Findings on Repeat Posttraumatic Brain Computed Tomography Scans in Older Patients With Minimal Head Trauma and the Impact of Existing Antithrombotic Use.

STUDY OBJECTIVE: Evaluate the utility of routine rescanning of older, mild head trauma patients with an initial negative brain computed tomography (CT), who is on a preinjury antithrombotic (AT) agent by assessing the rate of delayed intracranial hemorrhage (dICH), need for surgery, and attributable mortality. METHODS: Participating centers were trained and provided data collection instruments per institutional review board-approved protocols. Data were obtained from manual chart review and electronic medical record download. Adults ≥55 years seen at Level I/II Trauma Centers, between 2017 and 2019 with suspected head trauma, Glasgow Coma Scale 14 to 15, negative initial brain CT, and no other Abbreviated Injury Scale injuries >2 were identified, grouped by preinjury AT therapy (AT- or AT+) and compared on dICH rate, need for operative neurosurgical intervention, and attributable mortality using univariate analysis (α=.05). RESULTS: A total of 2,950 patients from 24 centers were enrolled; 280 (9.5%) had a repeat brain CT. In those rescanned, the dICH rate was 15/126 (11.9%) for AT- and 6/154 (3.9%) in AT+. Assuming nonrescanned patients did not suffer clinically meaningful dICH, the dICH rate would be 15/2001 (0.7%) for AT- and 6/949 (0.6%) for AT+. No surgical operations were done for dICH. All-cause mortality was 9/2950 (0.3%) and attributable mortality was 1/2950 (0.03%). The attributable death was an AT+, dICH patient whose family declined intervention. CONCLUSION: In older patients with an initial Glasgow Coma Scale of 14 to 15 and a negative initial brain CT scan, the dICH rate is low (<1%) and of minimal clinical consequence, regardless of AT use. In addition, no patient had operative neurosurgical intervention. Therefore, routine rescanning is not supported based on the results of this study.

Current Australian clinical practice in use of botulinum toxin-A to manage paediatric hypertonicity.

AIM: To describe current rehabilitation paediatricians' use of intramuscular botulinum toxin-A (BoNT-A) to manage hypertonicity. METHODS: Cross-sectional survey. RESULTS: In late 2019, 32 of the 35 identified Australian rehabilitation paediatricians who use BoNT-A to manage paediatric hypertonicity completed the survey. Annually, they administer just over 3750 courses of BoNT-A to manage hypertonicity with a mean of 11 years of clinical experience. Sedation was used by all but 1 clinician who used a number of other strategies during the procedure. Mean (and median) maximum dose of OnabotulinumtoxinA (Botox) was 400 Units (range 300-450 Units). Only three clinicians indicated that they used AbobotulinumtoxinA (Dysport) - the other BoNT-A preparation approved for children available in Australia; analysis of its use was not performed. Dose modifications were made by clinicians according to a patient's response to a previous course of BoNT-A (88% of respondents); patient experience of a previous adverse event (78%); history of aspiration or dysphagia (65 and 63%, respectively); and the presence of dystonia; and where the patient was GMFCS level V (53% each). Intervals between courses ranged from 3 to 24 months with the variation due to clinical circumstances. CONCLUSION: Clinical practice in BoNT-A management of paediatric hypertonicity was largely consistent in regard to maximum doses of OnabotulinumtoxinA (Botox) used. Dose modification and time between injection courses varied according to individual clinical presentation. Procedural sedation was used extensively.

Correction to: Effects of Physician Experience, Specialty Training, and Self-referral on Inappropriate Diagnostic Imaging.

There were some errors in the variables in this paper.

Effects of Physician Experience, Specialty Training, and Self-referral on Inappropriate Diagnostic Imaging.

