Naming racism as a root cause of inequities in palliative care research: a scoping review.

BACKGROUND: Racial and ethnic inequities in palliative care are well-established. The way researchers design and interpret studies investigating race- and ethnicity-based disparities has future implications on the interventions aimed to reduce these inequities. If racism is not discussed when contextualizing findings, it is less likely to be addressed and inequities will persist. OBJECTIVE: To summarize the characteristics of 12 years of academic literature that investigates race- or ethnicity-based disparities in palliative care access, outcomes and experiences, and determine the extent to which racism is discussed when interpreting findings. METHODS: Following Arksey & O'Malley's methodology for scoping reviews, we searched bibliographic databases for primary, peer reviewed studies globally, in all languages, that collected race or ethnicity variables in a palliative care context (January 1, 2011 to October 17, 2023). We recorded study characteristics and categorized citations based on their research focus-whether race or ethnicity were examined as a major focus (analyzed as a primary independent variable or population of interest) or minor focus (analyzed as a secondary variable) of the research purpose, and the interpretation of findings-whether authors directly or indirectly discussed racism when contextualizing the study results. RESULTS: We identified 3000 citations and included 181 in our review. Of these, most were from the United States (88.95%) and examined race or ethnicity as a major focus (71.27%). When interpreting findings, authors directly named racism in 7.18% of publications. They were more likely to use words closely associated with racism (20.44%) or describe systemic or individual factors (41.44%). Racism was directly named in 33.33% of articles published since 2021 versus 3.92% in the 10 years prior, suggesting it is becoming more common. CONCLUSION: While the focus on race and ethnicity in palliative care research is increasing, there is room for improvement when acknowledging systemic factors - including racism - during data analysis. Researchers must be purposeful when investigating race and ethnicity, and identify how racism shapes palliative care access, outcomes and experiences of racially and ethnically minoritized patients.

Specifications of the ACMG/AMP variant curation guidelines for the analysis of germline ATM sequence variants.

The ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer (HBOP) Variant Curation Expert Panel (VCEP) is composed of internationally recognized experts in clinical genetics, molecular biology and variant interpretation. This VCEP made specifications for ACMG/AMP guidelines for the ataxia telangiectasia mutated (ATM) gene according to the Food and Drug Administration (FDA)-approved ClinGen protocol. These gene-specific rules for ATM were modified from the American College of Medical Genetics and Association for Molecular Pathology (ACMG/AMP) guidelines and were tested against 33 ATM variants of various types and classifications in a pilot curation phase. The pilot revealed a majority agreement between the HBOP VCEP classifications and the ClinVar-deposited classifications. Six pilot variants had conflicting interpretations in ClinVar and reevaluation with the VCEP's ATM-specific rules resulted in four that were classified as benign, one as likely pathogenic and one as a variant of uncertain significance (VUS) by the VCEP, improving the certainty of interpretations in the public domain. Overall, 28 the 33 pilot variants were not VUS leading to an 85% classification rate. The ClinGen-approved, modified rules demonstrated value for improved interpretation of variants in ATM.

Surface wear of PyroCarbon implant in metacarpophalangeal joint arthroplasty without radiographic abnormality: A case report.

CASE: A 54-year-old male with osteoarthritis of the right long finger metacarpophalangeal joint underwent PyroCarbon joint arthroplasty. Seven years later the patient presented for metacarpophalangeal joint swelling and pain. The workup was benign, without signs of implant complication or osseous abnormality. He underwent washout and two-stage revision, where gross implant wear and debris not demonstrated by radiograph were found. He then returned to the operating room for reimplantation of a PyroCarbon implant. CONCLUSION: This case demonstrates a novel presentation of aseptic PyroCarbon implant failure in the hand without radiographic abnormality that can alter operative management by reducing operating room returns.

Patient outcomes, efficiency, and adverse events for elective hip and knee replacement in private and NHS hospitals: a population-based cohort study in England.

