Prophylactic Mesh Reinforcement for Prevention of Midline Incisional Hernias: A Publication Bias Adjusted Meta-analysis.

OBJECTIVE: To systematically review the published literature on the use of prophylactic mesh reinforcement of midline laparotomy closures for prevention of VIH. SUMMARY OF BACKGROUND DATA: VIH are common complications of abdominal surgery. Prophylactic mesh has been proposed as an adjunct to prevent their occurrence. METHODS: PubMed, Embase, Scopus, and Cochrane were reviewed for RCTs that compared prophylactic mesh reinforcement versus conventional suture closure of midline abdominal surgery. Primary outcome was the incidence of VIH at postoperative follow-up ≥24 months. Secondary outcomes included surgical site infection and surgical site occurrence (SSO). Pooled risk ratios were obtained through random effect meta-analyses and adjusted for publication bias. Network meta-analyses were performed to compare mesh types and locations. RESULTS: Of 1969 screened articles, 12 RCTs were included. On meta-analysis there was a lower incidence of VIH with prophylactic mesh [11.1% vs 21.3%, Relative risk (RR) = 0.32; 95% confidence interval (CI) = 0.19-0.55, P < 0.001), however, publication bias was highly likely. When adjusted for this bias, prophylactic mesh had a more conservative effect (RR = 0.52; 95% CI = 0.39-0.70). There was no difference in risk of surgical site infection (9.1% vs 8.9%, RR = 1.08, 95% CI = 0.82-1.43; P = 0.118), however, prophylactic mesh increased the risk of SSO (14.2% vs 8.9%, RR = 1.57, 95% CI = 1.19-2.05; P < 0.001). CONCLUSION: Current RCTs suggest that in mid-term follow-up prophylactic mesh prevents VIH with increased risk for SSO. There is limited long-term data and substantial publication bias.

Reproducing Statistics Performed in Published Randomized Controlled Trials.

INTRODUCTION: Randomized controlled trials (RCT) represent evidence at the lowest potential risk for bias. Clinicians in all specialties depend upon RCTs to guide patient care. Issues such as statistical discordance, or reporting statistical results that cannot be reproduced, should be uncommon. Our aim was to confirm the statistical reproducibility of published RCTs. METHODS: PubMed was searched using "randomized controlled trial." Studies were selected using a random number generator. Studies were included if the primary outcome could be reproduced using the data and statistical test reported in the manuscript. The reproduced p-value from our analysis and the published p-value were compared. Primary outcome was the number of studies that reported p-values that differed in statistical significance (crossed p-value=0.05) from the reproduction analysis. Assuming an alpha of 0.05, a beta of 0.80, an estimated rate of statistical discordance of 5% for RCTs, a total of at least 568 studies were required. RESULTS: Overall, 572 RCTs were selected involving six specialties. Of these, 45% were positive (p<0.05) studies. Eleven (2%) published results that differed from the reproduction analysis and crossed the p=0.05 threshold. All 11 studies were positive studies (while the reproduction analysis demonstrated p≥0.05). CONCLUSION: Less than 5% of published RCTs reported a discordant p-value that crossed the "p=0.05" threshold. Although the occurrence is uncommon, the existence of even one RCT publishing nonreproducible results is concerning. Future studies should seek to identify why some RCTs report discordant statistics and how to prevent this from occurring.

Impact of COVID-19 on nationwide pediatric otolaryngology practice: Adenotonsillectomies (TA) and tonsil-related diagnoses trends.

OBJECTIVES/HYPOTHESIS: To determine the effects of the COVID-19 pandemic on Adenotonsillectomies (TA), Tonsil Related Cases (TC), and Peritonsillar Abscess (PTA) Trends. STUDY DESIGN: Retrospective Cohort Study. METHODS: This is a retrospective cohort study using the Pediatric Health Information System® (PHIS) database, which consists of 51 children's hospitals. Regions were defined according to PHIS rules with at least five children's hospitals per region. We compared monthly total TA, TC, TC as a proportion of all hospital visits, and PTA from all encounters at each hospital from January 1, 2019, through December 31, 2021. RESULTS: Compared to 2019, April 2020 saw mean TC drop significantly from 371.62 to 68.37 (p < 0.001). Interestingly, June, September, and December 2020 had significantly higher mean TC compared to 2019. TC as a proportion of all hospital visits decreased significantly throughout the majority of 2021. Similarly, TA significantly decreased during 2020 and 2021 across all regions in the US, starting in March 2020 and this reduction in TA extended through the end of 2021 without any signs of recovery. PTA rates did not change significantly over the three years. CONCLUSIONS: The pandemic-plagued 2020 saw a noticeable decrease in overall TC and TA but then rebounded quickly to even higher than pre-pandemic levels. However, this rebound halted for the majority of 2021 and subsequently decreased to lower than pre-pandemic levels, which differs from other communicable pathologies such as otitis media which decreased initially then recovered to pre-pandemic levels by Summer of 2021.

