Warren B. Bilker

Extended-Spectrum β-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae: Risk Factors for Infection and Impact of Resistance on Outcomes

The prevalence of antibiotic resistance among extended-spectrum beta-lactamase (ESBL)--producing Escherichia coli and Klebsiella pneumoniae has increased markedly in recent years. Thirty-three patients with infection due to ESBL-producing E. coli or K. pneumoniae (case patients) were compared with 66 matched controls. Total prior antibiotic use was the only independent risk factor for ESBL-producing E. coli or K. pneumoniae infection (odds ratio, 1.10; 95% confidence interval, 1.03--1.18; P=.006). Case patients were treated with an effective antibiotic a median of 72 hours after infection was suspected, compared with a median of 11.5 hours after infection was suspected for controls (P<.001). ESBL-producing E. coli or K. pneumoniae infection was associated with a significantly longer duration of hospital stay and greater hospital charges (P=.01 and P<.001, respectively). Finally, many ESBL-producing E. coli and K. pneumoniae isolates were closely related. ESBL-producing E. coli and K. pneumoniae infections have a significant impact on several important clinical outcomes, and efforts to control outbreaks of infection with ESBL-producing E. coli and K. pneumoniae should emphasize judicious use of all antibiotics as well as barrier precautions to reduce spread.

Risk of Bladder Cancer Among Diabetic Patients Treated With Pioglitazone: Interim report of a longitudinal cohort study

OBJECTIVE Some preclinical in vivo studies and limited human data suggest a possible increased risk of bladder cancer with pioglitazone therapy. This is an interim report of an ongoing cohort study examining the association between pioglitazone therapy and the risk of bladder cancer in patients with diabetes. RESEARCH DESIGN AND METHODS This study includes 193,099 patients in the Kaiser Permanente Northern California diabetes registry who were ≥40 years of age between 1997 and 2002. Those with prior bladder cancer were excluded. Ever use of each diabetes medication (defined as two or more prescriptions within 6 months) was treated as a time-dependent variable. Cox regression–generated hazard ratios (HRs) compared pioglitazone use with nonpioglitazone use adjusted for age, sex, race/ethnicity, diabetes medications, A1C, heart failure, household income, renal function, other bladder conditions, and smoking. RESULTS The group treated with pioglitazone comprised 30,173 patients. There were 90 cases of bladder cancer among pioglitazone users and 791 cases of bladder cancer among nonpioglitazone users. Overall, ever use of pioglitazone was not associated with risk of bladder cancer (HR 1.2 [95% CI 0.9–1.5]), with similar results in men and women (test for interaction P = 0.8). However, in the a priori category of >24 months of therapy, there was an increased risk (1.4 [1.03–2.0]). Ninety-five percent of cancers diagnosed among pioglitazone users were detected at early stage. CONCLUSIONS In this cohort of patients with diabetes, short-term use of pioglitazone was not associated with an increased incidence of bladder cancer, but use for more than 2 years was weakly associated with increased risk.

Emotion recognition deficit in schizophrenia: association with symptomatology and cognition.

BACKGROUND Previous investigations have found impaired recognition of facial affect in schizophrenia. Controversy exists as to whether this impairment represents a specific emotion recognition deficit when compared with other face recognition control tasks. Regardless of whether the emotion processing deficit is differential, it may uniquely influence other manifestations of schizophrenia. We compared patients and healthy control subjects on computerized tasks of emotion and age recognition. Performances on emotion and age recognition tasks were correlated with cognitive functioning and with symptomatology. METHODS Thirty-five patients with schizophrenia and 45 healthy people underwent computerized testing for emotion and age recognition. Participants were assessed neuropsychologically, and patients were rated for positive and negative symptoms. RESULTS The patients with schizophrenia performed worse than control subjects on emotion and age recognition without differential deficit. In both groups, we found higher error rates for identification of emotion in female faces and for identification of sad versus happy faces. In schizophrenic patients, emotion but not age recognition correlated with severity of negative and positive symptoms. In healthy control subjects, neither task correlated with cognitive functions. In schizophrenic patients, emotion but not age recognition correlated with attention, verbal and spatial memory, and language abilities. CONCLUSIONS This study did not reveal a specific deficit for emotion recognition in schizophrenia; however, our findings lend support to the concept that emotion recognition is uniquely associated in schizophrenia with core symptomatology and cognitive domains.

Treatment of osteoporosis: are physicians missing an opportunity?