Background: Since the early 2000s, the National Health Service (NHS) in England has expanded provision of publicly funded care in private hospitals as a strategy to meet growing demand for elective care. This study aims to compare patient outcomes, efficiency and adverse events in private and NHS hospitals when providing elective hip and knee replacement. Methods: We conducted a population-based cohort study including patients ≥18 years, undergoing a publicly funded elective hip or knee replacement in private and NHS hospitals in England between January 1st 2016 and March 31st 2019. Comparative probability was estimated for three patient outcome measures (in-hospital mortality, emergency readmissions with 28 days, hospital transfers), two efficiency measures (pre-operative length of stay (LOS) >0 day and post-operative LOS >2 days), and four adverse events (hospital-associated infection, adverse drug reactions, pressure ulcers, venous thromboembolism). Probit regression was used to adjust for observable confounding followed by instrumental variable (IV) analyses to also account for unobserved confounding at the patient-level. Propensity score matching was then used as a robustness check. Findings: Our study sample included 169,232 patients in private hospitals, and 262,659 patients in NHS hospitals. Estimates from probit regression indicated that treatment in private hospital was associated with reduced probability of in-hospital mortality (-0.0009, 95% CI -0.0010, -0.0007), emergency readmissions (-0.0181, 95% CI -0.0191, -0.0172), hospital transfers (-0.0076, 95% CI -0.0084, -0.0068), prolonged post-operative LOS (-0.1174, 95% CI -0.1547, -0.0801), hospital-associated infection (-0.0115, 95% CI -0.0123, -0.0107), adverse drug reactions (-0.0051, 95% CI -0.0056, -0.0046), pressure ulcers (-0.0017, 95% CI -0.0019, -0.0014), and venous thromboembolism (-0.0027, 95% CI -0.0031, -0.0022). IV analyses produced no significant differences between private and NHS hospitals, except for lower probability in private hospitals of hospital-associated infection (-0.0057, 95% CI -0.0081, -0.0032), and greater probability in private hospitals of prolonged post-operative LOS (0.2653, 95% CI 0.1833, 0.3472). Propensity score matching produced similar results to probit regression. Interpretation: Our findings indicate there is potentially important unobservable confounding at the patient-level between private and NHS hospitals not adjusted for when using probit regression or propensity score matching. Funding: This research did not receive any dedicated funding.

The Year in Thoracic Anesthesia: Selected Highlights from 2022.

This article reviews research highlights in the field of thoracic anesthesia. The highlights of this year included new developments in the preoperative assessment and prehabilitation of patients requiring thoracic surgery, updates on the use of devices for one-lung ventilation (OLV) in adults and children, updates on the anesthetic and postoperative management of these patients, including protective OLV ventilation, the use of opioid-sparing techniques and regional anesthesia, and outcomes using enhanced recovery after surgery, as well as the use of expanding indications for extracorporeal membrane oxygenation, specialized anesthetic techniques for airway surgery, and nonintubated video-assisted thoracic surgery.

Specifications of the ACMG/AMP Variant Classification Guidelines for Germline DICER1 Variant Curation.

Germline pathogenic variants in DICER1 predispose individuals to develop a variety of benign and malignant tumors. Accurate variant curation and classification is essential for reliable diagnosis of DICER1-related tumor predisposition and identification of individuals who may benefit from surveillance. Since 2015, most labs have followed the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP) sequence variant classification guidelines for DICER1 germline variant curation. However, these general guidelines lack gene-specific nuances and leave room for subjectivity. Consequently, a group of DICER1 experts joined ClinGen to form the DICER1 and miRNA-Processing Genes Variant Curation Expert Panel (VCEP), to create DICER1- specific ACMG/AMP guidelines for germline variant curation. The VCEP followed the FDA-approved ClinGen protocol for adapting and piloting these guidelines. A diverse set of 40 DICER1 variants were selected for piloting, including 14 known Pathogenic/Likely Pathogenic (P/LP) variants, 12 known Benign/Likely Benign (B/LB) variants, and 14 variants classified as variants of uncertain significance (VUS) or with conflicting interpretations in ClinVar. Clinically meaningful classifications (i.e., P, LP, LB, or B) were achieved for 82.5% (33/40) of the pilot variants, with 100% concordance among the known P/LP and known B/LB variants. Half of the VUS or conflicting variants were resolved with four variants classified as LB and three as LP. These results demonstrate that the DICER1-specific guidelines for germline variant curation effectively classify known pathogenic and benign variants while reducing the frequency of uncertain classifications. Individuals and labs curating DICER1 variants should consider adopting this classification framework to encourage consistency and improve objectivity.

