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Background: Neonatal encephalopathy (NE) continues to be a significant risk for death and disability. To address this risk, regional guidelines were developed with the support of a malpractice insurance patient safety organization. A NE registry was also established to include 14 centers representing around 50% of deliveries in the state of Massachusetts. The aim of this study was to identify areas of variation in practice that could benefit from quality improvement projects., Methods: This manuscript reports on the establishment of the registry and the primary findings to date., Results: From 2018 to 2020, 502 newborns with NE were evaluated for Therapeutic Hypothermia (TH), of which 246 (49%) received TH, representing a mean of 2.91 per 1000 live births. The study reports on prenatal characteristics, delivery room resuscitation, TH eligibility screening, and post-natal management of newborns with NE who did and did not receive TH., Conclusions: The registry has allowed for the identification of areas of variation in clinical practices, which have guided ongoing quality improvement projects. The authors advocate for the establishment of local and regional registries to standardize and improve NE patient care. They have made the registry data collection tools freely available for other centers to replicate this work., Impact: Malpractice insurance companies can take an active role in supporting clinicians in establishing clinical practice guidelines and regional registries. Establishing a collaborative regional neonatal encephalopathy (NE) registry is feasible. Data Collection tools for a NE registry have been made publicly available to be adopted and replicated by other groups. Establishing a regional NE registry allowed for the identification of gaps in knowledge, variations in practice, and the opportunity to advance care through quality improvement projects., (© 2023. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background: The use of Hyperbaric Oxygen Therapy (HBOT) in diabetic wounds has been studied extensively. Even though venous insufficiency is the most common cause of lower limb ulceration, there is comparatively little evidence regarding the use of HBOT for Venous Leg Ulcers (VLU). We performed a systematic-review to evaluate and synthesise available evidence, to evaluate whether patients with VLU, when treated with HBOT, had greater rates of (i) complete VLU healing or (ii) reduction in VLU area, than controls., Methods: In keeping with PRISMA guidelines, database searches of PubMed, Scopus and Embase was performed. After removal of duplicates, titles were screened for relevance by two authors, then abstracts, and in turn full text manuscripts. Data were extracted from relevant sources including one published abstract. Included studies were assessed for risk of bias using the Risk of Bias 2 (RoB-2) and Risk Of Bias In Nonrandomized Studies (ROBINS-I) tools., Results: Six studies were included. There was significant heterogeneity across the studies, with no standard control intervention, method of outcome reporting, or duration of follow up. Two studies reported 12 week follow up results and pooled analysis of complete ulcer healing showed no statistically significant difference between HBOT and controls for the outcome of complete ulcer healing OR 1.54 (95%CI = .50-4.75) P = .4478. A similar non-signifiacnt result was seen in four studies reporting 5-6 week follow up; OR 5.39 (95%CI = .57-259.57) P = .1136. Change in VLU area was reported in all studies, and pooled standardised mean difference was 1.70 (95%CI = .60 to 2.79) P = .0024, indicating a statistically significant benefit of HBOT in reducing ulcer area., Conclusion: Existing evidence suggests that HBOT does not significantly affect complete healing of VLU. There is a statistically significant benefit in terms of reducing ulcer size, though in the absence of ulcer healing the clinical significance of this is not established. Current evidence does not justify widespread use of HBOT for VLU.

Acute myelogenous leukemia (AML), a disease of the blood and bone marrow, is characterized by the inability of myeloblasts to differentiate into mature cell types. Dihydroorotate dehydrogenase (DHODH) is an enzyme well-known in the pyrimidine biosynthesis pathway; however, small molecule DHODH inhibitors were recently shown to induce differentiation in multiple AML subtypes. Using virtual screening and structure-based drug design approaches, a new series of N-heterocyclic 3-pyridyl carboxamide DHODH inhibitors were discovered. Two lead compounds, 19 and 29 , have potent biochemical and cellular DHODH activity, favorable physicochemical properties, and efficacy in a preclinical model of AML.

