Large Multicenter Prospective Cohort Study Research Articles

Changes in quality of life 1 year after intensive care: a multicenter prospective cohort of ICU survivors

BackgroundWith survival rates of critical illness increasing, quality of life measures are becoming an important outcome of ICU treatment. Therefore, to study the impact of critical illness on quality of life, we explored quality of life before and 1 year after ICU admission in different subgroups of ICU survivors.MethodsData from an ongoing prospective multicenter cohort study, the MONITOR-IC, were used. Patients admitted to the ICU in one of eleven participating hospitals between July 2016 and June 2021 were included. Outcome was defined as change in quality of life, measured using the EuroQol five-dimensional (EQ-5D-5L) questionnaire, and calculated by subtracting the EQ-5D-5L score 1 day before hospital admission from the EQ-5D-5L score 1 year post-ICU. Based on the minimal clinically important difference, a change in quality of life was defined as a change in EQ-5D-5L score of ≥ 0.08. Subgroups of patients were based on admission diagnosis.ResultsA total of 3913 (50.6%) included patients completed both baseline and follow-up questionnaires. 1 year post-ICU, patients admitted after a cerebrovascular accident, intracerebral hemorrhage, or (neuro)trauma, on average experienced a significant decrease in quality of life. Conversely, 11 other subgroups of ICU survivors reported improvements in quality of life. The largest average increase in quality of life was seen in patients admitted due to respiratory disease (mean 0.17, SD 0.38), whereas the largest average decrease was observed in trauma patients (mean -0.13, SD 0.28). However, in each of the studied 22 subgroups there were survivors who reported a significant increase in QoL and survivors who reported a significant decrease in QoL.Conclusions This large prospective multicenter cohort study demonstrated the diversity in long-term quality of life between, and even within, subgroups of ICU survivors. These findings emphasize the need for personalized information and post-ICU care.Trial registration: The MONITOR-IC study was registered at ClinicalTrials.gov: NCT03246334 on August 2nd 2017.

Fibroblast Growth Factor 23 and Risk of Heart Failure Subtype: The CRIC (Chronic Renal Insufficiency Cohort) Study

Heart failure (HF) is an important cause of morbidity and mortality among individuals with chronic kidney disease (CKD). A large body of evidence from preclinical and clinical studies implicates excess levels of fibroblast growth factor 23 (FGF23) in HF pathogenesis in CKD. It remains unclear whether the relationship between elevated FGF23 levels and HF risk among individuals with CKD varies by HF subtype. Prospective cohort study. A total of 3,502 participants were selected in the Chronic Renal Insufficiency Cohort study. Baseline plasma FGF23. Incident HF by subtype and total rate of HF hospitalization. HF was categorized as HF with preserved ejection fraction (HFpEF, ejection fraction [EF]≥ 50%), HF with reduced EF (HFrEF, EF<50%) and HF with unknown EF (HFuEF). Multivariable-adjusted cause-specific Cox proportional hazards models were used to investigate associations between FGF23 and incident hospitalizations for HF by subtype. The Lunn-McNeil method was used to compare hazard ratios across HF subtypes. Poisson regression models were used to evaluate the total rate of HF. During a median follow-up time of 10.8 years, 295 HFpEF, 242 HFrEF, and 156 HFuEF hospitalizations occurred. In multivariable-adjusted cause-specific Cox proportional hazards models, FGF23 was significantly associated with the incidence of HFpEF (HR, 1.41; 95% CI, 1.21-1.64), HFrEF (HR, 1.27; 95% CI, 1.05-1.53), and HFuEF (HR, 1.40; 95% CI, 1.13-1.73) per 1 standard deviation (SD) increase in the natural log of FGF23. The Lunn-McNeil method determined that the risk association was consistent across all subtypes. The rate ratio of total HF events increased with FGF23 quartile. In multivariable-adjusted models, compared with quartile 1, FGF23 quartile 4 had a rate ratio of 1.81 (95% CI, 1.28-2.57) for total HF events. Self-report of HF hospitalizations and possible lack of an echocardiogram at time of hospitalization. In this large multicenter prospective cohort study, elevated FGF23 levels were associated with increased risks for all HF subtypes. Heart failure (HF) is a prominent cause of morbidity and mortality in individuals with chronic kidney disease (CKD). Identifying potential pathways in the development of HF is essential in developing therapies to prevent and treat HF. In a large cohort of individuals with CKD, the Chronic Renal Insufficiency Cohort (N=3,502), baseline fibroblast growth factor-23 (FGF23), a hormone that regulates phosphorous, was evaluated in relation to the development of incident and recurrent HF with reduced, preserved, and unknown ejection fraction. In this large multicenter prospective cohort study, elevated FGF23 levels were associated with increased risk of all HF subtypes. These findings demonstrate the need for further research into FGF23 as a target in preventing the development of HF in individuals with CKD.