Background: Medical treatment of women with established osteoporosis may decrease the incidence of future fractures. Postmenopausal women who have sustained a distal radial fracture have decreased bone-mineral density and nearly twice the risk of a future hip fracture. The purpose of this study was to evaluate the adequacy of diagnosis and treatment of osteoporosis in postmenopausal women following an acute fracture of the distal part of the radius. Methods: A retrospective cohort study was performed with use of a claims database that includes more than three million patients, from thirty states, enrolled in multiple health plans. All women, fifty-five years of age or older, who sustained a distal radial fracture between July 1, 1994, and June 30, 1997, were identified in the database. Only patients with at least six months of continuous and complete medical and pharmaceutical health-care coverage from the date of the fracture were enrolled, to ensure that all health-care claims would be captured in the database. This cohort of patients was then evaluated to determine the proportion who had undergone either a diagnostic bone-density scan or treatment with any recommended medication for established osteoporosis (estrogen, a bisphosphonate, or calcitonin) within six months following the fracture. Results: A search of the database identified 1162 women, fifty-five years of age or older, who had a distal radial fracture. Of these 1162 patients, thirty-three (2.8 percent) underwent a bone-density scan and 266 (22.9 percent) were treated with at least one of the medications approved for treatment of established osteoporosis. Twenty women had both a bone-density scan and drug treatment. Therefore, only 279 (24.0 percent) of the 1162 women who sustained a distal radial fracture underwent either diagnostic evaluation or treatment of osteoporosis. There was a significant decrease in the rate of treatment of osteoporosis with increasing patient age at the time of the fracture (p < 0.0001). Conclusions: Current physician practice may be inadequate for the diagnosis and treatment of osteoporosis in postmenopausal women who have sustained a distal radial fracture.

Telling truth from lie in individual subjects with fast event‐related fMRI

Deception is a clinically important behavior with poorly understood neurobiological correlates. Published functional MRI (fMRI) data on the brain activity during deception indicates that, on a multisubject group level, lie is distinguished from truth by increased prefrontal and parietal activity. These findings are theoretically important; however, their applied value will be determined by the accuracy of the discrimination between single deceptive and truthful responses in individual subjects. This study presents the first quantitative estimate of the accuracy of fMRI in conjunction with a formal forced‐choice paradigm in detecting deception in individual subjects. We used a paradigm balancing the salience of the target cues to elicit deceptive and truthful responses and determined the accuracy of this model in the classification of single lie and truth events. The relative salience of the task cues affected the net activation associated with lie in the superior medial and inferolateral prefrontal cortices. Lie was discriminated from truth on a single‐event level with an accuracy of 78%, while the predictive ability expressed as the area under the curve (AUC) of the receiver operator characteristic curve (ROC) was 85%. Our findings confirm that fMRI, in conjunction with a carefully controlled query procedure, could be used to detect deception in individual subjects. Salience of the task cues is a potential confounding factor in the fMRI pattern attributed to deception in forced choice deception paradigms. Hum Brain Mapp, 2005.

Computerized neurocognitive scanning: I. Methodology and validation in healthy people

Neuropsychological testing batteries are applied in neurobehavioral evaluations of brain disorders, including neuropsychiatric populations. They are lengthy, require expert administrators and professional scorers, and are prone to data handling errors. We describe a brief computerized neurocognitive “scan” that assesses similar domains with adequate reliability. The scan and a traditional battery were administered to a sample of 92 healthy individuals (44 men, 48 women) in a counterbalanced order. Both approaches showed a significant “sex-typical” gradient, with women outperforming men in verbal memory relative to spatial tasks. Both methods also yielded similar profiles of sex differences, with the additional computerized measure of face memory showing better performance in women. Age effects were evident for both methods, but the computerized scan isolated the effects to speed rather than accuracy. Therefore, the computerized scan has favorable reliability and construct validity and can be applied efficiently to study healthy variability related to age and gender.

Identification of medications that cause cognitive impairment in older people: the case of oxybutynin chloride.

OBJECTIVES: To evaluate the cognitive effects of acute challenges with the antispasmodic agent oxybutynin hydrochloride in normal older volunteers and to compare these effects with those attributable to diphenhydramine, another commonly used medication with anticholinergic (muscarinicblocking) activity.