Impact of COVID-19 on nationwide pediatric otolaryngology: Otitis media and myringotomy tube trends.

PURPOSE: The pandemic related to the novel coronavirus (COVID-19) has led to a decrease in communicable diseases due to social distancing and mask-wearing. How have the prevalence of otitis media (OM) and its associated procedures changed during the pandemic? STUDY DESIGN: Retrospective Cohort Study. METHODS: This is a retrospective cohort study using the Pediatric Health Information System® (PHIS) database, which consists of 48 children's hospitals. Regions were defined according to PHIS rules. We compared proportion of OM to total diagnoses codes, and collected mastoiditis, and MT placements from all encounters through January 1, 2019-June 31, 2021. RESULTS: In April 2020, there was a decrease in mean proportion of OM cases per 100 hospital visits (7 v. 2, p < 0.0001) and this was sustained through 2020 and until June 2021 (6-7 v. 2-4, p < 0.05; p < 0.05). Compared to 2020, the months of April and June 2021 showed an increase in mean proportion of OM cases (6-7 v. 3-4, p < 0.05) while May did not. This relative increase in OM cases through April-June were primarily driven by the South, the Midwest, and the Northeast in April and the South and the Midwest in June. MT procedures followed similar trends. In 2020, there was no difference in mastoiditis as a proportion of OM cases compared to 2019 however there was a statistically higher rate of mastoiditis in 2020 compared to 2021. CONCLUSIONS: The COVID-19 pandemic led to declines in OM and MT case volumes that have started to increase. A geographic relationship may exist, and this connection could be influenced by mask mandates and social distancing.

Interventions to decrease complications after shoulder dystocia: a systematic review and Bayesian meta-analysis.

OBJECTIVE: This study aimed to evaluate the outcomes associated with the implementation of simulation exercises to reduce the sequela of shoulder dystocia. DATA SOURCES: Electronic databases (Ovid MEDLINE, Embase, the Cumulative Index to Nursing and Allied Health Literature database, and Scopus) were initially queried in June 2020 and updated in November 2020. The following 3 concepts were introduced and refined using the controlled vocabulary of the database: vaginal birth, shoulder dystocia, and simulation training. There were no limitations to the year of publication as part of the search strategy. STUDY ELIGIBILITY CRITERIA: We included all studies that reported on the frequency of shoulder dystocia and the associated complications before and after the implementation of interventional exercises to improve outcomes. METHODS: Two authors independently assessed the abstracts and full-text articles of all studies for eligibility and evaluated the quality of the included studies using the Newcastle-Ottawa Scale. Any inconsistencies related to study evaluation or data extraction were resolved by a third author. The coprimary outcomes of this systematic review and meta-analysis were neonatal brachial plexus palsy diagnosed following deliveries complicated by shoulder dystocia and persistence of brachial palsy at 12 months or later. The secondary outcomes were the frequency of shoulder dystocia and cesarean delivery. Study effects were combined using a Bayesian meta-analysis and were reported as risk ratios and 95% credible intervals (Crs). RESULTS: Of the 372 articles reviewed, 16 publications, which included 428,552 deliveries with 217,713 (50.8%) deliveries during the preintervention and 210,839 (49.2%) deliveries during the postinterventional period, were included in the meta-analysis. The incidence of neonatal brachial plexus palsy after shoulder dystocia decreased from 12.1% to 5.7% (risk ratio, 0.37; 95% Cr, 0.26-0.57; probability of reduction 100%). The overall proportion of neonatal brachial plexus palsy decreased, but with less precision, from 0.3% to 0.1% (risk ratio, 0.53; 95% Cr, 0.21-1.26; probability of reduction 94%). Two studies followed newborns with brachial plexus palsy for at least 12 months. One study that reported on persistent neonatal brachial plexus palsy at 12 months among 1148 shoulder dystocia cases noted a reduction in persistent neonatal brachial plexus palsy from 1.9% to 0.2% of shoulder dystocia cases (risk ratio, 0.13; 95% confidence interval, 0.04-0.49). In contrast, the study that reported on persistent neonatal brachial plexus palsy at 12 months for all deliveries noted that it did not change significantly, namely from 0.3 to 0.2 per 1000 births (risk ratio, 0.77; 95% confidence interval, 0.31-1.90). Following the implementation of shoulder dystocia interventional exercises, the diagnosis of shoulder dystocia increased significantly from 1.2% to 1.7% of vaginal deliveries (risk ratio, 1.39; 95% Cr, 1.19-1.65; probability of increase 100%). Compared with the preimplementation period, the cesarean delivery rate increased postimplementation from 21.2% to 25.9% (risk ratio, 1.22; 95% Cr, 0.93-1.59; probability of increase 93%). We created an online tool (https://ccrebm-bell.shinyapps.io/sdmeta/) that permits calculation of the absolute risk reduction and absolute risk increase attributable to the intervention vis-à-vis the incidence of shoulder dystocia, neonatal brachial plexus palsy, and cesarean deliveries. CONCLUSION: Introduction of shoulder dystocia interventional exercises decreased the rate of neonatal brachial plexus palsy per shoulder dystocia case; the data on persistence of neonatal brachial plexus palsy beyond 12 months is limited and contradictory. Implementation of the interventions was associated with an increase in the diagnosis of shoulder dystocia and rate of cesarean deliveries.