A 72-year-old man was referred to our urology outpatient department with a left hemi-scrotal swelling increasing in size over a matter of weeks, initially suspicious for a left hydrocoele. Initial investigation with ultrasound (US) identified a heterogenous enlargement of the left testis and epididymis with a soft tissue mass extending through the inguinal canal. Subsequent CT detected this soft tissue mass to extend along the left gonadal vein to the level of the left renal vein. A biopsy of the retroperitoneal mass confirmed a diagnosis of diffuse large B-cell lymphoma. Immunohistochemical staining further categorised this lymphoma as double expressor but not double hit.Through multidisciplinary team involvement the patient was treated with combination steroids and chemotherapy. Given the scrotal involvement this was considered a sanctuary site for chemotherapy therefore the patient also received radiotherapy to the scrotum. He recovered well following his treatment. This case highlights how early specialist referral can identify rare variants of disease. Essential preoperative imaging with US prior to treating a presumed hydrocoele prevented inappropriate surgical excision. A multidisciplinary team approach improved the patient's outcome and is hoped to have improved his chances of recurrence-free survival., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Twenty-five years after the seminal work of the Harvard Medical Practice Study, the numbers and specific types of health care measures of harm have evolved and expanded. Using the World Café method to derive expert consensus, we sought to generate a contemporary list of triggers and adverse event measures that could be used for chart review to determine the current incidence of inpatient and outpatient adverse events., Methods: We held a modified World Café event in March 2018, during which content experts were divided into 10 tables by clinical domain. After a focused discussion of a prepopulated list of literature-based triggers and measures relevant to that domain, they were asked to rate each measure on clinical importance and suitability for chart review and electronic extraction (very low, low, medium, high, very high)., Results: Seventy-one experts from 9 diverse institutions attended (primary acceptance rate, 72%). Of 525 total triggers and measures, 67% of 391 measures and 46% of 134 triggers were deemed to have high or very high clinical importance. For those triggers and measures with high or very high clinical importance, 218 overall were deemed to be highly amenable to chart review and 198 overall were deemed to be suitable for electronic surveillance., Conclusions: The World Café method effectively prioritized measures/triggers of high clinical importance including those that can be used in chart review, which is considered the gold standard. A future goal is to validate these measures using electronic surveillance mechanisms to decrease the need for chart review., Competing Interests: This work was funded by a grant from CRICO (Boston, MA). Dr. Bates consults for EarlySense, which makes patient safety monitoring systems. He receives cash compensation from CDI (Negev), Ltd, which is a not-for-profit incubator for health IT startups. He receives equity from Valera Health, which makes software to help patients with chronic diseases. He receives equity from Clew, which makes software to support clinical decision making in intensive care. He receives equity from MDClone, which takes clinical data and produces deidentified versions of it. He will be receiving research funding from IBM Watson Health. The other authors report no conflicts of interest., (Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc.)

Mantle cell lymphoma (MCL) presenting in elderly, unfit patients represents a clinical challenge. Front-line 'attenuated' or low-intensity immunochemotherapy is often employed, although outcomes are relatively unexplored. We report outcomes of attenuated immunochemotherapy in 95 patients with MCL across 19 centres in the UK and Ireland considered unfit for full-dose rituximab-bendamustine or rituximab-cyclophosphamide, doxorubicin, vincristine, prednisolone (R-CHOP). Regimens examined were rituximab-cyclophosphamide, vincristine, prednisolone (R-CVP) (n = 19), dose-attenuated R-CHOP (n = 22), dose attenuated rituximab-bendamustine (n = 24) and rituximab-chlorambucil (n = 30). The primary outcome was progression-free survival (PFS). The secondary outcomes included overall response, overall survival (OS) and toxicity. The median (range) age was 79 (58-89) years and 50% were aged ≥80 years. The median (range) Cumulative Illness Rating Scale-Geriatric score was 6 (0-24). The median PFS for all patients was 15 months [95% confidence interval (CI) 8·7-21·2) and median OS was 31·4 months (95% CI 19·7-43·2). By multivariable analysis (MVA), the only clinical factor associated with an inferior PFS was blastoid morphology [hazard ratio (HR) 2·90, P = 0·01). Notably, higher treatment intensity (R-CHOP/R-bendamustine composite) provided an independently superior PFS compared with R-CVP/R-chlorambucil (MVA HR 0·49, P = 0·02). Factors associated with inferior OS by MVA were Eastern Cooperative Oncology Group Performance Status (HR 2·14, P = 0·04), blastoid morphology (HR 4·08, P = 0·001) and progression of disease at <24 months status (HR 5·68, P < 0·001). Overall, survival after front-line dose-attenuated immunochemotherapy is unsatisfactory. Clinical trials investigating novel agents such as Bruton tyrosine kinase and B-cell lymphoma 2 inhibitors in this specific clinical setting are warranted., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)

Little is known about the effectiveness of primary care practices' efforts to engage patients in their health and health care. We examine the association between patient engagement efforts and patients' experiences of care. We found no association between an unweighted count of patient engagement activities and patient experience. Compared with the bottom quartile of practices, however, the top quartile had better performance on patient experience domains of communication, front-office staff, and organizational access (out of nine domains). Furthermore, patients reporting a diagnosis of depression have higher ratings across five domains of patient experience when in practices with higher levels of patient engagement activities measured using an unweighted scale. Future research is needed to understand how the benefits of patient engagement activities can accrue to more patient subgroups. These promising results suggest that payers and policy makers should continue to support implementation and benchmarking of patient engagement efforts across practices.