BACKGROUND: Although previous research has demonstrated high rates of inappropriate diagnostic imaging, the potential influence of several physician-level characteristics is not well established. OBJECTIVE: To examine the influence of three types of physician characteristics on inappropriate imaging: experience, specialty training, and self-referral. DESIGN: A retrospective analysis of over 70,000 MRI claims submitted for commercially insured individuals. Physician characteristics were identified through a combination of administrative records and primary data collection. Multi-level modeling was used to assess relationships between physician characteristics and inappropriate MRIs. SETTING: Massachusetts PARTICIPANTS: Commercially insured individuals who received an MRI between 2010 and 2013 for one of three conditions: low back pain, knee pain, and shoulder pain. MEASUREMENTS: Guidelines from the American College of Radiology were used to classify MRI referrals as appropriate/inappropriate. Experience was measured from the date of medical school graduation. Specialty training comprised three principal groups: general internal medicine, family medicine, and orthopedics. Two forms of self-referral were examined: (a) the same physician who ordered the procedure also performed it, and (b) the physicians who ordered and performed the procedure were members of the same group practice and the procedure was performed outside the hospital setting. RESULTS: Approximately 23% of claims were classified as inappropriate. Physicians with 10 or less years of experience had significantly higher odds of ordering inappropriate MRIs. Primary care physicians were almost twice as likely to order an inappropriate MRI as orthopedists. Self-referral was not associated with higher rates of inappropriate MRIs. LIMITATIONS: Classification of MRIs was conducted with claims data. Not all self-referred MRIs could be detected. CONCLUSIONS: Inappropriate imaging continues to be a driver of wasteful health care spending. Both physician experience and specialty training were highly associated with inappropriate imaging.

Magnitude and financial implications of inappropriate diagnostic imaging for three common clinical conditions.

OBJECTIVE: To quantify the level of adherence to imaging guidelines for three common clinical indications for a commercially insured population. DESIGN: Retrospective analysis of administrative claims data for commercially insured individuals with diagnostic imaging claims (MRI and X-ray) for either uncomplicated low back pain, non-traumatic knee pain or non-traumatic shoulder pain. SETTING: The State of Massachusetts for 2010 and 2013. PARTICIPANTS: Adults with no chronic conditions and without evidence of prior management in the 12 months preceding to the initial office visit for each of the clinical indications. MAIN OUTCOMES MEASURES: Imaging procedures performed within 30 days of the initial office visit were classified as appropriate or inappropriate according to adherence to imaging guidelines from American College of Radiology. RESULTS: More than 60% of lumbar spine MRI's were deemed inappropriate in 2010 and in 2013. Over 30% of MRI's for shoulder pain and knee pain were inappropriate in 2010 and in 2013. Patients age 18-59 with inappropriate imaging claims had significantly lower rates of surgical procedures within 90 days of imaging than those with appropriate imaging. Inappropriate imaging accounted for over 20% of annual imaging costs for the three clinical indications. CONCLUSIONS: Reducing inappropriate imaging procedures can lead to substantial savings through the elimination of unnecessary and low value procedures. Increased awareness of and adherence to best practice guidelines should be a focus of efforts to cut waste in our healthcare system.

Impact of ACA Medicaid Expansion on Hospitals' Financial Status.

EXECUTIVE SUMMARY: The Patient Protection and Affordable Care Act's insurance reforms were expected to have significant and positive implications for hospital finances. In particular, state expansion of Medicaid programs held the promise of reducing hospitals' uncompensated care costs as a result of expanding health insurance to many previously uninsured individuals. Recent research indicates that in the early phases of Medicaid expansion, many hospitals did experience a substantial decline in uncompensated care costs. However, studies to date have not considered whether Medicaid expansion resulted in payment shortfalls that offset some of what hospitals saved from lower uncompensated care costs. We examined filings submitted by hospitals to the Internal Revenue Service (IRS)-one of the few publicly available sources of national data on both uncompensated care costs and Medicaid payment shortfalls. We also compared changes in uncompensated care costs and Medicaid payment shortfalls for hospitals in expansion states with those in nonexpansion states. Our findings indicate that state expansion of Medicaid led to substantial reductions in hospitals' uncompensated care costs, but the savings were offset somewhat by increased Medicaid payment shortfalls. Therefore, studies that focus only on reductions in uncompensated care costs can overstate the benefits of Medicaid expansion on hospitals finances.

Systemic adverse events after botulinum neurotoxin A injections in children with cerebral palsy.

