Interprofessional Extracorporeal Membrane Oxygenation Cardiopulmonary Resuscitation Simulations Aimed at Decreasing Actual Cannulation Times: A Longitudinal Study.

BACKGROUND: Since 2013, the cardiac intensive care unit (CICU) at Children's National has conducted annual extracorporeal membrane oxygenation cardiopulmonary resuscitation (ECPR) simulations that focus on team dynamics, room setup, and high-quality CPR. In 2019 and 2020, the simulations were expanded to include the surgical and extracorporeal membrane oxygenation (ECMO) teams in an effort to better understand and improve this process. METHODS: During a 4-week period in 2019, 7 peripheral ECPR simulations were conducted, and through a 3-week period in 2020, 7 central ECPR simulations were conducted. Participants in each session included: 8 to 10 CICU nurses, 1 CICU attending, 1 to 2 ICU or cardiology fellows, 1 cardiovascular surgery fellow or attending, and 1 ECMO specialist. For each session, the scenario continued until the simulated patient was on full cardiopulmonary bypass. An ECMO trainer was used for peripheral simulations and a 3-dimensionally-printed heart was used for central cannulations. An ECMO checklist was used to objectively determine when the patient and room were fully prepared for surgical intervention, and simulated cannulation times were recorded for both groups. A retrospective chart review was conducted to compare actual cannulation times before and after the intervention period, and video was used to review the events and assist in dividing them into medical versus surgical phases. Control charts were used to trend the total ECPR times before and after the intervention period, and mean and P values were calculated for both ECPR times and for all other categorical data. RESULTS: Mean peripheral ECPR times decreased significantly from 71.7 to 45.1 minutes ( P = 0.036) after the intervention period, and this was reflected by a centerline shift. Although we could not describe a similar decrease in central ECPR times because there were only 6 postintervention events, the times for each of these events were shorter than the historical mean of 37.8 minutes. There was a trend in improved survival, which did not meet significance both among patients undergoing peripheral ECPR (15.4% ± 10% to 43.8% ± 12.4%, P = 0.10) and central ECPR (36.4% ± 8.4% to 50% ± 25%, P = 0.60). The percentage of time dedicated to the medical phases of the actual versus simulated procedures was very consistent among both peripheral (33.0% vs. 31.9%) and central (39.6% vs. 39.8%) cannulations. CONCLUSIONS: We observed a significant decrease in peripheral cannulation times at our institution after conducting interprofessional ECPR simulations taken to the establishment of full cardiopulmonary bypass. The use of an ECMO trainer and a 3-dimensionally-printed heart allowed for both the medical and surgical phases of the procedure to be studied in detail, providing opportunities to streamline and improve this complex process. Larger multisite studies will be needed in the future to assess the effect of efforts like these on patient survival.

Autoantibody cluster analysis in juvenile lupus nephritis.

OBJECTIVE: Demographics, clinical features, and biomarkers do not consistently anticipate risk of end-stage renal disease (ESRD) in juvenile lupus nephritis (LN). Here, the existence of autoantibody clusters predictive of ESRD was explored in a cohort of biopsy-proven juvenile LN. METHODS: A retrospective chart review was performed of patients with juvenile systemic lupus erythematosus (jSLE) and biopsy-confirmed LN. Primary endpoints were ESRD and mortality. Patients were included for K-medians cluster analysis if they had a complete autoantibody profile, which included ANA titer, anti-dsDNA, anti-Smith, anti-RNP, anti-Ro/SSA, anti-La/SSB. Chi-square test was used for categorical variables and one-way ANOVA for continuous measures. Significance was p<0.05. RESULTS: Fifty-three met inclusion criteria, of which 45 were female and 37 were black. Over 80% developed LN within one year of jSLE onset and more than half (n=29) had LN at diagnosis of jSLE. Six developed ESRD. No mortalities were reported. Forty-six had a complete autoantibody profile, including four with ESRD. Three clusters were identified. Group 1 (n=8) was defined by anti-dsDNA; group 2 (n=28) by high-titer ANA (>1:1280), anti-Smith, anti-RNP, and anti-Ro/SSA; and group 3 (n=10) by anti-dsDNA and anti-Ro/SSA. There was no difference between the groups in demographics, jSLE manifestations, or markers of renal function. One in group 2 and three in group 3 developed ESRD. Those in group 3 were younger at diagnosis of LN (p=0.084) and had the highest frequency of ESRD (p=0.025). CONCLUSION: Cluster analysis revealed the highest frequency of ESRD in the group with LN defined by anti-Ro/SSA and anti-dsDNA co-positivity. Key Points • Lupus nephritis commonly is present at diagnosis of juvenile systemic lupus erythematosus or develops within the first year. • End-stage renal disease was more frequent in the cluster defined by anti-dsDNA and anti-Ro/SSA co-positivity; patients with this profile may benefit from more aggressive immunosuppression.

