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Background: ABO blood group is associated with pancreatic cancer risk. Whether ABO blood group alone or when combined with inherited mutation status of index pancreatic cancer cases (probands) can enhance pancreatic cancer risk estimation in first-degree relatives (FDR) is unclear. We examined FDRs' risk for pancreatic cancer based on probands' ABO blood group and probands' cancer susceptibility gene mutation status. Methods: Data on 23,739 FDRs, identified through 3,268 pancreatic cancer probands, were analyzed. Probands' ABO blood groups were determined serologically or genetically, and 20 cancer susceptibility genes were used to classify probands as “mutation-positive” or “mutation-negative.” SIRs and 95% confidence intervals (CI) were calculated, comparing observed pancreatic cancer cases in the FDRs with the number expected in SEER-21 (reference population). Results: Overall, FDRs had 2-fold risk of pancreatic cancer (SIR = 2.00; 95% CI = 1.79–2.22). Pancreatic cancer risk was higher in FDRs of mutation-positive (SIR = 3.80; 95% CI = 2.81–5.02) than mutation-negative (SIR = 1.79; 95% CI = 1.57–2.04) probands (P < 0.001). The magnitude of risk did not differ by ABO blood group alone (SIRblood-group-O = 1.57; 95% CI = 1.20–2.03, SIRnon-O = 1.83; 95% CI = 1.53–2.17; P = 0.33). Among FDRs of probands with non-O blood group, pancreatic cancer risk was higher in FDRs of mutation-positive (SIR = 3.98; 95% CI = 2.62–5.80) than mutation-negative (SIR = 1.66; 95% CI = 1.35–2.03) probands (P < 0.001), but risk magnitudes were statistically similar when probands had blood group O (SIRmutation-positive = 2.65; 95% CI = 1.09–5.47, SIRmutation-negative = 1.48; 95% CI = 1.06–5.47; P = 0.16). Conclusions: There is a range of pancreatic cancer risk to FDRs according to probands' germline mutation status and ABO blood group, ranging from 1.48 for FDRs of probands with blood group O and mutation-negative to 3.98 for FDRs of probands with non-O blood group and mutation-positive. Impact: Combined ABO blood group and germline mutation status of probands can inform pancreatic cancer risk estimation in FDRs.

Introduction A long dwell time is associated with higher inferior vena cava (IVC) filter retrieval complication rates. Manufacturers advise that “excessive force should not be used” during filter retrieval; however, the term “excessive” is subjective and is likely to lead to variability amongst operators. The aims of this study were to 1) ascertain what interventional radiologists consider to be excessive force during filter retrieval and 2) to understand the variability in interventional radiologists’ perception of force. Methods The authors recruited interventional radiologists to perform a benchtop simulated filter retrieval. Participants were invited to pull on a modified force tester attached to a Gunther Tulip filter retrieval set (GTRS). The participants were asked to pull as if they were retrieving an IVC filter and stop when they felt it was clinically unsafe to apply greater force. They were then asked to replicate forces of 10N and 50N, respectively. Each of the three tasks was completed three times. Data were obtained on the clinical experience of the participants with specific questions focusing on their filter retrieval practices. Results The range of maximum forces applied during filter retrieval varied between 0.8 and 79.8N. When asked to replicate 10N and 50N, for attempt-1, the median forces produced were 23.5N and 38.1N, respectively. A trend analysis showed that those who overestimate 10N are more likely to apply a greater overall maximum force (rs = 0.622; P Conclusion There is wide variation in what interventional radiologists consider to be the maximum safe force to apply during IVC filter retrieval. Implications for practice Manufacturers and operators should consider methods in which only a safe range of forces can be applied during an IVC filter retrieval. Operators may wish to undertake ‘personal’ force calibration as part of training in interventional radiology.

PURPOSE Cholangiocarcinomas (CCA) are a group of heterogeneous tumors arising from the biliary epithelia. Significant sequencing efforts have provided further insights into the molecular mechanisms of this disease including fibroblast growth factor receptor ( FGFR) alterations, which occurs in approximately 15%-20% of intrahepatic CCAs. Herein, we describe the FGFR inhibitor (FGFRi)-associated treatment toxicity and cancer-specific outcomes from a multicenter single-institution cohort. METHODS This is a retrospective study of patients with CCA and known FGFR alterations treated with FGFRi. We describe the toxicity and efficacy in patients treated at Mayo Clinic between January 2010 and December 2020. RESULTS Our group identified 61 patients with advanced or metastatic CCA, 19 males (31%) and 42 females (69%), harboring FGFR alterations who received FGFRi. The most common grade 1 or higher adverse events for all patients included fatigue (92%), AST elevations (78%), anemia (80%), decreased platelet count (63%), and hyperphosphatemia (74%). Median progression-free survival on FGFRi was 5.8 months for all patients (95% CI, 4.9 to 9.0). Females had significantly longer progression-free survival at 6.9 months (95% CI, 5.2 to 11.8) on FGFRi compared with males at 4.9 months (95% CI, 2.8 to not estimable; P = .038). CONCLUSION FGFRi are well tolerated with clinical efficacy. With the recent approval of FGFRi by the US Food and Drug Administration and ongoing clinical trials for new FGFRi, understanding outcomes and toxicity associated with these medications is important for precision oncology.

Patients with connective tissue disease (CTD) and advanced lung disease are often considered suboptimal candidates for lung transplantation (LTx) due to their underlying medical complexity and potential surgical risk. There is substantial variability across LTx centers regarding the evaluation and listing of these patients. The International Society for Heart and Lung Transplantation-supported consensus document on lung transplantation in patients with CTD standardization aims to clarify definitions of each disease state included under the term CTD, to describe the extrapulmonary manifestations of each disease requiring consideration before transplantation, and to outline the absolute contraindications to transplantation allowing risk stratification during the evaluation and selection of candidates for LTx.

Background Neoadjuvant chemotherapy (NAC) is an integral part of preoperative treatment for patients with borderline resectable/locally advanced (BR/LA) pancreatic ductal adenocarcinoma (PDAC). The identification of a chemotherapeutic regimen that is both effective and tolerable is critical for NAC to be of oncologic benefit. After initial first-line (FL) NAC, some patients have lack of response or therapeutic toxicities precluding further treatment with the same regimen; optimal decision making regarding this patient population is unclear. Chemotherapy switch (CS) may allow for a larger proportion of patients to undergo curative-intent resection after NAC. Methods We reviewed our surgical database for patients undergoing combinatorial NAC for BR/LA PDAC. Variant histologic exocrine carcinomas, intraductal papillary mucinous neoplasm-associated PDAC, and patients without research consent were excluded. Results Overall, 468 patients with BR/LA PDAC receiving FL chemotherapy were reviewed, of whom 70% (329/468) continued with FL chemotherapy followed by surgical resection. The remaining 30% (139/468) underwent CS, with 72% (100/139) of CS patients going on to curative-intent surgical resection. Recurrence-free survival (RFS) and overall survival (OS) were not significantly different between the resected FL and CS cohorts (30.0 vs. 19.1 months, p = 0.13, and 41.4 vs. 36.4 months, p = 0.94, respectively) and OS was significantly worse in those undergoing CS without subsequent resection (19 months, p Conclusion CS in patients undergoing NAC for BR/LA pancreatic cancer does not incur oncologic detriment. The incorporation of CS into NAC treatment sequencing may allow a greater proportion of patients to proceed to curative-intent surgery.

Objectives Previous literature finds that having a child with a cleft lip and/or palate (CL/P) may pose social and emotional challenges for parents. For parents of children born during the Covid-19 pandemic, such challenges may be heightened. Further, novel demands brought about by the pandemic could have caused additional hardships. The aim of this study was to describe the impact of the pandemic on new parents through qualitative exploration of their experiences. Design Semi-structured interviews were conducted with 14 parents of children born in the United Kingdom with CL/P between January and June 2020, around the start of the pandemic. Data were analysed using inductive thematic analysis. Results Three themes, with sub-themes, were identified. The first theme, “ Changes to Healthcare: The Impact of Restrictions and Reduced Contact”, discussed the impact of the pandemic on perinatal care, the care received from the specialist CL/P teams, and parents’ experiences of virtual consultations. The second theme, “Family Functioning During the Pandemic”, covered parental anxiety, fathers’ experiences, and social support. The third theme, “ Surgical Prioritisation: Delays and Uncertainty”, addressed changes to surgical protocols, coping with uncertainty, complications associated with delayed surgery, and how parents created positive meaning from this period. Conclusions A range of increased and additional psychosocial impacts for parents were identified, along with several coping strategies, utilization of social support, and the positive aspects of their experiences. As the pandemic continues, close monitoring of families affected by CL/P remains imperative, particularly for those at risk of emotional distress.

