Lori Lyn Price

Epidemiology and Outcomes of Acute Renal Failure in Hospitalized Patients: A National Survey

The aim of this study was to provide a broad characterization of the epidemiology of acute renal failure (ARF) in the United States using national administrative data and describe its impact on hospital length of stay (LOS), patient disposition, and adverse outcomes. Using the 2001 National Hospital Discharge Survey, a nationally representative sample of discharges from nonfederal acute care hospitals in the United States, new cases of ARF were obtained from hospital discharge records coded according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). Multivariate regression analyses were used to explore the relation of ARF to hospital LOS and mortality as well as discharge disposition. Review of discharge data on a projected total of 29,039,599 hospitalizations identified 558,032 cases of ARF, with a frequency of 19.2 per 1000 hospitalizations. ARF was more commonly coded for in older patients; men; black individuals; and the setting of chronic kidney disease, congestive heart failure, chronic lung disease, sepsis, and cardiac surgery. ARF was associated with an adjusted prolongation of hospital LOS by 2 d (P < 0.001) and an adjusted odds ratio of 4.1 for hospital mortality and of 2.0 for discharge to short- or long-term care facilities. In a US representative sample of hospitalized patients, the presence of an ICD-9-CM code for ARF in discharge records is associated with prolonged LOS, increased mortality, and, among survivors, a greater requirement for posthospitalization care. These findings suggest that in the United States, ARF is associated with increased in-hospital and post-hospitalization resource utilization.

Impact of Hospital-Associated Hyponatremia on Selected Outcomes

BACKGROUND Hyponatremia is the most common electrolyte disorder encountered in hospitalized patients. METHODS We evaluated whether hospital-associated hyponatremia has an independent effect on all-cause mortality, hospital length of stay (LOS), and patient disposition. This cohort study included all adult hospitalizations at an academic medical center occurring between 2000-2007 for which an admission serum sodium concentration ([Na(+)]) was available (N = 53 236). We examined community-acquired hyponatremia (admission serum [Na(+)], <138 mEq/L [to convert to millimoles per liter, multiply by 1.0]), hospital-aggravated hyponatremia (community-acquired hyponatremia complicated by worsening in serum [Na(+)]), and hospital-acquired hyponatremia (nadir serum [Na(+)], <138 mEq/L with a normal admission serum [Na(+)]). The independent associations of these hyponatremic presentations with in-hospital mortality, LOS, and patient disposition were evaluated using generalized estimating equations adjusted for age, sex, race, admission service, and Deyo-Charlson Comorbidity Index score. RESULTS Community-acquired hyponatremia occurred in 37.9% of hospitalizations and was associated with adjusted odds ratios (ORs) of 1.52 (95% confidence interval [CI], 1.36-1.69) for in-hospital mortality and 1.12 (95% CI, 1.08-1.17) for discharge to a short- or long-term care facility and a 14% (95% CI, 11%-16%) adjusted increase in LOS. Hospital-acquired hyponatremia developed in 38.2% of hospitalizations longer than 1 day in which initial serum [Na(+)] was 138 to 142 mEq/L. Hospital-acquired hyponatremia was associated with adjusted ORs of 1.66 (95% CI, 1.39-1.98) for in-hospital mortality and 1.64 (95% CI, 1.55-1.74) for discharge to a facility and a 64% (95% CI, 60%-68%) adjusted increase in LOS. The strength of these associations tended to increase with hyponatremia severity. CONCLUSIONS Hospital-associated hyponatremia is a common occurrence. All forms of hyponatremia are independently associated with in-hospital mortality and heightened resource consumption.

Sex-based differences in response to recombinant tissue plasminogen activator in acute ischemic stroke: a pooled analysis of randomized clinical trials.