Validity of Early Outcomes as Indicators for Comparing Hospitals on Quality of Stroke Care.

Background Insight into outcome variation between hospitals could help to improve quality of care. We aimed to assess the validity of early outcomes as quality indicators for acute ischemic stroke care for patients treated with endovascular therapy (EVT). Methods and Results We used data from the MR CLEAN (Multicenter Randomized Controlled Trial of Endovascular Treatment for Acute Ischemic Stroke in the Netherlands)Registry, a large multicenter prospective cohort study including 3279 patients with acute ischemic stroke undergoing EVT. Random effect linear and proportional odds regression were used to analyze the effect of case mix on between-hospital differences in 2 early outcomes: the National Institutes of Health Stroke Scale (NIHSS) score at 24 to 48 hours and the expanded thrombolysis in cerebral infarction score. Between-hospital variation in outcomes was assessed using the variance of random hospital effects (tau2). In addition, we estimated the correlation between hospitals' EVT-patient volume and (case-mix-adjusted) outcomes. Both early outcomes and case-mix characteristics varied significantly across hospitals. Between-hospital variation in the expanded thrombolysis in cerebral infarction score was not influenced by case-mix adjustment (tau 2=0.17 in both models). In contrast, for the NIHSS score at 24 to 48 hours, case-mix adjustment led to a decrease in variation between hospitals (tau 2 decreases from 0.19 to 0.17). Hospitals' EVT-patient volume was strongly correlated with higher expanded thrombolysis in cerebral infarction scores (r=0.48) and weakly with lower NIHSS score at 24 to 48 hours (r=0.15). Conclusions Between-hospital variation in NIHSS score at 24 to 48 hours is significantly influenced by case-mix but not by patient volume. In contrast, between-hospital variation in expanded thrombolysis in cerebral infarction score is strongly influenced by EVT-patient volume but not by case-mix. Both outcomes may be suitable for comparing hospitals on quality of care, provided that adequate adjustment for case-mix is applied for NIHSS score.

The Emicizumab Switch: Real-World Data of 251 Pediatric Patients from the Pednet Registry

Background: Despite the rapid uptake of emicizumab in the pediatric hemophilia A (HA) population, real-world data on emicizumab safety and efficacy outcomes are limited to the HAVEN-2 trial (N = 85) and single center cohort studies. Aim: To report on bleeding and safety in children and adolescents with HA receiving emicizumab prophylaxis in a large prospective multicenter cohort study. Methods: Data were extracted from the ongoing PedNet Registry (Clin.gov.trial-NCT02979119; date of extraction: Jan 2022). Patients were included if they had a diagnosis of congenital hemophilia A with a baseline factor FVIII up to 25% and were < 18 years old at start of emicizumab. Patients were required to have maintenance therapy of emicizumab and bleeding data available for a minimum of 4 weeks. Patients with concomitant coagulopathies were excluded (N = 2). Bleeding data were compared during emicizumab to bleeding data before emicizumab up to a maximum of two years prior to the start of emicizumab. Patient characteristics were summarized as numbers (%) and median with IQR (P25-P75). Mean annualized bleeding rate (ABR) and annualized joint bleeding rate (AJBR) were estimated and compared between prophylactic regimens by negative binomial regression modelling. Results: 251 patients were included from 30 hemophilia treatment centers, see Table 1 for patient characteristics. The median age at start of emicizumab therapy was 6.1 years (IQR: 2.1 - 12.0). Median follow-up time before emicizumab was 1.51 years and during emicizumab was 1.23 years with a total of 361 patient years reported on emicizumab therapy. Most patients (94%) had severe HA and 76% of the patients were younger than 12 years at start of emicizumab therapy. Approximately one third (37%) of the patients had an inhibitor at start of emicizumab with a median peak titer of 128 BU/ml (IQR: 34 - 600). The ABR and AJBR significantly improved during emicizumab therapy in patients with and without inhibitors, see Figure 1. In patients without inhibitors the mean ABR reduced from 2.8 prior to emicizumab to 1.1 during emicizumab (p < 0.001), while the AJBR reduced from 0.8 to 0.3 (p < 0.001). Similar results were seen in patients with inhibitors. The mean ABR reduced from 5.5 to 1.1 (p<0.001), while the AJBR reduced from 2.3 to 0.3 (p<0.001). In this cohort, two serious adverse events and six adverse events were reported during emicizumab therapy in eight patients (3% of total cohort). Serious adverse events included one death unrelated to emicizumab therapy (retroperitoneal bleed in a baby treated with LMWH for CVL thrombosis) and one patient developed anti-drug antibodies without breakthrough bleeding, who continued emicizumab therapy. Non serious adverse events were all related to local injection site reaction in six patients. No TMA or thrombotic events were observed. Conclusions: This large cohort study with prospectively collected data showed improved bleeding control compared to previous therapy and a favorable safety profile during emicizumab treatment in pediatric patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Prevalence of Intracranial Atherosclerotic Disease in Patients with Low-Risk Transient or Persistent Neurologic Events.