AIM: To identify factors that increase the likelihood of systemic adverse events after botulinum neurotoxin A (BoNT-A) injections in children with cerebral palsy (CP). METHOD: A prospective observational study of patients attending a BoNT-A clinic at a tertiary paediatric hospital (2010-2014). Occurrences of systemic adverse events, defined as lower respiratory tract illnesses, generalized weakness, dysphagia, and death were determined at follow-up. The relationship between systemic adverse events and eight preinjection variables (age, Gross Motor Function Classification System [GMFCS] level, history of dysphagia, gastrostomy, aspiration pneumonia, recent history of illness, BoNT-A dose, and type of sedation) were examined using univariable and multivariable logistic regression with generalized estimating equations methods. RESULTS: In total 591 children underwent 2219 injection episodes with follow-up in 2158 (97%) cases. Systemic adverse events were reported in 77 (3.6%) injection episodes. Univariable analysis suggested that GMFCS levels IV and V, a history of dysphagia, gastrostomy, aspiration pneumonia, and increasing BoNT-A dose increase the likelihood of systemic adverse events. In multivariable analysis, a history of dysphagia (odds ratio [OR] 3.42) and/or aspiration pneumonia (OR 2.31) remained associated with increased likelihood of systemic adverse events. INTERPRETATION: A history of dysphagia and/or aspiration pneumonia are the factors that most increase the likelihood of systemic adverse events after BoNT-A. WHAT THIS PAPER ADDS: Systemic adverse events occur in 3.6% of botulinum neurotoxin A (BoNT-A) injection episodes. Dysphagia and/or aspiration pneumonia are associated with increased likelihood of systemic adverse events. Multivariable models showed no evidence of association between Gross Motor Function Classification System and systemic adverse events. Multivariable models showed no evidence of association between BoNT-A dose and systemic adverse events.

Severity of cerebral palsy and likelihood of adverse events after botulinum toxin A injections.

AIM: To determine the incidence of common adverse events after botulinum toxin A (BoNT-A) injections in children with cerebral palsy (CP) and to identify whether the severity of CP influences the incidence of adverse events. METHOD: This was an observational study of patients attending a BoNT-A clinic at a tertiary paediatric hospital (2010-2014). Data examined included procedural adverse events at the time of injection and at follow-up. Systemic adverse events were defined as lower respiratory tract illnesses, generalized weakness, dysphagia, and death. Severity of CP was categorized by the Gross Motor Function Classification System (GMFCS). The relationships between GMFCS and adverse events were analysed using negative binomial regression models. RESULTS: In total, 591 children underwent 2219 injection episodes. Adverse events were reported during the procedure (130 [6%] injection episodes) and at follow-up (492 [22%] injection episodes). There were significantly increased rates of systemic adverse events in injection episodes involving children in GMFCS level IV (incidence rate ratio [IRR] 3.92 [95% confidence interval] 1.45-10.57]) and GMFCS level V (IRR 7.37 [95% confidence interval 2.90-18.73]; p<0.001). INTERPRETATION: Adverse events after BoNT-A injections are common but mostly mild and self-limiting. Children in GMFCS levels IV and V are at increased risk of systemic adverse events. The relationship between CP severity and BoNT-A adverse events is complex and further research is required to better understand this relationship. WHAT THIS PAPER ADDS: Adverse events reported at the time of botulinum toxin A injection occurred in 6% of injection episodes. Adverse events were reported at follow-up in 22% of injection episodes. Children in Gross Motor Function Classification System (GMFCS) levels IV and V have increased rates of systemic adverse events. Children in GMFCS levels IV and V report less local weakness and pain.

The Progress of US Hospitals in Addressing Community Health Needs.

OBJECTIVES: To identify how US tax-exempt hospitals are progressing in regard to community health needs assessment (CHNA) implementation following the Patient Protection and Affordable Care Act. METHODS: We analyzed data on more than 1500 tax-exempt hospitals in 2013 to assess patterns in CHNA implementation and to determine whether a hospital's institutional and community characteristics are associated with greater progress. RESULTS: Our findings show wide variation among hospitals in CHNA implementation. Hospitals operating as part of a health system as well as hospitals participating in a Medicare accountable care organization showed greater progress in CHNA implementation whereas hospitals serving a greater proportion of uninsured showed less progress. We also found that hospitals reporting the highest level of CHNA implementation progress spent more on community health improvement. CONCLUSIONS: Hospitals widely embraced the regulations to perform a CHNA. Less is known about how hospitals are moving forward to improve population health through the implementation of programs to meet identified community needs.