Cardiac arrest and ventricular arrhythmia in patients taking antipsychotic drugs: cohort study using administrative data

Abstract Objective: To examine the rates of cardiac arrest and ventricular arrhythmia in patients with treated schizophrenia and in non-schizophrenic controls. Design: Cohort study of outpatients using administrative data. Setting: 3 US Medicaid programmes. Participants: Patients with schizophrenia treated with clozapine, haloperidol, risperidone, or thioridazine; a control group of patients with glaucoma; and a control group of patients with psoriasis. Main outcome measure: Diagnosis of cardiac arrest or ventricular arrhythmia. Results: Patients with treated schizophrenia had higher rates of cardiac arrest and ventricular arrhythmia than controls, with rate ratios ranging from 1.7 to 3.2. Overall, thioridazine was not associated with an increased risk compared with haloperidol (rate ratio 0.9, 95% confidence interval 0.7 to 1.2). However, thioridazine showed an increased risk of events at doses 600 mg (2.6, 1.0 to 6.6; P=0.049) and a linear dose-response relation (P=0.038). Conclusions: The increased risk of cardiac arrest and ventricular arrhythmia in patients with treated schizophrenia could be due to the disease or its treatment. Overall, the risk with thioridazine was no worse than that with haloperidol. Thioridazine may, however, have a higher risk at high doses, although this finding could be due to chance. To reduce cardiac risk, thioridazine should be prescribed at the lowest dose needed to obtain an optimal therapeutic effect. What is already known on this topic Thioridazine seems to prolong the electrocardiographic QT interval more than haloperidol Although QT prolongation is used as a marker of arrhythmogenicity, it is unknown whether thioridazine is any worse than haloperidol with regard to cardiac safety What this study adds Patients taking antipsychotic drugs had higher risks of cardiac events than control patients with glaucoma or psoriasis Overall, the risk of cardiac arrest and ventricular arrhythmia was not higher with thioridazine than haloperidol Thioridazine may carry a greater risk than haloperidol at high doses Patients should be treated with the lowest dose of thioridazine needed to treat their symptoms

Epidemiological Investigation of Fluoroquinolone Resistance in Infections Due to Extended-Spectrum β-Lactamase—Producing Escherichia coli and Klebsiella pneumoniae

The incidence of infections due to extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EK) has increased markedly in recent years. Treatment is difficult because of frequent multidrug resistance. Although fluoroquinolones offer effective therapy for ESBL-EK infections, their usefulness is threatened by increasing fluoroquinolone resistance. To identify risk factors for fluoroquinolone resistance in ESBL-EK infections, a case-control study of all patients with ESBL-EK infections from 1 June 1997 through 30 September 1998 was conducted. Of 77 ESBL-EK infections, 43 (55.8%) were resistant to fluoroquinolones. Independent risk factors for fluoroquinolone resistance were fluoroquinolone use (odds ratio [OR], 11.20; 95% confidence interval [CI], 1.99-63.19), aminoglycoside use (OR, 5.83; 95% CI, 1.12-30.43), and long-term care facility residence (OR, 3.39; 95% CI, 1.06-10.83). The genotypes of fluoroquinolone-resistant ESBL-EK isolates were closely related. Efforts should be directed at modification of these risk factors to preserve the utility of fluoroquinolones in the treatment of ESBL-EK infections.

Effect of adherence to newly initiated antiretroviral therapy on plasma viral load

ObjectiveTo determine whether differences in adherence to newly initiated antiretroviral therapy exist between subjects who do and do not achieve undetectable plasma viral loads. DesignObservational cohort study monitoring adherence and virological and immunological parameters over the initial 4 months of therapy with nelfinavir. Adherence was measured using the microelectronic monitoring system (MEMS; APREX Corporation, Menlo Park, California, USA). SettingGeneral Clinical Research Center at a tertiary care center. ParticipantsForty-one protease inhibitor-naive subjects with viral loads > 10 000 copies/ml newly starting a regimen including nelfinavir, referred from HIV clinics in Philadelphia. Main outcome measuresThe primary outcome was undetectable viral load (< 50 copies/ml) after 4 months. Secondary measures included changes in viral load and CD4 cell counts. We hypothesized that adherence would be greater in subjects who achieved undetectable viral loads. ResultsAdherence was greater in undetectable subjects, who took a median of 93% of prescribed doses [interquartile range (IQR) 84–96%], whereas detectable subjects took a median of 70% (IQR 46–93%). Adherence correlated with viral load decrease (Spearmans ρ = 0.38, P < 0.01) and CD4 cell count increase (Spearmans ρ = 0.25, P = 0.06). Despite differences between the groups over 4 months of therapy, there were no adherence differences over the first month [undetectables, 95% (IQR 88–98%) versus detectables, 94% (IQR 87–98%), P > 0.50]. ConclusionsAdherence is important in determining whether or not individuals achieve suppression with a newly initiated antiretroviral regimen. Adherence begins to wane after the first month of therapy. Therefore, closer assessment of adherence particularly after this first month is important.