Prognostic value of ambulatory blood pressure and clinical use of echocardiography to detect left ventricular hypertrophy in children evaluated for primary hypertension.

BACKGROUND: Hypertension (HTN) is common in children and often associated with pathologic progression to end organ damage, specifically left ventricular hypertrophy (LVH). METHODS: The primary goal of this retrospective chart review is to determine if patients with higher blood pressure were more likely to complete echocardiogram (ECHO) and more likely to have LVH, among a pediatric population referred for hypertension evaluation before the 2017 American Academy of Pediatrics (AAP) guidelines. To meet this goal, the number of patients evaluated by ECHO and prevalence of LVH was examined for independent associations with blood pressure and BMI categories by logistic regression. RESULTS: It was found that higher blood pressure was associated with having an ECHO evaluation (p = 0.012). Among patients evaluated by ECHO, one-third had LVH but the presence of LVH was not associated with blood pressure severity or use of anti-hypertensive medication. Instead, BMI was the only factor associated with LVH cardiac remodeling in our population (p = 0.025). CONCLUSIONS: Newly updated AAP practice guidelines recommend evaluation of HTN via ABPM, with ECHO performed only at the initiation of pharmaceutical therapy. It is notable that BMI, the only risk factor of LVH found in this study, is not addressed in the current AAP guidelines for ECHO evaluation among hypertensive children. This study suggests that ECHO evaluation may be warranted in a larger subset of children as is recommended by current European Society of Hypertension pediatric guidelines.

Distance Traveled to a Fetal Center and Pregnancy Outcomes in Twin-Twin Transfusion Syndrome.

BACKGROUND: Fetoscopic laser photocoagulation (FLP) is the definitive treatment for twin-twin transfusion syndrome (TTTS). Due to variability in geographic proximity to high-volume fetal centers, many patients travel great distances to receive experienced care. We sought to determine whether distance traveled (DT) is associated with gestational age (GA) at delivery and neonatal survival. METHODS: A prospective cohort study of patients within the continental United States referred to our center between September 23, 2011 and July 25, 2018 undergoing planned FLP for TTTS (n = 393; GA 20.6 ± 2.5 weeks; stage I: n = 50; stage II: n = 118; stage III: n = 208; stage IV: n = 17) was performed. The great-circle distance to our center was calculated using patients' home zip codes. DT was stratified into groups containing equal patient numbers and pregnancy outcomes assessed. RESULTS: A total of 393 patients met the inclusion criteria. The threshold distance from our center was <250 miles (n = 181), 250-499 miles (n= 119), and ≥500 miles (n = 93). There was no significant difference between any of the preoperative variables among the three groups, with the exception of race and rural status. Furthermore, there was no significant association between DT and GA at delivery (p = 0.34), time interval from procedure to delivery (p = 0.37), and the number of neonatal survivors (p= 0.21). Preterm premature rupture of membranes (PPROM) at <34 weeks was highest (47.9%, p = 0.04) in the group traveling 250-499 miles. CONCLUSION: To our knowledge, this is the largest study to show that in TTTS, DT is not associated with GA at delivery, time interval from procedure to delivery, or neonatal survival. Although PPROM at <34 weeks was higher in the group traveling 250-499 miles, there was no significant difference in GA at delivery. While patients with advanced disease may choose to seek treatment based on proximity, traveling long distances does not adversely affect pregnancy outcomes.