Disrupted modular organization of resting-state cortical functional connectivity in U.S. military personnel following concussive 'mild' blast-related traumatic brain injury.

Blast-related traumatic brain injury (TBI) has been one of the "signature injuries" of the wars in Iraq and Afghanistan. However, neuroimaging studies in concussive 'mild' blast-related TBI have been challenging due to the absence of abnormalities in computed tomography or conventional magnetic resonance imaging (MRI) and the heterogeneity of the blast-related injury mechanisms. The goal of this study was to address these challenges utilizing single-subject, module-based graph theoretic analysis of resting-state functional MRI (fMRI) data. We acquired 20min of resting-state fMRI in 63 U.S. military personnel clinically diagnosed with concussive blast-related TBI and 21 U.S. military controls who had blast exposures but no diagnosis of TBI. All subjects underwent an initial scan within 90days post-injury and 65 subjects underwent a follow-up scan 6 to 12months later. A second independent cohort of 40 U.S. military personnel with concussive blast-related TBI served as a validation dataset. The second independent cohort underwent an initial scan within 30days post-injury. 75% of the scans were of good quality, with exclusions primarily due to excessive subject motion. Network analysis of the subset of these subjects in the first cohort with good quality scans revealed spatially localized reductions in the participation coefficient, a measure of between-module connectivity, in the TBI patients relative to the controls at the time of the initial scan. These group differences were less prominent on the follow-up scans. The 15 brain areas with the most prominent reductions in the participation coefficient were next used as regions of interest (ROIs) for single-subject analyses. In the first TBI cohort, more subjects than would be expected by chance (27/47 versus 2/47 expected, p<0.0001) had 3 or more brain regions with abnormally low between-module connectivity relative to the controls on the initial scans. On the follow-up scans, more subjects than expected by chance (5/37, p=0.044) but fewer subjects than on the initial scans had 3 or more brain regions with abnormally low between-module connectivity. Analysis of the second TBI cohort validation dataset with no free parameters provided a partial replication; again more subjects than expected by chance (8/31, p=0.006) had 3 or more brain regions with abnormally low between-module connectivity on the initial scans, but the numbers were not significant (2/27, p=0.276) on the follow-up scans. A single-subject, multivariate analysis by probabilistic principal component analysis of the between-module connectivity in the 15 identified ROIs, showed that 31/47 subjects in the first TBI cohort were found to be abnormal relative to the controls on the initial scans. In the second TBI cohort, 9/31 patients were found to be abnormal in identical multivariate analysis with no free parameters. Again, there were not substantial differences on the follow-up scans. Taken together, these results indicate that single-subject, module-based graph theoretic analysis of resting-state fMRI provides potentially useful information for concussive blast-related TBI if high quality scans can be obtained. The underlying biological mechanisms and consequences of disrupted between-module connectivity are unknown, thus further studies are required.

Detection of blast-related traumatic brain injury in U.S. military personnel.

BACKGROUND: Blast-related traumatic brain injuries have been common in the Iraq and Afghanistan wars, but fundamental questions about the nature of these injuries remain unanswered. METHODS: We tested the hypothesis that blast-related traumatic brain injury causes traumatic axonal injury, using diffusion tensor imaging (DTI), an advanced form of magnetic resonance imaging that is sensitive to axonal injury. The subjects were 63 U.S. military personnel who had a clinical diagnosis of mild, uncomplicated traumatic brain injury. They were evacuated from the field to the Landstuhl Regional Medical Center in Landstuhl, Germany, where they underwent DTI scanning within 90 days after the injury. All the subjects had primary blast exposure plus another, blast-related mechanism of injury (e.g., being struck by a blunt object or injured in a fall or motor vehicle crash). Controls consisted of 21 military personnel who had blast exposure and other injuries but no clinical diagnosis of traumatic brain injury. RESULTS: Abnormalities revealed on DTI were consistent with traumatic axonal injury in many of the subjects with traumatic brain injury. None had detectable intracranial injury on computed tomography. As compared with DTI scans in controls, the scans in the subjects with traumatic brain injury showed marked abnormalities in the middle cerebellar peduncles (P<0.001), in cingulum bundles (P=0.002), and in the right orbitofrontal white matter (P=0.007). In 18 of the 63 subjects with traumatic brain injury, a significantly greater number of abnormalities were found on DTI than would be expected by chance (P<0.001). Follow-up DTI scans in 47 subjects with traumatic brain injury 6 to 12 months after enrollment showed persistent abnormalities that were consistent with evolving injuries. CONCLUSIONS: DTI findings in U.S. military personnel support the hypothesis that blast-related mild traumatic brain injury can involve axonal injury. However, the contribution of primary blast exposure as compared with that of other types of injury could not be determined directly, since none of the subjects with traumatic brain injury had isolated primary blast injury. Furthermore, many of these subjects did not have abnormalities on DTI. Thus, traumatic brain injury remains a clinical diagnosis. (Funded by the Congressionally Directed Medical Research Program and the National Institutes of Health; ClinicalTrials.gov number, NCT00785304.).