Impact of Anaerobic Antibacterial Spectrum on Cystic Fibrosis Airway Microbiome Diversity and Pulmonary Function.

BACKGROUND: The role of anaerobic organisms in the cystic fibrosis (CF) lung microbiome is unclear. Our objectives were to investigate the effect of broad (BS) versus narrow (NS) spectrum antianaerobic antibiotic activity on lung microbiome diversity and pulmonary function, hypothesizing that BS antibiotics would cause greater change in microbiome diversity without a significant improvement in lung function. METHODS: Pulmonary function tests and respiratory samples were collected prospectively in persons with CF before and after treatment for pulmonary exacerbations. Treatment antibiotics were classified as BS or NS. Gene sequencing data from 16S rRNA were used for diversity analysis and bacterial genera classification. We compared the effects of BS versus NS on diversity indices, lung function and anaerobic/aerobic ratios. Statistical significance was determined by multilevel mixed-effects generalized linear models and mixed-effects regression models. RESULTS: Twenty patients, 6-20 years of age, experienced 30 exacerbations. BS therapy had a greater effect on beta diversity than NS therapy when comparing time points before antibiotics to after and at recovery. After antibiotics, the NS therapy group had a greater return toward baseline forced expiratory volume at 1 second and forced expiratory flow 25%-75% values than the BS group. The ratio of anaerobic/aerobic organisms showed a predominance of anaerobes in the NS group with aerobes dominating in the BS group. CONCLUSIONS: BS antianaerobic therapy had a greater and possibly longer lasting effect on the lung microbiome of persons with CF, without achieving the recovery of pulmonary function seen with the NS therapy. Specific antibiotic therapies may affect disease progression by changing the airway microbiome.

Multisystem Inflammatory Syndrome of Children: Subphenotypes, Risk Factors, Biomarkers, Cytokine Profiles, and Viral Sequencing.

OBJECTIVE: To assess demographic, clinical, and biomarker features distinguishing patients with multisystem inflammatory syndrome in children (MIS-C); compare MIS-C sub-phenotypes; identify cytokine biosignatures; and characterize viral genome sequences. STUDY DESIGN: We performed a prospective observational cohort study of 124 children hospitalized and treated under the institutional MIS-C Task Force protocol from March to September 2020 at Children's National, a quaternary freestanding children's hospital in Washington, DC. Of this cohort, 63 of the patients had the diagnosis of MIS-C (39 confirmed, 24 probable) and 61 were from the same cohort of admitted patients who subsequently had an alternative diagnosis (controls). RESULTS: Median age and sex were similar between MIS-C and controls. Black (46%) and Latino (35%) children were over-represented in the MIS-C cohort, with Black children at greatest risk (OR 4.62, 95% CI 1.151-14.10; P = .007). Cardiac complications were more frequent in critically ill patients with MIS-C (55% vs 28%; P = .04) including systolic myocardial dysfunction (39% vs 3%; P = .001) and valvular regurgitation (33% vs 7%; P = .01). Median cycle threshold was 31.8 (27.95-35.1 IQR) in MIS-C cases, significantly greater (indicating lower viral load) than in primary severe acute respiratory syndrome coronavirus 2 infection. Cytokines soluble interleukin 2 receptor, interleukin [IL]-10, and IL-6 were greater in patients with MIS-C compared with controls. Cytokine analysis revealed subphenotype differences between critically ill vs noncritically ill (IL-2, soluble interleukin 2 receptor, IL-10, IL-6); polymerase chain reaction positive vs negative (tumor necrosis factor-α, IL-10, IL-6); and presence vs absence of cardiac abnormalities (IL-17). Phylogenetic analysis of viral genome sequences revealed predominance of GH clade originating in Europe, with no differences comparing patients with MIS-C with patients with primary coronavirus disease 19. Treatment was well tolerated, and no children died. CONCLUSIONS: This study establishes a well-characterized large cohort of MIS-C evaluated and treated following a standardized protocol and identifies key clinical, biomarker, cytokine, viral load, and sequencing features. Long-term follow-up will provide opportunity for future insights into MIS-C and its sequelae.