Peritoneal dialysis catheter outcomes in infants initiating peritoneal dialysis for end-stage renal disease.

BACKGROUND: End-stage renal disease (ESRD) although rare among infants presents many management challenges. We sought to evaluate factors associated with PD catheter failure among infants initiated on chronic PD. METHODS: A retrospective chart review of all children under two years of age who had PD catheters placed for initiation of chronic PD from 2002 to 2015. Data was extracted for catheter related events occurring within 12 months of catheter placement. Cox and Poisson regression models were used to delineate factors associated catheter complications. RESULTS: Twenty-five infants with median age 18 days had PD catheters placed for chronic dialysis. Common complications included leakage around the exit site (31%), blockage (26%), migration or malposition (23%), catheter-related infections (18%), and other complications (2%). Predictors of initial PD catheter failure were age less than one month at catheter placement (hazard ratio (HR) 7.77, 95% CI, 1.70-35.39, p = 0.008), use of catheter within three days of placement (HR 5.67, 95% CI, 1.39-23.10, p = 0.015) and presence of a hernia (HR 8.64, 95% CI, 1.19-62.36, p = 0.033). In an adjusted Poisson regression model, PD catheter use within three days of placement was the only predictor of any catheter complication over the12 months of follow up. CONCLUSIONS: Use of PD catheters within three days of placement was associated with catheter failure. We recommend that when possible, catheters should be allowed to heal for at least three days prior to use to reduce risk of complications and improve catheter survival.

Recent Thymus Emigrant CD4+ T Cells Predict HIV Disease Progression in Patients With Perinatally Acquired HIV.

BACKGROUND: Robust immune restoration in human immunodeficiency virus (HIV)-positive patients is dependent on thymic function. However, few studies have investigated thymic function and its correlation with disease progression over time in HIV-positive patients. METHODS: In this longitudinal prospective study, we followed 69 HIV-positive patients who were perinatally infected. Peripheral blood mononuclear cells were stained with monoclonal anti-CD4 and anti-CD31 and recent thymic emigrants (CD4+recently emigrated from the thymus (RTE), CD4+CD31+) quantified by flow cytometry. Statistical analysis used Wilcoxon rank sum test, Kruskal-Wallis, Spearman correlation, and Kaplan-Meier estimates; Cox regression models were performed for the longitudinal analysis. RESULTS: Median age of HIV positive patients enrolled was 13 years (interquartile range [IQR], 8.6). CD4+RTE% decreased with age and was higher in females. Median CD4+RTE% was 53.5%, IQR, 22.9. CD4+RTE% was closely related to CD4+% and absolute counts but independent of viral load and CD8+CD38+%. Antiretroviral compliance as well as higher nadir CD4+% were associated with higher CD4+RTE%. Low CD4+RTE% predicted poor progression of VL and CD4+% over time. CONCLUSIONS: CD4+RTE% predicts disease progression and may reflect history of disease in HIV-positive patients and adolescents. They are easy to measure in the clinical setting and may be helpful markers in guiding treatment decisions.

Prevalence of Pancreatic Steatosis at a Pediatric Tertiary Care Center.

OBJECTIVES: Pancreatic steatosis in adults has been proposed to be associated with obesity; however, data on pancreatic steatosis in children are lacking. Our study aimed to measure the prevalence of pancreatic steatosis in children and to examine its association with obesity and nonalcoholic fatty liver disease. METHODS: This is a retrospective chart review study of 232 patients 2 to 18 years old who underwent abdominal computed tomographic imaging in the emergency department or inpatient ward within a 1-year time span and from whom demographics, anthropometrics, and medical history were obtained. Our radiologist determined mean Hounsfield unit (HU) measurements for the pancreas, liver, and spleen. A difference of -20 between the pancreas and spleen (psHU) and between the liver and spleen was used to determine fatty infiltration. RESULTS: Of the 232 patients, 11.5% had a psHU less than -20. The prevalence of pancreatic steatosis was more than double among obese children (19%) than that in nonobese groups (8%). There is a significant correlation between the psHU and liver-spleen HU (r = 0.50, P < 0.001). CONCLUSIONS: Pancreatic steatosis was identified in 10% of the study population and is associated with obesity. Also, pancreatic steatosis is significantly associated with nonalcoholic fatty liver disease. This is the first study assessing the prevalence of pancreatic steatosis in children.

Resistin deficiency in mice has no effect on pulmonary responses induced by acute ozone exposure.

