prices assigned to service units provided in a S/HMO are modeled. The costs for case mix groups with different health and functional characteristics varied significantly. Cost differences between case mix classes differed between the S/HMO and FFS populations.

Aged↗

PubMed1998

Comparing the subjective, psychomotor and physiological effects of intravenous pentazocine and morphine in normal volunteers.

The purposes of this study were to characterize the subjective, psychomotor and physiological effects of pentazocine in non-drug-abusing volunteers and to compare and contrast the effects of pentazocine with those of morphine. Sixteen subjects without histories of opiate dependence were injected in an upper extremity vein with 0, 7.5, 15 or 30 mg/70 kg pentazocine or 10 mg/70 kg morphine, using a randomized, double-blind, crossover design. Pentazocine increased scores on the pentobarbital-chlorpromazine-alcohol group and lysergic acid diethylamide scales and decreased scores on the benzedrine group scale of the Addiction Research Center Inventory, increased adjective checklist ratings of "nodding," "sweating" and "turning of stomach" and increased visual analog scale ratings of "difficulty concentrating," "drunk" and "having unpleasant bodily sensations." Pentazocine (30 mg) had a greater propensity to increase ratings associated with dysphoria than did 10 mg of morphine. Pentazocine produced impairment on four measures of psychomotor performance. Ten milligrams of morphine produced minimal psychomotor impairment. Both pentazocine and morphine induced miosis, but 10 mg of morphine had a greater magnitude of effect than 30 mg of pentazocine. The results of the present study demonstrate that 7.5 to 30 mg of pentazocine had orderly, dose-related effects on subjective, psychomotor and physiological variables. Further, a clinically relevant dose of pentazocine, 30 mg, produced a greater magnitude of dysphoric subjective effects than did 10 mg of morphine, which is consistent with the literature reporting that pentazocine has a greater likelihood of inducing psychotomimesis than do other opioids.

Adult↗

PubMed2005

Behavioral response to novelty correlates with dopamine receptor availability in striatum of Göttingen minipigs.

Behavioral response to novelty in rats has been linked both to dopamine transmission in the ventral striatum, and to propensity to self-administer psychostimulant drugs. In order to probe the relationship between behavioral response to novelty and dopamine systems we have developed a behavioral model for correlation with positron emission tomography (PET) of dopamine transmission in brain of Göttingen minipigs. In the present study, we measured exploration of a novel object by recording the number of contacts, and duration of contact with a novel object, in groups of six male and six female adult minipigs. We hypothesized that these novelty scores would correlate with the amphetamine-evoked dopamine release in ventral striatum, measured 2 weeks later in a PET study of the availability of binding sites for the dopamine D2/3 antagonist [11C]raclopride. There were significant correlations between duration of contact with a novel object and the amphetamine-evoked reductions in binding potential (DeltapB) in the left ventral striatum of the 12 animals; Comparison of results by gender revealed that the correlation was driven mainly by the male group, and was not present in the female group. We interpret these results to show that propensity to explore an unfamiliar object is relatively elevated in pigs with low basal occupancy of dopamine D2/3 receptors by endogenous dopamine, and with high amphetamine-induced occupancy of released dopamine in the male pigs.

Adaptation, Psychological↗

PubMed2004

An autosomal genome scan for loci influencing longitudinal burden of body mass index from childhood to young adulthood in white sibships: The Bogalusa Heart Study.