SPAG7 deletion causes intrauterine growth restriction, resulting in adulthood obesity and metabolic dysfunction.

From a forward mutagenetic screen to discover mutations associated with obesity, we identified mutations in the Spag7 gene linked to metabolic dysfunction in mice. Here, we show that SPAG7 KO mice are born smaller and develop obesity and glucose intolerance in adulthood. This obesity does not stem from hyperphagia, but a decrease in energy expenditure. The KO animals also display reduced exercise tolerance and muscle function due to impaired mitochondrial function. Furthermore, SPAG7-deficiency in developing embryos leads to intrauterine growth restriction, brought on by placental insufficiency, likely due to abnormal development of the placental junctional zone. This insufficiency leads to loss of SPAG7-deficient fetuses in utero and reduced birth weights of those that survive. We hypothesize that a 'thrifty phenotype' is ingrained in SPAG7 KO animals during development that leads to adult obesity. Collectively, these results indicate that SPAG7 is essential for embryonic development and energy homeostasis later in life.

Obesity rates are climbing worldwide, leading to an increase in associated conditions such as type 2 diabetes. While new pharmaceutical approaches are available to help individuals manage their weight, many patients do not respond to them or experience prohibitive side effects. Identifying alternative treatments will likely require pinpointing the genes and molecular actors involved in the biological processes that control weight regulation. Previous research suggests that a protein known as SPAG7 could help shape how mice use and store the energy they extract from food. Flaherty et al. therefore set out to investigate the role this protein plays in the body. To do so, they created a line of mice born without SPAG7, which they monitored closely throughout life. These animals were underweight at birth and did not eat more than other mice, yet they were obese as adults. Their ability to exercise was reduced, their muscles were weaker and contained fibers with functional defects. The mice also exhibited biological changes associated with the onset of diabetes. Yet deleting SPAG7 during adulthood led to no such changes; these mice maintained normal muscle function and body weight. Closely examining how SPAG7-deficient mice developed in the womb revealed placental defects which likely caused these animals to receive fewer nutrients from their mother. Such early-life deprivation is known to be associated with the body shifting towards maximizing its use of resources and privileging fat storage, even into and throughout adulthood. By shedding light on the biological role of SPAG7, the work by Flaherty et al. helps to better understand how developmental events can increase the likelihood of obesity later in life. Further investigations are now needed to explore whether this knowledge could help design interventions relevant to human health.

Hepatic Activin E mediates liver-adipose inter-organ communication, suppressing adipose lipolysis in response to elevated serum fatty acids.