Background: Venous leg ulceration is a widespread, debilitating pathology with high recurrence rates. Conservative treatment using graduated compression dressings may be associated with unacceptable ulcer recurrence rates. Early superficial venous ablation encourages ulcer healing and reduces recurrence. However, many of this cohort display concomitant ilio-caval stenosis, which further contributes to lower limb venous hypertension and ulceration. An approach that combines early superficial venous ablation with early treatment of ilio-caval stenotic disease may significantly improve ulcer healing and recurrence rates. We question whether early iliac vein interrogation with intravascular ultrasound (IVUS), stenting of significant occlusive disease plus superficial venous ablation, in patients with active venous leg ulceration, will produce superior ulcer healing to standard therapy., Methods: This is a prospective, multi-centre, randomised controlled, feasibility trial recruiting patients with lower limb venous ulceration and saphenous venous incompetence. Patients will be randomised to undergo either truncal ablation and compression therapy or truncal ablation, simultaneous iliac interrogation with intravascular ultrasound and stenting of significant (> 50%) iliac vein lesions plus compression therapy. The primary feasibility outcome will be the rate of eligible patient participation while the primary clinical outcomes will be ulcer healing and procedural safety. Secondary outcomes include time to healing, quality of life and clinical scores, ulcer recurrence rates and rates of post-thrombotic syndrome. Follow-up will be over a 5-year period. This feasibility trial is designed to include 60 patients. Should it be practicable a total of 594 patients would be required to adequately power the trial to definitively address ulcer-healing rates., Discussion: This trial will be the first randomised trial to examine the role iliac interrogation and intervention in conjunction with standard operative therapy in the management of venous ulceration related to superficial truncal venous incompetence., Ethical Committee Reference: C.A. 2111 Galway Clinical Research Ethics Committee REGISTRATION: Clinical Trials.gov registration NCT03640689 , Registered on 21 August 2018.

Standard first-line therapy choice for essential thrombocythaemia (ET) requiring cytoreduction, supported by randomized trials, is low-dose aspirin with hydroxycarbamide, but the role of recombinant interferon-alfa (IFNα)-2a/2b and pegylated (PEG)-IFN-α-2a/2b is increasingly highlighted. Longer-term outcome data, however, remains somewhat scarce, particularly in the 'real world'. We hereby report on a large, well-annotated cohort of ET patients from a single referral centre undergoing therapy with either IFNα or (PEG)-IFN-α-2a/2b and demonstrate high rates of complete haematological responses, good tolerability and safety, low rates of thromboembolic events in compliant patients and confirm feasibility of long-term therapy in a significant proportion of patients., (© 2019 British Society for Haematology and John Wiley & Sons Ltd.)

Research into the incidence of harm and death resulting from medical error has continued after the release of "To Err Is Human." Although debate of the incidence of harm from medical errors continues, patient safety experts agree that medical errors still occur at considerable and unacceptable rates. Continued attention and examination of medical errors are required. Patient Safety Organizations are a federal program that enables providers across the health care delivery system to analyze and learn from errors with the protection of privilege and confidentiality., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology.