Background It is estimated that millions of North Americans would qualify for lung cancer screening and that billions of dollars of national health expenditures would be required to support population-based computed tomography lung cancer screening programs. The decision to implement such programs should be informed by data on resource utilization and costs. Methods Resource utilization data were collected prospectively from 2059 participants in the Pan-Canadian Early Detection of Lung Cancer Study using low-dose computed tomography (LDCT). Participants who had 2% or greater lung cancer risk over 3 years using a risk prediction tool were recruited from seven major cities across Canada. A cost analysis was conducted from the Canadian public payer's perspective for resources that were used for the screening and treatment of lung cancer in the initial years of the study. Results The average per-person cost for screening individuals with LDCT was USD453 (95% confidence interval [CI], USD400–USD505) for the initial 18-months of screening following a baseline scan. The screening costs were highly dependent on the detected lung nodule size, presence of cancer, screening intervention, and the screening center. The mean per-person cost of treating lung cancer with curative surgery was USD33,344 (95% CI, USD31,553–USD34,935) over 2 years. This was lower than the cost of treating advanced-stage lung cancer with chemotherapy, radiotherapy, or supportive care alone, (USD47,792; 95% CI, USD43,254–USD52,200; p = 0.061). Conclusion In the Pan-Canadian study, the average cost to screen individuals with a high risk for developing lung cancer using LDCT and the average initial cost of curative intent treatment were lower than the average per-person cost of treating advanced stage lung cancer which infrequently results in a cure.

Purpose Radiation safety performance is often evaluated using dose parameters measured by personal dosimeters and/or the C-arm, which provide limited information about teams' actual radiation safety behaviors. This study aimed to develop a rating scale to evaluate team radiation safety behaviors more accurately and investigate its reliability. Materials and Methods A modified Delphi consensus was organized involving European vascular surgeons (VS), interventional radiologists, and interventional cardiologists. Initial items and anchors were drafted a priori and rated using five-point Likert scales. Participants could suggest additional items or adjustments. Consensus was defined as >= 80% agreement (rating >= 4) with Cronbach's alpha >= .80. Two VS with expertise in radiation safety evaluated 15 video-recorded endovascular repairs of infrarenal aortic aneurysms (EVAR) to assess usability, inter and intrarater reliability. Results Thirty-one of 46 invited specialists completed three rating rounds to generate the final rating scale. Five items underwent major adjustments. In the final round, consensus was achieved for all items (alpha = .804; agreement > 87%): 'Pre-procedural planning', 'Preparation in angiosuite/operating room', 'Shielding equipment', 'Personal protective equipment', 'Position of operator/team', 'Radiation usage awareness', 'C-arm handling', 'Adjusting image quality', 'Additional dose reducing functions', 'Communication/leadership', and 'Overall radiation performance and ALARA principle'. All EVARs were rated, yielding excellent Cronbach's alpha (.877) with acceptable interrater and excellent intrarater reliability (ICC = .782; ICC = .963, respectively). Conclusion A reliable framework was developed to assess radiation safety behaviors in endovascular practice and provide teams with formative feedback. The final scale is provided in this publication.

Background: We describe the treatment of a renal artery aneurysm with complex anatomy using coils and the Pipeline (TM) Embolization Device (Medtronic, Irvine, CA), a flow-diverting stent typically used for the treatment of intracranial aneurysms. Methods: A 62-year-old female with history of an asymptomatic right renal artery aneurysm that was discovered incidentally 10 years ago was found to have enlargement of the aneurysm (1.9cm to 2.7cm) on a repeat surveillance CT scan. She was successfully treated with combined Pipeline Embolization Device and coil embolization of the aneurysm sac. Results: Post-procedural angiography showed complete occlusion of the aneurysm with maintenance of perfusion to the entire kidney. Conclusion: Pipeline (TM) assisted coil embolization may be an option for parenchyma-sparing treatment of renal artery aneurysms with complex anatomy.

It is unknown how active asthma management influences symptom control among inner-city pregnant women who have unique exposures and socioeconomic limitations affecting their care.To assess the impact of an integrated subspecialty intervention composed of education and monitoring on asthma control among underserved women in an antenatal clinic setting.We conducted a prospective cohort study of pregnant asthmatic patients participating in a subspecialty clinic integrated into routine prenatal care. We compared baseline characteristics and objective measurements of asthma control between women at an initial visit and those who were evaluated in at least one follow-up. For follow-up, we measured symptom control at successive visits and the incidence of asthma-related complications.Among 85 women enrolled, 53 (62.4%) returned for at least one follow-up visit. Mean baseline Asthma Control Test scores were similarly low (≤19) between groups (one or more follow-up and no follow-up), as were self-administered Asthma Quality of Life Questionnaire scores (4.7). A total of 72 women had inadequate asthma control resulting in step-up therapy after the initial visit (84.7%). There was a significant increase in ACT scores between the initial and first follow-up visits. For those with an intervening self-administered Asthma Quality of Life Questionnaire, there was also a significant increase by 1.39 ± 0.67 (P = .0003).We found that uncontrolled asthma is common among urban women seeking routine obstetric care. Our results suggest that even one interventional visit can result in significant improvement in asthma control. Further investigation into mechanisms for optimizing treatment strategies may improve the quality of asthma care during pregnancy in this underserved population.

Objective To evaluate the prognostic significance of detectable circulating cell-free DNA (cfDNA) BRAF V600E/K mutations in patients with advanced melanoma enrolled in a clinical trial without BRAF-targeted therapy. Patients and Methods BRAF V600E/K mutation status was determined on archived tissue and pretreatment stored plasma from 149 patients with unresectable stage IV melanoma who were enrolled between May 5, 2010 and May 2, 2014 in the North Central Cancer Treatment Group/Alliance N0879 randomized phase 2 clinical trial. Results were reported as presence or absence of cfDNA BRAF V600E/K detection of assay vs tissue. Progression-free survival (PFS) and overall survival (OS) were assessed for patients with and without detectable BRAF mutation. Results In total, 63 of 149 (42.3%) patients had BRAF V600E/K results for tissue and blood, and 20 of 63 (31.7%) patients had tissue-diagnosed mutant BRAF. Of these, 11 of 20 (55.0%) patients had detectable plasma cfDNA BRAF. Among patients with tissue-mutant BRAF V600E/K, PFS and OS were shorter for those with corresponding cfDNA mutations (PFS, 5.8 vs 12.0 months; P=.051; OS, 9.2 vs 27.1 months; P=.054). Our assay demonstrated sensitivity of 55% (95% CI, 0.322 to 0.768), specificity of 97.7% (95% CI, 0.932 to 1.000), positive predictive value of 91.7% (95% CI, 0.760 to 1.000), and negative predictive value of 82.4% (95% CI, 0.719 to 0.928). Conclusion In advanced melanoma, detectable cfDNA BRAF V600E/K mutation is present in about half the patients with stage IV with BRAF-mutant melanoma tumor tissue and appears to confer a poorer prognosis when detectable. Given the poorer prognosis, cfDNA can be used to risk-stratify patients with metastatic melanoma in practice or clinical trials.Trial Registration: clinicaltrials.gov Identifier: NCT00976573

OBJECTIVE: To evaluate whether hospital entry into the 340B Drug Pricing Program - which entitles eligible hospitals to discounts on drug purchases and intends for hospitals to use associated savings to devote more resources to the care of low-income populations - is associated with changes in hospital provision of uncompensated care. STUDY DESIGN: We analyzed secondary data on 340B participation and uncompensated care provision among general acute care hospitals and critical access hospitals from 2003–2015. We constructed an annual, hospital-level dataset on hospital 340B participation from the Office of Pharmacy Information Systems and on uncompensated care provision from the Hospital Cost Reporting Information System. METHODS: Focusing on two periods of Program expansion, we separately analyzed trends in uncompensated care costs for 340B-eligible general acute-care hospitals and critical access hospitals, stratified by year of 340B Program entry, including a stratum of eligible hospitals that never participated. We used a differences-in-differences approach to quantify whether there were differential changes in provision of uncompensated care after hospitals enter the 340B Program relative to hospitals that did not participate or had not yet entered. RESULTS: We do not find evidence that hospitals increased provision of uncompensated care after entry into the 340B Program differentially more than hospitals that never entered or had not yet entered the Program. CONCLUSIONS: Relying on hospitals to invest surplus into care for the underserved without marginal incentives to do so or strong oversight may not be an effective strategy to expand safety net care.