Early Inflammatory Markers are Associated With Inadequate Post-Induction Infliximab Trough in Pediatric Crohn's Disease.

OBJECTIVES: In pediatric Crohn's disease, infliximab trough concentrations after standard weight-based induction therapy are commonly below 7 µg/mL. Clinical treatment outcomes are associated with post-induction infliximab trough concentration. Markers of inflammation are associated with low infliximab concentrations during maintenance dosing. We sought to determine if early markers of disease activity are associated with inadequate post-induction infliximab trough concentrations in pediatric Crohn's disease. METHODS: We performed a retrospective single-center case-control study of pediatric Crohn's disease patients to assess the association between baseline and week-2 biomarkers (albumin, C-reactive protein, and erythrocyte sedimentation rate) and inadequate post-induction infliximab trough concentration (<7 µg/mL) in patients treated with standard 5 mg/kg dosing. Baseline and week-2 biomarker values were coded as dichotomous variables at clinically useful thresholds. Univariable logistic regression was used to calculate odds ratios of developing an inadequate infliximab trough concentration for each threshold, as well as thresholds in combination. RESULTS: Fifty-five patients were evaluated. Early biomarker thresholds significantly associated with inadequate post-induction infliximab trough concentrations included baseline C-reactive protein >1 mg/dL (odds ratio [OR] 4.58; 95% confidence interval [CI] 1.24--17.01), both baseline C-reactive protein >0.5 mg/dL and albumin <3.5 g/dL (OR 8.31; 95% CI 1.99--34.63), and week-2 C-reactive protein >0.5 mg/dL or albumin <3.5 mg/dL or erythrocyte sedimentation rate >25 mm/hour (OR 11.08; 95% CI 2.14--57.22). CONCLUSIONS: Routine baseline and week-2 markers of disease activity at clinically useful thresholds were associated with inadequate post-induction infliximab trough concentration in pediatric Crohn's disease patients receiving standard weight-based induction dosing.

Sedation, Analgesia, and Neuromuscular Blockade: An Assessment of Practices From 2009 to 2016 in a National Sample of 66,443 Pediatric Patients Cared for in the ICU.

OBJECTIVES: To describe the pharmaceutical management of sedation, analgesia, and neuromuscular blockade medications administered to children in ICUs. DESIGN: A retrospective analysis using data extracted from the national database Health Facts. SETTING: One hundred sixty-one ICUs in the United States with pediatric admissions. PATIENTS: Children in ICUs receiving medications from 2009 to 2016. EXPOSURE/INTERVENTION: Frequency and duration of administration of sedation, analgesia, and neuromuscular blockade medications. MEASUREMENTS AND MAIN RESULTS: Of 66,443 patients with a median age of 1.3 years (interquartile range, 0-14.5), 63.3% (n = 42,070) received nonopioid analgesic, opioid analgesic, sedative, and/or neuromuscular blockade medications consisting of 83 different agents. Opioid and nonopioid analgesics were dispensed to 58.4% (n = 38,776), of which nonopioid analgesics were prescribed to 67.4% (n = 26,149). Median duration of opioid analgesic administration was 32 hours (interquartile range, 7-92). Sedatives were dispensed to 39.8% (n = 26,441) for a median duration of 23 hours (interquartile range, 3-84), of which benzodiazepines were most common (73.4%; n = 19,426). Neuromuscular-blocking agents were dispensed to 17.3% (n = 11,517) for a median duration of 2 hours (interquartile range, 1-15). Younger age was associated with longer durations in all medication classes. A greater proportion of operative patients received these medication classes for a longer duration than nonoperative patients. A greater proportion of patients with musculoskeletal and hematologic/oncologic diseases received these medication classes. CONCLUSIONS: Analgesic, sedative, and neuromuscular-blocking medications were prescribed to 63.3% of children in ICUs. The durations of opioid analgesic and sedative medication administration found in this study can be associated with known complications, including tolerance and withdrawal. Several medications dispensed to pediatric patients in this analysis are in conflict with Food and Drug Administration warnings, suggesting that there is potential risk in current sedation and analgesia practice that could be reduced with practice changes to improve efficacy and minimize risks.

