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Berlin Brandenburg

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  • 1
    In: Medical Care, 2005, Vol.43(10), pp.979-984
    Description: OBJECTIVE:: The objective of this study was to compare the ability of risk stratification models derived from administrative data to classify groups of patients for enrollment in a tailored chronic disease management program. SUBJECTS:: This study included 19,548 Medicaid patients with chronic heart failure or diabetes in the Indiana Medicaid data warehouse during 2001 and 2002. MEASURES:: To predict costs (total claims paid) in FY 2002, we considered candidate predictor variables available in FY 2001, including patient characteristics, the number and type of prescription medications, laboratory tests, pharmacy charges, and utilization of primary, specialty, inpatient, emergency department, nursing home, and home health care. METHODS:: We built prospective models to identify patients with different levels of expenditure. Model fit was assessed using R statistics, whereas discrimination was assessed using the weighted kappa statistic, predictive ratios, and the area under the receiver operating characteristic curve. RESULTS:: We found a simple least-squares regression model in which logged total charges in FY 2002 were regressed on the log of total charges in FY 2001, the number of prescriptions filled in FY 2001, and the FY 2001 eligibility category, performed as well as more complex models. This simple 3-parameter model had an R of 0.30 and, in terms in classification efficiency, had a sensitivity of 0.57, a specificity of 0.90, an area under the receiver operator curve of 0.80, and a weighted kappa statistic of 0.51. CONCLUSION:: This simple model based on readily available administrative data stratified Medicaid members according to predicted future utilization as well as more complicated models.
    Keywords: Medicine ; Public Health;
    ISSN: 0025-7079
    E-ISSN: 15371948
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  • 2
    In: Journal of Child Psychology and Psychiatry, July 2012, Vol.53(7), pp.726-734
    Description: Preliminary evidence suggests that prenatal testosterone exposure may be associated with language delay. However, no study has examined a large sample of children at multiple time‐points. Umbilical cord blood samples were obtained at 861 births and analysed for bioavailable testosterone (BioT) concentrations. When participating offspring were 1, 2 and 3 years of age, parents of 767 children (males = 395; females = 372) completed the Infant Monitoring Questionnaire (IMQ), which measures Communication, Gross Motor, Fine Motor, Adaptive and Personal–Social development. Cut‐off scores are available for each scale at each age to identify children with ‘clinically significant’ developmental delays. Chi‐square analyses and generalized estimating equations examined longitudinal associations between sex‐specific quartiles of BioT concentrations and the rate of developmental delay. Significantly more males than females had language delay (Communication scale) at age 1, 2 and 3 years (‐values ≤. 01). Males were also more likely to be classified as delayed on the Fine‐Motor ( = .04) and Personal–Social (〈 .01) scales at age 3 years. Chi‐square analyses found a significant difference between BioT quartiles in the rate of language delay (but not Fine‐Motor and Personal–Social delay) for males (age 3) and females (age 1 and 3). Generalized estimating equations, incorporating a range of sociodemographic and obstetric variables, found that males in the highest BioT quartile were at increased risk for a clinically significant language delay during the first 3 years of life, with an odds ratio (OR) of 2.47 (95% CI: 1.12, 5.47). By contrast, increasing levels of BioT reduced the risk of language delay among females (Quartile 2: OR = 0.23, 95% CI: 0.09, 0.59; Quartile 4: 0.46, 95% CI: 0.21, 0.99). These data suggest that high prenatal testosterone levels are a risk factor for language delay in males, but may be a protective factor for females.