OBJECTIVE: To examine genetic loci linked to a long-term burden and trend of obesity traits, such as body mass index (BMI), from childhood to adulthood. DESIGN: : Longitudinal study using serial measurements of BMI from childhood. SUBJECTS: A total of 782 unselected white siblings (representing 521 full and 39 half sib-pairs) from 342 families enrolled in the Bogalusa Heart Study. MEASUREMENTS: A total of 357 microsatellite markers with an average spacing of 9.0 cM spanning the 22 autosomal chromosomes were typed. A quadratic growth curve was developed using a random effects model based on serial measurements of BMI from childhood to adulthood. The serial changes in BMI were measured in terms of long-term burden (area under the curve (AUC) divided by follow-up years) and the long-term trend (incremental AUC, calculated as total AUC-baseline AUC). RESULTS: Heritability estimates of long-term measures were 0.78 for total AUC and 0.43 for incremental AUC. In a variance-component-based multipoint linkage analysis with SOLAR, linkage to the long-term measures of BMI was observed on chromosomes 1, 5, 7, 12, 13 and 18. For total AUC, LOD scores were 3.0 at 110 cM on chromosome 12, 2.9 at 26 cM and 2.4 at 52 cM on chromosome 7, and 2.2 at 126 cM on chromosome 5. For incremental AUC, LOD scores were 2.9 at 26 cM, 2.1 at 97 cM and 2.3 at 110 cM on chromosome 12, 2.2 at 69 cM on chromosome 7, 2.2 at 91 cM and 2.5 at 150 cM on chromosome 1, 2.0 at 119 cM on chromosome 5, 2.0 at 54 cM on chromosome 13 and 2.0 at 7 cM on chromosome 18. Several important obesity-related candidate genes are located in the regions or near the markers showing positive linkage. CONCLUSION: Linkage evidence found in this study indicates that regions on these chromosomes might harbor genetic loci that affect the propensity to develop obesity from childhood.

Adolescent↗

PubMed2003

Preiser's disease: identification of two patterns.

PURPOSE: A large series of patients with Preiser's disease was reviewed to compare 2 potentially different categories of this disorder: complete versus partial vascular impairment of the scaphoid bone as determined by magnetic resonance imaging (MRI). METHODS: Nineteen patients with Preiser's disease were identified retrospectively from 2 institutions. Using MRI criteria, 2 disease patterns were identified: diffuse necrosis and/or ischemia of the scaphoid (type 1 disease, 11 cases) and segmental vascular impairment of the scaphoid (type 2 disease, 8 cases). Risk factors for osteonecrosis, treatment methods, and serial radiographs were reviewed in all cases. Sixteen patients were examined for the purpose of this study at an average follow-up of 25 months. RESULTS: MRI signal changes of necrosis and/or ischemia involved 100% of the scaphoid in type 1 cases and on average approximately 42% in type 2 cases (range, 33% to 66%). In type 1 cases, regardless of the treatment used, the scaphoid typically fragmented and collapsed. In type 2 cases, scaphoid architecture was altered minimally after similar treatment methods. A history of wrist trauma was significantly more common in type 2 cases, and the results of treatment were generally better in this group of patients (mean Mayo modified wrist scores, 86 vs 58 points). CONCLUSIONS: This study supports the concept of 2 patterns of scaphoid involvement in Preiser's disease. Type 1 cases are characterized by MRI signal changes of necrosis and/or ischemia involving the entire scaphoid bone. Patients in this group have a propensity for scaphoid deterioration. Type 2 cases have MRI signal changes involving only part of the scaphoid. These patients commonly report a history of wrist trauma, show fewer tendencies toward scaphoid fragmentation, and may have a more favorable clinical outcome.

Adult↗

PubMed2002

Use of dynamic negative airway pressure (DNAP) to assess sedative-induced upper airway obstruction.