Changes in microbiome diversity following beta-lactam antibiotic treatment are associated with therapeutic versus subtherapeutic antibiotic exposure in cystic fibrosis.

In persons with cystic fibrosis (CF), decreased airway microbial diversity is associated with lower lung function. Conflicting data exist on the impact of short-term antibiotics for treatment of acute pulmonary exacerbations. However, whether differences in antibiotic exposure impacts airway microbiome changes has not been studied. We hypothesized that subtherapeutic beta-lactam antibiotic exposure, determined by the pharmacokinetics and pharmacodynamics (PK/PD) after intravenous (IV) antibiotic administration, would be associated with different patterns of changes in CF airway microbial diversity. Eligible children were enrolled when well; study assessments were performed around the time of pulmonary exacerbation. Plasma drug concentrations and bacterial minimum inhibitory concentrations (MICs) were used to determine therapeutic versus subtherapeutic beta-lactam antibiotic exposure. Respiratory samples were collected from children, and extracted bacterial DNA was amplified for the V4 region of the 16S rRNA gene. Twenty children experienced 31 APEs during the study; 45% (n = 14) of antibiotic courses were deemed therapeutic. Those in the therapeutic group had more significant decreases in alpha diversity at end of treatment and post-recovery compared to baseline than those in the subtherapeutic group. Therapeutic and subtherapeutic beta-lactam use is associated with different patterns of changes in CF airway microbial diversity following antibiotic administration.

Relationship of Pulmonary Outcomes, Microbiology, and Serum Antibiotic Concentrations in Cystic Fibrosis Patients.

OBJECTIVES: To determine the frequency of subtherapeutic exposure to intravenously administered ß-lactam antibiotics in a cohort of cystic fibrosis (CF) patients who were treated for a pulmonary exacerbation, and its impact on pulmonary function. METHODS: Nineteen CF patients between the ages of 5 and 21 years treated at Children's National Health System for a pulmonary exacerbation were followed between March 2015 and August 2016 in a prospective, longitudinal study. Pharmacokinetic modeling and minimum inhibitory concentrations (MICs) of the involved pathogens were used to determine therapeutic or subtherapeutic ß-lactam antibiotic exposure based on the time the antibiotic concentration was above the MIC. Clinical outcomes were measured by spirometry values. RESULTS: The 19 participants were treated with a total of 29 courses of antibiotics. The most common ß-lactam antibiotics used in a treatment course were ceftazidime (62%) and meropenem (45%). There was no difference in age, CF genotype, or creatinine clearance between the 9 participants (47%) who reached therapeutic concentrations versus the 10 (53%) who did not. Those who achieved sufficiently high antibiotic exposure had more significant improvement of their pulmonary function tests. CONCLUSIONS: We found that sufficient antibiotic exposure during treatment of CF pulmonary exacerbations was associated with improved pulmonary function. Moreover, it was impossible to predict, solely from the dosing regimen used, which patients were going to reach therapeutic ß-lactam antibiotic serum concentrations. This suggests that CF patients may benefit from closer monitoring of their ß-lactam exposure and bacterial MIC for optimal clinical outcomes.

Variation in Preoperative Testing and Antireflux Surgery in Infants.

BACKGROUND: Despite the availability of objective tests, gastroesophageal reflux disease (GERD) diagnosis and management in infants remains controversial and highly variable. Our purpose was to characterize national variation in diagnostic testing and surgical utilization for infants with GERD. METHODS: Using the Pediatric Health Information System, we identified infants <1 year old diagnosed with GERD between January 2011 and March 2015. Outcomes included progression to antireflux surgery (ARS) and use of relevant diagnostic testing. By using adjusted generalized linear mixed models, we compared facility-level ARS utilization. RESULTS: Of 5 299 943 infants, 149 190 had GERD (2.9%), and 4518 (3.0%) of those patients underwent ARS. Although annual rates of GERD and ARS decreased, there was a wide range of GERD diagnoses (1.8%-6.2%) and utilization of ARS (0.2%-11.2%). Facilities varied in the use of laparoscopic versus open ARS (mean: 66%, range: 23%-97%). Variation in facility-level ARS rates persisted after adjustment. Overall 3.8% of patients underwent diagnostic testing, whereas 22.8% of ARS patients underwent diagnostic testing. The proportion of surgeries done laparoscopically was independently associated with ARS utilization (odds ratio: 1.57; 95% confidence interval: 1.21-2.02). Facility-level utilization of diagnostics (P > .1) and prevalence of GERD (P > .1) were not associated with utilization of ARS. CONCLUSIONS: There is notable variation in the overall utilization of ARS and in the surgical and diagnostic approach in infants with GERD. Fewer than 4% of infants with GERD undergo diagnostic testing. This variation in care merits development of consensus guidelines and further research.