BACKGROUND There are very few studies in the literature focusing on neonatal burns, and to our knowledge this is the largest study on this topic. METHODS A retrospective review was conducted over a 10-year period from 2010 to 2020 to investigate the incidence, mechanisms involved and outcomes for burn injuries in neonates in Western Australia. This study included children aged 4 weeks or younger who sustained a burns injury requiring admission to hospital or during their hospital admission. Premature infants who sustained burns during a hospital admission in the neonatal intensive care unit and were under 4 weeks corrected age were also included. Short-term outcomes of burn injuries included infection and need for surgery, and the long-term outcomes included scarring and requirement for laser therapy. RESULTS Over the 10-year period, 30 burn injuries were sustained by 27 neonates. Thirteen (43.3%) of these burns occurred at home or in the community, and 17 (56.7%) occurred in hospital. Scalds (n = 4) and sunburn (n = 4) were the most common mechanism in the community, while chemical (n = 12) burns including extravasation injuries were the most common sustained in hospital. No neonates required theatre for skin grafting or laser therapy for scarring. There were no infected burns in the cohort. Time to healing ranged from 2 to 62 days with a mean of 12.1 days. CONCLUSION Outcomes for burns sustained in the neonatal period in Western Australia are generally positive, and have not been associated with infection and have low rates of scarring.

Concerns about avoidance or delays in seeking emergency care during the COVID-19 pandemic are widespread, but national data on emergency department (ED) visits and subsequent rates of hospitalization and outcomes are lacking. Using data on all traditional Medicare beneficiaries in the US from October 1, 2018, to September 30, 2020, we examined trends in ED visits and rates of hospitalization and thirty-day mortality conditional on an ED visit for non-COVID-19 conditions during several stages of the pandemic and for areas that were considered COVID-19 hot spots versus those that were not. We found reductions in ED visits that were largest by the first week of April 2020 (52 percent relative decrease), with volume recovering somewhat by mid-June (25 percent relative decrease). These reductions were of similar magnitude in counties that were and were not designated as COVID-19 hot spots. There was an early increase in hospitalizations and in the relative risk for thirty-day mortality, starting with the first surge of the pandemic, peaking at just over a 2-percentage-point increase. These results suggest that patients were presenting with more serious illness, perhaps related to delays in seeking care.

BackgroundAdjunctive metformin is the most well-studied intervention in the pharmacological management of antipsychotic-induced weight gain (AIWG). Although a relatively unaddressed area, among guidelines recommending consideration of metformin, prescribing information that would facilitate its applied use by clinicians, for example, provision of a dose titration schedule is absent. Moreover, recommendations differ regarding metformin’s place in the hierarchy of management options. Both represent significant barriers to the applied, evidence-based use of metformin for this indication.ObjectiveTo produce a guideline solely dedicated to the optimised use of metformin in AIWG management, using internationally endorsed guideline methodology.MethodsA list of guideline key health questions (KHQs) was produced. It was agreed that individual recommendations would be ‘adopted or adapted’ from current guidelines and/or developed de novo, in the case of unanswered questions. A systematic literature review (2008–2020) was undertaken to identify published guidelines and supporting (or more recent) research evidence. Quality appraisal was undertaken using the Appraisal of Guidelines Research and Evaluation II tool, A Measurement Tool to Assess Systematic Reviews (AMSTAR) assessment,and the Cochrane Risk of Bias 2 tool, where appropriate. Assessment of evidence certainty and recommendation development was undertaken using Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.FindingsWe confirmed that no published guideline—of appropriate quality, solely dedicated to the use of metformin to manage AIWG was available. Recommendations located within other guidelines inadequately addressed our KHQs.ConclusionAll 11 recommendations and 7 supporting good practice developed here were formulated de novo.Clinical implicationsThese recommendations build on the number and quality of recommendations in this area, and facilitate the optimised use of metformin when managing AIWG.

The COVID‐19 pandemic has proven the need for countries worldwide to implement strategies that promote health systems strengthening and ensure epidemic preparedness. Many African countries are burdened by fragile healthcare systems, hence, this paper emphasises the need for African policymakers to improve healthcare quality in their countries. Through a brief review of various online literatures concerning health systems strengthening in Africa, this paper focuses on the nature of healthcare in Nigeria amidst the COVID‐19 pandemic. The major stress areas include COVID‐19 testing capacity, health workforce, infection prevention and control, health information and surveillance systems, health insurance, public‐private partnerships, and governance. The COVID‐19 pandemic has amplified several challenges ravaging Africa's already fragile healthcare systems, leaving the health sectors of most African countries ill‐prepared to deal with the pandemic. If Nigeria and many other African countries had invested sufficiently in strengthening their healthcare systems prior to COVID‐19, their pandemic response efforts would have been more effective. Health systems strengthening is necessary to ensure steady progress toward universal health coverage and global health security. Through health systems strengthening, Nigeria and other African countries can greatly improve their infection prevention and control measures.

Objectives This study sought to better characterize patient characteristics, treatment options, and outcomes for osteoclast-like giant cell carcinoma of the pancreas, a rare subtype of pancreatic adenocarcinoma. Methods This is a retrospective study of all patients with osteoclast-like giant cell carcinoma of pancreatic origin treated at Mayo Clinic from 2000 to present. Baseline patient characteristics, treatment modalities utilized, and outcomes were compiled. Overall survival (OS) and progression-free survival were assessed using Kaplan-Meier analysis with a significance level of P ≤ 0.05. Results Fifteen patients met criteria for inclusion. Four patients had distant metastases at diagnosis, the remaining 11 with locoregional disease. Median OS for the entire cohort was 11 months. Metastatic disease was associated with significantly shorter OS (3.5 vs 14.1 months; P = 0.005). Three patients had no evidence of disease at time of analysis; all 3 were treated with complete resection followed by adjuvant chemotherapy. Conclusions Osteoclast-like giant cell carcinoma of the pancreas is an aggressive malignancy with poor prognosis. For patients with locoregional disease, surgical resection followed by adjuvant chemoradiation may play a role in extended disease-free survival. Metastatic disease presents a challenging entity to treat with little data to support any effective chemotherapy regimens.

Author(s): Sutphin, John E; Ying, Gui-Shuang; Bunya, Vatinee Y; Yu, Yinxi; Lin, Meng C; McWilliams, Kathleen; Schmucker, Elizabeth; Kuklinski, Eric J; Asbell, Penny A; Maguire, Maureen G; Dry Eye Assessment and Management (DREAM) Study Research Group | Abstract: PurposeThe purpose of this study was to compare objective, noninvasive assessments of tear function using the OCULUS Keratograph with the corresponding clinical assessments [tear break-up time (TBUT), Schirmer test, and bulbar erythema] among patients with moderate-to-severe dry eye disease.MethodsParticipants in the Dry Eye Assessment and Management study at centers having an OCULUS Keratograph were assessed using standardized procedures. Associations between the assessments from the Keratograph [noninvasive keratograph break-up time (NIKBUT), tear meniscus height (TMH), and bulbar redness (BR)] and clinical examination (TBUT, Schirmer test, and bulbar erythema) and between these test results and Ocular Surface Disease Index (OSDI) scores were summarized with Spearman correlation coefficients (rs); 95% confidence intervals (95% CI) accounted for intereye correlation.ResultsAmong 288 patients (576 eyes), the mean (standard deviation) age was 56.6 (13.8) years, 78.1% were female, and the mean baseline OSDI score was 44.3 (14.0). The mean was 2.9 (1.5) seconds for TBUT and 8.2 (5.7) seconds for NIKBUT (their correlation rs = 0.18, 95% CI = 0.09-0.28). The mean was 10.6 (7.6) mm for the Schirmer test and 0.3 (0.2) mm for TMH (rs = 0.15, 95% CI = 0.04-0.25). The median clinical grade redness was mild, and the mean BR score was 1.1 (0.5) (rs = 0.25, 95% CI = 0.15-0.35). Correlation between results of each of the 6 tests and OSDI scores was low (rs from -0.07 to 0.05).ConclusionsIn the Dry Eye Assessment and Management study, NIKBUT, TMH, and BR were weakly correlated with their clinical counterparts. No measurements were correlated with the OSDI score.

Objectives Glucocorticosteroids (GCs) are recommended to suppress inflammation in people with active RA. This systematic review and meta-analysis aimed to quantify the effects of systemic GCs on RA pain. Methods A systematic literature review of randomized controlled trials (RCTs) in RA comparing systemic GCs to inactive treatment. Three databases were and spontaneous pain and evoked pain outcomes were extracted. Standardized mean differences (SMDs) and mean differences were meta-analysed. Heterogeneity (I2, tau statistics) and bias (funnel plot, Egger’s test) were assessed. Subgroup analyses investigated sources of variation. This study was pre-registered (PROSPERO CRD42019111562). Results A total of 18 903 titles, 880 abstracts and 226 full texts were assessed. Thirty-three RCTs suitable for the meta-analysis included 3123 participants. Pain scores (spontaneous pain) decreased in participants treated with oral GCs; SMD = −0.65 (15 studies, 95% CI −0.82, −0.49, P 3–6 months and −7 mm (95% CI −13, 0) at >6 months. Similar findings were obtained when evoked pain outcomes were examined. Data from five RCTs suggested improvement also in fatigue during GC treatment. Conclusion Oral GCs are analgesic in RA. The benefit is greatest shortly after initiation and GCs might not achieve clinically important pain relief beyond 3 months. Treatments other than anti-inflammatory GCs should be considered to reduce the long-term burden of pain in RA.