Acute exposure to ozone (O3), an air pollutant, causes pulmonary inflammation, airway epithelial desquamation, and airway hyperresponsiveness (AHR). Pro-inflammatory cytokines-including IL-6 and ligands of chemokine (C-X-C motif) receptor 2 [keratinocyte chemoattractant (KC) and macrophage inflammatory protein (MIP)-2], TNF receptor 1 and 2 (TNF), and type I IL-1 receptor (IL-1α and IL-1ß)-promote these sequelae. Human resistin, a pleiotropic hormone and cytokine, induces expression of IL-1α, IL-1ß, IL-6, IL-8 (the human ortholog of murine KC and MIP-2), and TNF. Functional differences exist between human and murine resistin; yet given the aforementioned observations, we hypothesized that murine resistin promotes O3-induced lung pathology by inducing expression of the same inflammatory cytokines as human resistin. Consequently, we examined indexes of O3-induced lung pathology in wild-type and resistin-deficient mice following acute exposure to either filtered room air or O3. In wild-type mice, O3 increased bronchoalveolar lavage fluid (BALF) resistin. Furthermore, O3 increased lung tissue or BALF IL-1α, IL-6, KC, TNF, macrophages, neutrophils, and epithelial cells in wild-type and resistin-deficient mice. With the exception of KC, which was significantly greater in resistin-deficient compared with wild-type mice, no genotype-related differences in the other indexes existed following O3 exposure. O3 caused AHR to acetyl-ß-methylcholine chloride (methacholine) in wild-type and resistin-deficient mice. However, genotype-related differences in airway responsiveness to methacholine were nonexistent subsequent to O3 exposure. Taken together, these data demonstrate that murine resistin is increased in the lungs of wild-type mice following acute O3 exposure but does not promote O3-induced lung pathology.

Prevalence and risk factors associated with resistance-associated mutations to etravirine in a cohort of perinatally HIV-infected children.

BACKGROUND: Etravirine is a second-generation non-nucleoside reverse transcriptase inhibitor (NNRTI) with reduced cross-resistance to first-generation NNRTIs. Because many perinatally HIV-infected patients have been treated with first-generation NNRTIs, they may have acquired resistance-associated mutations to etravirine (RAMe). METHODS: We determined for the interval 1998-2009 the prevalence and factors associated with the presence of RAMe. RESULTS: Twenty-three of 66 (34.8%) children had RAMe; the most common were 181C (19.6%), 190A (7.5%), 98G (6%), 106I (4.5%), 179D (4.5%), 100I (3%), 181I (1.5%), 138A (1.5%) and 179T (1.5%). Eleven children with RAMe (17%) had a mutation score between 2.5 and 3.5 and 1 (1.5%) a score ≥4, indicating an intermediate and reduced response to etravirine. For each 1% increase in CD4% there is a 7% decrease in the odds of RAMe (OR 0.93; 95% CI 0.88-0.97; P < 0.01). History of nevirapine use (OR 8.95; 95% CI 2.31-34.73; P < 0.01) and Hispanic ethnicity (OR 4.76; 95% CI 1.03-21.87; P = 0.04) are significantly associated with risk of RAMe. CONCLUSIONS: RAMe are present and common among antiretroviral-experienced perinatally HIV-infected children without previous exposure to etravirine. This could limit the efficacy of etravirine-based regimens. In addition, our results underscore the importance of taking previous history of nevirapine into account for combined antiretroviral therapy regimens that contain etravirine.

Myoglobin removal using high-volume high-flux hemofiltration in patients with oliguric acute kidney injury.

BACKGROUND: Rhabdomyolysis can cause acute kidney injury (AKI). It remains controversial whether or not myoglobin can be removed from the circulation with extracorporeal therapy and decrease the incidence of AKI. Therefore, we examined myoglobin removal in a series of 11 patients with oliguric AKI treated with high-volume hemofiltration. METHODS: Patients received prefilter hemofiltration using a polysulphone filter with a molecular size cutoff of 65 kDa and a surface area of 1.7 m(2). Sieving coefficients and myoglobin clearances were calculated at 6, 12, and 24 h after the start of hemofiltration. RESULTS: The mean sieving coefficient was 0.158, and the mean myoglobin clearance was 8.7 ml/min. CONCLUSION: Despite the use of high-volume hemofiltration, the removal of myoglobin was negligible. In patients with normal renal function, the anticipated amount of extracorporeal removal would not significantly impact renal exposure to myoglobin.

N-of-1 Trials vs. Usual Care in Children With Hypertension: A Pilot Randomized Clinical Trial.