BACKGROUND: Traditional methods of assessing ventilatory effects of sedative agents do not measure their propensity to cause upper airway obstruction (UAO). The primary objective of this study was to develop a method, using dynamic negative airway pressure (DNAP), for replicating UAO during deep sedation. METHODS: A state of deep sedation (defined as an Observer Assessment of Alertness and Sedation score of 3 and a bispectral index < 80) was attained in 10 healthy volunteers, aged 19-41, using midazolam. Volunteers breathed through a chamber connected to a regulated source of negative pressure that was gradually adjusted downward to produce UAO based on maximal inspiratory flow. The study consisted of three phases: A control phase while awake, a study phase during midazolam deep sedation, and a recovery phase after flumazenil administration. RESULTS: During the control phase no subject demonstrated airway obstruction at negative pressures to -30-cm H2O. All subjects exhibited complete UAO during DNAP episodes while sedated. Negative pressures required to cause complete UAO (Pcrit) ranged from -2 to -14 cm H2O. After administration of flumazenil, all subjects attained full consciousness within 5 min and did not demonstrate UAO at negative pressures to -30-cm H2O. CONCLUSIONS: Dynamic Negative Airway Pressure is a useful method for provoking midazolam-induced UAO, and may potentially be used to compare the potential for different sedatives and patient factors to cause UAO. Flumazenil was completely effective in reversing the potential for midazolam to cause UAO.

Adult↗

PubMed2004

Propensity analysis of long-term survival after surgical or percutaneous revascularization in patients with multivessel coronary artery disease and high-risk features.

BACKGROUND: Although most randomized clinical trials have suggested that long-term survival rates after percutaneous coronary intervention (PCI) or surgical multivessel coronary revascularization (CABG) are equivalent, some post hoc analyses in high-risk groups and adjustment for severity of coronary disease have suggested higher mortality after PCI. METHODS AND RESULTS: We studied 6033 consecutive patients who underwent revascularization in the late 1990s. PCI was performed in 872 patients; 5161 underwent CABG. Half the patients had significant left ventricular dysfunction or diabetes. Propensity analysis to predict the probability of undergoing PCI according to 22 variables and their interactions was used. The C-statistic for this model was 0.90, indicating excellent discrimination between treatments. There were 931 deaths during 5 years of follow-up. The 1- and 5-year unadjusted mortality rates were 5% and 16% for PCI and 4% and 14% for CABG (unadjusted hazard ratio, 1.13; 95% CI, 1.0 to 1.4; P=0.07). PCI was associated with an increased risk of death (propensity-adjusted hazard ratio, 2.3; 95% CI, 1.9 to 2.9; P<0.0001). This difference was observed across all categories of propensity for PCI and in patients with diabetes or left ventricular dysfunction. Other independent predictors of mortality (P< or =0.01 for all) were renal dysfunction, age, diabetes mellitus, chronic lung disease, peripheral vascular disease, left main trunk stenosis, and extent of coronary disease (Duke angiographic score). CONCLUSIONS: In patients with multivessel coronary artery disease and many high-risk characteristics, CABG was associated with better survival than PCI after adjustment for risk profile.

Aged↗

PubMed1989

Distractibility in schizophrenia: state and trait aspects.

This report compared the selective attention of 19 schizophrenic in-patients, 10 recently discharged schizophrenic out-patients, 21 schizophrenic out-patients in stable clinical remission, 33 first-degree relatives of schizophrenics from 15 families, 25 students who scored deviantly on questionnaire measures of magical ideation, perceptual aberrations, and physical anhedonia, and 20 normal controls. Results indicated that distractors only disrupted the performance of schizophrenic in-patients, suggesting that differential deficits in selective attention are a marker of episodes of schizophrenia. A propensity to interject phonemes from the distracting message was found not only in patients in or just emerging from a psychotic episode, but also in the remaining vulnerable but non-psychotic groups, suggesting that intrusion errors might be a mediating vulnerability marker. The findings suggest both state and possibly trait aspects to distractibility in schizophrenia.

Adult↗

PubMed1997

Induction and transmission of chromosome aberrations in mouse oocytes after treatment with butadiene diepoxide.