OBJECTIVE: The liver is a central regulator of energy metabolism exerting its influence both through intrinsic processing of substrates such as glucose and fatty acid as well as by secreting endocrine factors, known as hepatokines, which influence metabolism in peripheral tissues. Human genome wide association studies indicate that a predicted loss-of-function variant in the Inhibin ßE gene (INHBE), encoding the putative hepatokine Activin E, is associated with reduced abdominal fat mass and cardiometabolic disease risk. However, the regulation of hepatic Activin E and the influence of Activin E on adiposity and metabolic disease are not well understood. Here, we examine the relationship between hepatic Activin E and adipose metabolism, testing the hypothesis that Activin E functions as part of a liver-adipose, inter-organ feedback loop to suppress adipose tissue lipolysis in response to elevated serum fatty acids and hepatic fatty acid exposure. METHODS: The relationship between hepatic Activin E and non-esterified fatty acids (NEFA) released from adipose lipolysis was assessed in vivo using fasted CL 316,243 treated mice and in vitro using Huh7 hepatocytes treated with fatty acids. The influence of Activin E on adipose lipolysis was examined using a combination of Inhbe knockout mice, a mouse model of hepatocyte-specific overexpression of Activin E, and mouse brown adipocytes treated with Activin E enriched media. RESULTS: Increasing hepatocyte NEFA exposure in vivo by inducing adipose lipolysis through fasting or CL 316,243 treatment increased hepatic Inhbe expression. Similarly, incubation of Huh7 human hepatocytes with fatty acids increased expression of INHBE. Genetic ablation of Inhbe in mice increased fasting circulating NEFA and hepatic triglyceride accumulation. Treatment of mouse brown adipocytes with Activin E conditioned media and overexpression of Activin E in mice suppressed adipose lipolysis and reduced serum FFA levels, respectively. The suppressive effects of Activin E on lipolysis were lost in CRISPR-mediated ALK7 deficient cells and ALK7 kinase deficient mice. Disruption of the Activin E-ALK7 signaling axis in Inhbe KO mice reduced adiposity upon HFD feeding, but caused hepatic steatosis and insulin resistance. CONCLUSIONS: Taken together, our data suggest that Activin E functions as part of a liver-adipose feedback loop, such that in response to increased serum free fatty acids and elevated hepatic triglyceride, Activin E is released from hepatocytes and signals in adipose through ALK7 to suppress lipolysis, thereby reducing free fatty acid efflux to the liver and preventing excessive hepatic lipid accumulation. We find that disrupting this Activin E-ALK7 inter-organ communication network by ablation of Inhbe in mice increases lipolysis and reduces adiposity, but results in elevated hepatic triglyceride and impaired insulin sensitivity. These results highlight the liver-adipose, Activin E-ALK7 signaling axis as a critical regulator of metabolic homeostasis.

Chronic UCN2 treatment desensitizes CRHR2 and improves insulin sensitivity.

Urocortin 2 (UCN2) acts as a ligand for the G protein-coupled receptor corticotropin-releasing hormone receptor 2 (CRHR2). UCN2 has been reported to improve or worsen insulin sensitivity and glucose tolerance in vivo. Here we show that acute dosing of UCN2 induces systemic insulin resistance in male mice and skeletal muscle. Inversely, chronic elevation of UCN2 by injection with adenovirus encoding UCN2 resolves metabolic complications, improving glucose tolerance. CRHR2 recruits Gs in response to low concentrations of UCN2, as well as Gi and ß-Arrestin at high concentrations of UCN2. Pre-treating cells and skeletal muscle ex vivo with UCN2 leads to internalization of CRHR2, dampened ligand-dependent increases in cAMP, and blunted reductions in insulin signaling. These results provide mechanistic insights into how UCN2 regulates insulin sensitivity and glucose metabolism in skeletal muscle and in vivo. Importantly, a working model was derived from these results that unifies the contradictory metabolic effects of UCN2.

Timing and Type of Venous Thromboembolic Chemoprophylaxis Is Associated with Acute Traumatic Brain Injury Outcomes.