Retrospective Cohort Study on the Limitations of Direct-to-Consumer Genetic Screening in Hereditary Breast and Ovarian Cancer.

PURPOSE: Among cancer predisposition genes, most direct-to-consumer (DTC) genetic tests evaluate three Ashkenazi Jewish (AJ) founder mutations in BRCA1/2, which represent a small proportion of pathogenic or likely pathogenic variants (PLPV) in cancer predisposing genes. In this study, we investigate PLPV in BRCA1/2 and other cancer predisposition genes that are missed by testing only AJ founder BRCA1/2 mutations. METHODS: Individuals were referred to genetic testing for personal diagnoses of breast and/or ovarian cancer (clinical cohort) or were self-referred (nonindication-based cohort). There were 348,692 participants in the clinical cohort and 7,636 participants in the nonindication-based cohort. Both cohorts were analyzed for BRCA1/2 AJ founder mutations. Full sequence analysis was done for PLPV in BRCA1/2, CDH1, PALB2, PTEN, STK11, TP53, ATM, BARD1, BRIP1, CHEK2 (truncating variants), EPCAM, MLH1, MSH2/6, NF1, PMS2, RAD51C/D, and 22 other genes. RESULTS: BRCA1/2 AJ founder mutations accounted for 10.8% and 29.7% of BRCA1/2 PLPV in the clinical and nonindication-based cohorts, respectively. AJ founder mutations accounted for 89.9% of BRCA1/2 PLPV in those of full AJ descent, but only 69.6% of those of partial AJ descent. In total, 0.5% of all individuals had a BRCA1/2 AJ founder variant, while 7.7% had PLPV in a high-risk breast/ovarian cancer gene. For non-AJ individuals, limiting evaluation to the AJ founder BRCA1/2 mutations missed >90% of mutations in actionable cancer risk genes. Secondary analysis revealed a false-positive rate of 69% for PLPV outside of non-AJ BRCA 1/2 founder mutations. CONCLUSION: DTC genetic testing misses >90% of BRCA1/2 PLPV in individuals of non-AJ ancestry and about 10% of BRCA1/2 PLPV among AJ individuals. There is a high false-positivity rate for non-AJ BRCA 1/2 PLPV with DTC genetic testing.

Germline pathogenic SMARCA4 variants in neuroblastoma.

Heterozygous germline pathogenic variants (GPVs) in SMARCA4, the gene encoding the ATP-dependent chromatin remodelling protein SMARCA4 (previously known as BRG1), predispose to several rare tumour types, including small cell carcinoma of the ovary, hypercalcaemic type, atypical teratoid and malignant rhabdoid tumour, and uterine sarcoma. The increase in germline testing of SMARCA4 in recent years has revealed putative GPVs affecting SMARCA4 in patients with other cancer types. Here we describe 11 patients with neuroblastoma (NBL), including 4 previously unreported cases, all of whom were found to harbour heterozygous germline variants in SMARCA4 Median age at diagnosis was 5 years (range 2 months-26 years); nine were male; and eight of nine cases had tumour location information in the adrenal gland. Eight of the germline variants were expected to result in loss of function of SMARCA4 (large deletion, truncating and canonical splice variants), while the remaining four were missense variants. Loss of heterozygosity of the wild-type SMARCA4 allele was found in all eight cases where somatic testing was performed, supporting the notion that SMARCA4 functions as a classic tumour suppressor. Altogether, these findings strongly suggest that NBL should be included in the spectrum of SMARCA4-associated tumours.