Background Delirium is a common complication in patients in Intensive Care Units (ICU). Interventions such as mobilization are effective in the prevention and treatment of delirium, although this is usually completed during the daytime. Aim The aim of this study was to assess the feasibility of mobilization in the evening to prevent and treat ICU patients from delirium by an additional mobility team over 2 weeks. Methods The design was a pilot, multi-centre, randomized, controlled trial in four mixed ICUs over a period of 2 weeks. The mobility team consisted of trained nurses and physiotherapists. Patients in the intervention group were mobilized onto the edge of the bed or more between 21.00 and 23.00. Patients in the control group received usual care. The primary outcome parameter was the feasibility of the study, measured as recruitment rate, delivery rate, and safety. Secondary outcomes were duration and incidence of delirium, mortality, duration of mechanical ventilation (MV), and hospital length of stay for 28 days follow-up, and power calculation for a full trial. Results Out of 185 patients present in the ICUs, 28.6% (n = 53) were eligible and could be recruited, of which 24.9% (n = 46, Intervention = 26, Control = 20) were included in the final analysis. In the intervention group, mobilization could be delivered in 75% (n = 54) of 72 possible occasions; mobilization-related safety events appeared in 16.7% (n = 9) without serious consequences. Secondary parameters were similar, with less delirium in the intervention group albeit not significant. With an association of Cramer's V = 0.237, a complete study reaching statistical significance would require at least 140 patients, last 6 weeks, and cost >30 000 €. Conclusions In a mixed ICU population, mobilization in the evening was feasible in one-quarter of patients with a low rate of safety events. Future trials seem to be feasible and worth conducting.

Reducing postacute care in skilled nursing facilities (SNFs) in favor of home-based care is a leading cost-saving strategy in new payment models. Yet the extent to which SNF stays can be safely shortened remains unclear. We leveraged the exposure of fee-for-service Medicare beneficiaries without supplemental coverage to cost sharing after SNF benefit day 20 as a cause of shortened stays. Marked reductions in length-of-stay because of cost sharing shifted patients to home more than a week earlier than expected without cost sharing, producing a discharge spike. These reductions were not associated with clear evidence of compromised patient safety as measured by death, hospitalization for fall-related injuries, or all-cause hospitalization within nine days of the spike. Adverse consequences requiring hospitalization could not be excluded for a small proportion of shortened stays. These findings suggest potential for improving postacute care efficiency, as SNF stays may be unnecessarily long to ensure safety.

Aim To evaluate the impact of the implementation of a best practice infection prevention and control bundle on healthcare associated burn wound infections in a paediatric burns unit. Background Burn patients are vulnerable to infection. For this patient population, infection is associated with increased morbidity and mortality, thereby representing a significant challenge for burns clinicians who care for them. Methods An interrupted time series was used to compare healthcare associated burn wound infections in paediatric burn patients before and after implementation of an infection prevention and control bundle. Prospective surveillance of healthcare associated burn wound infections was conducted from 2012 to 2014. Other potential healthcare associated infection rates were also reviewed over the study period, including urinary tract infections, pneumonia, upper respiratory tract infections and sepsis. An infection prevention and control bundle developed in collaboration between the paediatric burn unit and infection control clinicians was implemented in 2013 in addition to previous standard practice. Results During the study period a total of 626 patients were admitted to the paediatric burns unit. Healthcare associated burn wound infections reduced from 34 in 2012 to 0 in 2014 following the implementation of the infection prevention and control bundle. Pneumonia and sepsis also reduced to 0 in 2013 and 2014, however one upper respiratory tract infection occurred in 2013 and urinary tract infections persisted in 2013. Conclusion The implementation of an infection prevention and control bundle was effective in reducing healthcare associated burn wound infections, pneumonia and sepsis within our paediatric burns unit. Urinary tract infections remain a challenge for future improvement.

Multiple studies have demonstrated that diet (e.g., fatty acid composition, antioxidants) and exercise training affect the metabolic performance of songbirds during aerobic activity, although the physiological mechanisms that cause such an effect remain unclear. We tested the hypothesis that elevated proportions of dietary linoleic acid (18:2n6) and amounts of dietary anthocyanins (a hydrophilic antioxidant class) influence the activity and protein expression of oxidative enzymes in flight and leg muscle of European Starlings (Sturnus vulgaris N = 96), a subset of which were flown over 15 days in a wind tunnel. Carnitine palmitoyl transferase (CPT) and citrate synthase (CS) activity displayed 18:2n6-dependent relationships with soluble protein concentration. Lactate dehydrogenase (LDH) was similarly related to protein concentration although also dependent on both dietary anthocyanins and flight training. 3-Hydroxyacyl CoA Dehydrogenase (HOAD) activity increased throughout the experiment in flight muscle, whereas this relationship was dependent on dietary anthocyanins in the leg muscle. Soluble protein concentration also increased throughout the experiment in the flight muscle, but was unrelated to date in the leg muscle, instead being influenced by both dietary anthocyanins and flight training. Training also produced additive increases in CPT and leg muscle HOAD activity. FAT/CD36 expression was related to both dietary 18:2n6 and training and changed over the course of the experiment. These results demonstrate a notable influence of our diet manipulations and flight training on the activity of these key oxidative enzymes, and particularly CPT and CS. Such influence suggests a plausible mechanism linking diet quality and metabolic performance in songbirds.

Background The National Early Warning Score (NEWS2) is currently recommended in the UK for the risk stratification of COVID-19 patients, but little is known about its ability to detect severe cases. We aimed to evaluate NEWS2 for the prediction of severe COVID-19 outcome and identify and validate a set of blood and physiological parameters routinely collected at hospital admission to improve upon the use of NEWS2 alone for medium-term risk stratification. Methods Training cohorts comprised 1276 patients admitted to King’s College Hospital National Health Service (NHS) Foundation Trust with COVID-19 disease from 1 March to 30 April 2020. External validation cohorts included 6237 patients from five UK NHS Trusts (Guy’s and St Thomas’ Hospitals, University Hospitals Southampton, University Hospitals Bristol and Weston NHS Foundation Trust, University College London Hospitals, University Hospitals Birmingham), one hospital in Norway (Oslo University Hospital), and two hospitals in Wuhan, China (Wuhan Sixth Hospital and Taikang Tongji Hospital). The outcome was severe COVID-19 disease (transfer to intensive care unit (ICU) or death) at 14 days after hospital admission. Age, physiological measures, blood biomarkers, sex, ethnicity, and comorbidities (hypertension, diabetes, cardiovascular, respiratory and kidney diseases) measured at hospital admission were considered in the models. Results A baseline model of ‘NEWS2 + age’ had poor-to-moderate discrimination for severe COVID-19 infection at 14 days (area under receiver operating characteristic curve (AUC) in training cohort = 0.700, 95% confidence interval (CI) 0.680, 0.722; Brier score = 0.192, 95% CI 0.186, 0.197). A supplemented model adding eight routinely collected blood and physiological parameters (supplemental oxygen flow rate, urea, age, oxygen saturation, C-reactive protein, estimated glomerular filtration rate, neutrophil count, neutrophil/lymphocyte ratio) improved discrimination (AUC = 0.735; 95% CI 0.715, 0.757), and these improvements were replicated across seven UK and non-UK sites. However, there was evidence of miscalibration with the model tending to underestimate risks in most sites. Conclusions NEWS2 score had poor-to-moderate discrimination for medium-term COVID-19 outcome which raises questions about its use as a screening tool at hospital admission. Risk stratification was improved by including readily available blood and physiological parameters measured at hospital admission, but there was evidence of miscalibration in external sites. This highlights the need for a better understanding of the use of early warning scores for COVID.