BACKGROUND: Blood pressure (BP) is often inadequately controlled in children treated for hypertension, and personalized (n-of-1) trials show promise for tailoring treatment choices. We assessed whether patients whose treatment choices are informed by an n-of-1 trial have improved BP control compared to usual care. METHODS: A randomized clinical trial was conducted in a pediatric hypertension clinic in Houston from April 2018 to September 2020. Hypertensive adolescents and young adults 10-22 years old were randomized 1:1 to a strategy of n-of-1 trial using ambulatory BP monitoring to inform treatment choice or usual care, with treatment selected by physician preference. The primary outcome was the proportion of patients with ambulatory BP control at 6 months in a Bayesian analysis. RESULTS: Among 49 participants (23 randomized to n-of-1 trials and 26 to usual care), mean age was 15.6 years. Using skeptical priors, we found a 69% probability that n-of-1 trials increased BP control at 6 months (Bayesian odds ratio (OR) 1.24 (95% credible interval (CrI) 0.51, 2.97), and 74% probability using neutral informed priors (OR 1.45 (95% CrI 0.48, 4.53)). Systolic BP was reduced in both groups, with a 93% probability of greater reduction in the n-of-1 trial group (mean difference between groups = -3.6 mm Hg (95% CrI -8.3, 1.28). There was no significant difference in side effect experience or caregiver satisfaction. CONCLUSIONS: Among hypertensive adolescents and young adults, n-of-1 trials with ambulatory BP monitoring likely increased the probability of BP control. A large trial is needed to assess their use in clinical practice. CLINICALTRIALS.GOV: NCT03461003. CLINICAL TRIAL REGISTRY: ClinicalTrials.gov; NCT03461003.

Tumor thickness in mesothelioma predicts differential response to neoadjuvant therapy and survival.

OBJECTIVE: Neoadjuvant systemic therapy in resectable malignant pleural mesothelioma remains controversial and demonstrates variable responses. We sought to evaluate tumor thickness as a predictor of response to neoadjuvant therapy and as a prognostic marker for overall survival. METHODS: Data from patients who underwent neoadjuvant therapy followed by cytoreductive surgery from 2002 to 2019 were reviewed. Baseline and postneoadjuvant therapy tumor thickness were measured on computed tomography. Radiological tumor response was categorized as progressive disease (≥20% increase), partial response (≥30% decrease), or stable disease (in between). Tumor response outcomes were modeled using logistic regression and multinomial regression models. Overall survival was evaluated based on tumor thickness and tumor response. RESULTS: Of the 143 patients reviewed, 36 (25%) had progressive disease, 54 (38%) had stable disease, and 56 (39%) had partial response. The baseline tumor thickness of the progressive disease group (36 mm) was lower than in both stable disease and partial response groups (both 63 mm; P < .001). Both logistic regression and multinomial regression analyses demonstrated that thicker baseline tumor thickness was associated with decreased probability of progressive disease and increased probability of partial response. In a multivariable Cox model, thicker postneoadjuvant therapy tumor thickness was associated with worse overall survival (hazard ratio, 1.01, 95% confidence interval, 1.00-1.01, P = .008). The same trend was observed for thicker baseline tumor thickness (hazard ratio, 1.02, 95% confidence interval, 1.01-1.04, P = .008), and the risk was decreased in tumors with partial response (hazard ratio, 0.98, 95% confidence interval, 0.96-0.100, P = .014). CONCLUSIONS: We present the first study demonstrating the relationship between baseline tumor thickness and differential radiographic response to neoadjuvant therapy and survival. Further studies are needed to validate tumor thickness as both a prognostic and predictive biomarker.

Randomized controlled trials published on patients with hernias have a high percentage of unreproducible statistics.

INTRODUCTION: Surgeons rely on randomized controlled trials (RCT) to compare the effectiveness of treatments. RCTs require careful planning and substantial effort to complete. Because of the careful study design, statistics performed are often easy to reproduce such as Chi-squared or t-test. Issues such as statistical discordance, or reporting statistical results that cannot be reproduced, should be uncommon. METHODS: RCTs pertaining to hernias were identified in PubMed using the search terms "hernia" and "randomized controlled trial." Studies were selected using a random number generator. Studies were included if the primary outcome could be reproduced using the data and statistical test reported in the manuscript. Discordance between the obtained p-value from our analysis and the published p-value was assessed. Primary outcome was the number of studies that reported p-values that crossed the level of statistical significance (p-value = 0.05) but on reproduction analysis did not. RESULTS: Of the 100 included RCTs, five reported p-values that crossed the "p = 0.05" threshold that our team was unable to reproduce using the statistical test reported in the manuscript. An additional three studies reported p-values that crossed the "p = 0.05" threshold that our team was unable to reproduce using the appropriate statistical test (i.e., Fisher's exact test when all expected cell counts < 5). All eight studies published p-values < 0.05, whereas, our re-analysis demonstrated p ≥ 0.05. CONCLUSION: Eight percent of the RCTs analyzed in this study reported p-values < 0.05 that on reproduction analysis was ≥ 0.05. The next steps should be to determine reasons for discordance and how to prevent this from happening.