Venous thromboembolic (VTE) prophylaxis in acute traumatic brain injury (TBI) is a controversial topic with wide practice variations. This study examined the association of VTE chemoprophylaxis with inpatient mortality and VTE events among isolated TBI patients. This was a retrospective cohort study of 87 trauma centers within a large hospital system in the United States analyzing 23,548 patients with isolated TBI, 7977 of whom had moderate-to-severe TBI. Primary outcomes were inpatient mortality and VTE events. The control group received no chemoprophylaxis. Other groups received low-molecular-weight heparin (LMWH), unfractionated heparin (UFH), and combined LMWH and UFH chemoprophylaxis. Multi-variable regression accounted for confounders. Outcomes were stratified by timing of administration, body mass index (BMI), and TBI type. Patients without VTE prophylaxis had the least VTE events. LMWH had the lowest mortality for both all-isolated and moderate-to-severe isolated TBI populations at adjusted odds ratio (aOR) 0.24 (95% confidence interval [CI], 0.14-0.43) and aOR 0.25 (95% CI, 0.14-0.44), respectively. Clinically significant progression of TBI was lowest among the LMWH group (0.1%; p value, 0.001). After stratifying by timing of VTE chemoprophylaxis, only patients with subdural hematoma and LMWH between 6 and 24 h (N = 62), as well as patients with ≥35 BMI and LMWH between 6 and 24 h (N = 65) or >24-48 h (N = 54), had no VTE events. VTE chemoprophylaxis timing may have prevented VTE in certain subgroups of isolated TBI patients. Though VTE chemoprophylaxis did not prevent VTE for most TBI patients, LMWH VTE chemoprophylaxis was associated with reduced mortality.

Updating and Integrating Core Outcome Sets for Localised, Locally Advanced, Metastatic, and Nonmetastatic Castration-resistant Prostate Cancer: An Update from the PIONEER Consortium.

CONTEXT: Harmonisation of outcome reporting and definitions for clinical trials and routine patient records can enable health care systems to provide more efficient outcome-driven and patient-centred interventions. We report on the work of the PIONEER Consortium in this context for prostate cancer (PCa). OBJECTIVE: To update and integrate existing core outcome sets (COS) for PCa for the different stages of the disease, assess their applicability, and develop standardised definitions of prioritised outcomes. EVIDENCE ACQUISITION: We followed a four-stage process involving: (1) systematic reviews; (2) qualitative interviews; (3) expert group meetings to agree standardised terminologies; and (4) recommendations for the most appropriate definitions of clinician-reported outcomes. EVIDENCE SYNTHESIS: Following four systematic reviews, a multinational interview study, and expert group consensus meetings, we defined the most clinically suitable definitions for (1) COS for localised and locally advanced PCa and (2) COS for metastatic and nonmetastatic castration-resistant PCa. No new outcomes were identified in our COS for localised and locally advanced PCa. For our COS for metastatic and nonmetastatic castration-resistant PCa, nine new core outcomes were identified. CONCLUSIONS: These are the first COS for PCa for which the definitions of prioritised outcomes have been surveyed in a systematic, transparent, and replicable way. This is also the first time that outcome definitions across all prostate cancer COS have been agreed on by a multidisciplinary expert group and recommended for use in research and clinical practice. To limit heterogeneity across research, these COS should be recommended for future effectiveness trials, systematic reviews, guidelines and clinical practice of localised and metastatic PCa. PATIENT SUMMARY: Patient outcomes after treatment for prostate cancer (PCa) are difficult to compare because of variability. To allow better use of data from patients with PCa, the PIONEER Consortium has standardised and recommended outcomes (and their definitions) that should be collected as a minimum in all future studies.

Adverse events and health status following botulinum toxin type A injections in children with cerebral palsy.

AIM: The aim of this study was to assess changes in health status before and after, as well as adverse events after, botulinum toxin type A (BoNT-A) injections in children with cerebral palsy (CP). METHOD: A total of 334 children (190 male; 144 female) aged 1y 6mo to 19y 4mo (mean 9y 2mo, SD 4y) with CP who were undergoing BoNT-A injections (596 injection courses in total) were clinically audited over a 16-month period. Of the 334 children, 62 were classified at Gross Motor Function Classification System (GMFCS) level I, 52 of whom had unilateral CP and 10 of whom had bilateral CP. Eighty-six children were classified at GMFCS level II, 39 of whom had unilateral CP and 47 of whom had bilateral CP. Forty-four children were classified at GMFCS level III, two of whom had unilateral CP and 42 of whom had bilateral CP. Sixty-six of the 334 children were classified at GMFCS level IV and 76 as level V. All the children classified as level IV or V had bilateral involvement. The health status of the children in the month before and a prospective audit of health status and adverse events in the month after BoNT-A injections were examined in order to assess the effects of the toxin. RESULTS: The data gathered for the month before administration of BoNT-A indicated that children with CP had significant background morbidities. After injection of BoNT-A, adverse events occurred in 23.2% of children. All adverse events were temporary and there were no deaths. INTERPRETATION: The results of this audit indicate that there is insufficient evidence to warrant restriction of the administration of BoNT-A in children with CP at any GMFCS level in our service.

