Dendritic stratification differs among retinal OFF bipolar cell types in the absence of rod photoreceptors.

Retinal OFF bipolar cells show distinct connectivity patterns with photoreceptors in the wild-type mouse retina. Some types are cone-specific while others penetrate further through the outer plexiform layer (OPL) to contact rods in addition to cones. To explore dendritic stratification of OFF bipolar cells in the absence of rods, we made use of the 'cone-full' Nrl-/- mouse retina in which all photoreceptor precursor cells commit to a cone fate including those which would have become rods in wild-type retinas. The dendritic distribution of OFF bipolar cell types was investigated by confocal and electron microscopic imaging of immunolabeled tissue sections. The cells' dendrites formed basal contacts with cone terminals and expressed the corresponding glutamate receptor subunits at those sites, indicating putative synapses. All of the four analyzed cell populations showed distinctive patterns of vertical dendritic invasion through the OPL. This disparate behavior of dendritic extension in an environment containing only cone terminals demonstrates type-dependent specificity for dendritic outgrowth in OFF bipolar cells: rod terminals are not required for inducing dendritic extension into distal areas of the OPL.

Thyroid Hormone Signaling in the Mouse Retina.

Thyroid hormone is a crucial regulator of gene expression in the developing and adult retina. Here we sought to map sites of thyroid hormone signaling at the cellular level using the transgenic FINDT3 reporter mouse model in which neurons express ß-galactosidase (ß-gal) under the control of a hybrid Gal4-TRα receptor when triiodothyronine (T3) and cofactors of thyroid receptor signaling are present. In the adult retina, nearly all neurons of the ganglion cell layer (GCL, ganglion cells and displaced amacrine cells) showed strong ß-gal labeling. In the inner nuclear layer (INL), a minority of glycineric and GABAergic amacrine cells showed ß-gal labeling, whereas the majority of amacrine cells were unlabeled. At the level of amacrine types, ß-gal labeling was found in a large proportion of the glycinergic AII amacrines, but only in a small proportion of the cholinergic/GABAergic 'starburst' amacrines. At postnatal day 10, there also was a high density of strongly ß-gal-labeled neurons in the GCL, but only few amacrine cells were labeled in the INL. There was no labeling of bipolar cells, horizontal cells and Müller glia cells at both stages. Most surprisingly, the photoreceptor somata in the outer nuclear layer also showed no ß-gal label, although thyroid hormone is known to control cone opsin expression. This is the first record of thyroid hormone signaling in the inner retina of an adult mammal. We hypothesize that T3 levels in photoreceptors are below the detection threshold of the reporter system. The topographical distribution of ß-gal-positive cells in the GCL follows the overall neuron distribution in that layer, with more T3-signaling cells in the ventral than the dorsal half-retina.

Patient safety in the era of the 80-hour workweek.

OBJECTIVE: In 2003, duty-hour regulations (DHR) were initially implemented for residents in the United States to improve patient safety and protect resident's well-being. The effect of DHR on patient safety remains unclear. The study objective was to evaluate the effect of DHR on patient safety. DESIGN: Using an interrupted time series analysis, we analyzed selected patient safety indicators (PSIs) for 376 million discharges in teaching (T) vs nonteaching (NT) hospitals before and after implementation of DHR in 2003 that restricted resident work hours to 80 hours per week. The PSIs evaluated were postoperative pulmonary embolus or deep venous thrombosis (PEDVT), iatrogenic pneumothorax (PTx), accidental puncture or laceration, postoperative wound dehiscence (WD), postoperative hemorrhage or hematoma, and postoperative physiologic or metabolic derangement. Propensity scores were used to adjust for differences in patient comorbidities between T and NT hospitals and between discharge quarters. The primary outcomes were differences in the PSI rates before and after DHR implementation. The PSI differences between T and NT institutions were the secondary outcome. SETTING: T and NT hospitals in the United States. PARTICIPANTS: Participants were 376 million patient discharges from 1998 to 2007 in the Nationwide Inpatient Sample. RESULTS: Declining rates of PTx in both T and NT hospitals preintervention slowed only in T hospitals postintervention (p = 0.04). Increasing PEDVT rates in both T and NT hospitals increased further only in NT hospitals (p = 0.01). There were no differences in the PSI rates over time for hemorrhage or hematoma, physiologic or metabolic derangement, accidental puncture or laceration, or WD. T hospitals had higher rates than NT hospitals both preintervention and postintervention for all the PSIs except WD. CONCLUSIONS: Trends in rates for 2 of the 6 PSIs changed significantly after DHR implementation, with PTx rates worsening in T hospitals and PEDVT rates worsening in NT hospitals. Lack of consistent patterns of change suggests no measurable effect of the policy change on these PSIs.