There are limited data on the prevalence and outcome of intracranial atherosclerotic disease in patients with low-risk transient or persistent minor neurologic events. We sought to determine the prevalence and risk factors associated with intracranial atherosclerotic disease in patients with low-risk transient or persistent neurologic events. Participants with available intracranial vascular imaging from the Diagnosis of Uncertain-Origin Benign Transient Neurologic Symptoms (DOUBT) study, a large prospective multicenter cohort study, were included in this post hoc analysis. The prevalence of intracranial atherosclerotic disease of ≥50% was determined, and the association with baseline characteristics and DWI lesions was evaluated using logistic regression. We included 661 patients with a median age of 62 years (interquartile range, 53-70 years), of whom 53% were women. Intracranial atherosclerotic disease was found in 81 (12.3%) patients; asymptomatic intracranial atherosclerotic disease alone, in 65 (9.8%); and symptomatic intracranial atherosclerotic disease, in 16 (2.4%). The most frequent location was in the posterior cerebral artery (29%). Age was the only factor associated with any intracranial atherosclerotic disease (adjusted OR, 1.9 for 10 years increase; 95% CI, 1.6-2.5). Multivariable logistic regression showed a strong association between intracranial atherosclerotic disease and the presence of acute infarct on MR imaging (adjusted OR, 3.47; 95% CI, 1.91-6.25). Intracranial atherosclerotic disease is not rare in patients with transient or persistent minor neurologic events and is independently associated with the presence of MR imaging-proved ischemia in this context. Evaluation of the intracranial arteries could be valuable in establishing the etiology of such low-risk events.

HEMO2life® improves renal function independent of cold ischemia time in kidney recipients: A comparison with a large multicenter prospective cohort study

AbstractBackgroundM101 is an extracellular hemoglobin isolated from a marine lugworm and is present in the medical device HEMO2life®. The clinical investigation OXYOP was a paired kidney analysis (n = 60) designed to evaluate the safety and performance of HEMO2life® used as an additive to preservation solution in renal transplantation. The secondary efficacy endpoints showed less delayed graft function (DGF) and better renal function in the HEMO2life® group but due to the study design cold ischemia time (CIT) was longer in the contralateral kidneys.MethodsAn additional analysis was conducted including OXYOP patients and patients from the ASTRE database (n = 6584) to verify that the decrease in DGF rates observed in the HEMO2life® group may not be due solely to the shorter CIT but also to HEMO2life® performance. Kaplan–Meier estimate curves of cumulative probability of achieving a creatinine level below 250 µmol/L were generated and compared in both groups. A Cox model was used to test the effect of the explanatory variables (use of HEMO2life® and CIT). Finally, a bootstrap strategy was used to randomly select smaller samples of patients and test them for statistical comparison in the ASTRE database.ResultsKaplan–Meier estimate curves confirmed the existence of a relation between DGF and CIT and Cox analysis showed a benefit in the HEMO2life® group regardless of the associated CIT. Boostrap analysis confirmed these results.ConclusionsThe present study suggested that the better recovery of renal function observed among kidneys preserved with HEMO2life® in the OXYOP study is a therapeutic benefit of this breakthrough innovative medical device.