    Keywords: Testosterone ; Language Delay ; Sex‐Difference ; Developmental Language Disorder ; Raine Study
    ISSN: 0021-9630
    E-ISSN: 1469-7610
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  • 3
    Language: English
    In: PLoS ONE, 2010, Vol.5(1), p.e8792
    Description: Obesity is a worldwide epidemic, and severe obesity is a risk factor for many diseases, including diabetes, heart disease, stroke, and some cancers. Endocannabinoid system (ECS) signaling in the brain and peripheral tissues is activated in obesity and plays a role in the regulation of body weight. The main research question here was whether quantitative measurement of plasma endocannabinoids, anandamide, and related N-acylethanolamines (NAEs), combined with genotyping for mutations in fatty acid amide hydrolase ( FAAH ) would identify circulating biomarkers of ECS activation in severe obesity. ; Plasma samples were obtained from 96 severely obese subjects with body mass index (BMI) of ≥40 kg/m, and 48 normal weight subjects with BMI of ≤26 kg/m. Triple-quadrupole mass spectroscopy methods were used to measure plasma ECS analogs. Subjects were genotyped for human gene mutations. The principal analysis focused on the 385 C→A (P129T) mutation by comparing plasma ECS metabolite levels in the 385 minor A allele carriers versus wild-type C carriers in both groups. The main finding was significantly elevated mean plasma levels of anandamide (15.1±1.4 pmol/ml) and related NAEs in study subjects that carried the 385 A mutant alleles versus normal subjects (13.3±1.0 pmol/ml) with wild-type genotype (p = 0.04), and significance was maintained after controlling for BMI. ; Significantly increased levels of the endocannabinoid anandamide and related NAEs were found in carriers of the 385 A mutant alleles compared with wild-type controls. This evidence supports endocannabinoid system activation due to the effect of 385 mutant A genotype on plasma AEA and related NAE analogs. This is the first study to document that 385 A mutant alleles have a direct effect on elevated plasma levels of anandamide and related NAEs in humans. These biomarkers may indicate risk for severe obesity and may suggest novel ECS obesity treatment strategies.
    Keywords: Research Article ; Chemical Biology ; Public Health And Epidemiology ; Genetics And Genomics -- Complex Traits
    E-ISSN: 1932-6203
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  • 4
    In: PLoS ONE, 2018, Vol.13(6)
    Description: It is suggested that testosterone may play a part in the higher prevalence of Autism Spectrum Disorder (ASD) in males compared to females. Previous studies have reported elevated postnatal testosterone levels in children and women with ASD but not in men. We compared levels of salivary testosterone across 67 undergraduate males ( M age 19.5 yrs, SD 1.92) selected for low, mid-range and high levels of autistic traits assessed using the Autism-spectrum Quotient. Analyses revealed no significant differences in testosterone concentrations across the three groups. The current data add to the increasing evidence for the lack of relationship between autistic traits and postnatal levels of testosterone in men.
    Keywords: Research Article ; Biology And Life Sciences ; Biology And Life Sciences ; Biology And Life Sciences ; Social Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Social Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Biology And Life Sciences ; Medicine And Health Sciences ; Physical Sciences ; Physical Sciences ; People And Places ; Social Sciences ; People And Places ; People And Places
    E-ISSN: 1932-6203
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  • 5
    In: Diseases of the Esophagus, April 2012, Vol.25(3), pp.222-227
    Description: Leventhal's common sense model has provided a useful framework for explaining psychological distress in several chronic illnesses. The model indicates that a person's perception of their illness and their coping strategies are the key determinants of their experience of psychological distress. The present research examines whether illness perceptions and coping strategies are related to levels of psychological distress among survivors of esophageal cancer. Everyone registered with the Oesophageal Patients' Association in the UK was mailed a questionnaire booklet, which included the Illness Perception Questionnaire‐Revised, the Cancer Coping Questionnaire, and the Hospital Anxiety and Depression Scale. Complete responses were received from 484 people. Regression models indicated that the variables measured could explain 51% of the variance in anxiety and 42% of the variance in depression. Perceptions of esophageal cancer explained the majority of this variance. Positive focus coping strategies were also found to be important in explaining psychological distress. The results of this study are consistent with previous research demonstrating that illness perceptions are stronger correlates of adaptive outcomes than coping strategies. The findings suggest that cognition‐based interventions could potentially be most effective in minimizing emotional distress among survivors of esophageal cancer.