60-Hz frequency effect on gait in Parkinson's disease with subthalamic nucleus deep brain stimulation.

OBJECTIVE: Gait dysfunction is common in advancing Parkinson's disease and has a disappointing response to dopamine replacement and subthalamic nucleus deep brain stimulation programming parameters. Low-frequency stimulation, less than 130 Hz in combination with increased voltage, has been shown to decrease freezing episodes and number of steps with little impact on overall performance measured by the Unified Parkinson's Disease Rating Scale. This was in the setting of delivering the same total energy, which required both a change in voltage and frequency. We wanted to determine if the benefit came from low frequency alone. MATERIALS AND METHODS: We enrolled 20 Parkinson's patients who were at least three months in postbilateral subthalamic deep brain stimulation and reported gait changes. Subjects held their Parkinson's medications overnight, and following a baseline evaluation, they were randomly assigned to both 60 and 130 Hz stimulation in a blinded fashion with all other parameters held constant. Each subject was set at each frequency twice during the study, with a 60-min stimulation interval prior to each gait evaluation. RESULTS: There was no significant difference between the two frequencies, with the primary outcome measure of stride length. Two of the 20 patients reported a significant subjective improvement in their gait with no statistical difference in their outcomes. There also was less tremor control at 60 Hz. CONCLUSION: We were unable to demonstrate improved gait with lower frequency stimulation as suggested by prior studies. This may have been because of the decreased energy delivered from the lower frequency and unchanged voltage.

Retinal cone photoreceptors of the deer mouse Peromyscus maniculatus: development, topography, opsin expression and spectral tuning.

A quantitative analysis of photoreceptor properties was performed in the retina of the nocturnal deer mouse, Peromyscus maniculatus, using pigmented (wildtype) and albino animals. The aim was to establish whether the deer mouse is a more suitable model species than the house mouse for photoreceptor studies, and whether oculocutaneous albinism affects its photoreceptor properties. In retinal flatmounts, cone photoreceptors were identified by opsin immunostaining, and their numbers, spectral types, and distributions across the retina were determined. Rod photoreceptors were counted using differential interference contrast microscopy. Pigmented P. maniculatus have a rod-dominated retina with rod densities of about 450.000/mm(2) and cone densities of 3000-6500/mm(2). Two cone opsins, shortwave sensitive (S) and middle-to-longwave sensitive (M), are present and expressed in distinct cone types. Partial sequencing of the S opsin gene strongly supports UV sensitivity of the S cone visual pigment. The S cones constitute a 5-15% minority of the cones. Different from house mouse, S and M cone distributions do not have dorsoventral gradients, and coexpression of both opsins in single cones is exceptional (<2% of the cones). In albino P. maniculatus, rod densities are reduced by approximately 40% (270.000/mm(2)). Overall, cone density and the density of cones exclusively expressing S opsin are not significantly different from pigmented P. maniculatus. However, in albino retinas S opsin is coexpressed with M opsin in 60-90% of the cones and therefore the population of cones expressing only M opsin is significantly reduced to 5-25%. In conclusion, deer mouse cone properties largely conform to the general mammalian pattern, hence the deer mouse may be better suited than the house mouse for the study of certain basic cone properties, including the effects of albinism on cone opsin expression.

Reducing blood culture contamination in the emergency department: an interrupted time series quality improvement study.