Surgical Outcomes in Benign Gynecologic Surgery Patients during the COVID-19 Pandemic (SOCOVID study)

Study ObjectiveTo determine the incidence of perioperative coronavirus disease (COVID-19) in women undergoing benign gynecologic surgery and to evaluate perioperative complication rates in patients with active, previous, or no previous severe acute respiratory syndrome coronavirus 2 infection.DesignA multicenter prospective cohort study.SettingTen institutions in the United States.PatientsPatients aged >18 years who underwent benign gynecologic surgery from July 1, 2020, to December 31, 2020, were included. All patients were followed up from the time of surgery to 10 weeks postoperatively. Those with intrauterine pregnancy or known gynecologic malignancy were excluded.InterventionsBenign gynecologic surgery.Measurements and Main ResultsThe primary outcome was the incidence of perioperative COVID-19 infections, which was stratified as (1) previous COVID-19 infection, (2) preoperative COVID-19 infection, and (3) postoperative COVID-19 infection. Secondary outcomes included adverse events and mortality after surgery and predictors for postoperative COVID-19 infection. If surgery was delayed because of the COVID-19 pandemic, the reason for postponement and any subsequent adverse event was recorded. Of 3423 patients included for final analysis, 189 (5.5%) postponed their gynecologic surgery during the pandemic. Forty-three patients (1.3% of total cases) had a history of COVID-19. The majority (182, 96.3%) had no sequelae attributed to surgical postponement. After hospital discharge to 10 weeks postoperatively, 39 patients (1.1%) became infected with severe acute respiratory syndrome coronavirus 2. The mean duration of time between hospital discharge and the follow-up positive COVID-19 test was 22.1 ± 12.3 days (range, 4–50 days). Eleven (31.4% of postoperative COVID-19 infections, 0.3% of total cases) of the newly diagnosed COVID-19 infections occurred within 14 days of hospital discharge. On multivariable logistic regression, living in the Southwest (adjusted odds ratio, 6.8) and single-unit increase in age-adjusted Charlson comorbidity index (adjusted odds ratio, 1.2) increased the odds of postoperative COVID-19 infection. Perioperative complications were not significantly higher in patients with a history of positive COVID-19 than those without a history of COVID-19, although the mean duration of time between previous COVID-19 diagnosis and surgery was 97 days (14 weeks).ConclusionIn this large multicenter prospective cohort study of benign gynecologic surgeries, only 1.1% of patients developed a postoperative COVID-19 infection, with 0.3% of infection in the immediate 14 days after surgery. The incidence of postoperative complications was not different in those with and without previous COVID-19 infections.

The Role of Upfront Hematopoietic Stem Cell Transplantation (HSCT) in Peripheral T-Cell Lymphoma (PTCL) Patients in Complete Remission (CR) with a Special Focus on Nodal PTCL: Report from the Comprehensive Oncology Measures for Peripheral T-Cell Lymphoma Treatment (COMPLETE), a Prospective Multicenter Cohort Study

The Role of Upfront Hematopoietic Stem Cell Transplantation (HSCT) in Peripheral T-Cell Lymphoma (PTCL) Patients in Complete Remission (CR) with a Special Focus on Nodal PTCL: Report from the Comprehensive Oncology Measures for Peripheral T-Cell Lymphoma Treatment (COMPLETE), a Prospective Multicenter Cohort Study

Sex differences in intracranial and extracranial atherosclerosis in patients with acute ischemic stroke.

Background and aimTo investigate sex differences with respect to presence and location of atherosclerosis in acute ischemic stroke patients.MethodsParticipants with acute ischemic stroke were included from the Dutch acute stroke trial, a large prospective multicenter cohort study performed between May 2009 and August 2013. All patients received computed tomography/computed tomography-angiography within 9 h of stroke onset. We assessed presence of atherosclerosis in the intra- and extracranial internal carotid and vertebrobasilar arteries. In addition, we determined the burden of intracranial atherosclerosis by quantifying internal carotid and vertebrobasilar artery calcifications, resulting in calcium volumes. Prevalence ratios between women and men were calculated with Poisson regression analysis and adjusted prevalence ratio for potential confounders (age, hypertension, hyperlipidemia, diabetes, smoking, and alcohol use).ResultsWe included 1397 patients with a mean age of 67 years, of whom 600 (43%) were women. Presence of atherosclerosis in intracranial vessel segments was found as frequently in women as in men (71% versus 72%, adjusted prevalence ratio 0.95; 95% CI 0.89–1.01). In addition, intracranial calcification volume did not differ between women and men in both intracranial internal carotid (large burden 35% versus 33%, adjusted prevalence ratio 0.93; 95% CI 0.73–1.19) and vertebrobasilar arteries (large burden 26% versus 40%, adjusted prevalence ratio 0.69; 95% CI 0.41–1.12). Extracranial atherosclerosis was less common in women than in men (74% versus 81%, adjusted prevalence ratio 0.86; 95% CI 0.81–0.92).ConclusionsIn patients with acute ischemic stroke the prevalence of intracranial atherosclerosis does not differ between women and men, while extracranial atherosclerosis is less often present in women compared with men.