Background and Purpose— Women experience worse outcomes after stroke compared with men. Prior work has suggested sex-based differences in coagulation and fibrinolysis markers in subjects with acute stroke. We explored whether sex might modify the effect of recombinant tissue plasminogen activator (rtPA) on outcomes in patients with acute ischemic stroke. Methods— Using a combined database including subjects from the National Institute of Neurological Disorders and Stroke (NINDS), Alteplase Thrombolysis for Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) A and B, and the Second European Cooperative Acute Stroke Study (ECASS II) trials, we examined 90-day outcomes in patients randomized to rtPA versus placebo by sex. We used logistic regression to control for potential confounders. Results— Among 988 women treated between 0 and 6 hours from symptom onset, patients receiving rtPA were significantly more likely than those receiving placebo to have a modified Rankin Score ≤1 (40.5% versus 30.3%, P<0.0008). Among 1190 men, the trend toward benefit in the overall group did not reach statistical significance (38.5% versus 36.7%, P=0.52). An unadjusted analysis showed that women were significantly more likely to benefit from rtPA compared with men (P=0.04). Controlling for age, baseline National Institutes of Health Stroke Scale, diabetes, symptom onset to treatment time, prior stroke, systolic blood pressure, extent of hypoattenuation on baseline computed tomography scan and several significant interaction terms (including onset to treatment time–by-treatment and systolic blood pressure–by treatment) did not substantially change the strength of the interaction between gender and rtPA treatment (P=0.04). Conclusions— In this pooled analysis of rtPA in acute ischemic stroke, women benefited more than men, and the usual gender difference in outcome favoring men was not observed in the thrombolytic therapy group. For patients presenting at later time intervals, when the risks and benefits of rtPA are more finely balanced, sex may be an important variable to consider for patient selection.

Toxicity of Three-Dimensional Conformal Radiotherapy for Accelerated Partial Breast Irradiation

PURPOSE To assess the incidence and severity of late normal tissue toxicity using three-dimensional conformal radiotherapy to deliver accelerated partial breast irradiation. METHODS AND MATERIALS A total of 60 patients were treated with three-dimensional conformal radiotherapy for accelerated partial breast irradiation. Treatment planning and delivery were in strict accordance with the technique and specified dose-volume constraints of the National Surgical Adjuvant Breast and Bowel Project B-39/Radiation Therapy Oncology Group 0413 protocol. Late toxicity was evaluated according to the Radiation Therapy Oncology Group grading schema. The cosmetic outcome was scored using the Harvard criteria. Univariate logistic regression analysis was performed to evaluate the correlation of dosimetric variables with outcome. RESULTS At a median follow-up of 15 months, moderate-to-severe late toxicity developed in 10% of patients. The most pronounced late toxicity was subcutaneous fibrosis: 25% Grade 2-4 and 8.3% Grade 3-4. The modified planning tumor volume/whole breast volume ratio, ratio of the volume of breast tissue receiving 5%, 20%, 50%, and 80% of the prescription dose to the whole breast volume, and maximal dose within the breast correlated with the development of fibrosis (p = .10, p = .03, p = .04, p = .06, p = .09, and p = .046, respectively). The overall cosmetic outcome was good to excellent in 81.7%, fair in 11.7%, and poor in 6.7%. The presence of subcutaneous fibrosis, modified planning tumor volume/whole breast volume ratio, ratio of the volume of breast tissue receiving 5% and 20% of the prescription dose to the whole breast volume, and pathologic specimen volume correlated with the risk of a fair/poor cosmetic outcome (p < .001, p = .02, p = .05, p = .04, p = .01, respectively). CONCLUSION The three-dimensional conformal radiotherapy technique for accelerated partial breast irradiation as specified in the National Surgical Adjuvant Breast and Bowel Project B-39/Radiation Therapy Oncology Group 0413 protocol resulted in a remarkably high rate of moderate-to-severe late normal tissue effects, despite the relatively brief follow-up period. The toxic events correlated clearly with several dose-volume parameters.