OBJECTIVES: Blood culture contamination is a common problem in the emergency department (ED) that leads to unnecessary patient morbidity and health care costs. The study objective was to develop and evaluate the effectiveness of a quality improvement (QI) intervention for reducing blood culture contamination in an ED. METHODS: The authors developed a QI intervention to reduce blood culture contamination in the ED and then evaluated its effectiveness in a prospective interrupted times series study. The QI intervention involved changing the technique of blood culture specimen collection from the traditional clean procedure to a new sterile procedure, with standardized use of sterile gloves and a new materials kit containing a 2% chlorhexidine skin antisepsis device, a sterile fenestrated drape, a sterile needle, and a procedural checklist. The intervention was implemented in a university-affiliated ED and its effect on blood culture contamination evaluated by comparing the biweekly percentages of blood cultures contaminated during a 48-week baseline period (clean technique) and 48-week intervention period (sterile technique), using segmented regression analysis with adjustment for secular trends and first-order autocorrelation. The goal was to achieve and maintain a contamination rate below 3%. RESULTS: During the baseline period, 321 of 7,389 (4.3%) cultures were contaminated, compared to 111 of 6,590 (1.7%) during the intervention period (p < 0.001). In the segmented regression model, the intervention was associated with an immediate 2.9% (95% confidence interval [CI] = 2.2% to 3.2%) absolute reduction in contamination. The contamination rate was maintained below 3% during each biweekly interval throughout the intervention period. CONCLUSIONS: A QI assessment of ED blood culture contamination led to development of a targeted intervention to convert the process of blood culture collection from a clean to a fully sterile procedure. Implementation of this intervention led to an immediate and sustained reduction of contamination in an ED with a high baseline contamination rate.

Nearly complete elimination of the 7-valent pneumococcal conjugate vaccine serotypes in Tennessee.

BACKGROUND: Invasive pneumococcal disease (IPD) rates decreased after 7-valent pneumococcal conjugate vaccine (PCV) introduction in 2000. We assessed whether previously described decreases were sustained. METHODS: Active laboratory-based surveillance identified IPD cases in 5 Tennessee Counties. For each case, clinical data were collected, and antibiotic susceptibility testing and serotyping were performed. Penicillin resistance was defined as intermediate- or high-level resistance to penicillin. Serotypes were classified as PCV7, PCV13 (6 additional serotypes not in PCV7), pneumococcal polysaccharide vaccine (PPV23, 11 additional serotypes not in PCV13 and nonvaccine serotypes. Total and penicillin-resistant IPD rates were calculated for persons <2, 2-14 and ≥15 years of age before (1998 to 1999) and after (2001 to 2008) PCV7 introduction. RESULTS: Annual IPD rates in children <2 years of age declined by 75% after PCV7 introduction (P < 0.001). Annual IPD rates in children 2-14 years of age declined by 51% after PCV7 introduction (P < 0.001). IPD rates in persons ≥15 of age years initially decreased 40% from 22 to 13 per 100,000 person-years (from 1998 through 2004), and then increased to 18 per 100,000 person-years in 2008. Both IPD and penicillin-resistant IPD PCV7 serotypes were almost completely eliminated in all age groups by 2008. During 2005 to 2008, 52.5%, 58% and 38% of IPD serotypes in children <2, 2-14 and ≥15 years of age, respectively, were the additional 6 serotypes in PCV13. CONCLUSIONS: Overall, 9 years after PCV7 introduction both penicillin-susceptible and resistant IPD rates PCV7 serotypes have been nearly eliminated in Tennessee in all age groups. Total IPD rates remain reduced in children <15 years of age, whereas total IPD rates in persons ≥15 years of age have approached pre-PCV7 rates due to modest increases in nonvaccine serotypes.

Initiation of tumor necrosis factor α antagonists and risk of fractures in patients with selected rheumatic and autoimmune diseases.