A study was conducted on the genotoxicity of butadiene diepoxide (DEB) in mouse oocytes. Superovulated female mice were injected intraperitoneally with DEB and mated with untreated males. Oocyte exposure occurred approximately 1.5 days before ovulation. DEB doses ranged between 26 and 52 mg/kg. Chromosome aberrations were scored in C-banded metaphases of one-cell embryos. The percentage of mated females, the average number of zygotes harvested per female, the frequencies of unfertilized oocytes and developmentally delayed zygotes did not reveal any overt sign of chemical toxicity which hindered the propensity of animals to mate or affected the ovulation, fertilization, or cell cycle progression of treated oocytes. A dose-dependent induction of chromosome aberrations was observed which was best fitted by a linear-quadratic equation. Half of all the aberrations transmitted by DEB-treated oocytes were chromatid-type breaks or exchanges. Among chromosome-type aberrations, double fragments for exceeded chromosome exchanges. This spectrum of structural aberrations differed markedly from what was previously observed in one-cell embryos conceived by DEB-treated sperm, where 97% were chromosome-type aberrations and 40% were dicentrics or translocations. This difference suggests that chromosome damage in one-cell embryos can be fixed by different mutagenic pathways influenced by the targeted gamete and its specific chromatin configuration. After exposure to the same dose, oocytes transmitted to one-cell embryos between 4 and 8 times fewer aberrations than DEB-treated sperm. While the rate of aberration induction suggests that female germ cells may be less at risk than mature sperm, especially at low-dose levels, the higher threshold for reproductive toxicity observed in female than in male mice may justify inclusion of data on female germ cell mutagenicity in the genetic risk assessment of butadiene exposure.

Animals↗

PubMed1996

Characteristics of physicians with participatory decision-making styles.

OBJECTIVES: To identify physician and practice characteristics associated with a physician's propensity to involve patients in diagnostic and treatment decisions, or participatory decision-making style. DESIGN: A representative cross-sectional sample of patients participating in the Medical Outcomes Study characterized each physician's style by using a self-reported questionnaire. A single averaged style score was generated for each physician. Style scores were compared among physicians who differed in age, sex, minority status, specialty, primary care training or training in interviewing skills, satisfaction with professional autonomy, and practice volume. SETTINGS: Solo practices, multispecialty groups, and health maintenance organizations in Boston, Chicago, and Los Angeles. PARTICIPANTS: 7730 patients sampled over 9 days from the practices of 300 physicians. Physicians were practicing general internal medicine, family medicine, cardiology, and endocrinology. MEASUREMENTS: Participatory decision-making style was measured using a three-item scale on a questionnaire that was completed by patients after their office visit. Physician and practice characteristics were reported by physicians on self-administered questionnaires. RESULTS: Among patients of physicians who were rated in the lowest (least participatory) quartile, one third changed physicians in the following year; among patients of physicians who were rated in the highest quartile, only 15% changed physicians. Higher scores were associated with greater patient satisfaction. Physicians who had had primary care training or training in interviewing skills scored higher than those without such training. Physicians in higher-volume practices were rated as less participatory than those in lower-volume practices. Physicians who were satisfied with their level of professional autonomy were rates as more participatory than those who were dissatisfied. CONCLUSION: Participatory decision-making style is influenced by physicians' background, training, practice volume, and professional autonomy. Because participatory decision-making style is related to patient satisfaction and loyalty to the physician, cost-containment strategies that reduce time with patients and decrease physician autonomy may result in suboptimal patient outcomes.

Cross-Sectional Studies↗

PubMedDate not supplied

Changing patterns of pediatric pelvic fractures with skeletal maturation: implications for classification and management.

Orthopaedic traumatologists have recognized the unique fracture patterns and injury constellations of pediatric pelvic fractures. However, an understanding of the effect of advancing skeletal maturation is needed to avoid applying adult classifications and management. The authors determined how pelvic fracture patterns and management change with advancing skeletal maturity. At their pediatric trauma center, they identified 166 consecutive pelvic fractures. Eighty percent of patients had plain radiographs adequate to evaluate the triradiate cartilage. Physes were scored as open, narrowed, or closed. The Risser sign, fracture pattern, survival after injury, and need for open reduction and internal fixation were recorded. Ninety-seven patients (mean age 5.7 years) had an open triradiate or an "immature pelvis." Thirty-two patients (mean age 14 years) had a closed triradiate cartilage or a "mature pelvis." The immature group had a higher propensity for isolated pubic rami and iliac wing fractures. The mature group had a higher predilection for acetabular fractures and pubic or sacroiliac diastasis. All patients requiring open reduction and internal fixation had a mature pelvis. The incidences of specific pelvic fracture patterns between the two groups were statistically different. Management of fractures to the immature pelvis should focus on associated injuries. Once the triradiate cartilage has closed, adult pelvic fracture classifications and management principles should be used.

