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Introduction The type of blood collection tube used when obtaining samples for therapeutic drug monitoring (TDM) has important implications on the accuracy of results. Serum tubes without a gel separator are currently considered best practice. We sought to evaluate the performance of of Barricor™, a novel plasma tube that utilizes an inert mechanical separator, as well as a gel-based tube (PST™) for testing acetaminophen, digoxin, gentamicin, methotrexate, phenobarbital, phenytoin, salicylate, vancomycin, valproic acid, carbamazepine, and theophylline on a Roche Cobas® 8000 platform. Methods Paired patient samples were collected from individuals taking at least one of the medications evaluated. These were supplemented with spiked specimens to ensure a minimum of 40 paired samples per drug. All drugs were measured within two hours of collection on Roche e602 or c502 instruments. Deming regression was used to assess bias between Barricor™ vs serum and PST™ vs serum. Seven-day refrigerated stability was also assessed in Barricor™, PST™, and serum tubes in a subset of samples (n=10) for each drug. Results Drug concentrations in Barricor™ were similar to serum for each drug assessed. In contrast, a negative bias was observed in PST™ compared to serum tubes for carbamazepine (-7.6%) and phenytoin (-6.8%) although this did not surpass our total allowable error goal of 10%. All drugs recovered within ±10% of baseline value when samples were stored refrigerated for 7 days except for carbamazepine, phenytoin, and phenobarbital where significant analyte loss was observed within the first day in PST™ tubes. Conclusion Barricor™ tubes are a suitable alternative to serum for TDM on the Roche Cobas® 8000 platform.

Abnormal atrioventricular valve present great challenges to the surgeon in achieving a successful repair, and thus present a great opportunity for enhanced 3D imaging to guide pre- and intra-operative management. Spatial and temporal resolution of 3D echocardiography enables 3D printing of valve morphology. However, non-linearity, angle dependence, speckle, blur, and resampling complicate segmentation compared to computed tomography (CT) and magnetic resonance imaging (MRI). A case of complex mitral valve disease in a pediatric patient is therefore presented to illustrate the technical challenges of segmentation and 3D printing from echocardiographic data.

In the military health system, there has been a growing demand for mental health services over the last two decades. Partial hospitalization programs fill a critical niche between outpatient and inpatient services. The present study evaluated immediate and long-term outcomes of a military mental health partial hospitalization program at a large military treatment facility. This study collected retrospective data of active duty patients who completed a 6-day partial hospitalization program within a 2-year period. Results showed that the majority of participants were young, male, and junior enlisted service members endorsing suicidal ideation as well as adjustment/stressor- and depressive-related psychiatric symptoms. Immediately after treatment, participants showed a significant reduction in psychiatric symptoms and dysfunction after treatment. In the long-term, most participants engaged in mental health services post-discharge, though engagement with services decreased over time. In addition, career-impacting medical recommendations were made for over half of participants with almost three-quarters of these recommendations made before or during enrollment in the program. This study expanded the limited evidence base for military mental health partial hospitalization programs. In addition, this study offered data on the frequency of career-impacting medical recommendations made for patients engaged in care at this level of acuity.

Context Classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency (21OHD) is characterized by impaired cortisol synthesis and excess androgen production. Corticotropin-releasing factor type 1 receptor (CRF1R) antagonism may decrease adrenal androgen production. Objective This work aimed to evaluate the safety, tolerability, and efficacy of crinecerfont (NBI-74788), a selective CRF1R antagonist, in 21OHD. Methods This open-label, phase 2 study, with sequential cohort design (NCT03525886), took place in 6 centers in the United States. Participants included men and women, aged 18 to 50 years, with 21OHD. Interventions included 4 crinecerfont regimens, each administered orally for 14 consecutive days: 50 or 100 mg once daily at bedtime (cohorts 1 and 2, respectively); 100 mg once daily in the evening (cohort 3); and 100 mg twice daily (cohort 4). Participants could enroll in more than 1 cohort. Main outcomes included changes from baseline to day 14 in adrenocorticotropin (ACTH), 17-hydroxyprogesterone (17OHP), androstenedione, and testosterone. Results Eighteen participants (11 women, 7 men) were enrolled: cohort 1 (n = 8), cohort 2 (n = 7), cohort 3 (n = 8), cohort 4 (n = 8). Mean age was 31 years; 94% were White. Median percent reductions were more than 60% for ACTH (–66%), 17OHP (–64%), and androstenedione (–64%) with crinecerfont 100 mg twice a day. In female participants, 73% (8/11) had a 50% or greater reduction in testosterone levels; male participants had median 26% to 65% decreases in androstenedione/testosterone ratios. Conclusion Crinecerfont treatment for 14 days lowered ACTH and afforded clinically meaningful reductions of elevated 17OHP, androstenedione, testosterone (women), or androstenedione/testosterone ratio (men) in adults with 21OHD. Longer-term studies are required to evaluate the effects of crinecerfont on clinical end points of disordered steroidogenesis and glucocorticoid exposure in patients with 21OHD.

PURPOSE: Obesity increases the risk of cancer recurrence and death in survivors of breast cancer. This study tested the hypothesis that exercise alone, diet alone, and the combination of exercise plus diet reduce body weight and improve body composition in survivors of breast cancer. METHODS: In this 2×2 factorial trial, 351 survivors of breast cancer with overweight or obesity were randomized to one of four treatment groups for 52 weeks: control, exercise alone, diet alone, or exercise plus diet. Endpoints included body weight and body composition measured by dual-energy x-ray absorptiometry. RESULTS: After 52 weeks, compared with control, diet alone [−5.39 kg (95% CI: −7.24, −3.55); −6.0% (95% CI: −8.0, −3.9)] and exercise plus diet [−6.68 kg (95% CI: −8.46, −4.90); −7.4% (95% CI: −9.4, −5.4)] reduced body weight; exercise alone did not change body weight. Compared with control, diet alone [−3.59 kg (95% CI: −5.00, −2.17)] and exercise plus diet [−4.28 kg (95% CI: −5.71, −2.84)] reduced fat mass; exercise alone did not change fat mass. Compared with control, diet alone [−0.82 kg (95% CI: −1.50, −0.15)] and exercise plus diet [−1.24 kg (95% CI: −1.92, −0.56)] reduced lean mass; exercise alone did not change lean mass. Compared with control, exercise alone, diet alone, and exercise plus diet did not change bone mineral density. CONCLUSION: In survivors of breast cancer with overweight or obesity, diet alone or diet plus exercise produced clinically meaningful weight loss at week 52. The majority of weight loss was fat mass.

OBJECTIVE Chronic overlapping pain conditions (COPCs) represent a co-aggregation of widespread pain disorders. We characterized differences in physical and psychosocial functioning in patients with chronic migraine (CM) and those with CM and COPCs. BACKGROUND Patients with CM and COPCs have been identified as a distinct subgroup of patients with CM, and these patients may be vulnerable to greater symptom severity and burden. METHODS Data were extracted from Collaborative Health Outcomes Information Registry (an open-source learning health-care system), completed at the patients' first visit at a large tertiary care pain management center and electronic medical records. In 1601 patients with CM, the number of non-cephalic areas of pain endorsed on a body map was used to examine the differences in pain, physical and psychosocial function, adverse life experience, and health-care utilization. RESULTS Patients endorsing more body map regions reported significantly worse symptoms and function across all domains. Scored on a t-score metric (mean = 50, SD = 10), endorsement of one additional body map region corresponded with a 0.69-point increase in pain interference (95% CI = 0.55, 0.82; p

Chronic neuropathic pain (NP) is a common and often debilitating secondary condition for persons with spinal cord injury (SCI) and is minimally responsive to existing pharmacological and nonpharmacological treatments. The current preliminary investigation describes the feasibility and initial comparative efficacy of an interactive virtual reality walking intervention, which is a novel extension of visual feedback/illusory walking therapies shown to reduce SCI NP. Virtual reality walking intervention builds on previous research by, for the first time, allowing individuals with SCI NP to volitionally control virtual gait to interact with a fully immersive virtual environment. The current pilot study compared this interactive, virtual walking intervention to a passive, noninteractive virtual walking condition (analogous to previous illusory walking interventions) in 27 individuals with complete paraplegia (interactive condition, n = 17; passive condition, n = 10; nonrandomized design). The intervention was delivered over 2 weeks in individuals' homes. Participants in the interactive condition endorsed significantly greater reductions in NP intensity and NP-related activity interference preintervention to postintervention. Notable improvements in mood and affect were also observed both within individual sessions and in response to the full intervention. These results, although preliminary, highlight the potentially potent effects of an interactive virtual walking intervention for SCI NP. The current study results require replication in a larger, randomized clinical trial and may form a valuable basis for future inquiry regarding the mechanisms and clinical applications of virtual walking therapies.