OBJECTIVE: We tested the hypothesis that initiation of tumor necrosis factor α (TNFα) antagonists reduced the risk of fractures compared to nonbiologic comparators in patients with autoimmune diseases. METHODS: Using 4 large administrative databases, we assembled retrospective cohorts of patients with autoimmune diseases who initiated either a TNFα antagonist or a nonbiologic medication. We identified 3 mutually exclusive disease groups: rheumatoid arthritis (RA), inflammatory bowel disease (IBD), and a combined group: psoriasis (PsO), psoriatic arthritis (PsA), or ankylosing spondylitis (AS). We used baseline covariate data to calculate propensity scores (PS) for each disease group and used Cox regression to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). We compared the risk of combined hip, radius/ulna, humerus, or pelvic fractures between PS-matched cohorts of new users of TNFα antagonists and nonbiologic comparators. RESULTS: We identified 9,020, 2,014, and 2,663 new PS-matched episodes of TNFα antagonist and nonbiologic comparator use in RA, IBD, and PsO-PsA-AS cohorts, respectively. The risk of combined fractures was similar between new users of TNFα antagonists and nonbiologic comparators for each disease (HR 1.17, 95% CI 0.91-1.51; HR 1.49, 95% CI 0.72-3.11; and HR 0.92, 95% CI 0.47-1.82 for RA, IBD, and PsO-PsA-AS, respectively). In RA, the risk of combined fractures was associated with an average daily dosage of prednisone equivalents >10 mg/day at baseline compared with no glucocorticoid (HR 1.54, 95% CI 1.03-2.30). CONCLUSION: The risk of fractures did not differ between initiators of a biologic agent and a nonbiologic comparator for any disease studied. Among RA patients, use of >10 mg/day of prednisone equivalents at baseline increased the fracture risk.

Adherence to transcranial Doppler screening guidelines among children with sickle cell disease.

BACKGROUND: Little is known about adherence to guidelines recommending yearly screening with transcranial Doppler (TCD) ultrasonography to detect stroke risk for children with severe sickle cell disease. The objective was to determine the proportion of children with hemoglobin SS (HbSS) or sickle-ß(0) -thalassemia (HbSß(0) ) aged 2-16 years who received recommended TCD screening from 1997 to 2008, and to identify factors associated with adherence. PROCEDURE: A retrospective cohort study included patients enrolled in Tennessee Medicaid with HbSS or HbSß(0) who received care at the two largest sickle cell centers in Tennessee. The outcome of interest was adherence with guidelines for annual screening TCD's, identified from computer claims and validated through medical record review. The cumulative rate of children who received a TCD per year was calculated using the Kaplan-Meier method. Cox proportional hazards regression was used to examine the association of child, family, and health care use characteristics with receiving a TCD. RESULTS: Among 338 TCD eligible at-risk children, 232 (68.6%) had at least one TCD during the study period. The yearly cumulative incidence of annual TCD's increased from 2.5% in 1997 to 68.3% in 2008. In multivariate models, calendar year, maternal education, and increased number of sickle cell related outpatient visits were associated with an increased rate of receiving a TCD. CONCLUSIONS: Publicly insured children with HbSS or HbSß(0) had increasing adherence with TCD screening guidelines between 1997 and 2008, though 31% had no TCD at all during follow-up. Increasing number of sickle cell related outpatient visits was associated with increasing adherence to screening guidelines.

Increasing use of atypical antipsychotics and anticonvulsants during pregnancy.

PURPOSE: To quantify maternal use of atypical antipsychotics, typical antipsychotics, anticonvulsants, and lithium during pregnancy. METHODS: Tennessee birth and death records were linked to Tennessee Medicaid data to conduct a retrospective cohort study of 296,817 women enrolled in Tennessee Medicaid throughout pregnancy who had a live birth or fetal death from 1985 to 2005. RESULTS: During the study time period, the adjusted rate of use of any study medication during pregnancy increased from nearly 14 to 31 per 1000 pregnancies (ß = 0.08, 95% CI = 0.07, 0.09). Significant increases were reported in use of anticonvulsants alone among mothers with pain and other psychiatric disorders, atypical antipsychotics alone among mothers with bipolar disorders, schizophrenia, unipolar depressive disorders, and other psychiatric disorders, and more than one studied medication for mothers with epilepsy, pain disorders, bipolar disorders, unipolar depressive disorders, and other psychiatric disorders. Significant decreases were reported in use of lithium alone and typical antipsychotics alone for all clinically meaningful diagnosis groups. CONCLUSIONS: There was a substantial increase in use of atypical antipsychotics alone, anticonvulsants alone, and medications from multiple studied categories among Tennessee Medicaid-insured pregnant women during the study period. Further examination of the maternal and fetal consequences of exposure to these medications during pregnancy is warranted.