From suspicion of physical child abuse to reporting: Primary care clinician decision-making

OBJECTIVES. The goals were to determine how frequently primary care clinicians reported suspected physical child abuse, the levels of suspicion associated with reporting, and what factors influenced reporting to child protective services. METHODS. In this prospective observational study, 434 clinicians collected data on 15003 child injury visits, including information about the injury, child, family, likelihood that the injury was caused by child abuse (5-point scale), and whether the injury was reported to child protective services. Data on 327 clinicians indicating some suspicion of child abuse for 1683 injuries were analyzed. RESULTS. Clinicians reported 95 (6%) of the 1683 patients to child protective services. Clinicians did not report 27% of injuries considered likely or very likely caused by child abuse and 76% of injuries considered possibly caused by child abuse. Reporting rates were increased if the clinician perceived the injury to be inconsistent with the history and if the patient was referred to the clinician for suspected child abuse. Patients who had an injury that was not a laceration, who had >1 family risk factor, who had a serious injury, who had a child risk factor other than an inconsistent injury, who were black, or who were unfamiliar to the clinician were more likely to be reported. Clinicians who had not reported all suspicious injuries during their career or who had lost families as patients because of previous reports were more likely to report suspicious injuries. CONCLUSIONS. Clinicians had some degree of suspicion that ∼10% of the injuries they evaluated were caused by child abuse. Clinicians did not report all suspicious injuries to child protective services, even if the level of suspicion was high (likely or very likely caused by child abuse). Child, family, and injury characteristics and clinician previous experiences influenced decisions to report.

Clinicians' description of factors influencing their reporting of suspected child abuse: Report of the child abuse reporting experience study research group

OBJECTIVES. Primary care clinicians participating in the Child Abuse Reporting Experience Study did not report all suspected physical child abuse to child protective services. This evaluation of study data seeks (1) to identify factors clinicians weighed when deciding whether to report injuries they suspected might have been caused by child abuse; (2) to describe clinicians’ management strategies for children with injuries from suspected child abuse that were not reported; and (3) to describe how clinicians explained not reporting high-suspicion injuries. METHODS. From the 434 pediatric primary care clinicians who participated in the Child Abuse Reporting Experience Study and who indicated they had provided care for a child with an injury they perceived as suspicious, a subsample of 75 of 81 clinicians completed a telephone interview. Interviewees included 36 clinicians who suspected child abuse but did not report the injury to child protective services (12 with high suspicion and 24 with some suspicion) and 39 who reported the suspicious injury. Interviews were analyzed for major themes and subthemes, including decision-making regarding reporting of suspected physical child abuse to child protective services and alternative management strategies. RESULTS. Four major themes emerged regarding the clinicians’ reporting decisions, that is, familiarity with the family, reference to elements of the case history, use of available resources, and perception of expected outcomes of reporting to child protective services. When they did not report, clinicians planned alternative management strategies, including active or informal case follow-up management. When interviewed, some clinicians modified their original opinion that an injury was likely or very likely caused by abuse, to explain why they did not report to child protective services. CONCLUSIONS. Decisions about reporting to child protective services are guided by injury circumstances and history, knowledge of and experiences with the family, consultation with others, and previous experiences with child protective services.

Liver regeneration and surgical outcome in donors of right-lobe liver grafts.

Introduction. Previous studies of healthy live‐liver donors have suggested that complete liver regeneration occurs within a matter of weeks; however, there have been no long‐term studies evaluating liver regeneration and few studies documenting long‐term donor outcome. Materials and Methods. Fifty‐one donors who provided right‐lobe grafts underwent volumetric spiral computed tomography scans preoperatively and postoperatively at time intervals of 1 week and 1, 3, 6, and 12 months. Patient demographics, surgical data, and postoperative outcome were correlated with liver regeneration data. Donor surgical outcome was followed prospectively and recorded in a comprehensive database. Results. Thirty‐three males and 18 females (mean age 36.0±9.6 years) provided 51 right‐lobe grafts. Mean follow‐up was 9.8±3.4 months. No donor operation was aborted, and surgical morbidity and mortality rates were 39% and 0%, respectively. Donor remnant liver volume was 49.4±5.7% of the original total liver volume (TLV). Overall liver regeneration was 83.3±9.0% of the TLV by 1 year. Female donors had significantly slower liver regrowth when compared with males at 12 months (79.8±9.3% vs. 85.6±8.2%, P<0.01). There was no effect of age, body mass index, operative time, estimated blood loss, postoperative complications, or perioperative liver function tests on liver regeneration. Discussion. Liver regeneration continues throughout the first postoperative year. Only one donor achieved complete liver regeneration during this time period; however, all donors have maintained normal liver function without long‐term complications. Longer follow‐up is needed to determine whether donors ever achieve original TLV.