Summary Pathology records of bats submitted to the University of Georgia from managed care settings were reviewed to identify naturally occurring diseases. Fifty-nine cases were evaluated during an 11-year period (2008–2019), including representatives from four families: Pteropodidae (Yinpterochiroptera), Phyllostomidae, Vespertilionidae and Molossidae (Yangochiroptera). Pathology reports were reviewed to determine the primary pathological process resulting in death or the decision to euthanize. Cases were categorized as non-infectious (34/59; 58%), infectious/inflammatory (17/59; 29%) or undetermined due to advanced autolysis (8/59; 14%). Musculoskeletal diseases and reproductive losses were the most frequent pathological processes. Among the infectious processes identified, bacterial infections of the reproductive and haemolymphatic systems were most frequently observed. The first two reports of neoplasia in small flying foxes (Pteropus hypomelanus) are described. Bats under managed care present with a wide range of histopathological lesions. In this cohort, non-infectious disease processes were common.

Background: This brief review considers major aspects of COVID toes as currently understood. Topics discussed include etiology, pathophysiology, differential diagnosis, treatment, and management. Media characterization, potentially leading to intense public interest in COVID toes during the summer of 2020, is also discussed. Methods: The literature review was conducted by selecting articles from PUBMED, SCOPUS, EMBASE, and Google Scholar based on the relevance to our topic. To determine the relative search interest of the general population, a Google Trends analysis was queried on 11/17/20 for the retrospective duration of 11/17/2019–11/17/2020. Results: The majority of patients who have presented with COVID toes are children and young adults. COVID toes generally present as acro-ischemic lesions, which are microthrombotic events in the extremities, leading to symptoms such as pseudo-chilblains or pernio-like lesions. Chilblains are histologically classified as an inflammatory disorder with a prominent perivascular lymphocytic infiltrate seen on microscopy. The regions are described as appearing erythematous to purple purpuric macules, papules, and/or vesicles. In many cases, COVID toes symptoms are self-limiting. Conclusion: The development of COVID toes represents an additional manifestation of COVID-19 that should lead to additional testing. Knowledge of these symptoms can give healthcare workers and the general public another tool for recognizing COVID-19. Keywords: COVID toes, COVID-19, coronavirus, chilblains, pernio

Cutaneous injury and irritation among health care workers has substantially risen during the COVID-19 pandemic. In a field already laden with skin-induced injury and irritation due to high levels of handwashing and glove wearing, increases have been reported in handwashing-induced xerosis, irritant dermatitis, and contact dermatitis from N95 respirators and other surgical masks. Masks, goggles, face shields, and gloves all potentially create abrasions from long hours of use, leading to itching, pain, and aggravation of underlying skin conditions. Personal protective equipment (PPE)-related skin injury can be serious, and the American Academy of Dermatology has released recommendations on preventing and treating occupationally induced dermatologic conditions during the COVID-19 pandemic. These are reviewed and discussed in conjunction with overarching guidelines for mitigating the spread of the virus.

Background: Adiponectin, leptin, and pro- and anti-inflammatory cytokines are implicated in breast cancer risk and recurrence. Weight loss, via the dynamic interplay of energy balance through exercise and/or caloric restriction, decreases risk of breast cancer recurrence. Methods: We investigated the effects of lifestyle modifications (exercise only, or combined caloric restriction and exercise) on adipokines, IL2, IL6, IL8, IL10, C-reactive protein (CRP), and TNFα biomarkers in breast cancer survivors. Searches were completed in June and July of 2019 to identify randomized controlled trials that met inclusion criteria. Weighted mean difference was calculated using random- or fixed-effects models based on the heterogeneity of the studies. Results: 2501 records were identified, with 30 ultimately meeting inclusion criteria of the systematic review; 21 studies provided data suitable for meta-analysis. We observed leptin levels were significantly reduced in the exercise-only group compared with sedentary control [WMD −5.66; 95% confidence interval (CI), −11.0 to −0.33; P = 0.04]. Conclusions: Leptin may be a primary mediator of exercise–induced improvements in breast cancer recurrence. Impact: This is the first review and meta-analysis to examine combined exercise and caloric restriction programs in breast cancer survivors. Future studies should further examine combined programs and their efficacy for altering leptin.

Despite a common assumption that reductions in chronic pain intensity must precede improvements in other pain-relevant domains, there has been limited empirical inquiry into the temporal ordering of improvements in chronic pain treatment. Cross-lagged models using retrospective clinical data examined relationships between average pain intensity and symptoms of psychological distress, difficulties with sleep initiation and maintenance, and disability in 666 treatment-seeking patients with chronic pain who demonstrated improvement in pain intensity (≥1-point reduction on 0-10 numeric rating scale) over a 1-year span. Results indicated that decreased difficulties with sleep initiation, depressive and anxious symptoms, and disability predicted later improvement in pain intensity, whereas greater pain intensity predicted only later difficulties in sleep initiation and maintenance. A combined lagged model highlighted fewer baseline symptoms of post-traumatic stress disorder and lower levels of baseline disability as significant predictors of later improvements in pain. Overall, our results indicate that reductions in pain intensity may not be the first factors to change in effective chronic pain management. The current findings should be replicated using prospective studies utilizing structured approaches to maximize data capture, as well as uniform interventional approaches to permit greater inferences regarding causal and temporal aspects of the model. Perspective This study demonstrates that pain intensity scores are not robust predictors of psychosocial outcomes longitudinally. Instead, other factors such as sleep initiation, psychological distress and disability appear to be important targets for intervention that may promote effective pain reduction.

Background Children hospitalized with severe acute malnutrition (SAM) have poor long-term outcomes following discharge, with high rates of mortality, morbidity, and impaired neurodevelopment. There is currently minimal guidance on how to support children with SAM following discharge from inpatient treatment. Objectives This systematic review and meta-analysis aimed to examine whether postdischarge interventions can improve outcomes in children recovering from complicated SAM. Methods Systematic searches of 4 databases were undertaken to identify studies of interventions delivered completely or partially after hospital discharge in children aged 6–59 mo, following inpatient treatment of SAM. The main outcome of interest was mortality. Random-effects meta-analysis was undertaken where ≥2 studies were sufficiently similar in intervention and outcome. Results Ten studies fulfilled the inclusion criteria, recruiting 39–1781 participants in 7 countries between 1975 and 2015. Studies evaluated provision of zinc (2 studies), probiotics or synbiotics (2 studies), antibiotics (1 study), pancreatic enzymes (1 study), and psychosocial stimulation (4 studies). Six studies had unclear or high risk of bias in ≥2 domains. Compared with standard care, pancreatic enzyme supplementation reduced inpatient mortality (37.8% compared with 18.6%, P

Injury to soft-tissues secondary to trauma is common and may require surgical intervention depending on the extent of the injury and the structures involved. Motor vehicle accidents are a leading cause of traumatic injury and often require surgical irrigation and debridement (I&D) to remove damaged and necrotic tissue while preserving tissue integrity and function. Surgical intervention carries its own risks, however, with the introduction of pathogens to the surgical site being a potential complication. This case of an 18 yr. old woman with a chronic would due to recurring skin and soft tissue infections (SSTIs) highlights the complications of surgical intervention and the difficulty of dealing with recurring SSTIs. The patient suffered a left knee injury with patellar tendon laceration secondary to trauma from a motor vehicle accident. She initially underwent surgical irrigation and debridement, followed by patellar tendon repair with a rotational flap to close the open wound. Following the initial closure in December 2019, the patient underwent 6 more I&Ds and wound debridement over a 5-month period due to a chronic non-healing wound with recurring SSTIs. Wound Healing was tentatively achieved with antibiotic coverage for both Staph Aureus and Pseudomonas Aeruginosa.

Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with critical illness may identify mechanistic targets for therapeutic development3. Here we report the results of the GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study in 2,244 critically ill patients with COVID-19 from 208 UK intensive care units. We have identified and replicated the following new genome-wide significant associations: on chromosome 12q24.13 (rs10735079,P=1.65×10−8) in a gene cluster that encodes antiviral restriction enzyme activators (OAS1,OAS2andOAS3); on chromosome 19p13.2 (rs74956615,P=2.3×10−8) near the gene that encodes tyrosine kinase 2 (TYK2); on chromosome 19p13.3 (rs2109069,P=3.98× 10−12) within the gene that encodes dipeptidyl peptidase 9 (DPP9); and on chromosome 21q22.1 (rs2236757,P=4.99×10−8) in the interferon receptor geneIFNAR2. We identified potential targets for repurposing of licensed medications: using Mendelian randomization, we found evidence that low expression ofIFNAR2, or high expression ofTYK2, are associated with life-threatening disease; and transcriptome-wide association in lung tissue revealed that high expression of the monocyte–macrophage chemotactic receptorCCR2is associated with severe COVID-19. Our results identify robust genetic signals relating to key host antiviral defence mechanisms and mediators of inflammatory organ damage in COVID-19. Both mechanisms may be amenable to targeted treatment with existing drugs. However, large-scale randomized clinical trials will be essential before any change to clinical practice.

Rib fractures are painful injuries that are treated with aggressive analgesia, which can include opioids. We sought to evaluate the patterns and predictors of opioid prescription and sustained use for rib fracture patients to identify opportunities for opiate reduction.We used TRICARE claims data (2006-2014) to identify adult (18-64 years) patients presenting to the emergency department with rib fracture(s) and isolated chest trauma. We used logistic regression and Cox proportional hazards model to identify factors associated with opioid prescription and duration of use.We identified 29,943 patients meeting inclusion criteria, and 2,542 (9%) patients were prescribed opioids. When prescribed, the median duration opioid use was 16 days (interquartile range 6-31) for opioid naïve patients, compared with 36 days (interquartile range 15-134) for those with prior opioid exposure. Increased number of ribs fractured (6+ fractures) (odds ratio 2.96 [95% confidence interval 2.23-3.94], P.001) and prior opioid exposure (odds ratio 32.95 [29.36-36.99], P.001) were significant predictors of initial opioid prescription. Patients with prior opioid exposure (hazard ratio 0.47 [0.43-0.52], P.001) had lower likelihood of opioid discontinuation. Injury characteristics did not significantly predict discontinuation.Prior opioid exposure was the strongest predictor of sustained opioid use after rib fractures, while the severity of injury did not predict the duration of use.

Background Insulinomas are found in 10–15 per cent of patients with multiple endocrine neoplasia type 1 (MEN1) and lead to life‐threatening hypoglycaemia. Surgical outcome and the optimal surgical strategy for MEN1‐related insulinoma are unknown. Methods Patients with MEN1‐related insulinomas were identified in 46 centres in Europe and North America between 1990 and 2016. Insulinomas were considered localized if the lesion was in the pancreatic head or body/tail. Patients with pancreatic neuroendocrine tumours throughout the pancreas were suspected of having multifocal insulinoma. The primary outcome was postoperative hypoglycaemia, defined as persistent hypoglycaemia, or recurrent hypoglycaemia caused by a new insulinoma or insulin‐producing liver metastases. Hypoglycaemia‐free survival was estimated by the Kaplan–Meier method. Results Ninety‐six patients underwent resection for MEN1‐related insulinoma. Sixty‐three and 33 patients had localized and multifocal insulinomas respectively. After a median follow‐up of 8 (range 1–22) years, one patient (1 per cent) had persistent disease and six (6 per cent) had developed recurrent disease, of whom four had a new insulinoma. The 10‐year hypoglycaemia‐free survival rate was 91 (95 per cent c.i. 80 to 96) per cent. Of those with localized disease, 46 patients underwent pancreatic resection and 17 enucleation. One of these patients had persistent disease and one developed recurrent insulinoma. Among patients with multifocal disease, three developed new insulinomas and two developed insulin‐producing liver metastases. Conclusion Surgery for MEN1‐related insulinoma is more successful than previously thought., In this cohort of 96 patients with resected multiple endocrine neoplasia 1 (MEN1)‐related insulinomas, seven patients (7 per cent) developed postoperative persistent or recurrent hypoglycaemia after a median follow‐up of 8 years. The 10‐year hypoglycaemia‐free survival rate was 91 (95 per cent c.i. 80 to 96) per cent. For patients with localized insulinoma, enucleation seems the preferred procedure. PPPD, pylorus‐preserving pancreatoduodenectomy. Outcomes good

Stroke is caused by obstructed blood flow (ischaemia) or unrestricted bleeding in the brain (haemorrhage). Global brain ischaemia occurs after restricted cerebral blood flow e.g. during cardiac arrest. Following ischaemic injury, restoration of blood flow causes ischaemia–reperfusion (I/R) injury which worsens outcome. Secondary injury mechanisms after any stroke are similar, and encompass inflammation, endothelial dysfunction, blood–brain barrier (BBB) damage and apoptosis. We developed a new model of transient global forebrain I/R injury (dual carotid artery ligation; DCAL) and compared the manifestations of this injury with those in a conventional I/R injury model (middle-cerebral artery occlusion; MCAo) and with intracerebral haemorrhage (ICH; collagenase model). MRI revealed that DCAL produced smaller bilateral lesions predominantly localised to the striatum, whereas MCAo produced larger focal corticostriatal lesions. After global forebrain ischaemia mice had worse overall neurological scores, although quantitative locomotor assessment showed MCAo and ICH had significantly worsened mobility. BBB breakdown was highest in the DCAL model while apoptotic activity was highest after ICH. VCAM-1 upregulation was specific to ischaemic models only. Differential transcriptional upregulation of pro-inflammatory chemokines and cytokines and TLRs was seen in the three models. Our findings offer a unique insight into the similarities and differences in how biological processes are regulated after different types of stroke. They also establish a platform for analysis of therapies such as endothelial protective and anti-inflammatory agents that can be applied to all types of stroke.

Background Malnutrition underlies 45% of under-5 deaths globally. Severe acute malnutrition (SAM) is the most serious form of undernutrition, characterized by wasting with or without edema. Mortality remains high (10%–40%) among children requiring hospitalization for complicated SAM. Objectives We aimed to systematically document the factors independently associated with inpatient mortality in children with SAM. Methods Embase, Ovid MEDINE, the Cochrane Library, and clinicaltrials.gov were searched for articles published between January 2000 and January 2020, using a prespecified protocol. Eligible studies included children aged ≤59 mo hospitalized with SAM and used multivariable analysis to assess the baseline factors independently associated with inpatient mortality. Random-effects meta-analysis, stratified by the stated measure of effect, was used where >20% of studies included the same factor in analyses. Results Twenty-eight of 1432 studies fulfilled inclusion criteria: 19 studies included all children with SAM and 9 included specific subgroups of children with SAM. All 19 main studies were from 8 countries across Africa, with a median of 400 children/study. The mean inpatient mortality was 15.7% (95% CI: 10.4%, 21.0%) and HIV prevalence ranged from 2.1% to 51%. Nine factors were included in the meta-analysis, stratified by HR and OR. HIV infection (HR: 4.32; 95% CI: 2.31, 8.08), weight-for-height z score (WHZ) (OR: 0.44; 95% CI: 0.24, 0.80), diarrhea (HR: 2.84; 95% CI: 1.40, 5.75), pneumonia (HR: 1.89; 95% CI: 1.19, 3.02), presence of shock (HR: 3.67; 95% CI: 2.24, 6.03), and lack of appetite (HR: 2.16; 95% CI: 1.48, 3.16) were associated with increased mortality, whereas child age and sex were not. The association between edema and mortality was difficult to ascertain from the available studies. Conclusions HIV infection, diarrhea, pneumonia, shock, lack of appetite, and lower WHZ are independent predictors of inpatient mortality in children with SAM. These factors may help to risk-stratify children being hospitalized with complicated SAM. This systematic review/meta-analysis protocol was registered at www.crd.york.ac.uk/prospero as CRD42019152267.