Low numeracy is associated with increased odds of 30-day emergency department or hospital recidivism for patients with acute heart failure.

BACKGROUND: More than 25% of Medicare patients hospitalized for heart failure are readmitted within 30 days. The contributions of numeracy and health literacy to recidivism for patients with acute heart failure (AHF) are not known. METHODS AND RESULTS: A cohort of patients with acute heart failure who presented to 4 emergency departments between January 2008 and September 2011. Research assistants administered subjective measures of numeracy and health literacy; 30-day follow-up was performed by phone interview. Recidivism was defined as any unplanned return to the emergency department or hospital within 30 days of the index emergency department visit for AHF. Multivariable logistic regression adjusting for patient age, sex, race, insurance status, hospital site, days eligible for recidivism, chronic kidney disease, abnormal hemoglobin, and low ejection fraction evaluated the relation between numeracy and health literacy with 30-day recidivism. Of the 709 patients included in the analysis, 390 (55%) had low numeracy skills and 258 (37%) had low literacy skills. Low numeracy was associated with increased odds of recidivism within 30 days (adjusted odds ratio, 1.41; 95% confidence interval, 1.00-1.98; P=0.048). For low health literacy, adjusted odds ratio of recidivism was 1.17 (95% confidence interval, 0.83-1.65; P=0.37). CONCLUSIONS: Low numeracy was associated with greater odds of 30-day recidivism. Further investigation is warranted to determine whether addressing numeracy and health literacy may reduce 30-day recidivism for patients with acute heart failure.

Trends in the use of antiepileptic drugs among pregnant women in the US, 2001-2007: a medication exposure in pregnancy risk evaluation program study.

BACKGROUND: Little is known about the extent of antiepileptic drug (AED) use in pregnancy, particularly for newer agents. Our objective was to assess whether AED use has increased among pregnant women in the US, 2001-2007. METHODS: We analysed data from the Medication Exposure in Pregnancy Risk Evaluation Program (MEPREP) database, 1 January 2001 to 31 December 2007. We identified liveborn deliveries among women, aged 15-45 years on delivery date, who were members of MEPREP health plans (n=585615 deliveries). Pregnancy exposure to AEDs, determined through outpatient pharmacy dispensing files. Older AEDs were available for clinical use before 1993; other agents were considered newer AEDs. Information on sociodemographic and medical/reproductive factors was obtained from linked birth certificate files. Maternal diagnoses were identified based on ICD-9 codes. RESULTS: Prevalence of AED use during pregnancy increased between 2001 (15.7 per 1000 deliveries) and 2007 (21.9 per 1000 deliveries), driven primarily by a fivefold increase in the use of newer AEDs. Thirteen per cent of AED-exposed deliveries involved a combination of two or more AEDs. Psychiatric disorders were the most prevalent diagnoses, followed by epileptic and pain disorders, among AED users regardless of AED type, year of conception or gestational period. CONCLUSIONS: AED use during pregnancy increased between 2001 and 2007, driven by a fivefold increase in the use of newer AEDs. Nearly one in eight AED-exposed deliveries involved the concomitant use of more than one AED. Additional investigations of the reproductive safety of newer AEDs may be needed.

Changes to the financial responsibility for juvenile court ordered psychiatric evaluations reduce inpatient services utilization: an interrupted time series study.