Rationale: Patients with severe coronavirus disease (COVID-19) have complex organ support needs that necessitate prolonged stays in the intensive care unit (ICU), likely to result in a high incidence of neuromuscular weakness and loss of well-being. Early and structured rehabilitation has been associated with improved outcomes for patients requiring prolonged periods of mechanical ventilation, but at present no data are available to describe similar interventions or outcomes in COVID-19 populations. Objectives: To describe the demographics, clinical status, level of rehabilitation, and mobility status at ICU discharge of patients with COVID-19. Methods: Adults admitted to the ICU with a confirmed diagnosis of COVID-19 and mechanically ventilated for >24 hours were included. Rehabilitation status was measured daily using the Manchester Mobility Score to identify the time taken to first mobilize (defined as sitting on the edge of the bed or higher) and highest level of mobility achieved at ICU discharge. Results: A total of n = 177 patients were identified, of whom n = 110 survived to ICU discharge and were included in the subsequent analysis. While on ICU, patients required prolonged periods of mechanical ventilation (mean 19 ± 10 d), most received neuromuscular blockade (90%) and 67% were placed in the prone position on at least one occasion. The mean ± standard deviation time to first mobilize was 14 ± 7 days, with a median Manchester Mobility Score at ICU discharge of 5 (interquartile range: 4–6), which represents participants able to stand and step around to a chair with or without assistance. Time to mobilize was significantly longer in those with higher body mass index (P

Purpose:To compare the clinical characteristics and overall survival (OS) of germline mutation carriers in homologous recombination repair (HRR) genes and noncarriers with pancreatic ductal adenocarcinoma (PDAC).Experimental Design:Germline DNA from 3,078 patients with PDAC enrolled in a prospective registry at Mayo Clinic between 2000 and 2017 was analyzed for mutations in 37 cancer predisposition genes. Characteristics and OS of patients with mutations in eight genes (ATM, BARD1, BRCA1, BRCA2, BRIP1, PALB2, RAD51C, and RAD51D) involved in HRR were compared with patients testing negative for mutations in all 37 genes.Results:The 175 HRR mutation carriers and 2,730 noncarriers in the study had a median duration of follow-up of 9.9 years. HRR mutation carriers were younger (median age at diagnosis: 63 vs. 66 years, P < 0.001) and more likely to have metastatic disease at diagnosis (46% vs. 36%, P = 0.004). In a multivariable model adjusting for sex, age at diagnosis, and tumor staging, patients with germline HRR mutations had a significantly longer OS compared with noncarriers [HR, 0.83; 95% confidence interval (CI), 0.70–0.97; P = 0.02]. Further gene-level analysis demonstrated that germline ATM mutation carriers had longer OS compared with patients without germline mutations in any of the 37 genes (HR, 0.72; 95% CI, 0.55–0.94; P = 0.01).Conclusions:This study demonstrates that germline mutation carrier status in PDAC is associated with longer OS compared with noncarriers. Further research into tumor biology and response to platinum-based chemotherapy in germline mutation carriers with PDAC are needed to better understand the association with longer OS.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disease with an estimated prevalence of 1 in 5000 that is characterized by the presence of vascular malformations (VMs). These result in chronic bleeding, acute hemorrhage, and complications from shunting through VMs. The goal of the Second International HHT Guidelines process was to develop evidence-based consensus guidelines for the management and prevention of HHT-related symptoms and complications.METHODS: The guidelines were developed using the AGREE II (Appraisal of Guidelines for Research and Evaluation II) framework and GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology. The guidelines expert panel included expert physicians (clinical and genetic) in HHT from 15 countries, guidelines methodologists, health care workers, health care administrators, patient advocacy representatives, and persons with HHT. During the preconference process, the expert panel generated clinically relevant questions in 6 priority topic areas. A systematic literature search was done in June 2019, and articles meeting a priori criteria were included to generate evidence tables, which were used as the basis for recommendation development. The expert panel subsequently convened during a guidelines conference to conduct a structured consensus process, during which recommendations reaching at least 80% consensus were discussed and approved.RECOMMENDATIONS: The expert panel generated and approved 6 new recommendations for each of the following 6 priority topic areas: epistaxis, gastrointestinal bleeding, anemia and iron deficiency, liver VMs, pediatric care, and pregnancy and delivery (36 total). The recommendations highlight new evidence in existing topics from the first International HHT Guidelines and provide guidance in 3 new areas: anemia, pediatrics, and pregnancy and delivery. These recommendations should facilitate implementation of key components of HHT care into clinical practice.

Training and diet are hypothesized to directly stimulate key molecular pathways that mediate animal performance, and flight training, dietary fats, and dietary antioxidants are likely important in modulating molecular metabolism in migratory birds. This study experimentally investigated how long-distance flight training, as well as diet composition, affected the expression of key metabolic genes in the pectoralis muscle and the liver of European starlings ( Sturnus vulgaris, n = 95). Starlings were fed diets composed of either a high or low polyunsaturated fatty acid (PUFA; 18:2n-6) and supplemented with or without a water-soluble antioxidant, and one-half of these birds were flight trained in a wind-tunnel while the rest were untrained. We measured the expression of 7 (liver) or 10 (pectoralis) key metabolic genes in flight-trained and untrained birds. Fifty percent of genes involved in mitochondrial metabolism and fat utilization were upregulated by flight training in the pectoralis ( P < 0.05), whereas flight training increased the expression of only one gene responsible for fatty acid hydrolysis [lipoprotein lipase (LPL)] in the liver ( P = 0.04). Dietary PUFA influenced the gene expression of LPL and fat transporter fatty acid translocase (CD36) in the pectoralis and one metabolic transcription factor [peroxisome proliferator-activated receptor (PPAR)-α (PPARα)] in the liver, whereas dietary antioxidants had no effect on the metabolic genes measured in this study. Flight training initiated a simpler causal network between PPARγ coactivators, PPARs, and metabolic genes involved in mitochondrial metabolism and fat storage in the pectoralis. Molecular metabolism is modulated by flight training and dietary fat quality in a migratory songbird, indicating that these environmental factors will affect the migratory performance of birds in the wild.

Lung cancer is the number one cause of cancer death worldwide. The benefits of lung cancer screening to reduce mortality and detect early-stage disease are no longer in any doubt based on the results of two landmark trials using LDCT. Lung cancer screening has been implemented in the US and South Korea and is under consideration by other communities. Successful translation of demonstrated research outcomes into the routine clinical setting requires careful implementation and co-ordinated input from multiple stakeholders. Implementation aspects may be specific to different healthcare settings. Important knowledge gaps remain, which must be addressed in order to optimize screening benefits and minimize screening harms. Lung cancer screening differs from all other cancer screening programmes as lung cancer risk is driven by smoking, a highly stigmatized behaviour. Stigma, along with other factors, can impact smokers' engagement with screening, meaning that smokers are generally 'hard to reach'. This review considers critical points along the patient journey. The first steps include selecting a risk threshold at which to screen, successfully engaging the target population and maximizing screening uptake. We review barriers to smoker engagement in lung and other cancer screening programmes. Recruitment strategies used in trials and real-world (clinical) programmes and associated screening uptake are reviewed. To aid cross-study comparisons, we propose a standardized nomenclature for recording and calculating recruitment outcomes. Once participants have engaged with the screening programme, we discuss programme components that are critical to maximize net benefit. A whole-of-programme approach is required including a standardized and multidisciplinary approach to pulmonary nodule management, incorporating probabilistic nodule risk assessment and longitudinal volumetric analysis, to reduce unnecessary downstream investigations and surgery; the integration of smoking cessation; and identification and intervention for other tobacco related diseases, such as coronary artery calcification and chronic obstructive pulmonary disease. National support, integrated with tobacco control programmes, and with appropriate funding, accreditation, data collection, quality assurance and reporting mechanisms will enhance lung cancer screening programme success and reduce the risks associated with opportunistic, ad hoc screening. Finally, implementation research must play a greater role in informing policy change about targeted LDCT screening programmes.

Abernethy malformation refer to a congenital absence of intrahepatic portal veins leading to a primarily extrahepatic congenital portosystemic shunt. The lack of intrahepatic portal veins leads to a characteristic set of physical exam and imaging findings that may include hyperandrogenism and liver masses such as hepatic adenomas or focal nodular hyperplasia. In this case report, we describe a 20-year-old female who presented with an enlarging hepatic adenoma. A separate hepatic adenoma had previously been biopsied and noted to have undergone malignant degeneration into hepatocellular carcinoma. For each lesion, she was treated with combination transarterial embolization and microwave ablation. On follow-up imaging after therapy, it was then noted that her extrahepatic portal vein drained directly into the inferior vena cava, consistent with congenital portosystemic shunt. Recognition of this vascular anomaly is critical in treatment planning, as early intervention with either medical therapy or surgery can prevent the metabolic sequela of this unique constellation of symptoms.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by the development of arteriovenous malformations. The arteriovenous shunts may result in high output heart failure, which predisposes to atrial dilatation and atrial fibrillation. Due to recurrent bleeding from epistaxis or the gastrointestinal tract, patients with HHT and atrial fibrillation are at high risk of bleeding if anticoagulated for stroke prevention. In this report, we present a case of a 74-year-old woman with a history of HHT and atrial fibrillation who developed a large left atrial thrombus that initially was thought to represent an atrial myxoma. The diagnosis was confirmed with cardiac magnetic resonance imaging, and the patient underwent surgical resection of the thrombus. This case demonstrates the role of different imaging modalities in the assessment of left atrial masses and presents an opportunity to review the data on safety of anticoagulation in patients with HHT.