Adolescent↗

PubMed2004

Aripiprazole: a comprehensive review of its pharmacology, clinical efficacy, and tolerability.

BACKGROUND: Recently approved for the treatment of schizophrenia, aripiprazole represents the sixth second-generation antipsychotic (SGA) introduced to the US market. Aripiprazole is considered a partial dopaminergic agonist, acting on both postsynaptic dopamine(2) receptors and presynaptic autoreceptors, in addition to displaying partial agonism at serotonin(1A) receptors and antagonism at serotonin(2A) receptors. OBJECTIVE: The aim of this study was to comprehensively review all available literature regarding the mechanism of action, pharmacokinetics, clinical efficacy, and adverse effects of aripiprazole. METHODS: Relevant data were collected using MEDLINE and International Pharmaceutical Abstracts searches with the terms aripiprazole and OPC-14597 and with no limitations on year. Abstracts and posters presented at national and international scientific meetings were also reviewed. RESULTS: Aripiprazole exhibits linear pharmacokinetics and is administered once daily. In multiple clinical trials, aripiprazole was effective in significantly reducing symptomatology associated with schizophrenia-related disorders compared with placebo (P < 0.05). Dosages > or =15 mg/d more consistently produced significant reductions from baseline of Positive and Negative Syndrome Scale total scores (P < 0.05) and were more likely to elicit a response than smaller dosages. Effects observed were comparable to those seen with risperidone and haloperidol, which were also significantly more effective than placebo (P < or = 0.05). Aripiprazole exhibited a favorable safety and tolerability profile, with a low propensity to cause extrapyramidal symptoms, weight gain, cardiovascular abnormalities, hyperprolactinemia, hypercholesterolemia, or glucose dysregulation. CONCLUSIONS: Aripiprazole represents a well-tolerated and effective addition to the antipsychotic armamentarium. However, definitive advantages associated with dopamine partial agonism have yet to be determined. Long-term, head-to-head comparisons with other SGAs are needed to establish the effects of chronic administration and the relative safety and efficacy of aripiprazole.

Antipsychotic Agents↗

PubMed2003

Plasma interleukin-6 is associated with psychological coronary risk factors: moderation by use of multivitamin supplements.

The current study examined the relation of plasma IL-6 to anger, hostility, and severity of depressive symptoms as a function of multivitamin supplement use in 96 healthy, nonsmoking men (aged 18-46). Plasma IL-6 was independently associated with anger, hostility, and severity of depressive symptoms, as well as with a composite factor score, but only among nonusers. Among users, these associations were not significant. Multivitamin use was associated with lower plasma IL-6 levels, but only among men with high composite factor scores. Statistical adjustments for age, body mass index, resting diastolic blood pressure, fasting total cholesterol, high-density lipoprotein cholesterol, alcohol use, exercise frequency, and educational level did not alter these results. These data suggest that plasma IL-6 is elevated among healthy men characterized by a propensity for anger, a hostile disposition, and greater severity of depressive symptoms and that multivitamin supplements could ameliorate plasma IL-6 levels among these men.

Adolescent↗

PubMed2002

Changes in chewing ability with ageing: a 7-year study of older adults.