    Keywords: Anxiety ; Depression ; Esophageal Cancer ; Psychological Adaptation
    ISSN: 1120-8694
    E-ISSN: 1442-2050
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  • 6
    In: The New England Journal of Medicine, 2011, Vol.365(20), pp.1896-1904
    Description: Background Adverse-event reports from North America have raised concern that the use of drugs for attention deficit–hyperactivity disorder (ADHD) increases the risk of serious cardiovascular events. Methods We conducted a retrospective cohort study with automated data from four health plans (Tennessee Medicaid, Washington State Medicaid, Kaiser Permanente California, and OptumInsight Epidemiology), with 1,200,438 children and young adults between the ages of 2 and 24 years and 2,579,104 person-years of follow-up, including 373,667 person-years of current use of ADHD drugs. We identified serious cardiovascular events (sudden cardiac death, acute myocardial infarction, and stroke) from health-plan data and vital records, with end points validated by medical-record review. We estimated the relative risk of end points among current users, as compared with nonusers, with hazard ratios from Cox regression models. Results Cohort members had 81 serious cardiovascular events (3.1 per 100,000 person-years). Current users of ADHD drugs were not at increased risk for serious cardiovascular events (adjusted hazard ratio, 0.75; 95% confidence interval [CI], 0.31 to 1.85). Risk was not increased for any of the individual end points, or for current users as compared with former users (adjusted hazard ratio, 0.70; 95% CI, 0.29 to 1.72). Alternative analyses addressing several study assumptions also showed no significant association between the use of an ADHD drug and the risk of a study end point. Conclusions This large study showed no evidence that current use of an ADHD drug was associated with an increased risk of serious cardiovascular events, although the upper limit of the 95% confidence interval indicated that a doubling of the risk could not be ruled out. However, the absolute magnitude of such an increased risk would be low. (Funded by the Agency for Healthcare Research and Quality and the Food and Drug Administration.) This large study found no increased risk of cardiovascular events in children and young adults using attention deficit–hyperactivity disorder (ADHD) drugs. Although the data are compatible with nearly a doubling of risk, the study was underpowered and the absolute event rate was quite low. Medications that are used to treat attention deficit–hyperactivity disorder (ADHD) are prescribed for more than 2.7 million children in the United States each year1 and have been considered to be relatively safe.2–5 However, reports of adverse events from Canada and the United States that have included cases of sudden death, myocardial infarction, and stroke in conjunction with the use of these drugs have raised concern about their safety.6,7 Although case reports from adverse-event reporting systems can be an important source for identifying medication safety signals, they cannot reliably quantify risk. Thus, there is a compelling need to obtain . . .
    Keywords: Medicine;
    ISSN: 0028-4793
    E-ISSN: 1533-4406
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  • 7
    Language: English
    In: Journal of Psychosomatic Research, 2011, Vol.70(5), pp.432-439
    Description: To examine the extent to which the illness perceptions of Oesophageal cancer survivors and the illness perceptions of their carers explain the survivors' levels of psychological distress (in terms of anxiety and depression symptoms) relative to demographic and biomedical variables and patients' coping strategies. Everyone registered with the Oesophageal Patients' Association in the UK was mailed a questionnaire booklet containing questions about medical and demographic variables, the Illness Perception Questionnaire-Revised, the Cancer Coping Questionnaire, and the Hospital Anxiety and Depression Scale. Patients were asked to pass a modified version of the Illness Perception Questionnaire-Revised to someone they identified as a carer. Complete responses were received from 317 dyads. Regression models indicated that the variables measured could explain 56% of the variance in anxiety and 54% of the variance in depression. Patients' illness perceptions explained the majority of this variance. Positive focus coping strategies were also found to be important in explaining psychological well-being. Some of the carers' illness perceptions made a significant contribution to the explanation of the patients' levels of psychological distress, and in some instances, carer perceptions were found to moderate the relationship between patients' perceptions and psychological distress. The findings suggest that cognition-based interventions could potentially be most effective in minimizing emotional distress among survivors of Oesophageal cancer. This study also shows that these interventions could usefully be delivered at the level of the patient–carer dyad.