Summary Objectives Subchondral bone may contribute to knee osteoarthritis (OA) pain. Nerve growth factor (NGF) can stimulate nerve growth through TrkA. We aimed to identify how sensory nerve growth at the osteochondral junction in human and rat knees associates with OA pain. Methods Eleven symptomatic chondropathy cases were selected from people undergoing total knee replacement for OA. Twelve asymptomatic chondropathy cases who had not presented with knee pain were selected post-mortem. OA was induced in rat knees by meniscal transection (MNX) and sham-operated rats were used as controls. Twice-daily oral doses (30 mg/kg) of TrkA inhibitor (AR786) or vehicle were administered from before and up to 28 days after OA induction. Joints were analysed for macroscopic appearances of articular surfaces, OA histopathology and calcitonin gene-related peptide-immunoreactive (CGRP-IR) sensory nerves in medial tibial plateaux, and rats were assessed for pain behaviors. Results The percentage of osteochondral channels containing CGRP-IR nerves in symptomatic chondropathy was higher than in asymptomatic chondropathy (difference: 2.5% [95% CI: 1.1–3.7]), and in MNX-than in sham-operated rat knees (difference: 7.8% [95%CI: 1.7–15.0]). Osteochondral CGRP-IR innervation was significantly associated with pain behavior in rats. Treatment with AR786 prevented the increase in CGRP-IR nerves in osteochondral channels and reduced pain behavior in MNX-operated rats. Structural OA was not significantly affected by AR786 treatment. Conclusions CGRP-IR sensory nerves within osteochondral channels are associated with pain in human and rat knee OA. Reduced pathological innervation of the osteochondral junction might contribute to analgesic effects of reduced NGF activity achieved by blocking TrkA.

Objective To explore the incidence of and potential risk factors for acute urine retention (AUR) after robot-assisted radical prostatectomy (RARP) and its effect on early urine continence. Methods A retrospective analysis of patients who underwent RARP by a single surgeon between July 2016 and June 2017 was performed to assess the incidence of AUR and its effect on early continence. Continence was assessed through self-reported questionnaires completed approximately three months after surgery. Early urine continence was defined as using zero pads per day at the time of the three-month follow-up. Descriptive statistics and logistic regression analysis were used to assess independent predictor of AUR. Results Of 379 patients, 19 (5%) developed AUR after RARP. No significant difference in baseline characteristics between those who developed AUR post-RARP and those who did not. There was no statistically significant difference in the reported early continence and number of pads used per day between patients with AUR and patients without AUR (31.6% vs. 23.1%, P = 0.39), (1.6 vs. 1.4, P = 0.913), respectively. Conclusion AUR post-RARP is an infrequent postoperative complication with no impact on early continence rate. No patient-related factors were associated with the development of AUR.

To compare two techniques-trocar and Seldinger-for performing percutaneous suprapubic cystostomy.125 patients, mean age 71.8 ± 16.5 years (range, 15-102 years), underwent primary suprapubic cystostomy from January 2013 to December 2018. Trocar access (N = 60) was performed as a single step using a puncture cannula without guidewire access. Seldinger access (N = 65) involved needle puncture, guidewire placement, and serial dilation. A retrospective review of patient records was conducted.All procedures were technically successful. Mean catheter size was 13.1 ± 2.0 and 13.9 ± 2.0 French for trocar and Seldinger, respectively (P = .044). Mean procedure time was significantly reduced using trocar technique, 12.4 ± 7.7 versus 25.7 ± 12.1 minutes (P.001), and was associated with lower anxiolytic dose, 1.2 ± 0.8 versus 1.9 ± 1.1 mg midazolam (P = .003), and less radiation exposure, 20.2 ± 59.5 versus 100.7 ± 98.5 mGy (P.001). Catheter occlusion was the most common complication (28.8%), followed by UTI (13.6%) and bladder spasm (8.0%). All but 2 complications were classified as Clavien-Dindo grade I or II. Catheter occlusion was more frequent in the trocar group (41.7% vs 16.9%, P = .003), while bladder spasms were more frequent in the Seldinger group (13.8% vs 1.7%, P = .018).Suprapubic cystostomy via trocar is associated with faster procedure time, lower anxiolytic dose, and less radiation. While major complications are rare, catheter occlusion is a common occurrence that may be overlooked. Although we detected more occlusions with trocar technique, this may be confounded by a catheter-tract size discrepancy.

OBJECTIVES Survival benefit of combination over single-agent chemotherapy for metastatic pancreatic ductal adenocarcinoma (PDAC) was demonstrated in younger patients in clinical trials. The authors aimed to evaluate whether this survival benefit of combination chemotherapy is present in elderly patients with metastatic PDAC. MATERIALS AND METHODS The authors identified elderly patients (age 65 y or older) with stage IV PDAC and extracted available clinical information from a prospectively maintained institutional pancreatic cancer registry from 2007 to 2016. The primary endpoint was overall survival. Cox proportional hazards regression was used for multivariable survival analyses. Survival outcomes for the entire cohort and by age group I (elderly, 65 to 75 y) and age group II (very elderly, older than 75 y) were assessed. RESULTS A total of 606 patients were included with a median age of 73.8 years. Among them, 239 patients (39%) received combination chemotherapy and 152 patients (25.1%) received single-agent chemotherapy as first-line treatment. Combination chemotherapy was associated with significantly longer median overall survival compared with single-agent chemotherapy (10.9 vs. 7.5 mo, P

Purpose of review To review phenotyping and risk classification of penicillin allergy and provide an update on penicillin allergy delabeling strategies for primary care. Recent findings Beta-lactams are considered the treatment of choice for a wide range of bacterial pathogens; however, many patients receive second-line agents due to being labeled as having an allergy to penicillin. This approach can lead to antibiotic resistance and inferior health outcomes. While 10% of the population is labeled as penicillin allergic, penicillin anaphylaxis occurs in less than 1% of patients. For patients with delayed benign skin rashes (e.g., urticaria or maculopapular exanthem >1 h after administration) attributable to beta-lactam administration occurring more than 12 months ago, direct oral challenge (rechallenge with antibiotic in the clinical setting) can be a safe and effective strategy, with immediate reactions occurring in less than 5% of such low-risk patients and delayed reactions appearing infrequently. In patients with penicillin-associated immediate urticaria, other IgE-mediated features, or anaphylaxis, further allergy evaluation and penicillin skin testing is warranted. Any severe idiosyncratic cutaneous adverse reaction is rare, but can be dangerous so prompt removal of the inciting agent is required. Summary Penicillin allergy delabeling is a high-value service that can be effectively delivered through a multidisciplinary collaborative approach.

Purpose: Clinical evidence shows minimal benefit to vitamin D screening and subsequent treatment in the general population. This study aims to assess the effectiveness of 2 light-touch interventions on reducing vitamin D test orders. Methods: The outcomes were weekly average vitamin D rates, computed from adult primary care encounters (preventive or nonpreventive) with a family medicine (FM) or internal medicine (IM) provider from June 14, 2018 through December 12, 2018. We conducted an interrupted time series analysis and estimated the cost impact of the interventions. The interventions consisted of an educational memo (August 9, 2018) distributed to providers and removal of the vitamin D test (FM: August 15, 2018; IM: October 17, 2018) from the providers’ quick order screen in the electronic health record. Change in order rates were analyzed among physicians (MDs and DOs), physician assistants (PAs), and nurse practitioners (NPs). Results: There were 587,506 primary care encounters (FM = 367,947; IM = 219,559). Vitamin D order rates decreased from 6.9% (FM = 5.1%; IM = 9.9%) to 5.2% (FM = 4% [P Conclusions: Emailed evidence-based provider education may be an effective tool for modifying providers’ vitamin D test ordering behavior. The lack of the effectiveness of the vitamin D test removal from the quick order screen found for IM highlights the challenges facing simple electronic health record interventions when multiple alternate ordering pathways exist.