One of the most important consequences of oral diseases and disorders is a reduction in the ability to chew. This paper reports the results of a study of changes in chewing ability in a population of community-dwelling older adults who were aged 50 years and over when first recruited. Data were collected at baseline, and at 3 and 7-year follow-ups using an index of chewing capacity consisting of six indicator foods, a four-item measure of the psychosocial impact of chewing dysfunction and a single-item rating of satisfaction with chewing ability. The percentage of subjects who reported a problem chewing increased from 24.0% at baseline to 25.2% at 3 years and 33.8% at 7 years. The increase in prevalence over 7 years was 5.3% in dentate subjects aged 64 years and under at baseline and 26.1% in edentulous subjects aged 65 years and over. Overall, there were increases in the proportion reporting some psychosocial impact and the proportion reporting dissatisfaction with their ability to chew. Patterns of change with respect to these variables differed across groups defined by age and dental status. Change scores computed from baseline and the 7-year follow-up indicated considerable within-subject change, with some individuals improving and some deteriorating. However, they confirmed that overall there was a decline in oral functioning in this population and that older edentulous subjects showed the greatest propensity to change. Factors which predict the patterns of change identified by this study need to be explored in order to enhance our understanding of changes in the chewing ability of this population as it ages.

Aged↗

PubMed2002

Distortion-product otoacoustic emissions in nonacoustic tumors of the cerebellopontine angle.

OBJECTIVES: The goal of the present study was to compare the frequencies of cochlear and non-cochlear patterns of distortion-product otoacoustic emissions (DPOAEs) in patients with nonacoustic (non-AN) tumors of the cerebellopontine angle (CPA)/internal auditory canal with those in patients with acoustic neuroma (AN). STUDY DESIGN AND SETTING: We conducted a prospective study of patients with non-AN internal auditory canal/CPA tumors treated between 1992 and 1999 in a tertiary care setting. We collected data on behavioral pure tone average, speech discrimination score, acoustic immittance tests, DPOAEs, and tumor size. DPOAEs were divided into those with a cochlear or a noncochlear pattern. Comparisons were made with a control group of patients with AN of the CPA. RESULTS: Twenty-four patients were included in the study: 12 patients in the non-AN group and 12 patients in the AN group. In the non-AN group, 5 (42%) patients had a cochlear pattern and 7 (58%) had a noncochlear pattern. In the AN group, 7 (58%) patients had a cochlear pattern and 5 (42%) had a noncochlear pattern. The differences between the non-AN and AN groups were statistically significant. In the non-AN group, patients with a cochlear-pattern DPOAE had significantly smaller tumors (P = 0.03) and a trend (P = 0.07) toward higher speech discrimination score. Age and pure tone average were not significantly different in the non-AN tumor patients. In the AN group, none of the study parameters were significantly related to the pattern of DPOAE. CONCLUSIONS: ANs appear to differ from other tumors of the CPA in their propensity to cause sensory versus neural hearing loss. A larger series of patients would be useful to confirm these preliminary findings.

Adolescent↗

PubMedDate not supplied

Obsessive-compulsive symptom dimensions as predictors of compliance with and response to behaviour therapy: results from a controlled trial.

BACKGROUND: Recent factor-analytic studies in obsessive-compulsive disorder (OCD) identified consistent symptom dimensions. Support for the validity of these dimensions comes from studies of psychiatric comorbidity, functional brain imaging, genetic transmission, and treatment response to medications. This study examined whether previously identified OCD symptom dimensions are associated with treatment compliance and response to behaviour therapy (BT) for OCD. METHODS: One hundred and fifty-three OCD outpatients who participated in a multi-centre randomised controlled trial of computer- versus clinician-guided BT for OCD were included in the study. Logistic and multiple regression models tested for significant predictors of compliance with and response to BT and relaxation. RESULTS: The patients studied were phenomenologically comparable (including the presence of 'pure' obsessions and mental rituals) to those in previous serotonin reuptake inhibitor (SRI) trials and those in clinical epidemiology studies. High scorers on the 'hoarding' dimension were more likely to drop out prematurely from the study and tended to improve less. For those completing treatment, the strongest predictor of outcome was pre-treatment severity. Initial depression scores were unrelated to outcome. After controlling for symptom severity, higher scores on the 'sexual/religious obsessions' factor predicted poorer outcome with BT, especially when computer-guided. CONCLUSIONS: BT is especially indicated for OCD patients with aggressive/checking, contamination/cleaning and symmetry/ordering symptoms. Previous accounts of unsuccessful BT in patients with hoarding symptoms may be due in part to their propensity to drop out earlier from treatment. Patients with sexual/religious obsessions, but not those with mental rituals, might respond less well to traditional BT techniques. Existing treatments need to be refined and/or new treatments developed to improve these patients' adherence and response to treatment.