Predictors of Failure After Surgical Treatment of Femoroacetabular Impingement: Results of a Multicenter Prospective Cohort of 621 Hips

Objectives: Surgical treatment of femoroacetabular impingement attempts to improve patients’ symptoms through treatment of intra-articular labrochondral pathology and correction of underlying bony deformity. The purpose of the current study was to determine independent predictors of failure after surgical treatment of femoroacetabular impingement in a large prospective multicenter cohort study. Methods: A prospective cohort study of the surgical treatment of FAI was performed. A total of 760 hips undergoing primary surgical treatment of FAI were enrolled across seven surgeons. Patient characteristics, baseline patient reported outcomes (PROs), imaging findings, intraoperative pathology, and surgical treatments were prospectively recorded. A total of 621 hips (81.6%) with minimum one year follow-up were included in the current study (mean 4.3 years). The mHHS was assessed relative to the minimally clinically important difference (MCID, 8 points) and patient acceptable symptom state (PASS, 74 points). Univariate analyses were performed to identify factors significantly associated with failure. Multivariate logistic regression was performed to identify independent predictors of failure. Results: A total of 621 hips undergoing surgical treatment of FAI were assessed at a mean 4.2 years postoperatively. This cohort had a mean age of 29.8 and included 56.8% females. Multivariate logistic regression identified independent predictors of each failure definition. Failure A (THA) was independently associated with increasing age, acetabular microfracture (both p&lt;0.001), and femoral head chondroplasty (p=0.02). Failure B (THA or revision surgery) was independently associated only with lower preoperative mHHS (p&lt;0.001) (p=0.01). A lower failure C (clinical failure) was independently associated with participation in competitive athletics (p=0.01), BMI (p&lt;0.001), and male gender (p&lt;0.001). Conclusion: This large multicenter cohort demonstrates the outcomes of FAI treatment at a mean of 4.3 years postoperative. Rates of THA and revision surgery were 4.0% and 6.9%. An additional 14.8% of patients demonstrates clinical failure based on patient-reported outcomes.

Sexual desire in transgender persons in relation with gender affirming hormone treatment: Results from ENIGI, a large multicenter prospective cohort study in transgender people

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

PO-01-023 Sexual desire in transgender persons in relation with gender affirming hormone treatment. Results from ENIGI, a large multicenter prospective cohort study in transgender people

Several steps in the transitioning process may affect sexual desire, including hormone therapy and gender affirming surgery. Testosterone therapy in transgender men (TM) generally leads to increased sexual desire, masturbation, sexual fantasies and arousal. Studies in transgender women (TW) are often inconclusive. This prospective cohort study was part of the European Network for the Investigation of Gender Incongruence (ENIGI). Upon first clinical contact, psychological questionnaires were completed. Sexual desire was prospectively assessed in 766 participants (401 TW, 364 TM) by the Sexual Desire Inventory (SDI) during a three-year follow-up period, starting at the initiation of hormone treatment (HT). Sex steroids were measured at each visit. Data were analyzed cross-sectionally and prospectively. Baseline SDI scores were comparable in TW and TM (P=0.342). In TW, SDI scores decreased from 39.0 [23.0 – 54.5] (baseline) to 33.0 [16.3 – 49.8] (12 months) (-4.77, P<0.001), returning to scores comparable to baseline after 18 months (P=0.114). After 36 months, SDI scores were higher than baseline scores (51.5 [39.5 – 61.0], P=0.003). In TM, total SDI scores increased from 40.0 [17.0 – 52.0] at baseline to 55.0 [40.5 – 67.0] (+14.61, P<0.001) after 12 months, remaining stable over the following year and returning to scores comparable to baseline scores (58.0 [23.0 – 62.0], P=0.250) after 36 months. People with a partner (P<0.001) and TW with lower levels of self-reported gender dysphoria (Utrecht Gender Dysphoria Scale) (ρ=0.336, P=0.002) reported higher SDI scores. Prospective SDI scores were not influenced by prospective changes in serum levels of sex steroids in TM and TW. Lower baseline levels of gender dysphoria (Utrecht Gender Dysphoria Scale) correlated to a higher prospective increase in SDI scores in TM after 12 months of HT (ρ=-0.355, P<0.001).