Robot-assisted radical prostatectomy (RARP) can generally be performed with 1–2 nights of postoperative monitoring before discharge from the hospital. Little is known about what causes individual patients to remain in hospital beyond the second postoperative day. Data for RARPs performed between 2013 and 2015 were extracted from the American College of Surgeons National Surgical Quality Improvement Program (NSQIP) database. The fraction of cases with prolonged length of stay (PLOS) that can be reasonably attributed to complications was examined. Logistic regression was performed to identify risk factors for PLOS in the overall population and separately in the population of patients with PLOS without any perioperative complications. Of 11,440 patients, 10,342 (90.4%) were discharged on postoperative days 0–2; 80.6% (887/1101) of patients with PLOS did not experience any perioperative complications. The most common complication was bleeding requiring transfusion, but this was present in only 5.6% (62/1101) of patients with PLOS. Logistic regression identified predictors of PLOS as age, race, wound class, American Society of Anesthesiologists class, smoking, diabetes, dyspnea, dependent functional health status, congestive heart failure, operative time, and pelvic lymph node dissection. Results of this regression were insensitive to the exclusion of patients who experienced no perioperative complications. This study utilizes logistic regression on NSQIP data to identify risk factors for PLOS after RARP and, in particular, to evaluate the role of postoperative complications in PLOS. The analysis shows that postoperative complications account for a small minority of cases of PLOS after RARP.

Although the consequences of splenectomy are well understood in mice, much less is known about the immunologic changes that occur following splenectomy in humans. We sought to characterize the circulating immune cell populations of patients before and after elective splenectomy to determine if these changes are related to postsplenectomy survival outcomes. Retrospective clinical information was collected from 95 patients undergoing elective splenectomy compared with 91 patients undergoing pancreaticoduodenectomy (Whipple procedure). We further analyzed peripheral blood from five patients in the splenectomy group, collected before and after surgery, using single-cell cytometry by time-of-flight mass spectrometry. We compared pre- and postsplenectomy data to characterize both the major and minor immune cell populations in significantly greater detail. Compared with patients undergoing a Whipple procedure, splenectomized patients had significant and long-lasting elevated counts of lymphocytes, monocytes, and basophils. Cytometry by time-of-flight mass spectroscopy analysis demonstrated that the elevated lymphocytes primarily consisted of naive CD4+ T cells and a population of activated CD25+CD56+CD4+ T cells, whereas the elevated monocyte counts were mainly mature, activated monocytes. We also observed a significant increase in the expression of the chemokine receptors CCR6 and CCR4 on several cellular populations. Taken together, these data indicate that significant immunological changes take place following splenectomy. Whereas other groups have compared splenectomized patients to healthy controls, this study compared patients undergoing elective splenectomy to those undergoing a similar major abdominal surgery. Overall, we found that splenectomy results in significant long-lasting changes in circulating immune cell populations and function.

ATG7 drives macroautophagy, hereafter “autophagy”, by generating ATG12–ATG5 conjugates and lipidating Atg8 homologs including LC3. A pioneering body of work has defined the requirement of ATG7 for survival in mice and shown that neural-specific atg7 deletion causes neurodegeneration, but it has not been ascertained whether human life is compatible with ATG7 dysfunction. Recently, we defined the importance of ATG7 in human physiology by identifying twelve patients from five families harboring pathogenic, biallelic ATG7 variants causing a neurodevelopmental disorder. Patient fibroblasts show undetectable or severely diminished ATG7 protein levels, and biochemical assessment via autophagic flux and long-lived protein degradation assays demonstrated that attenuated autophagy underpins the pathology. Confirming the pathogenicity of patient variants, mouse cells expressing mutated ATG7 are unable to rescue LC3/Atg8 lipidation to wild-type levels. Our work defines mutated ATG7 as an important cause of human neurological disease and expands our understanding of autophagy in longevity and human health. We demonstrated that in certain circumstances, human survival with relatively mild phenotypes is possible even with undetectable levels of a nonredundant core autophagy protein.

Highlights • Antibiotic prevalence survey of 2/5 hospitalised SARS-CoV-2 patients at the epidemic peak in Scotland • Antibiotics in 38% SARS-CoV-2 patients in wards and critical care units • Narrow spectrum antibiotics predominant in wards reflecting national recommendations • Broad spectrum antibiotics and antifungals in critical care indicative of suspected nosocomial bacterial and fungal infections • Lower odds of antibiotic associated with nosocomial COVID-19, diabetes and in elderly care, Background Concern regarding bacterial co-infection complicating SARS-CoV-2 has created a challenge for antimicrobial stewardship. Following introduction of national antibiotic recommendations for suspected bacterial respiratory tract infection complicating COVID-19, a point prevalence survey of prescribing was conducted across acute hospitals in Scotland. Methods Patients in designated COVID-19 units were included and demographic, clinical and antimicrobial data were collected from 15 hospitals on a single day between 20th and 30th April 2020. Comparisons were made between SARS-CoV-2 positive and negative patients and patients on non-critical care and critical care units. Factors associated with antibiotic prescribing in SARS-CoV-2 positive patients were examined using Univariable and multivariable regression analyses. Findings There were 820 patients were included, 64.8% were SARS-CoV-2 positive and 14.9% were managed in critical care, and 22.1% of SARS-CoV-2 infections were considered probable or definite nosocomial infections. On the survey day, antibiotic prevalence was 45.0% and 73.9% were prescribed for suspected respiratory tract infection. Amoxicillin, doxycycline and co-amoxiclav accounted for over half of all antibiotics in non-critical care wards and meropenem, piperacillin-tazobactam and co-amoxiclav accounted for approximately half prescribed in critical care. Of all SARS-CoV-2 patients, 38.3% were prescribed antibiotics. In a multivariable logistic regression analysis, COPD/chronic lung disease and CRP ≥ 100 mg/l were associated with higher odds and probable or confirmed nosocomial COVID-19, diabetes and management on an elderly care ward had lower odds of an antibiotic prescription. Systemic antifungals were prescribed in 9.8% of critical care patients and commenced a median of 18 days after critical care admission. Interpretation A relatively low prevalence of antibiotic prescribing in SARS-CoV-2 hospitalised patients and low proportion of broad spectrum antibiotics in non-critical care settings was observed potentially reflecting national antimicrobial stewardship initiatives. Broad spectrum antibiotic and antifungal prescribing in critical care units was observed indicating the importance of infection prevention and control and stewardship initiatives in this setting. Funding The Scottish Antibiotic Prescribing Group is funded by Scottish Government

Importance Medicare’s Merit-Based Incentive Payment System (MIPS), a public reporting and pay-for-performance program, adjusts clinician payments based on publicly reported measures that are chosen primarily by clinicians or their practices. However, measure selection raises concerns that practices could earn bonuses or avoid penalties by selecting measures on which they already perform well, rather than by improving care—a form of gaming. This has prompted calls for mandatory reporting on a smaller set of measures including patient experiences. Objective To examine (1) practices’ selection of Consumer Assessment of Healthcare Providers and Systems (CAHPS) patient experience measures for quality scoring under the pay-for-performance program and (2) the association between mandated public reporting on CAHPS measures and performance on those measures within precursor programs of the MIPS. Design, Setting, and Participants This cross-sectional study included 2 analyses. The first analysis examined the association between the baseline CAHPS scores of large practices (≥100 clinicians) and practices’ selection of these measures for quality scoring under a pay-for-performance program up to 2 years later. The second analysis examined changes in patient experiences associated with a requirement that large practices publicly report CAHPS measures starting in 2014. A difference-in-differences analysis of 2012 to 2017 fee-for-service Medicare CAHPS data was conducted to compare changes in patient experiences between large practices (111-150 clinicians) that became subject to this reporting mandate and smaller unaffected practices (50-89 clinicians). Analyses were conducted between October 1, 2020, and July 30, 2021. Main Outcomes and Measures The primary outcomes of the 2 analyses were (1) the association of baseline CAHPS scores of large practices with those practices’ selection of those measures for quality scoring under a pay-for-performance program; and (2) changes in patient experiences associated with a requirement that large practices publicly report CAHPS measures starting in 2014. Results Among 301 large practices that publicly reported patient experience measures, the mean (IQR) age of patients at baseline was 71.6 (70.4-73.2 ) years, and 55.8% of patients were women (IQR, 54.3%-57.7%). Large practices in the top vs bottom quintile of patient experience scores at baseline were more likely to voluntarily include these scores in the pay-for-performance program 2 years later (96.3% vs 67.9%), a difference of 28.4 percentage points (95% CI, 9.4-47.5 percentage points;P = .004). After 2 to 3 years of the reporting mandate, patient experiences did not differentially improve in affected vs unaffected practices (difference-in-differences estimate: −0.03 practice-level standard deviations of the composite score; 95% CI, −0.64 to 0.58;P = .92). Conclusions and Relevance In this cross-sectional study of US physician practices that participated in precursors of the MIPS, large practices were found to select measures on which they were already performing well for a pay-for-performance program, consistent with gaming. However, mandating public reporting was not associated with improved patient experiences. These findings support recommendations to end optional measures in the MIPS but also suggest that public reporting on mandated measures may not improve care.