BACKGROUND: The purpose of the current study was to evaluate the impact of a July 2008 Tennessee Court of Appeals opinion that shifted financial responsibility for juvenile court ordered psychiatric evaluations from the State to the County. METHODS: We used de-identified administrative data from the Tennessee Department of Mental Health and mid-year population estimates from the U.S. Census Bureau from July 1, 2006 to June 30, 2010, and an interrupted time series design with segmented regression analysis to quantify the impact of the implementation of the Court opinion. RESULTS: In the study period, there were 2,176 referrals for juvenile court ordered psychiatric evaluations in Tennessee; of these, 74.1% were inpatient evaluations. The Court opinion was associated with a decrease of 9.4 (95% C.I. = 7.9-10.8) inpatient and increase of 1.2 (95% C.I. = 0.4-2.1) outpatient evaluations per 100,000 Tennessee youth aged 12 to 19 years per month. CONCLUSIONS: The Court opinion that shifted financial responsibility for juvenile court ordered psychiatric evaluations from the State to the County was associated with a sudden and significant decrease in inpatient psychiatric evaluations, and more modest increase in outpatient evaluations.

Volume-outcome effects for children undergoing resection of renal malignancies.

INTRODUCTION: Adults undergoing oncologic resections at low-volume centers experience increased perioperative morbidity and mortality. The volume-outcome effect has not been extensively studied in pediatric oncologic resections. METHODS: To clarify volume-outcome effects in pediatric oncologic resections, we analyzed resection of renal malignancies in children less than 15 y of age. We conducted a cross-sectional analysis of hospital discharges included in the health care utilization project kids' inpatient database from 1997 to 2009, examining in-hospital operative complications, length of stay (LOS), and inflation-adjusted hospital charges. Hospital volume was expressed as low (n = 1-2), medium (n = 3-4), and high (n > 4) annual volume of resections. RESULTS: One thousand five hundred thirty-eight patients underwent renal malignancy resection. Of these, 527 patients had resection in low-, 422 in medium-, and 589 in high-volume hospitals. Relative to low-volume hospitals, those resected in medium-volume hospitals had an odds ratio of 0.62 (95% confidence interval 0.39-0.99, P = 0.046) for operative complication and those in high-volume hospitals had an odds ratio of 1.02 (95% confidence interval 0.63-1.65, P = 0.95). There was no detectable association with LOS (P = 0.113) or inflation-adjusted charges (P = 0.331). CONCLUSIONS: The number of complications, total charges, and LOS attributable to resection of a childhood renal malignancy did not differ among high-, medium-, or low-operative volume hospitals, although oncologic outcomes could not be determined because of the limited nature of this administrative database.

Azithromycin and the risk of cardiovascular death.

BACKGROUND: Although several macrolide antibiotics are proarrhythmic and associated with an increased risk of sudden cardiac death, azithromycin is thought to have minimal cardiotoxicity. However, published reports of arrhythmias suggest that azithromycin may increase the risk of cardiovascular death. METHODS: We studied a Tennessee Medicaid cohort designed to detect an increased risk of death related to short-term cardiac effects of medication, excluding patients with serious noncardiovascular illness and person-time during and shortly after hospitalization. The cohort included patients who took azithromycin (347,795 prescriptions), propensity-score-matched persons who took no antibiotics (1,391,180 control periods), and patients who took amoxicillin (1,348,672 prescriptions), ciprofloxacin (264,626 prescriptions), or levofloxacin (193,906 prescriptions). RESULTS: During 5 days of therapy, patients taking azithromycin, as compared with those who took no antibiotics, had an increased risk of cardiovascular death (hazard ratio, 2.88; 95% confidence interval [CI], 1.79 to 4.63; P<0.001) and death from any cause (hazard ratio, 1.85; 95% CI, 1.25 to 2.75; P=0.002). Patients who took amoxicillin had no increase in the risk of death during this period. Relative to amoxicillin, azithromycin was associated with an increased risk of cardiovascular death (hazard ratio, 2.49; 95% CI, 1.38 to 4.50; P=0.002) and death from any cause (hazard ratio, 2.02; 95% CI, 1.24 to 3.30; P=0.005), with an estimated 47 additional cardiovascular deaths per 1 million courses; patients in the highest decile of risk for cardiovascular disease had an estimated 245 additional cardiovascular deaths per 1 million courses. The risk of cardiovascular death was significantly greater with azithromycin than with ciprofloxacin but did not differ significantly from that with levofloxacin. CONCLUSIONS: During 5 days of azithromycin therapy, there was a small absolute increase in cardiovascular deaths, which was most pronounced among patients with a high baseline risk of cardiovascular disease. (Funded by the National Heart, Lung, and Blood Institute and the Agency for Healthcare Quality and Research Centers for Education and Research on Therapeutics.).