The ability of preoperative factors to predict patient-reported disability following surgery for rotator cuff pathology.

PURPOSE: Minimal research has examined the prognostic ability of shoulder examination data or psychosocial factors in predicting patient-reported disability following surgery for rotator cuff pathology. The purpose of this study was to examine these factors for prognostic value in order to help clinicians and patients understand preoperative factors that impact disability following surgery. METHODS: Sixty-two patients scheduled for subacromial decompression with or without supraspinatus repair were recruited. Six-month follow-up data were available for 46 patients. Patient characteristics, history of the condition, shoulder impairments, psychosocial factors, and patient-reported disability questionnaires were collected preoperatively. Six months following surgery, the Western Ontario Rotator Cuff Index (WORC) and global rating of change dichotomized subjects into responders versus nonresponders. Logistic regression quantified prognostic ability and created the most parsimonious model to predict outcome. RESULTS: Being on modified job duty (OR = .17, 95%CI: 0.03-0.94), and having a worker's compensation claim (OR = 0.08, 95%CI: 0.01-0.74) decreased probability of a positive outcome, while surgery on the dominant shoulder (OR = 11.96, 95%CI: 2.91-49.18) increased probability. From the examination, only impaired internal rotation strength was a significant univariate predictor. The Fear-avoidance Beliefs Questionnaire (FABQ) score (OR = 0.95, 95%CI: 0.91-0.98) and the FABQ_work subscale (OR = 0.92, 95%CI: 0.87-0.97) were univariate predictors. In the final model, surgery on the dominant shoulder (OR = 8.9, 95%CI 1.75-45.7) and FABQ_work subscale score ≤25 (OR = 15.3, 95%CI 2.3-101.9) remained significant. DISCUSSION: Surgery on the dominant arm resulted in greater improvement in patient-reported disability, thereby increasing the odds of a successful surgery. The predictive ability of the FABQ_work subscale highlights the potential impact of psychosocial factors on patient-reported disability. Implications for Rehabilitation Impairment-based shoulder measurements were not strong predictors of patient-reported outcome. Having high fear-avoidance behavior scores on the FABQ, especially the work subscale, resulted in a much lower chance of responding well to rotator cuff surgery as measured by self-reported disability. Having surgery on the dominant shoulder, as compared to the nondominant side, resulted in larger improvements in disability levels.

Impact of a rapid respiratory panel test on patient outcomes.

CONTEXT: Evolution of polymerase chain reaction testing for infectious pathogens has occurred concurrent with a focus on value-based medicine. OBJECTIVE: To determine if implementation of the FilmArray rapid respiratory panel (BioFire Diagnostics, Salt Lake City, Utah) (hereafter RRP), with a shorter time to the test result and expanded panel, results in different outcomes for children admitted to the hospital with an acute respiratory tract illness. DESIGN: Patient outcomes were compared before implementation of the RRP (November 1, 2011, to January 31, 2012) versus after implementation of the RRP (November 1, 2012, to January 31, 2013). The study included inpatients 3 months or older with an acute respiratory tract illness, most admitted through the emergency department. Testing before RRP implementation used batched polymerase chain reaction analysis for respiratory syncytial virus and influenza A and B, with additional testing for parainfluenza 1 through 3 in approximately 11% of patients and for human metapneumovirus in less than 1% of patients. The RRP tested for respiratory syncytial virus, influenza A and B, parainfluenza 1 through 4, human metapneumovirus, adenovirus, rhinovirus/enterovirus, and coronavirus NL62. RESULTS: The pre-RRP group had 365 patients, and the post-RRP group had 771 patients. After RRP implementation, the mean time to the test result was shorter (383 minutes versus 1119 minutes, P < .001), and the percentage of patients with a result in the emergency department was greater (51.6% versus 13.4%, P < .001). There was no difference in whether antibiotics were prescribed, but the duration of antibiotic use was shorter after RRP implementation (P = .003) and was dependent on receiving test results within 4 hours. If the test result was positive, the inpatient length of stay (P = .03) and the time in isolation (P = .03) were decreased after RRP implementation compared with before RRP implementation. CONCLUSIONS: The RRP decreases the duration of antibiotic use, the length of inpatient stay, and the time in isolation.