Informed consent is necessary for all medical, surgical and obstetric interventions. Whilst informed consent can be obtained for elective procedures, it is much more challenging to obtain for emergency interventions. It can be difficult for women to understand the need for emergency intervention when pregnancy has been low risk. This can lead to problems with psychological trauma from the delivery being foremost in their minds in the postnatal period and in future pregnancies. The Montgomery ruling of 2015 encouraged informing women about risks and benefits of interventions and letting the women take responsibility for their own decision-making. Here, a patient-focused survey collected information on pregnant women's knowledge and wishes regarding emergency interventions. The responses were analysed in relation to local and Scottish national delivery data. We have initiated a novel programme to ensure all of our pregnant women are empowered to give informed consent for emergency interventions.IMPACT STATEMENT

Background Changes in care providers and hospitals after emergency general surgery (EGS) (care discontinuity) are associated with increased morbidity and mortality. The cause of these worse outcomes is unknown. Our goal was to determine if hospital quality is associated with mortality after readmissions independent of continuity in care. Study Design This was a retrospective analysis of Medicare inpatient claims (2007 to 2015). All inpatients older than 65 years of age who underwent 1 of 7 EGS procedures shown to represent 80% of EGS volume, complications, and mortality nationally, were included. Care discontinuity was defined as readmission within 30 days to a nonindex hospital. Hospital quality was determined by hospital-level, risk-adjusted mortality rates by EGS procedure and categorized into high quality (HQ) and low quality (LQ). The primary outcome was overall mortality. Multivariate logistic regression analysis was used to determine the association of discontinuity and mortality. Results There were 882,929 EGS patients, 87,232 of whom were readmitted within 30 days of discharge. Care discontinuity was independently associated with mortality (odds ratio [OR] 1.23; 95% CI 1.17 to 1.29). When readmitted patients were stratified by quality of index and readmitting hospital, mortality was associated with the quality of both the index hospital and the readmitting hospital. The highest mortality rate was observed in patients with index admission at low-quality hospitals and readmission to a different low-quality hospital. Conclusions Both care discontinuity and hospital quality are independently associated with mortality in EGS patients. These data support maintaining continuity of care, even at low performing hospitals.

Background Various diagnostic tests are available to establish the primary aldosteronism (PA) diagnosis and to determine the disease laterality. Combined with the controversies in the literature, unawareness of guidelines and technical demands and high costs of some of these diagnostics, this could lead to significant differences in work-up strategies worldwide. Therefore, we investigated the work-up before surgery for PA in daily clinical practice within a multicenter study. Methods Patients who underwent unilateral adrenalectomy for PA within 16 centers in Europe, Canada, Australia and the USA between 2010 and 2016 were included. We did not exclude patients based on the performed diagnostic tests during work-up to make our data representative for current clinical practice. Adherence to the Endocrine Society Guideline and variables associated with not performing adrenal venous sampling (AVS) were analyzed. Results In total, 435 patients were eligible. An aldosterone-to-renin ratio, confirmatory test, computed tomography (CT), magnetic resonance imaging and AVS were performed in 82.9%, 32.9%, 86.9%, 17.0% and 65.3% of patients, respectively. A complete work-up, as recommended by the guideline, was performed in 13.1% of patients. Bilateral disease or normal adrenal anatomy on CT (OR 16.19; CI 3.50–74.99), smaller tumor size on CT (OR 0.06; CI 0.04–0.08) and presence of hypokalemia (OR 2.00; CI 1.19–3.32) were independently associated with performing AVS. Conclusions This study is the first to examine the daily clinical practice work-up of PA within a worldwide cohort of surgical patients. The results demonstrate significant variability in work-up strategies and low adherence to The Endocrine Society guideline.

As the overlap between heart disease and cancer patients increases as cancer-specific mortality is decreasing and the surviving population is aging, it is necessary to identify cancer patients who are at an increased risk of death from heart disease. The purpose of this study is to identify cancer patients at highest risk of fatal heart disease compared to the general population and other cancer patients at risk of death during the study time period. Here we report that 394,849 of the 7,529,481 cancer patients studied died of heart disease. The heart disease-specific mortality rate is 10.61/10,000-person years, and the standardized mortality ratio (SMR) of fatal heart disease is 2.24 (95% CI: 2.23–2.25). Compared to other cancer patients, patients who are older, male, African American, and unmarried are at a greatest risk of fatal heart disease. For almost all cancer survivors, the risk of fatal heart disease increases with time., As the overlap between heart disease and cancer patients increases as cancer-specific mortality is decreasing, identifying cancer patients who are at an increased risk of death from heart disease is important. Here the authors report on risk of death from heart diseases among more than 7.5 million cancer patients.

BackgroundThere are significant medical risks of long-term opioid therapy (LTOT) for chronic pain. Consequently, there is a need to identify effective interventions for the reduction of high-dose full-agonist opioid medication use.MethodsThe current study details a retrospective review of 240 patients with chronic pain and LTOT presenting for treatment at a specialty opioid refill clinic. Patients first were initiated on an outpatient taper or, if taper was not tolerated, transitioned to buprenorphine. This study analyzes potential predictors of successful tapering, successful buprenorphine transition, or failure to complete either intervention and the effects of this clinical approach on pain intensity scores.ResultsOne hundred seven patients (44.6%) successfully tapered their opioid medications under the Centers for Disease Control and Prevention guideline target dose (90 mg morphine-equianalgesic dosage), 45 patients (18.8%) were successfully transitioned to buprenorphine, and 88 patients (36.6%) dropped out of treatment: 11 patients during taper, eight during buprenorphine transition, and 69 before initiating either treatment. Conclusions. Higher initial doses of opioids predicted a higher likelihood of requiring buprenorphine transition, and a co-occurring benzodiazepine or z-drug prescription predicted a greater likelihood of dropout from both interventions. Patterns of change in pain intensity according to treatment were mixed: among successfully tapered patients, 52.8% reported greater pain and 23.6% reported reduced pain, whereas 41.8% reported increased pain intensity and 48.8% reported decreased pain after buprenorphine transition. Further research is needed on predictors of treatment retention and dropout, as well as factors that may mitigate elevated pain scores after reduction of opioid dosing.

Background Low hospital volume for emergency general surgery (EGS) procedures is associated with worse patient outcomes within the civilian health care system. The military maintains treatment facilities (MTFs) in remote locations to provide access to service members and their families. We sought to determine if patients treated at low-volume MTFs for EGS conditions experience worse outcomes compared with high-volume centers. Materials and methods We analyzed TRICARE data from 2006 to 2014. Patients were identified using an established coding algorithm for EGS admission. MTFs were divided into quartiles based on annual EGS volume. Outcomes included 30-d mortality, complications, and readmissions. Logistic regression models adjusting for clinical and sociodemographic differences in case-mix including EGS condition, surgical intervention, and comorbidities were used to determine the influence of hospital volume on outcomes. Results We identified 106,915 patients treated for an EGS condition at 79 MTFs. The overall mortality rate was 0.21%, with complications occurring in 8.55% and readmissions in 4.45%. After risk adjustment, lowest-volume MTFs did not demonstrate significantly higher odds of mortality (OR: 2.02, CI: 0.45-9.06) or readmissions (OR: 0.77, CI: 0.54-1.11) compared with the highest-volume centers. Lowest-volume facilities exhibited a lower likelihood of complications (OR: 0.76, CI: 0.59-0.98). Conclusions EGS patients treated at low-volume MTFs did not experience worse clinical outcomes when compared with high-volume centers. Remote MTFs appear to provide care for EGS conditions comparable with that of high-volume facilities. Our findings speak against the need to reduce services at small, critical access facilities within the military health care system.