Rural and micropolitan residence and mortality in patients on dialysis.

BACKGROUND AND OBJECTIVES: Micropolitan and rural patients face challenges when initiating dialysis, including healthcare access. Previous studies have shown little association of nonurban residence with dialysis outcomes but have not examined the association of dialysis modality with residence location. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This retrospective cohort study used data from the U.S. Renal Data System. Adults who initiated maintenance dialysis between January 1, 2006, and December 31, 2007, were classified as rural, micropolitan, or urban. Early and long-term mortality and kidney transplantation were examined with Cox regression stratified by dialysis modality. RESULTS: Of 204,463 patients, 80% were urban; 10.2%, micropolitan; and 9.8%, rural. Micropolitan and rural patients were older, were less racially diverse, had more comorbid conditions, and were more likely to start peritoneal dialysis (PD). Median follow-up was 2.0 years. Early mortality or long-term hemodialysis (HD) mortality did not significantly differ by geographic residence. After adjustment, micropolitan and rural PD patients had higher risk for long-term mortality (hazard ratio [HR], 1.21 [95% confidence interval (CI), 1.09-1.35] and 1.12 [95% CI, 1.01-1.24], respectively) than urban PD patients. After adjustment, kidney transplantation was more likely in micropolitan and rural HD patients (HR, 1.19 [95% CI, 1.11-1.28] and 1.30 [CI, 1.21-1.40]) than urban HD patients, and micropolitan PD patients (HR, 1.31 [95%, CI 1.13-1.51]) than urban PD patients. CONCLUSIONS: Micropolitan and rural residence is associated with higher mortality in PD patients and similar or higher likelihood of kidney transplantation among HD and PD patients. Studies examining the underlying mechanisms of these associations are warranted.

ED crowding and the use of nontraditional beds.

BACKGROUND AND OBJECTIVES: In an effort to compensate for crowding, many emergency departments (EDs) evaluate and treat patients in nontraditional settings such as gurneys in hallways and conference rooms. The impact of this practice on ED evaluation time is unknown. RESEARCH DESIGN AND SUBJECTS: A historical cohort of adult ED visits to an academic hospital between August 1, 2009 and August 1, 2010, was used to evaluate the relationship between ED bed assignment (traditional, hallway, or conference room bed) and mean ED evaluation time, defined as the time spent in an ED bed before admission or discharge. Chief complaints were categorized into the 5 most frequent categories: abdominal/genitourinary, joint/muscle, general (fever, malaise), head/neck, and other. Multiple linear regression and marginal prediction were used to calculate the mean ED evaluation times for each bed type, overall, and by chief complaint category. RESULTS: During the study period, 15 073 patient visits met the inclusion criteria. After adjustment for patient and ED factors, assignments to hallway and conference room beds were associated with increases in a mean ED evaluation time of 13.3 minutes (95% confidence interval, 13.2-13.3) and 10.9 minutes (95% confidence interval, 10.8-10.9), respectively, compared with the traditional bed ED evaluation time. This varied by chief complaint category. CONCLUSIONS: Use of nontraditional beds is associated with increases in mean ED evaluation time; however, these increases are small and may be further minimized by restricting the use of nontraditional beds to patients with specific chief complaints. Nontraditional beds may have a role in improving ED throughput during times of crowding.