Postpartum hemorrhage drills or simulations and adverse outcomes: a systematic review and Bayesian meta-analysis.

OBJECTIVE: To compare the rates of adverse outcomes with postpartum hemorrhage (PPH) before and after implementation of drills or simulation exercises. STUDY ELIGIBILITY CRITERIA: We included all English studies that reported on rates of PPH and associated complications during the pre- and post-implementation of interventional exercises. STUDY APPRASIAL AND SYNTHESIS METHODS: Two investigators independently reviewed the abstracts, and full articles for eligibility of all studies. Inconsistencies related to study evaluation or data extraction were resolved by a third author. The co-primary outcomes were the rate of PPH and of any transfusion; the secondary outcomes included admission to the intensive care unit (ICU), transfusion ≥ 4 units of packed red blood cells, hysterectomy, or maternal death. Study effects were combined by Bayesian meta-analysis and reported as risk ratios (RR) and 95% credible intervals (Cr). RESULTS: We reviewed 142 full length articles. Of these, 18 publications, with 355,060 deliveries-150,562 (42%) deliveries during the pre-intervention and 204,498 (57.6%) deliveries in the post-interventional period-were included in the meta-analysis. Using the Newcastle-Ottawa Scale, only three studies were considered good quality, and none of them were done in the US. The rate of PPH prior to intervention was 5.06% and 5.46% afterwards (RR 1.09, 95% CI 0.87-1.36; probability of reduction in the diagnosis being 21%). The likelihood of transfusion decreased from 1.68% in the pre-intervention to 1.27% in the post-intervention period (RR 0.80, 95% Cr 0.57-1.09). The overall probability of reduction in transfusion was 93%, albeit it varied among studies done in non-US countries (96%) versus in the US (23%). Transfusion of 4 units or more of blood occurred in 0.44% of deliveries before intervention and 0.37% afterwards (RR of 0.85, 95% CI 0.50-1.52), with the overall probability of reduction being 72% (76% probability of reduction in studies from non-US countries and 49% reduction with reports from the US). Surgical interventions to manage PPH, which was not reported in any US studies, occurred in 0.14% before intervention and 0.28% afterwards (RR 1.29; 95% CI 0.56-3.06; probability of reduction 27%). Admission to the ICU occurred in 0.10% before intervention and 0.08% subsequently (RR 0.92, 95% CI 0.58-1.43), with the overall probability of reduction being 65% (81% in studies from non-US countries and 27% from the study done in the US). Maternal death occurred in 0.17% in the pre-intervention period and 0.09% during the post-intervention (RR 0.62, 95% CI 0.33-1.05; probability of reduction 93% in studies from non-US countries and 82% in one study from the US). CONCLUSIONS: Interventions to reduce the sequelae of PPH are associated with decrease in adverse outcomes. The conclusion, however, ought not to be accepted reflexively for the US population. All of the studies on the topic done in the US are of poor quality and the associated probability of reduction in sequelae are consistently lower than those done in other countries. SYNOPSIS: Since the putative benefits of PPH drills or simulation exercises are based on poor quality pre- and post-intervention trials, policies recommending them ought to be revisited.

Allograft failure in kidney transplant recipients with membranoproliferative glomerulonephritis.