Hospital Employment Of Physicians In Massachusetts Is Associated With Inappropriate Diagnostic Imaging.

The transition among many US physicians from independent practice to hospital employment has raised concerns about whether employed physicians will be more inclined to refer patients for hospital-based services that are unnecessary or inappropriate. Using claims data for 2009-16, we conducted a difference-in-differences analysis to investigate whether this form of hospital-physician integration is associated with inappropriate referrals for magnetic resonance imaging (MRI), a widely used mode of diagnostic imaging, for three common medical conditions: lower back pain, knee pain, and shoulder pain. Study findings indicate that the odds of a patient receiving an inappropriate MRI referral increased by more than 20 percent after a physician transitioned to hospital employment. Most patients who received an MRI referral by an employed physician obtained the procedure at the hospital where the referring physician was employed. These results point to hospital-physician integration as a potential driver of low-value care.

A multicenter study on definitive surgery for isolated hip fracture within 24 hours.

INTRODUCTION: Isolated hip fractures (IHFs) in the elderly are high-frequency, life-altering events. Definitive surgery ≤24 hours of admission is associated with improved outcomes. An IHF process management guideline (IHF-PMG) to expedite definitive surgery ≤24 hours was developed for a multihospital network. We report on its feasibility and subsequent patient outcomes. METHODS: This is a prospective multicenter cohort study, involving 85 levels 1, 2, 3, and 4 trauma centers. Patients with an IHF between 65 and 100 years old were studied. Four cohorts were examined: (1) hospitals that did not implement any PMG, (2) hospitals that used their own PMG, (3) hospitals that partially used the network IHF-PMG, and (4) hospitals that used the network's IHF-PMG. Multivariable logistic regression with reliability adjustment was used to calculate the expected value of observed to expected (O/E) mortality. Statistical significance was defined as p < 0.05. RESULTS: Data on 24,457 IHF were prospectively collected. Following implementation of the IHF-PMG, overall IHF O/E mortality ratios decreased within the hospital network, from 1.13 in 2017 to 0.87 in 2018 and 0.86 in 2019. Hospitals that developed their own IHF-PMG or used the enterprise-wide IHF-PMG had the lowest inpatient O/E mortality at 0.59 and 0.65, respectively. CONCLUSION: Goal-directed IHF-PMG for definitive surgery ≤24 hours was implemented across a large hospital network. The IHF-PMG was associated with lower inpatient mortality. LEVEL OF EVIDENCE: Therapeutic/ Care management, Level III.

Management of colonic injuries in the combat theater.

PURPOSE: Combat injuries are more often associated with blast, penetrating, and high-energy mechanisms than civilian trauma, generating controversy about the management of combat colonic injury. Despite implementation of mandatory colostomy in World War II, recent civilian data suggest that primary repair without diversion is safe and feasible. This study describes the modern management of battle-related colonic injuries and seeks to determine whether management strategy affects early complications. METHODS: Records from the combat theater (downrange) and tertiary referral center in Germany were retrospectively reviewed from 2005 to 2006. Patient characteristics, management strategy, treatment course, and early complications were recorded. Comparison groups by management strategy were as follows: primary repair, diversion, and damage control. RESULTS: A total of 133 (97% male) patients sustained colonic injuries from penetrating (71%), blunt (5%), and blast (23%) mechanisms. Average injury severity score was 21 and length of stay in the referral center was 7.1 days. Injury distribution was 21% ascending, 21% descending, 15% transverse, 27% sigmoid, and 25% rectum. Downrange complications for primary repair, initial ostomy, and damage control groups were 14%, 15%, and 30%, respectively. On discharge from the center, 62% of patients had undergone a diversion. The complication rate was 18% overall and was unrelated to management strategy (P = .16). Multivariate analysis did not identify independent predictors of complications. CONCLUSION: Early complications were similar by mechanism, anatomic location, severity of injury, and management strategy. More diversions were performed for rectosigmoid injury. Good surgical judgment allows for low morbidity and supports primary repair in selected cases. Damage control surgery is effective in a multinational theater of operations.