The impact of beta-blocker therapy on anemia after traumatic brain injury.

BACKGROUND: An increase in endogenous catecholamine levels after traumatic brain injury (TBI) is well described. Animal studies suggest that postinjury anemia is exacerbated by a persistent hyperadrenergic state. This study aims to determine if beta-blocker (BB) exposure affects anemia after TBI. STUDY DESIGN AND METHODS: We reviewed a Level I trauma registry for patients with TBI, examining markers of anemia between patients who received BB with those who did not. RESULTS: A total of 174 patients were exposed to BB (BB+) and 245 were not exposed (BB-). The mean age in the BB+ group was 50 years (vs. 36 years in BB- group, p < 0.001). The mean injury severity score was 33.6 for the BB+ group (vs. 30.8 for BB- group, p = 0.01). While BB+ patients were more likely to receive a transfusion (60.9% vs. 35.1%, p < 0.001), BB+ patients reached their nadir hemoglobin (Hb) at a later day of hospitalization and their rate of decrease in Hb was significantly slower (both p < 0.001). Choosing Hb cutoffs for anemia of both 7 and 10 g/dL, Kaplan-Meier demonstrated a significant delay in time to anemia. CONCLUSION: This study suggests beta-blockade delays anemia after TBI. Elaboration of this effect may demonstrate an additional benefit of beta-blockade after head injury.

ADHD medications and risk of serious cardiovascular events in young and middle-aged adults.

CONTEXT: More than 1.5 million US adults use stimulants and other medications labeled for treatment of attention-deficit/hyperactivity disorder (ADHD). These agents can increase heart rate and blood pressure, raising concerns about their cardiovascular safety. OBJECTIVE: To examine whether current use of medications prescribed primarily to treat ADHD is associated with increased risk of serious cardiovascular events in young and middle-aged adults. DESIGN, SETTING, AND PARTICIPANTS: Retrospective, population-based cohort study using electronic health care records from 4 study sites (OptumInsight Epidemiology, Tennessee Medicaid, Kaiser Permanente California, and the HMO Research Network), starting in 1986 at 1 site and ending in 2005 at all sites, with additional covariate assessment using 2007 survey data. Participants were adults aged 25 through 64 years with dispensed prescriptions for methylphenidate, amphetamine, or atomoxetine at baseline. Each medication user (n = 150,359) was matched to 2 nonusers on study site, birth year, sex, and calendar year (443,198 total users and nonusers). MAIN OUTCOME MEASURES: Serious cardiovascular events, including myocardial infarction (MI), sudden cardiac death (SCD), or stroke, with comparison between current or new users and remote users to account for potential healthy-user bias. RESULTS: During 806,182 person-years of follow-up (median, 1.3 years per person), 1357 cases of MI, 296 cases of SCD, and 575 cases of stroke occurred. There were 107,322 person-years of current use (median, 0.33 years), with a crude incidence per 1000 person-years of 1.34 (95% CI, 1.14-1.57) for MI, 0.30 (95% CI, 0.20-0.42) for SCD, and 0.56 (95% CI, 0.43-0.72) for stroke. The multivariable-adjusted rate ratio (RR) of serious cardiovascular events for current use vs nonuse of ADHD medications was 0.83 (95% CI, 0.72-0.96). Among new users of ADHD medications, the adjusted RR was 0.77 (95% CI, 0.63-0.94). The adjusted RR for current use vs remote use was 1.03 (95% CI, 0.86-1.24); for new use vs remote use, the adjusted RR was 1.02 (95% CI, 0.82-1.28); the upper limit of 1.28 corresponds to an additional 0.19 events per 1000 person-years at ages 25-44 years and 0.77 events per 1000 person-years at ages 45-64 years. CONCLUSIONS: Among young and middle-aged adults, current or new use of ADHD medications, compared with nonuse or remote use, was not associated with an increased risk of serious cardiovascular events. Apparent protective associations likely represent healthy-user bias.

ADHD drugs and serious cardiovascular events in children and young adults.

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.).