Cerebral venous sinus thrombosis is an uncommon disorder that requires prompt diagnosis and treatment to prevent serious complications. Due to the broad spectrum of clinical presentations, patients typically undergo noncontrast CT as the first imaging study. The classical description of cerebal venous sinus thrombosis on noncontrast CT is a hyperdense thrombus within the dural venous sinus. We report an unusual case of a hypodense cerebral venous sinus thrombosis on unenhanced CT imaging. It is important for radiologists to be aware of this atypical appearance that to our knowledge has not been previously published. Keywords: Cerebral venous sinus thrombosis, Dural venous sinus thrombosis, Thrombosis

Background: The 2015 American Thyroid Association (ATA) clinical practice guidelines (CPGs) on management of thyroid nodules (TNs) and differentiated thyroid cancer (DTC) in adults were developed to inform clinicians, patients, researchers, and health policy makers about the best available evidence, and its limitations, relating to management of these conditions. Methods: We conducted a cross-sectional electronic survey of ATA members' perspectives of these CPGs, using a standardized survey (Clinician Guidelines Determinant Questionnaire) developed by the Guidelines International Network. A survey link was electronically mailed to members in February of 2019, with reminders sent to nonrespondents 2 and 5 weeks later. Data were descriptively summarized, after excluding missing responses. Results: The overall response rate was 19.8% (348/1761). The effective response rate was 20.2% (348/1720), after excluding a recently deceased member and individuals who had either invalid e-mail addresses or whose e-mails were returned. Of the respondents, 37.9% (132/348) were female, 60.4% (209/346) were endocrinologists, 27.5% (95/346) were surgeons, and 3.5% (12/346) were nuclear medicine specialists. The majority of respondents (71.9%; 250/348) were at a mid- or advanced-career level, and more than half were in academia (57.5%; 195/339). The majority (69.8%; 243/348) practiced in North America. The vast majority of respondents indicated that the CPGs explained the underlying evidence (92.3%; 298/323) and 92.9% (300/323) agreed or strongly agreed with the content. Most respondents stated that they regularly used the CPGs in their practice (83.0%; 268/323). Most respondents (83.0%; 268/323) also agreed or strongly agreed that the recommendations were easy to incorporate in their practice. The most popular CPG format was an electronic desktop file (78.8%; 252/320). Shorter more frequent CPGs were favored by 55.0% (176/320) of respondents, and longer traditional CPGs were favored by 39.7% (127/320). Conclusions: The clinical content and evidence explanations in the adult TN and DTC CPGs are widely accepted and applied among ATA survey respondents. Future ATA CPG updates need to be optimized to best meet users' preferences regarding format, frequency, and length.

Background Data are limited regarding the optimal dose and duration of amoxicillin treatment for community-acquired pneumonia in children. Objectives To determine the efficacy, safety and impact on antimicrobial resistance of shorter (3-day) and longer (7-day) treatment with amoxicillin at both a lower and a higher dose at hospital discharge in children with uncomplicated community-acquired pneumonia. Design A multicentre randomised double-blind 2 × 2 factorial non-inferiority trial in secondary care in the UK and Ireland. Setting Paediatric emergency departments, paediatric assessment/observation units and inpatient wards. Participants Children aged > 6 months, weighing 6–24 kg, with a clinical diagnosis of community-acquired pneumonia, in whom treatment with amoxicillin as the sole antibiotic was planned on discharge. Interventions Oral amoxicillin syrup at a dose of 35–50 mg/kg/day compared with a dose of 70–90 mg/kg/day, and 3 compared with 7 days’ duration. Children were randomised simultaneously to each of the two factorial arms in a 1 : 1 ratio. Main outcome measures The primary outcome was clinically indicated systemic antibacterial treatment prescribed for respiratory tract infection (including community-acquired pneumonia), other than trial medication, up to 28 days after randomisation. Secondary outcomes included severity and duration of parent/guardian-reported community-acquired pneumonia symptoms, drug-related adverse events (including thrush, skin rashes and diarrhoea), antimicrobial resistance and adherence to trial medication. Results A total of 824 children were recruited from 29 hospitals. Ten participants received no trial medication and were excluded. Participants [median age 2.5 (interquartile range 1.6–2.7) years; 52% male] were randomised to either 3 (n = 413) or 7 days (n = 401) of trial medication at either lower (n = 410) or higher (n = 404) doses. There were 51 (12.5%) and 49 (12.5%) primary end points in the 3- and 7-day arms, respectively (difference 0.1%, 90% confidence interval –3.8% to 3.9%) and 51 (12.6%) and 49 (12.4%) primary end points in the low- and high-dose arms, respectively (difference 0.2%, 90% confidence interval –3.7% to 4.0%), both demonstrating non-inferiority. Resolution of cough was faster in the 7-day arm than in the 3-day arm for cough (10 days vs. 12 days) (p = 0.040), with no difference in time to resolution of other symptoms. The type and frequency of adverse events and rate of colonisation by penicillin-non-susceptible pneumococci were comparable between arms. Limitations End-of-treatment swabs were not taken, and 28-day swabs were collected in only 53% of children. We focused on phenotypic penicillin resistance testing in pneumococci in the nasopharynx, which does not describe the global impact on the microflora. Although 21% of children did not attend the final 28-day visit, we obtained data from general practitioners for the primary end point on all but 3% of children. Conclusions Antibiotic retreatment, adverse events and nasopharyngeal colonisation by penicillin-non-susceptible pneumococci were similar with the higher and lower amoxicillin doses and the 3- and 7-day treatments. Time to resolution of cough and sleep disturbance was slightly longer in children taking 3 days’ amoxicillin, but time to resolution of all other symptoms was similar in both arms. Future work Antimicrobial resistance genotypic studies are ongoing, including whole-genome sequencing and shotgun metagenomics, to fully characterise the effect of amoxicillin dose and duration on antimicrobial resistance. The analysis of a randomised substudy comparing parental electronic and paper diary entry is also ongoing. Trial registration Current Controlled Trials ISRCTN76888927, EudraCT 2016-000809-36 and CTA 00316/0246/001-0006. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 60. See the NIHR Journals Library website for further project information.

This randomized clinical trial compares the need for re-treatment of respiratory infection following hospitalization for community-acquired pneumonia among children receiving amoxicillin at high doses vs low doses and at 3-days vs 7-days duration. Question For children with community-acquired pneumonia discharged from an emergency department, observational unit, or inpatient ward (within 48 hours), is subsequent outpatient treatment with oral amoxicillin at a dose of 35 to 50 mg/kg per day noninferior to 70 to 90 mg/kg per day, and is a 3-day course noninferior to 7 days, with regard to the need for antibiotic re-treatment? Findings In this 2 x 2 factorial randomized clinical trial of 814 children requiring amoxicillin for community-acquired pneumonia at hospital discharge, antibiotic re-treatment within 28 days occurred in 12.6% vs 12.4% of those randomized to lower vs higher doses, and in 12.5% vs 12.5% of those randomized to 3-day vs 7-day amoxicillin duration. Both comparisons met the prespecified 8% noninferiority margin. Meaning Among children with community-acquired pneumonia discharged from an emergency department, observational unit, or inpatient ward, further outpatient treatment with oral amoxicillin at a dose of 35 to 50 mg/kg per day was noninferior to a dose of 70 to 90 mg/kg per day and 3 days was noninferior to 7 days with regard to the need for later antibiotic re-treatment. Importance The optimal dose and duration of oral amoxicillin for children with community-acquired pneumonia (CAP) are unclear. Objective To determine whether lower-dose amoxicillin is noninferior to higher dose and whether 3-day treatment is noninferior to 7 days. Design, Setting, and Participants Multicenter, randomized, 2 x 2 factorial noninferiority trial enrolling 824 children, aged 6 months and older, with clinically diagnosed CAP, treated with amoxicillin on discharge from emergency departments and inpatient wards of 28 hospitals in the UK and 1 in Ireland between February 2017 and April 2019, with last trial visit on May 21, 2019. Interventions Children were randomized 1:1 to receive oral amoxicillin at a lower dose (35-50 mg/kg/d; n = 410) or higher dose (70-90 mg/kg/d; n = 404), for a shorter duration (3 days; n = 413) or a longer duration (7 days; n = 401). Main Outcomes and Measures The primary outcome was clinically indicated antibiotic re-treatment for respiratory infection within 28 days after randomization. The noninferiority margin was 8%. Secondary outcomes included severity/duration of 9 parent-reported CAP symptoms, 3 antibiotic-related adverse events, and phenotypic resistance in colonizing Streptococcus pneumoniae isolates. Results Of 824 participants randomized into 1 of the 4 groups, 814 received at least 1 dose of trial medication (median [IQR] age, 2.5 years [1.6-2.7]; 421 [52%] males and 393 [48%] females), and the primary outcome was available for 789 (97%). For lower vs higher dose, the primary outcome occurred in 12.6% with lower dose vs 12.4% with higher dose (difference, 0.2% [1-sided 95% CI -infinity to 4.0%]), and in 12.5% with 3-day treatment vs 12.5% with 7-day treatment (difference, 0.1% [1-sided 95% CI -infinity to 3.9]). Both groups demonstrated noninferiority with no significant interaction between dose and duration (P = .63). Of the 14 prespecified secondary end points, the only significant differences were 3-day vs 7-day treatment for cough duration (median 12 days vs 10 days; hazard ratio [HR], 1.2 [95% CI, 1.0 to 1.4]; P = .04) and sleep disturbed by cough (median, 4 days vs 4 days; HR, 1.2 [95% CI, 1.0 to 1.4]; P = .03). Among the subgroup of children with severe CAP, the primary end point occurred in 17.3% of lower-dose recipients vs 13.5% of higher-dose recipients (difference, 3.8% [1-sided 95% CI, -infinity to10%]; P value for interaction = .18) and in 16.0% with 3-day treatment vs 14.8% with 7-day treatment (difference, 1.2% [1-sided 95% CI, -infinity to 7.4%]; P value for interaction = .73). Conclusions and Relevance Among children with CAP discharged from an emergency department or hospital ward (within 48 hours), lower-dose outpatient oral amoxicillin was noninferior to higher dose, and 3-day duration was noninferior to 7 days, with regard to need for antibiotic re-treatment. However, disease severity, treatment setting, prior antibiotics received, and acceptability of the noninferiority margin require consideration when interpreting the findings.