PS-01-001 Is anger intensity related to serum testosterone levels and/or exogenous testosterone therapy? Results from ENIGI, a large multicenter prospective cohort study in transgender people

Anger is a state of emotions ranging from irritation to intense rage. Aggression is the externalization of anger through destructive/punitive behavior. The World Professional Association for Transgender Health (WPATH) Standards of Care, Edition 7 (SOC7) guidelines warn about aggression in transgender men (TM) on testosterone treatment. As aggression is often initiated by feelings of anger, we aimed to assess whether anger intensity increases in TM and decreases in transgender women (TW) after initiation of hormone therapy, and to identify predictors for anger intensity in transgender people. This prospective cohort study was part of the European Network for the Investigation of Gender Incongruence (ENIGI). Upon first clinical contact, psychological questionnaires were administered. Anger intensity was prospectively assessed in 898 participants (440 TM, 468 TW) by the STAXI-2 (State-Trait Anger Expression Inventory-2) State Anger (S-Anger) during a three-year follow-up period, starting at the initiation of hormone treatment. Sex steroids were measured at each follow-up visit. Data were analyzed cross-sectional and prospectively.

Estrogen-alone therapy and invasive breast cancer incidence by dose, formulation, and route of delivery: findings from the WHI observational study.

Research on the relationships between different hormone therapy doses, formulation and routes of delivery, and subsequent breast cancer incidence has been limited. This study directly compared different estrogen doses, formulations, and route of delivery of estrogen alone among women with a hysterectomy in relation to invasive breast cancer incidence. The Women's Health Initiative Observational Study is a large multicenter prospective cohort study conducted at 40 US sites. Analyses included 26,525 postmenopausal women with a hysterectomy, aged 50 to 79 years, at study entry, recruited between September, 1993 and December, 1998, with annual follow-up through September 12, 2005. Average follow-up was 8.2 years. For conjugated equine estrogen (CEE) users, no difference was observed between low-dose CEE (<0.625 mg) compared with conventional-dose CEE (0.625 mg) for breast cancer (hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.65, 1.48)]. Compared with conventional-dose CEE, transdermal estrogen was associated with a nonsignificant lower risk of invasive breast cancer (HR 0.75, 95% CI 0.47, 1.19). The low prevalence of transdermal use likely limited power for this comparison, and for a comparison of oral estradiol to conventional-dose CEE (HR 1.20, 95% CI 0.84, 1.39). Our results indicate that invasive breast cancer risk did not differ appreciably in women with a hysterectomy using estrogen-alone when directly comparing different doses, formulations, and routes of delivery to the conventional oral CEE. These findings suggest that the lower breast cancer risk found in the WHI estrogen-alone trial may extend to lower doses of CEE. Additional research is needed to confirm these hypotheses.

Costal Margin Tenderness and the Risk for Intraabdominal Injuries in Children With Blunt Abdominal Trauma.

The risk of radiation exposure from computed tomography (CT) imaging in children is well recognized. Patient history and physical examination findings, including costal margin tenderness (CMT), influence a physician's decision to image a child with blunt torso trauma. The objective of this study was to determine the importance of CMT for identifying children with intraabdominal injuries (IAI) found on CT and IAI undergoing acute intervention. We conducted an analysis of the Pediatric Emergency Care Applied Research Network (PECARN) IAI public use data set, representing a large prospective multicenter cohort study from May 2007 to January 2010. Isolated CMT was defined as CMT without other identified PECARN risk factors for IAI (i.e., abdominal or thoracic wall trauma, abdominal tenderness or pain, decreased breath sounds, or vomiting). Logistic regression was used to calculate adjusted odds of IAI in children presenting with isolated and nonisolated CMT. Risk differences were calculated to estimate the risk of IAI independently attributable to CMT in the setting of isolated PECARN risk factors. Finally, CT use among exposure groups was estimated to quantify potentially avoidable imaging. Among 9,174 children with Glasgow Coma Scale scores of 14 or 15 who sustained blunt torso trauma, 1,267 (13.8%) had CMT. Among those with CMT, 177 (14.0%) had isolated CMT and 1,090 (86.0%) had nonisolated CMT. No children (0/177; 0%, 95% confidence interval [CI]= 0.0%-2.1%) with isolated CMT had IAI, compared to 17.2% (187/1,090; 95% CI= 15.0%-19.5%) of those with nonisolated CMT. The risk differences were not statistically significant. 36/177 (20.3%; 95% CI= 14.7%-27.0%) children with isolated CMT underwent abdominal CT scans. The risk of IAI associated with isolated CMT is minimal. For children with blunt abdominal trauma and isolated CMT, abdominal CT scan is of low yield.

Clavicle Fracture Is Not Predictive of the Need for Microsurgery in Brachial Plexus Birth Palsy.