Optimising clinical care through CDH1-specific germline variant curation: improvement of clinical assertions and updated curation guidelines.

BACKGROUND: Germline pathogenic variants in CDH1 are associated with increased risk of diffuse gastric cancer and lobular breast cancer. Risk reduction strategies include consideration of prophylactic surgery, thereby making accurate interpretation of germline CDH1 variants critical for physicians deciding on these procedures. The Clinical Genome Resource (ClinGen) CDH1 Variant Curation Expert Panel (VCEP) developed specifications for CDH1 variant curation with a goal to resolve variants of uncertain significance (VUS) and with ClinVar conflicting interpretations and continues to update these specifications. METHODS: CDH1 variant classification specifications were modified based on updated genetic testing clinical criteria, new recommendations from ClinGen and expert knowledge from ongoing CDH1 variant curations. The CDH1 VCEP reviewed 273 variants using updated CDH1 specifications and incorporated published and unpublished data provided by diagnostic laboratories. RESULTS: Updated CDH1-specific interpretation guidelines include 11 major modifications since the initial specifications from 2018. Using the refined guidelines, 97% (36 of 37) of variants with ClinVar conflicting interpretations were resolved to benign, likely benign, likely pathogenic or pathogenic, and 35% (15 of 43) of VUS were resolved to benign or likely benign. Overall, 88% (239 of 273) of curated variants had non-VUS classifications. To date, variants classified as pathogenic are either nonsense, frameshift, splicing, or affecting the translation initiation codon, and the only missense variants classified as pathogenic or likely pathogenic have been shown to affect splicing. CONCLUSIONS: The development and evolution of CDH1-specific criteria by the expert panel resulted in decreased uncertain and conflicting interpretations of variants in this clinically actionable gene, which can ultimately lead to more effective clinical management recommendations.

Evaluation of the NHS England evidence-based interventions programme: a difference-in-difference analysis.

BACKGROUND: The NHS England evidence-based interventions programme (EBI), launched in April 2019, is a novel nationally led initiative to encourage disinvestment in low value care. METHOD: We sought to evaluate the effectiveness of this policy by using a difference-in-difference approach to compare changes in volume between January 2016 and February 2020 in a treatment group of low value procedures against a control group unaffected by the EBI programme during our period of analysis but subsequently identified as candidates for disinvestment. RESULTS: We found only small differences between the treatment and control group after implementation, with reductions in volumes in the treatment group 0.10% (95% CI 0.09% to 0.11%) smaller than in the control group (equivalent to 16 low value procedures per month). During the month of implementation, reductions in volumes in the treatment group were 0.05% (95% CI 0.03% to 0.06%) smaller than in the control group (equivalent to 7 low value procedures). Using triple difference estimators, we found that reductions in volumes were 0.35% (95% CI 0.26% to 0.44%) larger in NHS hospitals than independent sector providers (equivalent to 47 low value procedures per month). We found no significant differences between clinical commissioning groups that did or did not volunteer to be part of a demonstrator community to trial EBI guidance, but found reductions in volume were 0.06% (95% CI 0.04% to 0.08%) larger in clinical commissioning groups that posted a deficit in the financial year 2018/19 before implementation (equivalent to 4 low value procedures per month). CONCLUSIONS: Our analysis shows that the EBI programme did not accelerate disinvestment for procedures under its remit during our period of analysis. However, we find that financial and organisational factors may have had some influence on the degree of responsiveness to the EBI programme.

Serum Cytomegalovirus Polymerase Chain Reaction Test Is a Valuable Negative Predictor of Infection in Acute Severe Ulcerative Colitis.