    Keywords: Cancer ; Esophagus ; Carers ; Depression ; Anxiety
    ISSN: 0022-3999
    E-ISSN: 1879-1360
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  • 8
    In: The New England Journal of Medicine, 2004, Vol.351(11), pp.1089-1096
    Description: Background Oral erythromycin prolongs cardiac repolarization and is associated with case reports of torsades de pointes. Because erythromycin is extensively metabolized by cytochrome P-450 3A (CYP3A) isozymes, commonly used medications that inhibit the effects of CYP3A may increase plasma erythromycin concentrations, thereby increasing the risk of ventricular arrhythmias and sudden death. We studied the association between the use of erythromycin and the risk of sudden death from cardiac causes and whether this risk was increased with the concurrent use of strong inhibitors of CYP3A. Methods We studied a previously identified Tennessee Medicaid cohort that included 1,249,943 person-years of follow-up and 1476 cases of confirmed sudden death from cardiac causes. The CYP3A inhibitors used in the study were nitroimidazole antifungal agents, diltiazem, verapamil, and troleandomycin; each doubles, at least, the area under the time–concentration curve for a CYP3A substrate. Amoxicillin, an antimicrobial agent with similar indications but which does not prolong cardiac repolarization, and former use of erythromycin also were studied, to assess possible confounding by indication. Results The multivariate adjusted rate of sudden death from cardiac causes among patients currently using erythromycin was twice as high (incidence-rate ratio, 2.01; 95 percent confidence interval, 1.08 to 3.75; P=0.03) as that among those who had not used any of the study antibiotic medications. There was no significant increase in the risk of sudden death among former users of erythromycin (incidence-rate ratio, 0.89; 95 percent confidence interval, 0.72 to 1.09; P=0.26) or among those who were currently using amoxicillin (incidence-rate ratio, 1.18; 95 percent confidence interval, 0.59 to 2.36; P=0.65). The adjusted rate of sudden death from cardiac causes was five times as high (incidence-rate ratio, 5.35; 95 percent confidence interval, 1.72 to 16.64; P=0.004) among those who concurrently used CYP3A inhibitors and erythromycin as that among those who had used neither CYP3A inhibitors nor any of the study antibiotic medications. In contrast, there was no increase in the risk of sudden death among those who concurrently used amoxicillin and CYP3A inhibitors or those currently using any of the study antibiotic medications who had formerly used CYP3A inhibitors. Conclusions The concurrent use of erythromycin and strong inhibitors of CYP3A should be avoided. Erythromycin is known to prolong cardiac repolarization and has been associated with case reports of torsades de pointes. In this study, the use of oral erythromycin was found to increase the risk of sudden death from cardiac causes by a factor of two. The concurrent use of erythromycin and cytochrome P-450 inhibitors, such as verapamil or diltiazem, increased the risk by a factor of five. Thus, erythromycin should not be prescribed for patients receiving these drugs. The concurrent use of erythromycin and cytochrome P450 inhibitors increased the risk by a factor of five. Erythromycin is a commonly used macrolide antimicrobial agent with a long history of use, and it is considered largely free of serious toxicity. However, there have been case reports of torsades de pointes in patients receiving both oral and intravenous erythromycin.1–4 An increase in the risk of torsades de pointes is consistent with the effects of erythromycin on cardiac electrophysiology; studies have shown prolongation of the QT interval5,6 and blockade of the potassium channel encoded by the human ether-a-go-go–related gene (HERG).7 There are important clinical questions that these case reports have not addressed. Although there is . . .