Predicting cancer mortality: Developing a new cancer care variable using mixed methods and the quasi-statistical approach.

OBJECTIVE: To demonstrate the value of using a variable derived from qualitative analysis in subsequent quantitative analyses. DATA SOURCES/STUDY SETTING: Mixed methods data were combined with 10-year mortality outcomes. Participants with cancer were recruited from services at a large teaching hospital, and mortality data were from the Social Security Death Index. STUDY DESIGN: An observational concurrent or convergent mixed methods design was used to collect demographics and structured ratings along with qualitative data from 909 cancer patients at baseline. DATA COLLECTION/EXTRACTION METHODS: Coding rules for qualitative data were defined for open-ended responses from cancer participants speaking about their view of self, and a variable was numerically coded for each case. Mortality outcomes were matched to baseline data, including the view of self variable. PRINCIPAL FINDINGS: Individuals with an improved view of self had a significantly lower mortality rate than those for whom it was worse or unchanged, even when adjusting for age, gender, and cancer stage. CONCLUSIONS: Statistical analysis of qualitative data is feasible and can identify new predictors with health services' implications associated with cancer mortality. Future studies should consider the value of testing coded qualitative variables in relation with key health care outcomes.

Evaluation of urine biomarkers of kidney injury in polycystic kidney disease.

Progressive disruption of renal tubular integrity in the setting of increased cellular proliferation and apoptosis is a feature of autosomal dominant polycystic kidney disease (ADPKD). Here we evaluated the effect of these processes on the expression of Lcn2 (NGAL) and interleukin (IL)-18, markers of tubular injury, in rodent models and in the cyst fluid and urine of patients with ADPKD. Two mouse models where Pkd2 was inactivated, which resulted in early- or adult-onset cysts, were used to evaluate NGAL levels. Further, the Han:SPRD rat model of polycystic disease was used to study IL-18 levels. In four annual serial urine samples collected from 107 patients with ADPKD in the Consortium for Radiologic Imaging for the Study of Polycystic Kidney Disease (CRISP) study, NGAL and IL-18 excretion rates were determined in conjunction with measures of total kidney volume and estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease equation. Kidneys from affected mice and rats showed prominent expression of NGAL and IL-18/IL-18R, respectively, in epithelial cells lining kidney cysts. In human ADPKD cyst fluid, both NGAL and IL-18 were elevated. In CRISP patients, the mean percentage increase in total kidney volume was 5.4/year and the mean decline in eGFR 2.4 ml/min/year. The trend of increased mean urine NGAL and IL-18 over 3 years was statistically significant; however, there was no association between tertiles of IL-18 or quartiles of NGAL and change in total kidney volume or eGFR over this period. Thus, urinary NGAL and IL-18 excretion is mildly and stably elevated in ADPKD, but does not correlate with changes in total kidney volume or kidney function. This may be due, in part, to the lack of communication between individual cysts and the urinary collecting system in this disorder.

Analysis of baseline parameters in the HALT polycystic kidney disease trials.

HALT PKD consists of two ongoing randomized trials with the largest cohort of systematically studied patients with autosomal dominant polycystic kidney disease to date. Study A will compare combined treatment with an angiotensin-converting inhibitor and receptor blocker to inhibitor alone and standard compared with low blood pressure targets in 558 early-stage disease patients with an eGFR over 60 ml/min per 1.73 m(2). Study B will compare inhibitor-blocker treatment to the inhibitor alone in 486 late-stage patients with eGFR 25-60 ml/min per 1.73 m(2). We used correlation and multiple regression cross-sectional analyses to determine associations of baseline parameters with total kidney, liver, or liver cyst volumes measured by MRI in Study A and eGFR in both studies. Lower eGFR and higher natural log-transformed urine albumin excretion were independently associated with a larger natural log-transformed total kidney volume adjusted for height (ln(HtTKV)). Higher body surface area was independently associated with a higher ln(HtTKV) and lower eGFR. Men had larger height-adjusted total kidney volume and smaller liver cyst volumes than women. A weak correlation was found between the ln(HtTKV) and natural log-transformed total liver volume adjusted for height or natural log liver cyst volume in women only. Women had higher urine aldosterone excretion and lower plasma potassium. Thus, our analysis (1) confirms a strong association between renal volume and functional parameters, (2) shows that gender and other factors differentially affect the development of polycystic disease in the kidney and liver, and (3) suggests an association between anthropomorphic measures reflecting prenatal and/or postnatal growth and disease severity.