Adult↗

PubMed2006

Blinded validation of the isolated arterially perfused rabbit ventricular wedge in preclinical assessment of drug-induced proarrhythmias.

BACKGROUND: The development of preclinical models with high predictive value for the identification of drugs with a proclivity to induce Torsade de Pointes (TdP) in the clinic has long been a pressing goal of academia, industry and regulatory agencies alike. The present study provides a blinded appraisal of drugs, in an isolated arterially-perfused rabbit ventricular wedge preparation, with and without the potential to produce TdP. METHODS AND RESULTS: Thirteen compounds were tested for their potential for TdP using the rabbit left ventricular wedges. All investigators were blinded to the names, concentrations and molecular weights of the drugs. The compounds were prepared by the study sponsor and sent to the investigator as 4 sets of 13 stock solutions with the order within each set being assigned by a random number generator. Each compound was scored semi-quantitatively for its relative potential for TdP based on its effect on ventricular repolarization measured as QT interval, dispersion of repolarization measured as T(p-e)/QT ratio and early afterdepolarizations. Disclosure of the names and concentrations after completion of the study revealed that all compounds known to be free of TdP risk received a score of less or equal to 0.25, whereas those with known TdP risk received a score ranging from 1.00 to 7.25 at concentrations less than 100X their free therapeutic plasma C(max). CONCLUSIONS: Our study provides a blinded evaluation of the isolated arterially-perfused rabbit wedge preparation demonstrating both a high sensitivity and specificity in the assessment of 13 agents with varying propensity for causing TdP.

Action Potentials↗

PubMed2006

Corticosteroids influence the mortality and morbidity of acute critical illness.

INTRODUCTION: Use of corticosteroids for adrenal supplementation and attenuation of the inflammatory and immune response is widespread in acute critical illness. The study hypothesis was that exposure to corticosteroids influences the mortality and morbidity in acute critical illness. METHODS: This case-control retrospective study was performed in a single multidisciplinary intensive care unit at a tertiary care institution and consisted of 10,285 critically ill patients admitted between 1 January 1999 and 31 December 2004. Demographics, comorbidities, acute illness characteristics including severity measured by Sequential Organ Failure Assessment, concurrent medications, therapeutic interventions and incidence of infections were obtained from electronic medical records, were examined with multiple regression analysis and were adjusted for propensity of corticosteroid exposure. The primary outcome was hospital death, and the secondary outcome was transfer to a care facility at hospital discharge. RESULTS: Corticosteroid exposure in 2,632 (26%) patients was characterized by younger age, more females, higher Charlson comorbidity and maximal daily Sequential Organ Failure Assessment scores compared with control patients. Corticosteroids potentiated metabolic and neuromuscular sequels of critical illness with increased requirements for diuretics, insulin, protracted weaning from mechanical ventilation, need for tracheostomy and discharge to a care facility. Early exposure to corticosteroids predisposed to recurrent and late onset of polymicrobial and fungal hospital-acquired infections. Corticosteroids increased the risk for death or disability after adjustments for comorbidities and acute illness characteristics. CONCLUSION: Corticosteroids increased the risk for death or disability in critical illness. Hospital-acquired infections and metabolic and neuromuscular sequels of critical illness were exacerbated by corticosteroids. Careful appraisal of the indications for use of corticosteroids is necessary to balance the benefits and risks from exposure in acute critical illness.

Acute Disease↗