Background: Molecular syndromic panels can rapidly detect common pathogens responsible for acute gastroenteritis in hospitalized patients. Their impact on both patient and healthcare system outcomes is uncertain compared to conventional stool testing. This randomized trial evaluates the impact of molecular testing on in-hospital resource utilization compared to conventional stool testing.Methods: Hospitalized patients with acute diarrheal illness were randomized 1:1 to either conventional or molecular stool testing with the BioFire FilmArray gastrointestinal panel (FGP). The primary outcome was duration of contact isolation, and secondary outcomes included other in-hospital resource utilization such as diagnostic imaging and antimicrobial use. Results: A total of 156 patients were randomized. Randomization resulted in a balanced allocation of patients across all 3 age strata (Conclusions: There were no differences in in-hospital resource utilization observed between FGP and conventional stool testing groups. Trials Registration: ClinicalTrials.gov NCT04189874

Obesity-associated breast cancer recurrence is mechanistically linked with elevated insulin levels and insulin resistance. Exercise and weight loss are associated with decreased breast cancer recurrence, which may be mediated through reduced insulin levels and improved insulin sensitivity. This is a secondary analysis of the WISER Survivor clinical trial examining the relative effect of exercise, weight loss and combined exercise and weight loss interventions on insulin and insulin resistance. The weight loss and combined intervention groups showed significant reductions in levels of: insulin, C-peptide, homeostatic model assessment 2 (HOMA2) insulin resistance (IR), and HOMA2 beta-cell function (β) compared to the control group. Independent of intervention group, weight loss of ≥10% was associated with decreased levels of insulin, C-peptide, and HOMA2-IR compared to 0–5% weight loss. Further, the combination of exercise and weight loss was particularly important for breast cancer survivors with clinically abnormal levels of C-peptide.

We highlight the operations of The Free Clinic at Lubbock Impact, describing its services and the patient population it serves. Dermatology Nights have been an integral part to the clinic, addressing skin conditions that the uninsured and homeless population experience.

This guide for family physicians describes the advantages of Mohs surgery and which patients make good candidates for the procedure.

Aims This observational study characterized cardiovascular disease (CVD) mortality risk for multiple cancer sites, with respect to the following: (i) continuous calendar year, (ii) age at diagnosis, and (iii) follow-up time after diagnosis. Methods and results The Surveillance, Epidemiology, and End Results program was used to compare the US general population to 3 234 256 US cancer survivors (1973–2012). Standardized mortality ratios (SMRs) were calculated using coded cause of death from CVDs (heart disease, hypertension, cerebrovascular disease, atherosclerosis, and aortic aneurysm/dissection). Analyses were adjusted by age, race, and sex. Among 28 cancer types, 1 228 328 patients (38.0%) died from cancer and 365 689 patients (11.3%) died from CVDs. Among CVDs, 76.3% of deaths were due to heart disease. In eight cancer sites, CVD mortality risk surpassed index-cancer mortality risk in at least one calendar year. Cardiovascular disease mortality risk was highest in survivors diagnosed at Conclusion The majority of deaths from CVD occur in patients diagnosed with breast, prostate, or bladder cancer. We observed that from the point of cancer diagnosis forward into survivorship cancer patients (all sites) are at elevated risk of dying from CVDs compared to the general US population. In endometrial cancer, the first year after diagnosis poses a very high risk of dying from CVDs, supporting early involvement of cardiologists in such patients.

ObjectiveIncreased opioid prescription to relieve pain among patients with chronic pain is associated with increased risk for misuse, potentially leading to substance use disorders and overdose death. We aimed to characterize the relative importance and identify the most significant of several potential risk factors for the severity of self-reported prescribed opioid misuse behaviors.MethodsA sample of 1,193 patients (mean age ± SD = 50.72 ± 14.97 years, 64.04% female) with various chronic pain conditions completed a multidimensional registry assessing four pain severity measures and 14 physical, mental, and social health status factors using the National Institutes of Health’s Patient-Reported Outcomes Measurement Information System (PROMIS). A validated PROMIS measure of medication misuse was completed by 692 patients who endorsed currently taking opioid medication. Patients taking opioid medications were compared across all measures with those who do not take opioid medications. Subsequently, a data-driven regression analysis was used to determine which measures best explained variability in severity of misuse. We hypothesized that negative affect–related factors, namely anxiety, anger, and/or depression, would be key predictors of misuse severity due to their crucial role in chronic pain and substance use disorders.ResultsPatients taking opioid medications had significantly greater impairment across most measures. Above and beyond demographic variables, the only and most significant predictors of prescribed opioid misuse severity were as follows: anxiety (β = 0.15, P = 0.01), anger (β = 0.13, P = 0.02), Pain Intensity–worst (β = 0.09, P = 0.02), and depression (β = 0.13, P = 0.04).ConclusionsFindings suggest that anxiety, anger, and depression are key factors associated with prescribed opioid misuse tendencies in patients with chronic pain and that they are potential targets for therapeutic intervention.

Background Healthcare disparities are an issue in the surgical management of orthopaedic conditions in children. Although insurance expansion efforts may mitigate racial disparities in surgical outcomes, prior studies have not examined these effects on differences in pediatric orthopaedic care. To assess for racial disparities in pediatric orthopaedic care that may persist despite insurance expansion, we performed a case-control study of the outcomes of children treated for osteomyelitis in the TRICARE system, the healthcare program of the United States Department of Defense and a model of universal insurance and healthcare access. Questions/purposes We asked whether (1) the rates of surgical intervention and (2) 90-day outcomes (defined as emergency department visits, readmission, and complications) were different among TRICARE-insured pediatric patients with osteomyelitis when analyzed based on black versus white race and military rank-defined socioeconomic status. Methods We analyzed TRICARE claims from 2005 to 2016. We identified 2906 pediatric patients, of whom 62% (1810) were white and 18% (520) were black. A surgical intervention was performed in 9% of the patients (253 of 2906 patients). The primary outcome was receipt of surgical intervention for osteomyelitis. Secondary outcomes included 90-day complications, readmissions, and returns to the emergency department. The primary predictor variables were race and sponsor rank. Military rank has been used as an indicator of socioeconomic status before and during enlistment, and enlisted service members, particularly junior enlisted service members, may be at risk of having the same medical conditions that affect civilian members of lower socioeconomic strata. Patient demographic information (age, sex, race, sponsor rank, beneficiary category [whether the patient is an insurance beneficiary from an active-duty or retired service member], and geographic region) and clinical information (prior comorbidities, environment of care [whether clinical care was provided in a civilian or military facility], treatment setting, and length of stay) were used as covariates in multivariable logistic regression analyses. Results After controlling for demographic and clinical factors including age, sex, sponsor rank, beneficiary category, geographic region, Charlson comorbidity index (as a measure of baseline health), environment of care, and treatment setting (inpatient versus outpatient), we found that black children were more likely to undergo surgical interventions for osteomyelitis than white children (odds ratio 1.78; 95% confidence interval, 1.26-2.50; p = 0.001). When stratified by environment of care, this finding persisted only in the civilian healthcare setting (OR 1.85; 95% CI, 1.26-2.74; p = 0.002). Additionally, after controlling for demographic and clinical factors, lower socioeconomic status (junior enlisted personnel) was associated with a higher likelihood of 90-day emergency department use overall (OR 1.60; 95% CI, 1.02-2.51; p = 0.040). Conclusions We found that for pediatric patients with osteomyelitis in the universally insured TRICARE system, many of the historically reported disparities in care were absent, suggesting these patients benefitted from improved access to healthcare. However, despite universal coverage, racial disparities persisted in the civilian care environment, suggesting that no single intervention such as universal insurance sufficiently addresses differences in racial disparities in care. Future studies can address the pervasiveness of these disparities in other patient populations and the various mechanisms through which they exert their effects, as well as potential interventions to mitigate these disparities. Level of evidence Level III, prognostic study.