Effect of Vitamin D Supplementation on Progression of Knee Pain and Cartilage Volume Loss in Patients With Symptomatic Osteoarthritis: A Randomized Controlled Trial

IMPORTANCE Knee osteoarthritis (OA), a disorder of cartilage and periarticular bone, is a public health problem without effective medical treatments. Some studies have suggested that vitamin D may protect against structural progression. OBJECTIVE To determine whether vitamin D supplementation reduces symptom and structural progression of knee OA. DESIGN, SETTING, AND PATIENTS A 2-year randomized, placebo-controlled, double-blind, clinical trial involving 146 participants with symptomatic knee OA (mean age, 62.4 years [SD, 8.5]; 57 women [61%], 115 white race [79%]). Patients were enrolled at Tufts Medical Center in Boston between March 2006 and June 2009. INTERVENTION Participants were randomized to receive either placebo or oral cholecalciferol, 2000 IU/d, with dose escalation to elevate serum levels to more than 36 ng/mL. MAIN OUTCOME MEASURES Primary outcomes were knee pain severity (Western Ontario and McMaster Universities [WOMAC] pain scale, 0-20: 0, no pain; 20, extreme pain), and cartilage volume loss measured by magnetic resonance imaging. Secondary end points included physical function, knee function (WOMAC function scale, 0-68: 0, no difficulty; 68, extreme difficulty), cartilage thickness, bone marrow lesions, and radiographic joint space width. RESULTS Eighty-five percent of the participants completed the study. Serum 25-hydroxyvitamin D levels increased by a mean 16.1 ng/mL (95% CI, 13.7 to 18.6) in the treatment group and by a mean 2.1 mg/mL (95% CI, 0.5 to 3.7) (P < .001) in the placebo group. Baseline knee pain was slightly worse in the treatment group (mean, 6.9; 95% CI, 6.0 to 7.7) than in the placebo group (mean, 5.8; 95% CI, 5.0 to 6.6) (P = .08). Baseline knee function was significantly worse in the treatment group (mean, 22.7; 95% CI, 19.8 to 25.6) than in the placebo group (mean, 18.5; 95% CI, 15.8 to 21.2) (P = .04). Knee pain decreased in both groups by a mean -2.31 (95% CI, -3.24 to -1.38) in the treatment group and -1.46 (95% CI, -2.33 to -0.60) in the placebo group, with no significant differences at any time. The percentage of cartilage volume decreased by the same extent in both groups (mean, -4.30; 95% CI, -5.48 to -3.12 vs mean, -4.25; 95% CI, -6.12 to -2.39) (P = .96). There were no differences in any of the secondary clinical end points. CONCLUSION AND RELEVANCE Vitamin D supplementation for 2 years at a dose sufficient to elevate 25-hydroxyvitamin D plasma levels to higher than 36 ng/mL, when compared with placebo, did not reduce knee pain or cartilage volume loss in patients with symptomatic knee OA. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00306774.