BACKGROUND: Diagnosis of cytomegalovirus (CMV) colitis in the setting of severe ulcerative colitis (UC) remains a clinical challenge. This study aimed to determine the utility of serum CMV polymerase chain reaction (PCR) as a non-invasive test for the diagnosis of CMV superinfection in patients hospitalized with UC. METHODS: This retrospective study included consecutive admitted patients with UC who had serum testing for CMV completed as part of standard hospital procedure and CMV colitis diagnosed by expert pathologists. RESULTS: Two hundred and six patients with UC were included; 13 patients (6%) had histologically confirmed CMV colitis. Eleven of 13 patients with CMV colitis (84%) and 3 of 193 (1.5%) patients without CMV colitis had a positive serum PCR test (p < 0.0001). ROC analysis showed that a CMV PCR level of 259 IU/mL had a sensitivity and specificity of 77% and 99%, respectively, for diagnosis of CMV colitis with an AUC of 0.9 (p < 0.0001). Serum CMV PCR level significantly correlated to the number of inclusion bodies on biopsy specimens with data available (n = 8) (r = 0.8, p = 0.02). CMV positivity did not predict the need for salvage therapy, admission or 1-year colectomy rates. CONCLUSION: Serum CMV PCR has an excellent negative predictive value and demonstrates a strong correlation with CMV positivity on histology. This work supports a rationale for serum CMV PCR testing on admission to assess the risk of CMV colitis in patients with severe UC.

Changes in publicly and privately funded care in England following a national programme to reduce provision of low-value elective surgery.

BACKGROUND: This study assessed whether there is an association between changes in publicly and privately funded care for procedures classified as low value by the National Health Service (NHS) in England following implementation of the Evidence-Based Intervention (EBI) programme. Category 1 procedures should not be conducted and are no longer reimbursed by the NHS. Category 2 procedures are only reimbursed by the NHS in certain circumstances. METHODS: Changes in volumes of publicly and privately funded procedures per month in 2019-2020 compared with the previous year were analysed in private hospitals and local healthcare markets, and adjusted for volume of procedures and patient case mix including age, sex, co-morbidities, and deprivation. Supplementary analyses focused on the self-pay and insurance funding mechanisms. RESULTS: There was a statistically significant association between changes in publicly and privately funded care for category 2 procedures at the hospital (-0.19, 95 per cent c.i. -0.25 to -0.12) and local healthcare market level of analysis (-0.24, -0.32 to -0.15). A statistically significant association for category 1 procedures only existed at the hospital level of analysis (-0.19, -0.30 to -0.08). Findings were similar for patients accessing care through self-pay and insurance funding mechanisms. CONCLUSION: Stronger associations between changes in publicly and privately funded care for category 2 procedures may exist as they are clinically indicated in certain circumstances. Reductions in publicly funded care were likely a combined result of the EBI programme and growing NHS waiting lists, whereas increases in privately funded care were influenced by both patient and supplier-induced demand.

Case Report: Heterotopic Pancreatic Tissue Leading to Acute on Chronic Cholecystitis.

Heterotopic (ectopic) pancreatic tissue refers to tissue located outside the borders of the main pancreas. It is rarely found in gallbladders and can cause biliary disease, with only a few documented cases in the surgical literature. Here, we present the unusual case of a 21-year-old female with acute on chronic cholecystitis caused by obstruction of the cystic duct with ectopic pancreatic tissue. The aim of the paper is to describe the significance of ectopic pancreatic tissue in biliary pathology and bring awareness to clinicians about this rare entity.

Emergency contracting and the delivery of elective care services across the English National Health Service and independent sector during COVID-19: a descriptive analysis.