The effect of resident duty hour restriction on trauma center outcomes in teaching hospitals in the state of Pennsylvania.

BACKGROUND: Resident duty hour restriction was instituted to improve patient safety, but actual impact on patient care is unclear. We sought to determine the effect of duty hour restriction on trauma outcomes in Level I trauma centers (TCs; surgery residency programs) versus Level II TCs (those with no surgery residency programs) within the state of Pennsylvania, using noninferiority as our hypothesis testing. METHODS: Outcomes (mortality and length of stay [LOS]) were compared in Level II TCs without surgery residencies (n = 7) with Level I TCs (with surgery residencies; n = 14) PRE80 (2001-2003) and POST80 (2004-2007). The subcategories of critically injured patients, Injury Severity Score (ISS) >15, ISS >25, Trauma and Injury Severity Score (TRISS) ≤ 50, Abbreviated Injury Scale (AIS) head/chest/abdomen score >3, age >65 years, mechanism, and shock, functioned as outcome predictors. RESULTS: There was a decrease in mortality overall PRE80 to POST80 for Level I and II TCs. There was a decrease in mortality in Level I TCs POST80 in ISS >15 (16.5% vs. 14.8%, p = 0.0001), AIS (head) score >3 (20.8% vs. 17.8%, p < 0.0001), age >65 years (12.2% vs. 10.7%, p = 0.0013), and blunt mechanism (5.2% vs. 4.6%, p = 0.0004). LOS was reduced in ISS >15, AIS (head) score >3, age >65 years, and penetrating mechanism in Level I TCs POST80. A similar but more profound decrease was also seen in Level II TCs PRE80 and POST80 (ISS >15, 25; AIS (head) score; shock; blunt mechanism; and TRISS ≤ 50). Testing for inhomogeneity identified less-severely injured patients at Level II TCs POST80 compared with Level I TCs in certain subcategories (ISS >15, 25; AIS (head) score; shock; blunt mechanism; and TRISS ≤ 50) regarding mortality and LOS (TRISS >50%). CONCLUSIONS: Decreases in mortality and LOS during the study periods were likely not related to resident work hour restriction but rather to overall improvement in outcomes seen at Level II (no residents) and Level I (residents) TCs. Resident work hour restrictions had no discernible effect on patient care (noninferiority).

General health and knee function outcomes from 7 days to 12 weeks after spinal anesthesia and multimodal analgesia for anterior cruciate ligament reconstruction.

BACKGROUND: We previously reported that continuous perineural femoral analgesia reduces pain with movement during the first 2 days after anterior cruciate ligament reconstruction (ACLR, n = 270), when compared with multimodal analgesia and placebo perineural femoral infusion. We now report the prospectively collected general health and knee function outcomes in the 7 days to 12 wk after surgery in these same patients. METHODS: At three points during 12 wk after ACLR surgery, patients completed the SF-36 General Health Survey, and the Knee Outcome Survey (KOS). Generalized Estimating Equations were implemented to evaluate the association between patient-reported survey outcomes and (1) preoperative baseline survey scores, (2) time after surgery, and (3) three nerve block treatment groups. RESULTS: Two hundred seventeen patients' data were complete for analysis. In univariate and multiple regression Generalized Estimating Equations models, nerve block treatment group was not associated with SF-36 and KOS scores after surgery (all with P > or = 0.05). The models showed that the physical component summary of the SF-36 (P < 0.0001) and the KOS total score (P < 0.0001) increased (improved) over time after surgery and were also influenced by baseline scores. CONCLUSIONS: After spinal anesthesia and multimodal analgesia for ACLR, the nerve block treatment group did not predict SF-36 or knee function outcomes from 7 days to 12 wk after surgery. Further research is needed to determine whether these conclusions also apply to a nonstandardized anesthetic, or one that includes general anesthesia and/or high-dose opioid analgesia.