Comparison of Spectral / Fourier Domain Optical Coherence Tomography Instruments for Assessment of Normal Macular Thickness

Purpose: The purpose of this study was to report normal macular thickness measurements and assess reproducibility of retinal thickness measurements acquired by a time-domain optical coherence tomography (OCT) (Stratus, Carl Zeiss Meditec, Inc., Dublin, CA) and three commercially available spectral/Fourier domain OCT instruments (Cirrus HD-OCT, Carl Zeiss Meditec, Inc.; RTVue-100, Optovue, Inc., Fremont, CA; 3D OCT-1000, Topcon, Inc., Paramus, NJ). Methods: Forty randomly selected eyes of 40 normal, healthy volunteers were imaged. Subjects were scanned twice during 1 visit and a subset of 25 was scanned again within 8 weeks. Retinal thickness measurements were automatically generated by OCT software and recorded after manual correction. Regression and Bland–Altman plots were used to compare agreement between instruments. Reproducibility was analyzed by using intraclass correlation coefficients, and incidence of artifacts was determined. Results: Macular thickness measurements were found to have high reproducibility across all instruments with intraclass correlation coefficients values ranging 84.8% to 94.9% for Stratus OCT, 92.6% to 97.3% for Cirrus Cube, 76.4% to 93.7% for RTVue MM5, 61.1% to 96.8% for MM6, 93.1% to 97.9% for 3D OCT-1000 radial, and 31.5% to 97.5% for 3D macular scans. Incidence of artifacts was higher in spectral/Fourier domain instruments, ranging from 28.75% to 53.16%, compared with 17.46% in Stratus OCT. No significant age or sex trends were found in the measurements. Conclusion: Commercial spectral/Fourier domain OCT instruments provide higher speed and axial resolution than the Stratus OCT, although they vary greatly in scanning protocols and are currently limited in their analysis functions. Further development of segmentation algorithms and quantitative features are needed to assist clinicians in objective use of these newer instruments to manage diseases.

Albuminuria, Cognitive Functioning, and White Matter Hyperintensities in Homebound Elders

BACKGROUND Albuminuria, a kidney marker of microvascular disease, may herald microvascular disease elsewhere, including in the brain. STUDY DESIGN Cross sectional. SETTING & PARTICIPANTS Boston, MA, elders receiving home health services to maintain independent living who consented to brain magnetic resonance imaging. PREDICTOR Urine albumin-creatinine ratio (ACR). OUTCOME Performance on a cognitive battery assessing executive function and memory by using principal components analysis and white matter hyperintensity volume on brain imaging, evaluated in logistic and linear regression models. RESULTS In 335 participants, mean age was 73.4 +/- 8.1 years and 123 participants had microalbuminuria or macroalbuminuria. Each doubling of ACR was associated with worse executive function (beta = -0.05; P = 0.005 in univariate and beta = -0.07; P = 0.004 in multivariable analyses controlling for age, sex, race, education, diabetes, cardiovascular disease, hypertension, medications, and estimated glomerular filtration rate [eGFR]), but not with worse memory or working memory. Individuals with microalbuminuria or macroalbuminuria were more likely to be in the lower versus the highest tertile of executive functioning (odds ratio, 1.18; 95% confidence interval, 1.06 to 1.32; odds ratio, 1.19; 95% confidence interval, 1.05 to 1.35 per doubling of ACR in univariate and multivariable analyses, respectively). Albuminuria was associated with qualitative white matter hyperintensity grade (odds ratio, 1.13; 95% confidence interval, 1.02 to 1.25; odds ratio, 1.15; 95% confidence interval, 1.02 to 1.29 per doubling of ACR) in univariate and multivariable analyses and with quantitative white matter hyperintensity volume (beta = 0.11; P = 0.007; beta = 0.10; P = 0.01) in univariate and multivariable analyses of log-transformed data. Results were similar when excluding individuals with macroalbuminuria. LIMITATIONS Single measurement of ACR, indirect creatinine calibration, and reliance on participant recall for elements of medical history. CONCLUSIONS Albuminuria is associated with worse cognitive performance, particularly in executive functioning, as well as increased white matter hyperintensity volume. Albuminuria likely identifies greater brain microvascular disease burden.