Brachial plexus birth palsy (BPBP) and clavicle fractures occur concurrently as well as in isolation during difficult deliveries. The concept that concurrent clavicle fracture may spare nerve injury has been advocated. Our aim was to compare those children with BPBP presenting to a tertiary care center with and without concurrent clavicle fractures and assess the utility of the presence of a clavicle fracture as a predictor of injury severity in children with BPBP. Records of all patients belonging to a large prospective multicenter cohort study of infants with BPBP (Treatment and Outcomes of Brachial Plexus Injuries study) were analyzed for demographic information and birth information including risk factors, comorbidity, presence of clavicle fracture, and injury severity. The records of 639 children with BPBP were examined. Thirteen patients were excluded for incomplete data. Ninety-six children who sustained concurrent birth fracture and BPBP were identified (15%). Of these, 57 sustained clavicle fractures (9%), 44 sustained humerus fractures, and 4 sustained other fractures. Of the demographic factors analyzed, only the presence of gestational diabetes was found to be significantly higher in those children with fractures versus those without. The presence of a clavicle fracture did not change the rate of microsurgical intervention, nor did clavicle fracture rates differ by Toronto score, suggesting that there was no difference in injury severity between the 2 groups. In a large multicenter prospective study, 9% of children presenting with BPBP also sustained a clavicle fracture at birth. The presence of a clavicle fracture did not correlate with the severity of brachial plexus injury. We suggest that in study populations of children with severe enough BPBP to present to a tertiary care center, compared with studies collected in the obstetric population, the presence of a clavicle fracture is neither protective from nerve injury nor predictive of injury severity. Level 2-prognostic.

Longitudinal Associations of Exposure to Perfluoroalkylated Substances in Childhood and Adolescence and Indicators of Adiposity and Glucose Metabolism 6 and 12 Years Later: The European Youth Heart Study.

To investigate the long-term association of exposure to perfluoroalkylated substances, including perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA), during childhood (9 years) and adolescence (15 years) on indicators of adiposity and glucose metabolism in adolescence (15 years) and young adulthood (21 years). Secondarily, we aim to clarify the degree of tracking of exposure from childhood into young adulthood. Data derived from a large multicenter prospective cohort study, in which the same participants have been observed from childhood (N = 590), during adolescence (N = 444), and into young adulthood (N = 369). Stored plasma samples were analyzed for PFOS and PFOA. Indicators of adiposity comprising body height, body weight, sum of four skinfolds, and waist circumference, as well as indicators of glucose metabolism, comprising fasting blood glucose, triglyceride, and insulin levels, β-cell function, and insulin resistance, have been collected at all study waves. Multiple linear regression was applied in order to model earlier exposure on later outcome while controlling for baseline outcome levels, sex, age, and socioeconomic factors. Childhood exposure to PFOS was associated with indicators of adiposity at 15 years of age that are displayed in elevated BMI, skinfold thickness, and waist circumference, as well as increased skinfold thickness and waist circumference at 21 years of age. PFOA exposure in childhood was associated with decreased β-cell function at 15 years of age. We did not observe associations between exposure during adolescence and indicators of adiposity and glucose metabolism in young adulthood. This study found evidence for childhood exposure to PFOS and PFOA predicting adiposity at 15 and 21 years of age and impaired β-cell function at 15 years of age, respectively.

Diabetes and Onset of Natural Menopause

The age at natural menopause (ANM) in the Western world ranges from 40 to 60 years, with an average onset of 51 years. The exact mechanisms underlying the timing of ANM are not completely understood. Both genetic and environmental factors are involved. The best-established environmental factor affecting ANM is smoking; menopause occurs 1 to 2 years earlier in smokers. In addition to genetic and environmental factors, chronic metabolic diseases may influence ANM. Some evidence suggests that diabetes may accelerate menopausal onset. With more women of childbearing age receiving a diagnosis of diabetes, it is important to examine the impact of diabetes on reproductive health. This study was designed to determine whether ANM occurs at an earlier age among women who have diabetes before menopause than in women without diabetes. Data were obtained from the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a large multicenter prospective cohort study investigating the relationship between diet, lifestyle, and genetic factors and the incidence of cancer and other chronic diseases. A cohort of 519,978 men and women, mostly aged 27 to 70 years, were recruited primarily from the general population between 1992 and 2000. A total of 367,331 women participated in the EPIC study. After exclusions, 258,898 of these women met study inclusion criteria. Diabetes status at baseline and menopausal age were based on self-report and were obtained through questionnaires. Participants were asked if they had ever been diagnosed with diabetes and if so at what age. Associations of diabetes and age at diabetes diagnosis with ANM were estimated using time-dependent Cox regression analyses, with stratification by center and adjustments for age, smoking, reproductive, and known diabetes risk factors including smoking and with age from birth to menopause or censoring as the underlying time scale. Overall, there was no statistically significant lower risk of becoming menopausal among women with diabetes than women with no diabetes; the hazard ratio (HR) was 0.94, with a 95% confidence interval (CI) of 0.89 to 1.01. However, compared with women with no diabetes, women with diabetes before the age of 20 years had an earlier menopause (10-20 years [HR, 1.43; 95% CI, 1.02-2.01] and <10 years [HR, 1.59; 95% CI, 1.03-2.43]), whereas women with diabetes at age 50 years or older had a later menopause (HR, 0.81; 95% CI, 0.70-0.95). No association with ANM was found for diabetes onset between the ages 20 and 50 years. Strengths of the study include its large sample size and the measurement of a broad set of potential confounders. However, there were several limitations. First, results may have been underestimated because of survival bias. Second, the sequence of menopause and diabetes in women with a late age at diabetes is uncertain, as both events occur in a short period, and both diabetes and menopause status were based on self-report, not verified by medical records. Third, no distinction was made between types 1 and 2 diabetes. Although there is no overall association between diabetes and age at menopause, the data suggest that early-onset diabetes may accelerate menopause. The delaying effect of late-onset diabetes on ANM is not in agreement with other studies suggesting the opposite association.