A small sample randomized clinical trial methodology using N-of-1 designs and mixed model analysis.

BACKGROUND/OBJECTIVES: To date, research on substance abuse prevention relied extensively on large sample randomized clinical trials to evaluate intervention programs. These designs are appropriate for certain types of randomized prevention trials (e.g., efficacy or effectiveness for broad populations) but are unfeasible for other prevention science scenarios (e.g., rare pathologies, pilot studies, or replication tests at specific locales). METHODS: An alternative randomized clinical trial is described that relies on much smaller samples, less resources than the large sample designs, randomization, N-of-1 designs for the intervention group, and mixed model analysis. RESULTS: This methodology is illustrated using a small sample prevention study, which demonstrates its statistical power, flexibility, and sophistication for experimental testing of prevention-oriented research questions. SCIENTIFIC SIGNIFICANCE: This methodology can be applied to many existing prevention datasets to facilitate secondary analyses of existing datasets as well as novel studies. It is hoped that such efforts will include further development of the small sample design in substance abuse prevention contexts.

Perceived discrimination in health care and use of preventive health services.

OBJECTIVE: To examine the relationship between perceived discrimination and preventive health care utilization. DESIGN AND PARTICIPANTS: Cross-sectional analysis using the 2004 Behavioral Risk Factor Surveillance System "Reactions to Race" module (N = 28,839). MEASUREMENTS: Outcomes were self-reported utilization of seven preventive health services. Predictors included perceived negative and positive racial discrimination (vs. none) while seeking health care in the past year. Multivariable models adjusted for additional patient characteristics. MAIN RESULTS: In unadjusted models, negative discrimination was significantly associated with less utilization of mammogram, pap test, PSA test, blood stool test, and sigmoidoscopy/colonoscopy (ORs = 0.53-0.73, p < .05), but not flu or pneumococcal vaccines (ORs = 0.76 and 0.84). Positive discrimination was significantly associated with more utilization of all services (ORs = 1.29-1.58, p < .05) except pap test (OR = 0.94). In adjusted models, neither negative nor positive discrimination was predictive of utilization, except for PSA test (positive discrimination OR = 1.33, p < .05). CONCLUSIONS: Perceived racial discrimination in health care does not independently predict preventive health care utilization.

Prevalence of urinary tract infection in childhood: a meta-analysis.

BACKGROUND: Knowledge of baseline risk of urinary tract infection can help clinicians make informed diagnostic and therapeutic decisions. We conducted a meta-analysis to determine the pooled prevalence of urinary tract infection (UTI) in children by age, gender, race, and circumcision status. METHODS: MEDLINE and EMBASE databases were searched for articles about pediatric urinary tract infection. Search terms included urinary tract infection, cystitis, pyelonephritis, prevalence and incidence. We included articles in our review if they contained data on the prevalence of UTI in children 0-19 years of age presenting with symptoms of UTI. Of the 51 articles with data on UTI prevalence, 18 met all inclusion criteria. Two evaluators independently reviewed, rated, and abstracted data from each article. RESULTS: Among infants presenting with fever, the overall prevalence (and 95% confidence interval) of UTI was 7.0% (CI: 5.5-8.4). The pooled prevalence rates of febrile UTIs in females aged 0-3 months, 3-6 months, 6-12 months, and >12 months was 7.5%, 5.7%, 8.3%, and 2.1% respectively. Among febrile male infants less than 3 months of age, 2.4% (CI: 1.4-3.5) of circumcised males and 20.1% (CI: 16.8-23.4) of uncircumcised males had a UTI. For the 4 studies that reported UTI prevalence by race, UTI rates were higher among white infants 8.0% (CI: 5.1-11.0) than among black infants 4.7% (CI: 2.1-7.3). Among older children (<19 years) with urinary symptoms, the pooled prevalence of UTI (both febrile and afebrile) was 7.8% (CI: 6.6-8.9). CONCLUSIONS: Prevalence rates of UTI varied by age, gender, race, and circumcision status. Uncircumcised male infants less than 3 months of age and females less than 12 months of age had the highest baseline prevalence of UTI. Prevalence estimates can help clinicians make informed decisions regarding diagnostic testing in children presenting with signs and symptoms of urinary tract infection.