Background and Objective: Handoff communication errors are a leading source of sentinel events. We sought to determine the impact of a handoff improvement programme for nurses., Methods: We conducted a prospective pre-post intervention study on a paediatric intensive care unit in 2011-2012. The I-PASS Nursing Handoff Bundle intervention consisted of educational training, verbal handoff I-PASS mnemonic implementation, and visual materials to provide reinforcement and sustainability. We developed handoff direct observation and time motion workflow assessment tools to measure: (1) quality of the verbal handoff, including interruption frequency and presence of key handoff data elements; and (2) duration of handoff and other workflow activities., Results: I-PASS implementation was associated with improvements in verbal handoff communications, including inclusion of illness severity assessment (37% preintervention vs 67% postintervention, p=0.001), patient summary (81% vs 95%, p=0.05), to do list (35% vs 100%, p<0.001) and an opportunity for the receiving nurse to ask questions (34% vs 73%, p<0.001). Overall, 13/21 (62%) of verbal handoff data elements were more likely to be present following implementation whereas no data elements were less likely present. Implementation was associated with a decrease in interruption frequency pre versus post intervention (67% vs 40% of handoffs with interruptions, p=0.005) without a change in the median handoff duration (18.8 min vs 19.9 min, p=0.48) or changes in time spent in direct or indirect patient care activities., Conclusions: Implementation of the I-PASS Nursing Handoff Bundle was associated with widespread improvements in the verbal handoff process without a negative impact on nursing workflow. Implementation of I-PASS for nurses may therefore have the potential to significantly reduce medical errors and improve patient safety., Competing Interests: Competing interests: AJS reported receiving honoraria and travel reimbursement from multiple academic and professional organisations for delivering lectures on handoffs and patient safety. She has consulted with and holds equity in the I-PASS Institute, which seeks to train institutions in best handoff practices and aid in their implementation. CL likewise has consulted with and holds equity in the I-PASS Institute. In addition, he has served as a paid consultant to Virgin Pulse to help develop a Sleep and Health Program. He is supported in part by the Children’s Hospital Association for his work as an Executive Council member of the Pediatric Research in Inpatient Settings (PRIS) network. He has received monetary awards, honoraria and travel reimbursement from multiple academic and professional organisations for teaching and consulting on sleep deprivation, physician performance, handoffs, and safety, and has served as an expert witness in cases regarding patient safety and sleep deprivation. No other authors reported disclosures., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Background: Diagnostic errors are an underrecognized source of patient harm, and cardiovascular disease can be challenging to diagnose in the ambulatory setting. Although malpractice data can inform diagnostic error reduction efforts, no studies have examined outpatient cardiovascular malpractice cases in depth. A study was conducted to examine the characteristics of outpatient cardiovascular malpractice cases brought against general medicine practitioners., Methods: Some 3,407 closed malpractice claims were analyzed in outpatient general medicine from CRICO Strategies' Comparative Benchmarking System database-the largest detailed database of paid and unpaid malpractice in the world-and multivariate models were created to determine the factors that predicted case outcomes., Results: Among the 153 patients in cardiovascular malpractice cases for whom patient comorbidities were coded, the majority (63%) had at least one traditional cardiac risk factor, such as diabetes, tobacco use, or previous cardiovascular disease. Cardiovascular malpractice cases were more likely to involve an allegation of error in diagnosis (75% vs. 47%, p <0.0001), have high clinical severity (86% vs. 49%, p <0.0001) and result in death (75% vs. 27%, p <0.0001), as compared to noncardiovascular cases. Initial diagnoses of nonspecific chest pain and mimics of cardiovascular pain (for example, esophageal disease) were common and independently increased the likelihood of a claim resulting in a payment (p <0.01)., Conclusion: Cardiovascular malpractice cases against outpatient general medicine physicians mostly occur in patients with conventional risk factors for coronary artery disease and are often diagnosed with common mimics of cardiovascular pain. These findings suggest that these patients may be high-yield targets for preventing diagnostic errors in the ambulatory setting., (Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: Evaluate application of quality improvement approaches to key ambulatory malpractice risk and safety areas., Study Setting: In total, 25 small-to-medium-sized primary care practices (16 intervention; 9 control) in Massachusetts., Study Design: Controlled trial of a 15-month intervention including exposure to a learning network, webinars, face-to-face meetings, and coaching by improvement advisors targeting "3+1" high-risk domains: test result, referral, and medication management plus culture/communication issues evaluated by survey and chart review tools., Data Collection Methods: Chart reviews conducted at baseline and postintervention for intervention sites. Staff and patient survey data collected at baseline and postintervention for intervention and control sites., Principal Findings: Chart reviews demonstrated significant improvements in documentation of abnormal results, patient notification, documentation of an action or treatment plan, and evidence of a completed plan (all P<0.001). Mean days between laboratory test date and evidence of completed action/treatment plan decreased by 19.4 days (P<0.001). Staff surveys showed modest but nonsignificant improvement for intervention practices relative to controls overall and for the 3 high-risk domains that were the focus of PROMISES., Conclusions: A consortium of stakeholders, quality improvement tools, coaches, and learning network decreased selected ambulatory safety risks often seen in malpractice claims.