Background and aimClinical centres have seen an increase in tic-like movements during the COVID-19 pandemic. A series of children and adolescents are described.MethodsA retrospective chart review of 34 consecutive paediatric patients presenting with sudden onset tic-like movements, seen over 6 months.Results94% of patients were female, with an average age of sudden onset or increase of tic-like movements of 13.7 years. 44% had a previous diagnosis of tics, and 47% initially presented to an emergency department. Comorbid psychiatric and neurodevelopmental disorders were reported in 91% with 68% reporting anxiety.ConclusionWe highlight a dramatic presentation of sudden onset functional tic-like movements in predominantly female adolescents to help inform identification and management. There is need to research the neurobiological underpinnings and environmental exacerbating factors leading to these presentations and to explore effective therapeutic strategies.

Background Hepatic arteriovenous malformations (AVMs) in hereditary hemorrhagic telangiectasia (HHT) patients are most commonly hepatic artery to hepatic venous shunts which can result in high-output heart failure. This condition can be debilitating and is a leading cause of liver transplantation in HHT patients. However, it is not known what characteristics can discriminate between asymptomatic patients and those who will develop heart failure symptoms. Results 176 patients with HHT were evaluated with computed tomography angiography (CTA) between April 2004 and February 2019 at our HHT Center of Excellence. 63/176 (35.8%) patients were found to have hepatic AVMs on CTA. 18 of these patients were excluded because of the presence of another condition which could confound evaluation of heart failure symptoms. In the remaining 45 patients included in our cohort, 25/45 (55.6%) patients were classified as asymptomatic and 20/45 (44.4%) were classified as symptomatic, and these groups were compared. In symptomatic patients, mean common hepatic artery (CHA) diameter was significantly higher (11.1 versus 8.4 mm) and mean hemoglobin levels were significantly lower (10.7 vs 12.6 g/dL). A stepwise multiple logistic regression analysis demonstrated that both CHA diameter and hemoglobin level were independent predictors of heart failure symptoms with ORs of 2.554 (95% CI 1.372–4.754) and 0.489 (95% CI 0.299–0.799), respectively. The receiver operator characteristic (ROC) curve of our analysis demonstrated an AUC of 0.906 (95% CI 0.816–0.996), sensitivity 80.0% (95% CI 55.7–93.4%), and specificity 75.0% (95% CI 52.9–89.4%). Conclusions CTA is an effective and easily reproducible method to evaluate hepatic involvement of HHT. Utilizing CTA, clinical, and laboratory data we determined CHA diameter and hemoglobin level were independent predictors of heart failure symptoms.

We report the rare anatomical variant of the middle colic artery arising from the coeliac axis in a patient with symptoms of chronic mesenteric ischaemia. The anatomy is illustrated by 2D and 3D reconstructed images from contrast-enhanced CT scanning. We discuss the importance of recognising this anatomical variant, which has major implications for endovascular surgical planning. There are also significant risks if this variant anatomy is not recognised and the middle colic artery is inadvertently sacrificed.

We read with great interest the recent articles by Luchini et al 1 2 and Grant et al 3 highlighting the low prevalence (1%–2%) of mismatch repair deficient pancreatic ductal adenocarcinoma (dMMR PDAC) and offering further knowledge pertaining to the molecular spectrum of this disease subtype. A plea was raised to augment translational and clinical research efforts to improve our understanding of dMMR PDAC. However, from a practical perspective, only 20% of patients with PDAC reach surgical oncologic resection.4 These resection specimens have served as the source of prior dMMR PDAC analysis. Following the United States Food and Drug Administration approval of pembrolizumab as the first cancer therapy targeting a specific molecular signature, we identified a dMMR prevalence of 3% in a small retrospective cohort of archived pancreas endoscopic ultrasound fine-needle biopsy (EUS FNB) specimens.5 We recently completed an 18-month prospective evaluation of 218 consecutive treatment-naive PDAC patients diagnosed by EUS (fine-needle aspiration: 112 (51.4%), FNB: 91 (41.7%) or both: 15 (6.9%)) for MMR screening as a companion diagnostic test (table 1). A specimen adequate for ancillary studies was acquired in 193 (88.5%) patients …

Rationale: The NLST (National Lung Screening Trial) reported a 20% reduction in lung cancer mortality with low-dose computed tomography screening; however, important questions on how to optimize screening remain, including which selection criteria are most accurate at detecting lung cancers and what nodule management protocol is most efficient. The PLCOm2012 (Prostate, Lung, Colorectal and Ovarian) Cancer Screening Trial 6-year and PanCan (Pan-Canadian Early Detection of Lung Cancer) nodule malignancy risk models are two of the better validated risk prediction models for screenee selection and nodule management, respectively. Combined use of these models for participant selection and nodule management could significantly improve screening efficiency. Objectives: The ILST (International Lung Screening Trial) is a prospective cohort study with two primary aims: 1) Compare the accuracy of the PLCOm2012 model against U.S. Preventive Services Task Force (USPSTF) criteria for detecting lung cancers and 2) evaluate nodule management efficiency using the PanCan nodule probability calculator-based protocol versus Lung-RADS. Methods: ILST will recruit 4,500 participants who meet USPSTF and/or PLCOm2012 risk ≥1.51%/6-year selection criteria. Participants will undergo baseline and 2-year low-dose computed tomography screening. Baseline nodules are managed according to PanCan probability score. Participants will be followed up for a minimum of 5 years. Primary outcomes for aim 1 are the proportion of individuals selected for screening, proportion of lung cancers detected, and positive predictive values of either selection criteria, and outcomes for aim 2 include comparing distributions of individuals and the proportion of lung cancers in each of three management groups: next surveillance scan, early recall scan, or diagnostic evaluation recommended. Statistical powers to detect differences in the four components of primary study aims were ≥82%. Conclusions: ILST will prospectively evaluate the comparative accuracy and effectiveness of two promising multivariable risk models for screenee selection and nodule management in lung cancer screening. Clinical trial registered with www.clinicaltrials.gov (NCT02871856).

Author(s): Lee, Shimwoo; McWilliams, Justin P; Lee-Felker, Stephanie A | Abstract: Arterial pseudoaneurysms are contained ruptures of the arterial wall that require prompt intervention. Iatrogenic pseudoaneurysms may result from various diagnostic and therapeutic procedures. Iatrogenic axillary pseudoaneurysms are quite rare, with few reported cases in the literature. We report a case of a 45-year-old woman who sustained an axillary pseudoaneurysm after an ultrasound-guided, vacuum-assisted biopsy of the axillary lymph node. An arteriovenous fistula developed concomitantly. Despite two image-guided treatments, thrombin injection and endovascular coil embolization, the pseudoaneurysm had persistent flow and was ultimately surgically resected at the time when the patient underwent mastectomy for breast cancer.

OBJECTIVES: To evaluate whether a nurse navigator-led, multicomponent Sepsis Transition And Recovery program improves 30-day mortality and readmission outcomes after sepsis hospitalization. DESIGN: Multisite pragmatic randomized clinical trial. SETTING: Three hospitals in North Carolina from January 2019 to March 2020. PATIENTS: Eligible patients hospitalized for suspected sepsis and deemed high-risk for mortality or readmission by validated internal risk models. INTERVENTIONS: Patients were randomized to receive usual care alone (i.e., routine transition support, outpatient care; n = 342) or additional Sepsis Transition And Recovery support (n = 349). The 30-day intervention involved a multicomponent transition service led by a nurse navigator through telephone and electronic health record communication to facilitate best practice postsepsis care strategies during and after hospitalization including: postdischarge medication review, evaluation for new impairments or symptoms, monitoring comorbidities, and palliative care approach when appropriate. Clinical oversight was provided by a Hospital Medicine Transition Services team. MEASUREMENTS AND MAIN RESULTS: The primary outcome was a composite of mortality or hospital readmission at 30 days. Logistic regression models were constructed to evaluate marginal and conditional odds ratios (adjusted for prognostic covariates: age, comorbidity, and organ dysfunction at enrollment). Among 691 randomized patients (mean age = 63.7 ± 15.1 yr; 52% female), a lower percentage of patients in the Sepsis Transition And Recovery group experienced the primary outcome compared with the usual care group (28.7% vs 33.3%; risk difference, 4.7%; odds ratio, 0.80; 95% Cl, 0.58–1.11; adjusted odds ratio, 0.80; 95% Cl, 0.64–0.98). There were 74 deaths (Sepsis Transition And Recovery: 33 [9.5%] vs usual care: 41 [12.0%]) and 155 rehospitalizations (Sepsis Transition And Recovery: 71 [20.3%] vs usual care: 84 [24.6%]). CONCLUSIONS: In a multisite randomized clinical trial of patients hospitalized with sepsis, patients provided with a 30-day program using a nurse navigator to provide best practices for postsepsis care experienced a lower proportion of either mortality or rehospitalization within 30 days after discharge. Further research is needed to understand the contextual factors associated with successful implementation.