    Keywords: Medicine;
    ISSN: 0028-4793
    E-ISSN: 1533-4406
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  • 9
    Language: English
    In: Proceedings of the National Academy of Sciences of the United States, March 19, 2013, Vol.110(12), p.4667(6)
    Description: Mechanotransduction, the pathway by which mechanical forces are translated to biological signals, plays important but poorly characterized roles in physiology. PIEZOs are recently identified, widely expressed, mechanically activated ion channels that are hypothesized to play a role in mechanotransduction in mammals. Here, we describe two distinct PIEZO2 mutations in patients with a subtype of Distal Arthrogryposis Type 5 characterized by generalized autosomal dominant contractures with limited eye movements, restrictive lung disease, and variable absence of cruciate knee ligaments. Electrophysiological studies reveal that the two PIEZO2 mutations affect biophysical properties related to channel inactivation: both E2727del and I802F mutations cause the PIEZO2-dependent, mechanically activated currents to recover faster from inactivation, while E2727del also causes a slowing of inactivation. Both types of changes in kinetics result in increased channel activity in response to a given mechanical stimulus, suggesting that Distal Arthrogryposis Type 5 can be caused by gain-of-function mutations in PIEZO2. We further show that overexpression of mutated PIEZO2 cDNAs does not cause constitutive activity or toxicity to cells, indicating that the observed phenotype is likely due to a mechanotransduction defect. Our studies identify a type of channelopathy and link the dysfunction of mechanically activated ion channels to developmental malformations and joint contractures. congenital contractures | neuromuscular system | whole exome sequencing | whole genome sequencing doi/10.1073/pnas.1221400110
    Keywords: Genomics -- Genetic Aspects ; Genomics -- Research
    ISSN: 0027-8424
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  • 10
    In: Journal of the American Geriatrics Society, July 2000, Vol.48(7), pp.760-768
    Description: OBJECTIVES: The amount of medication dispensed to older adults for the treatment of chronic disease must be balanced carefully. Insufficient medication supplies lead to inadequate treatment of chronic disease, whereas excessive supplies represent wasted resources and the potential for toxicity. We used an electronic medical record system to determine the distribution of medications supplied to older urban adults and to examine the correlations of these distributions with healthcare costs and use. DESIGN: A cross‐sectional study using data acquired over 3 years (1994–1996). SETTING: A tax‐supported urban public healthcare system consisting of a 300‐bed hospital, an emergency department, and a network of community‐based ambulatory care centers. PATIENTS: Patients were 〉60 years of age and had at least one prescription refill and at least two ambulatory visits or one hospitalization during the 3‐year period. MEASUREMENTS: Focusing on 12 major categories of drugs used to treat chronic diseases, we determined the amounts and direct costs of these medications dispensed to older adult patients. Amounts of medications that were needed by patients to medicate themselves adequately were compared with the medication supply actually dispensed considering all sources of care (primary, emergency, and inpatient). We calculated the excess drug costs attributable to oversupply of medication (〉120% of the amount needed) and the drug cost reduction caused by undersupply of medication (〈80% of the amount needed). We also compared total healthcare use and costs for patients who had an over‐supply, an undersupply, or an appropriate supply of their medications. RESULTS: The cohort comprised 4164 patients with a mean age of 71 ± 7 (SD) who received a mean of 3 ± 2 (SD) drugs for chronic conditions. There were 668 patients (16%) who received 120% of the supply needed. The total direct cost of targeted medications for 3 years was $1.96 million or, on average, $654,000 annually. During the 3‐year period, patients receiving 〉120% of their needed medications had excess direct medication costs of $279,084 or $144 per patient, whereas patients receiving 〈80% of drugs needed had reduced medication costs of $423,438 or $634 per patient. Multivariable analyses revealed that both under‐ and over‐supplies of medication were associated with a greater likelihood of emergency department visits and hospital admissions. CONCLUSIONS: More than one‐half of the older adults in our study have under‐ or over‐supplies of medications for the treatment of their chronic diseases. Such inappropriate supplies of medications are associated with healthcare utilization and costs. .
    Keywords: Chronic Disease ; Drug Cost ; Drug Supplies ; Medication Possession Ratio
    ISSN: 0002-8614
    E-ISSN: 1532-5415
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