PURPOSE Active surveillance (AS) for testicular nonseminomatous germ cell tumors (NSGCT) is widely used. Although there is no consensus for optimal treatment at relapse on surveillance, globally patients typically receive chemotherapy. We describe treatment of relapses in our non–risk-adapted NSGCT AS cohort and highlight selective use of primary retroperitoneal lymph node dissection (RPLND). METHODS From December 1980 to December 2015, 580 patients with clinical stage I NSGCT were treated with AS, and 162 subsequently relapsed. First-line treatment was based on relapse site and extent. Logistic regression was used to explore factors associated with need for multimodal therapy on AS relapse. RESULTS Median time to relapse was 7.4 months. The majority of relapses were confined to the retroperitoneum (66%). After relapse, first-line treatment was chemotherapy for 95 (58.6%) and RPLND for 62 (38.3%), and five patients (3.1%) underwent other therapy. In 103 (65.6%), only one modality of treatment was required: chemotherapy only in 58 of 95 (61%) and RPLND only in 45 of 62 (73%). Factors associated with multimodal relapse therapy were larger node size (odds ratio, 2.68; P = .045) in patients undergoing chemotherapy and elevated tumor markers (odds ratio, 6.05; P = .008) in patients undergoing RPLND. When RPLND was performed with normal markers, 82% required no further treatment. Second relapse occurred in 30 of 162 patients (18.5%). With median follow-up of 7.6 years, there were five deaths (3.1% of AS relapses, but 0.8% of whole AS cohort) from NSGCT or treatment complications. CONCLUSION The retroperitoneum is the most common site of relapse in clinical stage I NSGCT on AS. Most are cured by single-modality treatment. RPLND should be considered for relapsed patients, especially those with disease limited to the retroperitoneum and normal markers, as an option to avoid chemotherapy.

There is a paucity of patient-reported data on thyroidectomy scar perception. The effect of neck scarring on quality of life is not known. We hypothesized that worse perception of neck appearance would be related to worse health-related quality of life and that perception improves with time.Survivors of thyroid cancer (n = 1,710) were surveyed online. Respondents were asked to score the appearance of their neck via a 5-point Likert scale. Quality of life was evaluated via the Patient-Reported Outcomes Measurement Information System 29. The relationships between neck appearance, patient characteristics, quality of life, and Patient-Reported Outcomes Measurement Information System domains were analyzed with multivariable models and Spearman partial correlations (rOlder age was associated with better perception of neck appearance (odds ratio 0.975/year; 95% confidence interval 0.967-0.983; P.001). Greater time since surgery was also associated with improved perception (odds ratio 0.962/year; 95% confidence interval 0.947-0.977; P.0001). We observed no statistically significant difference between current and preoperative baseline perception2 years after surgery. On multivariable analysis, age45 years,2 years since surgery, and higher self-reported quality of life were independent predictors of better self-reported neck appearance (P ≤ .0003). In patients ≤2 years after surgery (n = 568), the PROMIS domains of anxiety, depression, social function, and fatigue had weak but statistically significant correlations with worse perception of neck appearance (P.0001).Age45,2 years since surgery, and higher quality of life were independently associated with better self-reported neck appearance. Perception of neck appearance returned to preoperative baseline 2 years after surgery. PROMIS domains had a weak but significant association with neck appearance perception in patients ≤2 years after surgery. The impact of post-thyroidectomy neck appearance on quality of life appears to be mild and transient and returns to preoperative levels after 2 years.

BackgroundThe phase III research evaluating migraine prophylaxis therapy (PREEMPT) protocol was developed in low-risk migraine patients. We studied longitudinal response to treatment in a sequential retrospective observational cohort to evaluate predictors of effectiveness in patients with multiple overlapping pain syndromes treated in a quaternary pain management clinic.MethodsWe evaluated indicators of individual response in 402 consecutive chronic migraine patients who provided demographic information and used the Collaborative Health Outcomes Information Registry.ResultsThe patients were middle aged 47 (38–56) median (IQR) years old and 83% women. They reported multiple complex pain problems with 11 (6–18) regions represented on a pain body map. Evaluated with National Institutes of Health Patient-Reported Outcomes Measurement Information System measures, they reported higher scores for sleep impairment and disturbance, anxiety, depression, fatigue, pain behavior, pain interference and worse function and satisfaction with social roles compared with the general US population; pConclusionsOur findings point to the importance of identifying and addressing pain interference and depression early in chronic migraine management and, more broadly, highlights the importance of multidisciplinary evaluation and treatment in chronic migraine.

To assess the effect of Accountable Care Organizations (ACOs) on the use of surgical services among racial and ethnic minorities.Health reform efforts were expected to reduce healthcare disparities. The impact of ACOs on existing disparities in access to surgical care remains unknown.We used national Medicare data (2009-2014) to compare rates of surgery among white, African American, Hispanic, and Asian Medicare beneficiaries for coronary artery bypass grafting, colectomy, total hip arthroplasty, hip fracture repair, and lumbar spine surgery. We performed a pre-post difference in differences analysis between African American, Hispanic, and Asian patients receiving surgical care in ACO and non-ACO organizations before and after the implementation of ACOs. The time period 2009 to 2011 was considered the pre-ACO period, and 2012 to 2014 the post-ACO period.Rates of surgical intervention in the ACO cohort were significantly lower (P0.001) as compared to non-ACOs for whites, African Americans, Hispanics, and Asians in both the pre- and post-ACO periods. There was no significant difference in the adjusted change in the rate of surgical interventions among minority patients as compared to whites in ACOs and non-ACOs between 2009 to 2011 and 2012 to 2014. The odds of receiving surgical intervention were lowest for minority patients in ACOs during the post-ACO period (P0.001).We found persistent differences in the use of surgery among racial and ethnic minorities between the time periods 2009 to 2011 and 2012 to 2014. These disparities were not impacted by the formation of ACOs. Programs that specifically incentivize ACOs to improve surgical access for minorities may be necessary.

Objective The goal of this study was to develop and assess intra- and interrater reliability and validity of a clinical evaluation tool for breast cancer–related lymphedema, for use in the context of outcome evaluation in clinical trials. Design Blinded repeated measures observational study. Setting Outpatient research laboratory. Participants Breast cancer survivors with and without lymphedema (N=71). Interventions Not applicable. Main Outcome Measure The assessment of intraclass correlation coefficients (ICCs) for the Breast Cancer–Related Lymphedema of the Upper Extremity (CLUE) standardized clinical evaluation tool. Results Intrarater reliability for the CLUE tool was ICC: 0.88 (95% confidence interval [95% CI], 0.71-0.96). Interrater reliability for the CLUE tool was ICC: 0.90 (95% CI, 0.79-0.95). Concurrent validity of the CLUE score (Pearson r) was 0.79 with perometric interlimb difference and 0.53 with the Norman lymphedema overall score. Conclusions The CLUE tool shows excellent inter- and intrarater reliability. The overall CLUE score for the upper extremity also shows moderately strong concurrent validity with objective and subjective measures. This newly developed clinical, physical assessment of upper extremity lymphedema provides standardization and a single score that accounts for multiple constructs. Next steps include evaluation of sensitivity to change, which would establish usefulness to evaluate intervention efficacy.