BACKGROUND: Membranoproliferative glomerulonephritis types I (MPGN-I) and II (MPGN-II) are rare diseases that in limited case series have been reported to recur frequently in kidney transplants and have a negative impact on allograft survival. STUDY DESIGN: Retrospective database review. SETTING & PARTICIPANTS: 189,211 primary kidney transplants in the United Network for Organ Sharing (UNOS) database from September 1987 to May 2007. PREDICTOR OR FACTOR: MPGN-I (811 patients; 0.4%), MPGN-II (179 patients; 0.1%), other GN (58,129 patients; 30.7%), and all other diagnoses (130,092 patients; 68.7%). OUTCOMES: Death-censored and non-death-censored allograft survival. RESULTS: Compared with controls, patients with MPGN-I and MPGN-II were significantly younger at the time of transplant, with a median age of 36 and 27 years compared with 44 years in the GN group and 46 years in all other disease groups, respectively (all P < 0.001). Mortality in patients with MPGN-I (8.8%) was significantly lower compared with the GN (11.3%; P = 0.02) and other disease (16.6%; P < 0.001) populations and lower in those with MPGN-II (9.5%) compared with the other disease (16.6%; P = 0.01) population. Graft failure rates were significantly higher in the MPGN-I (44.5%) cohort, but not in the MPGN-II (45.3%) cohort compared with the GN (38.0%) population (P < 0.001 and P = 0.05, respectively); neither MPGN cohort differed from the other disease (43.0%) population (P = 0.4 and P = 0.5). Overall, 10-year death-censored graft survival was similar for MPGN-I (56.2%) and MPGN-II (57.5%); both were significantly worse than for GN (65.2%; P < 0.001 and P = 0.003, respectively), and only MPGN-I was significantly worse than the other disease (60.0%) population (P = 0.004). Of allograft failures with a reported cause, disease recurrence was the primary cause in 36 (14.5%) MPGN-I and 18 (29.5%) MPGN-II transplant recipients and was significantly higher compared with 879 (6.6%) GN and 1,319 (4.4%) all-other-disease recurrence failures (P < 0.001). LIMITATIONS: Limited pretransplant clinical and biopsy data. CONCLUSIONS: A diagnosis of MPGN-I or MPGN-II has a significant negative impact on overall primary allograft survival compared with other forms of glomerulonephritis, whereas only MPGN-I has a significant, but modest, negative effect compared with other causes of end-stage renal disease.

Ambulatory blood pressure status in children: comparing alternate limit sources.

The American Heart Association has included alternate ambulatory blood pressure (ABP) limits for children published by Wühl in 2002. These updated limits employ the same pediatric cohort data as the previous ABP limits published by Soergel in 1997 but differ in analysis technique. The implications of changing ABP limit source on the diagnosis of hypertension has yet to be examined in a large pediatric cohort. We reviewed 741 ABP monitorings performed in children referred to our hypertension clinic between 1991-2007. Hypertension was defined as 24-h mean blood pressure ≥ 95 th percentile or 24-h blood pressure load ≥ 25%, by Soergel and Wühl limits separately. Six hundred seventy-three (91%) children were classified the same by both limit sources. Wühl limits were more likely than Soergel to classify a child as hypertensive (443 vs. 409, respectively). There was an increased classification of prehypertension and decreased white-coat hypertension by the Wühl method, whereas ambulatory and severe hypertension counts remained relatively the same by both limits sources. The use of either limit source will not significantly affect most clinical outcomes but should remain consistent over long-term research projects. Collection of new normative data from a larger, multiethnic population is needed for better measurement of ABP in children.

Health-related quality of life and cognitive functioning in pediatric short stature: comparison of growth-hormone-naïve, growth-hormone-treated, and healthy samples.

The objective of this study was to evaluate the impact of short stature on generic health-related quality of life (HRQOL) and cognitive functioning in pediatric patients. Eighty-nine youth, 48 who were initially seen with short stature (SS group) and 41 with a history of short stature being treated with growth hormone (GHT group) and one of their legal guardians participated in the study. HRQOL and cognitive functioning were assessed using the PedsQL™ 4.0 Generic Core Scales and PedsQL™ Cognitive Functioning Scale. Comparisons were made between the study groups and with a previously obtained matched healthy sample. For the GHT group, height Z score was found to be a positive predictor of overall HRQOL while duration of GHT was found to be a predictor of physical functioning. For the SS group, the difference between midparental height Z score and height Z score was found to be a negative predictor of overall HRQOL and cognitive functioning. Comparison with the healthy sample demonstrated significant negative impact on HRQOL for child self-report and on HRQOL and cognitive functioning for parent proxy-report in both study groups. The GHT group had a significantly higher child self-reported Physical Functioning score than the SS group (effect size (ES) = 0.52, p < 0.05). In conclusion, the GHT group had slightly better HRQOL scores than the SS group, but the difference was not statistically significant. Both groups had significantly lower HRQOL and cognitive functioning scores than healthy sample. Predictors of HRQOL and cognitive functioning found in this study lend support to the use of the PedsQL™ 4.0 Generic Score Scales and PedsQL™ Cognitive Functioning Scale in routine assessment of children with short stature in order to identify children at increased risk for impaired HRQOL and cognitive functioning.