Abdominal aortic calcification and risk of fracture among older women — The SOF study

Data concerning the link between severity of abdominal aortic calcification (AAC) and fracture risk in postmenopausal women are discordant. This association may vary by skeletal site and duration of follow-up. Our aim was to assess the association between the AAC severity and fracture risk in older women over the short- and long term. This is a case–cohort study nested in a large multicenter prospective cohort study. The association between AAC and fracture was assessed using Odds Ratios (OR) and 95% confidence intervals (95%CI) for vertebral fractures and using Hazard Risks (HR) and 95%CI for non-vertebral and hip fractures. AAC severity was evaluated from lateral spine radiographs using Kauppila's semiquantitative score. Severe AAC (AAC score 5+) was associated with higher risk of vertebral fracture during 4years of follow-up, after adjustment for confounders (age, BMI, walking, smoking, hip bone mineral density, prevalent vertebral fracture, systolic blood pressure, hormone replacement therapy) (OR=2.31, 95%CI: 1.24–4.30, p<0.01). In a similar model, severe AAC was associated with an increase in the hip fracture risk (HR=2.88, 95%CI: 1.00–8.36, p=0.05). AAC was not associated with the risk of any non-vertebral fracture. AAC was not associated with the fracture risk after 15years of follow-up. In elderly women, severe AAC is associated with higher short-term risk of vertebral and hip fractures, but not with the long-term risk of these fractures. There is no association between AAC and risk of non-vertebral-non-hip fracture in older women. Our findings lend further support to the hypothesis that AAC and skeletal fragility are related.

Isolated Loss of Consciousness in Children with Minor Blunt Head Trauma: Lee LK, Monroe D, Bachman MC, et al. JAMA Pediatr 2014;168:837–43.

The objective of this study was to determine the risk for clinically important traumatic brain injury (ciTBI) in children with isolated loss of consciousness (LOC) > 5 s as a result of a traumatic event. This investigation was a planned secondary analysis of a large prospective multicenter cohort study conducted by the Pediatric Emergency Care Applied Research Network (PECARN). The study included 42,412 children ages 0–18 years with blunt head trauma and Glasgow Come Scale scores of 14 and 15 evaluated in 25 emergency departments from 2004–2006. The primary outcome for the study was ciTBI defined as death, neurosurgery, intubation > 24 h, or hospitalization for ≥ 2 nights. The investigators also compared the rates of ciTBI in children without LOC, any LOC, and isolated LOC (without other PECARN ciTBI predictors). A total of 40,693 children were included in the study. Of the participants, LOC occurred in 15.4% (6286 children). With any history of LOC the ciTBI was 2.5%, and for no history of LOC the ciTBI was 0.5% (difference 2.0%; 95% confidence interval [CI] 1.7–2.5). The ciTBI rate in children with isolated LOC, with no other PECARN predictors for ciTBI, was 0.5% (95% CI 0.2–0.8). In comparing children with isolated LOC with those who have LOC and other PECARN predictors, the risk ratio (RR) for ciTBI in children younger than 2 years was 0.13 (95% CI 0.005–0.72) and the RR for children 2 years or older was 0.10 (95% CI 0.06–0.19). The investigators concluded that children with minor blunt head trauma with isolated LOC are at low risk for ciTBI, and therefore do not routinely require computed tomography of the brain.