Background Growing laboratory and animal model evidence supports the potentially carcinogenic effects of some phthalates, chemicals used as plasticizers in a wide variety of consumer products, including cosmetics, medications, and vinyl flooring. However, prospective data on whether phthalates are associated with human breast cancer risk are lacking. Methods We conducted a nested case-control study within the Women’s Health Initiative (WHI) prospective cohort (n = 419 invasive case subjects and 838 control subjects). Control subjects were matched 2:1 to case subjects on age, enrollment date, follow-up time, and WHI study group. We quantified 13 phthalate metabolites and creatinine in two or three urine samples per participant over one to three years. Multivariable conditional logistic regression analysis was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for breast cancer risk associated with each phthalate biomarker up to 19 years of follow-up. Results Overall, we did not observe statistically significant positive associations between phthalate biomarkers and breast cancer risk in multivariable analyses (eg, 4th vs 1st quartile of diethylhexyl phthalate, OR = 1.03, 95% CI = 0.91 to 1.17). Results were generally similar in analyses restricted to disease subtypes, to nonusers of postmenopausal hormone therapy, stratified by body mass index, or to case subjects diagnosed within three, five, or ten years. Conclusions In the first prospective analysis of phthalates and postmenopausal breast cancer, phthalate biomarker concentrations did not result in an increased risk of developing invasive breast cancer.

Background Patient bathing basins are a potential source of health care–acquired infections. This descriptive study was designed to describe current patient bathing procedures and the cleaning and storage of disposable bath basins after use. Methods After instrument validation, a 20-item questionnaire designed by the researchers was delivered electronically to infection prevention professionals working in acute care facilities in the United States. Descriptive statistics including frequencies and percentages were used to analyze the data. Results A total of 344 participants completed the survey. Of those responding, most were employed in facilities with ≤300 beds and accredited by the Joint Commission. Many of the facility staff assisting patients with bathing were nursing aides. Participants reported varying bathing procedures in their facilities. Conclusions A collaborative approach is needed to ensure standard and efficient procedures that focus on quality, safety, and patient satisfaction. A mechanism to continually evaluate patient bathing practices should also be developed to address evolving changes in the health care system.

BACKGROUND CONTEXT The impact of Accountable Care Organizations (ACOs) on healthcare quality and outcomes, including morbidity, mortality, and readmissions, has not been substantially investigated, especially following spine surgery. PURPOSE To evaluate the impact of ACO formation on postoperative outcomes in the 90-day period following spine surgery. STUDY DESIGN Retrospective review of national Medicare claims data (2009–2014). PATIENT SAMPLE Patients who underwent one of four lumbar spine surgical procedures in an ACO or non-ACO. OUTCOME MEASURES The development of in-hospital mortality, complications or hospital readmission within 90 days of the surgical procedure. METHODS The primary outcome measures included postsurgical complications and readmissions at 90 days following surgery. In-hospital mortality and 30-day outcomes were considered secondarily. The primary predictor variable consisted of ACO enrollment designation. Multivariable logistic regression analysis was utilized to adjust for confounders and determine the independent effect of ACO enrollment on postsurgical outcomes. The multivariable model included a propensity score adjustment that accounted for factors associated with the preferential enrollment of patients in ACOs, namely, sociodemographic characteristics, medical co-morbidities, hospital teaching status, bed size, and location. RESULTS In all, there were 344,813 patients identified for inclusion in this analysis with 97% (n = 332,890) treated in non-ACOs and 3% (n = 11,923) in an ACO. Although modest changes were apparent across both ACOs and non-ACOs over the time-period studied, improvements were slightly more dramatic in non-ACOs leading to statistically significant differences in both 90-day complications and readmissions. Specifically, in the period 2012–2014, ACOs demonstrated an 18% increase in the odds of 90-day complications and a 14% elevation in the odds of 90-day readmissions when compared to non-ACOs. There was no difference in hospital mortality between ACOs and non-ACOs. CONCLUSIONS Our study of Medicare data from 2009 to 2014 failed to demonstrate superior reductions in postoperative morbidity, mortality, and readmissions for beneficiaries treated in ACOs as compared to non-ACOs. These results indicate that meaningful changes in postoperative outcomes should not be anticipated based on organizational participation in ACOs at present.

Background Cure of hypertension after adrenalectomy for primary aldosteronism is no certainty and therefore preoperative patient counseling is essential. The Primary Aldosteronism Surgical Outcome (PASO) Score is a useful prediction model with an area under the curve (AUC) of 0.839. The PASO Score includes ‘Target Organ Damage’ (TOD) (i.e., left ventricular hypertrophy and/or microalbuminuria), which is often unavailable during preoperative counseling and might therefore limit its use in clinical practice. We hypothesized that the PASO score would still be useful if TOD is unknown at time of counseling. Therefore, we aimed to examine the predictive performance of the simplified PASO Score, without taking TOD into account. Materials and methods In this retrospective cohort study, patients who underwent unilateral adrenalectomy between 2010 and 2016 in 16 medical centers from North America, Europe and Australia were included. TOD was unknown in our database and therefore assigned as absent. Patients were classified as complete, partial or absent clinical success using the PASO consensus criteria. Results A total of 380 (73.9%) patients were eligible for analysis. Complete, partial and absent clinical success were observed in 29.5%, 55.8% and 14.7% of patients, respectively. The simplified PASO Score had an AUC of 0.730 (95% confidence interval 0.674–0.785) in our total cohort. Conclusion Without taking TOD into account, the simplified PASO Score had a lower predictive value as compared to the original derivation cohort. Ideally, the complete PASO Score should be used, but when data on TOD are not readily available, the simplified PASO Score is a useful and reasonable alternative., Highlights • We aimed to examine the predictive performance of the PASO Score, without taking ‘target organ damage’ (TOD) into account. • This simplified PASO Score had a lower predictive value as compared to the PASO Score in the original derivation cohort. • The simplified PASO Score increases the applicability of the model and is reasonable for clinicians to use in daily practice. • Ideally, the complete PASO Score should be used, but the simplified PASO Score is a useful and reasonable alternative.

Background Obesity is a chronic, relapsing, and progressive disease; it is associated with poor health-related quality of life (HRQOL) in survivors of breast cancer. Methods In this 2 × 2 factorial trial, 351 survivors of breast cancer with overweight or obesity were randomized to 1 of 4 treatment groups for 52 weeks: control, exercise alone, diet alone, or exercise plus diet. HRQOL end points were measured at baseline and at week 52 using the 36-Item Medical Outcomes Survey-Short Form (SF-36). Repeated measures analysis of covariance quantified the estimated treatment difference (ETD). Results At baseline, participants had a mean (SD) age of 59.4 years (8.7), body mass index of 34.0 kg/m2 (5.9), and 71 participants (20.2%) self-reported fair or poor general health. After 52 weeks, compared with control, the exercise plus diet improved the physical health summary score (ETD: 5.39; 95% CI, 0.55-10.22); exercise alone (ETD: -1.91; 95% CI, -6.60 to 2.79) and diet alone (ETD: 3.16; 95% CI, -1.52 to 7.83) did not change the physical health summary score. Compared with control, exercise alone (ETD: -0.27; 95% CI, -6.60 to 2.79), diet alone (ETD: 3.25; 95% CI, -1.41 to 7.91), and the exercise plus diet (ETD: 1.75; 95% CI, -2.90 to 6.39) did not change the mental health summary score. Exercise alone did not impact any HRQOL subscale; diet alone improved the vitality subscale; exercise plus diet improved the physical functioning, role-physical and vitality subscales. Conclusion In survivors of breast cancer with overweight or obesity, exercise plus diet improved select HRQOL end points at week 52.

Inpatients with culture-positive diabetic foot infections are at elevated risk for subsequent invasive infection with the same causative organism. In outpatients with index diabetic foot ulcers, we found that wound culture positivity was independently associated with increased odds of 1-year admission for systemic infection when compared with culture-negative wounds.