BACKGROUND: Following a virtual standstill in the delivery of elective procedures in England, a national block contract between the NHS and the independent sector aimed to help restart surgical care. This study aims to describe subsequent changes in trends in elective care service delivery following implementation of the initial iteration of this contract. METHODS: Population-based retrospective cohort study, assessing the delivery of all publicly funded and privately funded elective care delivered in England between 1 April 2020 and 31 July 2020 compared with the same period in 2019. Discharge data from the Hospital Episode Statistics and private healthcare data from the Private Health Information Network was stratified by specialty, procedure, length of stay and patient complexity in terms of age and Charlson Comorbidity Index. RESULTS: COVID-19 significantly reduced publicly funded elective care activity, though changes were more pronounced in the independent sector (-65.1%) compared with the NHS (-52.7%), whereas reductions in privately funded elective care activity were similar in both independent sector hospitals (-74.2%) and NHS hospitals (-72.9%). Patient complexity increased in the independent sector compared with the previous year, with mixed findings in NHS hospitals. Most specialties, irrespective of sector or funding mechanisms, experienced a reduction in hospital admissions. However, some specialities, including medical oncology, clinical oncology, clinical haematology and cardiology, experienced an increase in publicly-funded elective care activity in the independent sector. CONCLUSION: Elective care delivered by the independent sector remained significantly below historic levels, although this overlooks significant variation between regions and specialities. There may be opportunities to learn from regions which achieved more significant increases in publicly funded elective care in independent sector providers as a strategy to address the growing backlog of elective care.

Lower Fracture Rates in Patients Treated with Radium-223, Abiraterone or Enzalutamide, When Given Concurrently with Bone Health Agents: A Real-World Analysis.

BACKGROUND: The phase 3 trial ERA223 demonstrated an increased fracture rate and no survival advantage for metastatic castration resistant prostate cancer (mCRPC) patients on Radium-223 (Ra-223) with abiraterone, leading to regulatory restrictions on combination therapy. However, less than half of trial patients received bone health agents (BHA). We reviewed electronic health record (EHR) data evaluating fracture rates for patients on BHA receiving Ra-223, androgen deprivation therapy and either abiraterone or enzalutamide. PATIENTS AND METHODS: We conducted a retrospective, cohort analysis of EHR data of mCRPC patients on Ra-223 treated at a single community center by a single provider between 2010 and 2018. The primary objective was evaluating fracture rates for patients on BHA receiving Ra-223 and abiraterone. We conducted a secondary analysis for enzalutamide. RESULTS: One hundred seventy-seven patients received Ra-223 concurrently with abiraterone or enzalutamide between November 2010 and August 2018. The median age was 73 at first Ra-223 dose (range 40-93). The median follow-up time from last Ra-223 dose was 30 months (range 2-106). One hundred sixty-four patients (93%) received BHAs. One hundred fifty-nine patients (89%) were on a BHA before and/or during Ra-223. Sixty-seven patients received denosumab (38%), 63 received zoledronic acid (36%), and 29 received both nonconcurrently (16%). Eleven patients (6.2%) experienced a fracture after starting Ra-223, 9 of which occurred while on prior and/or concurrent BHA. We observed a 5.7% fracture rate for mCRPC patients who received combination therapy and denosumab or zoledronic acid. CONCLUSION: This real-world analysis demonstrating a low fracture rate in patients with mCRPC receiving a BHA while on Ra-223 and abiraterone or enzalutamide may inform current clinical practice.

United Kingdom: Health System Review.

This analysis provides a review of developments in financing, governance, organisation and delivery, health reforms and performance of the health systems in the United Kingdom. The United Kingdom has enjoyed a national health service with access based on clinical need, and not ability to pay for over 70 years. This has provided several important benefits including protection against the financial consequences of ill-health, redistribution of wealth from rich to poor, and relatively low administrative costs. Despite this, the United Kingdom continues to lag behind many other comparable high-income countries in key measures including life expectancy, infant mortality and cancer survival. Total health spending in the United Kingdom is slightly above the average for Europe, but it is below many other comparable high-income countries such as Germany, France and Canada. The United Kingdom also has relatively lower levels of doctors, nurses, hospital beds and equipment than many other comparable high-income countries. Wider social determinants of health also contribute to poor outcomes, and the United Kingdom has one of the highest levels of income inequality in Europe. Devolution of responsibility for health care services since the late 1990s to Scotland, Wales and Northern Ireland has resulted in divergence in policies between countries, including in prescription charges, and eligibility for publicly funded social care services. However, more commonalities than differences remain between these health care systems. The United Kingdom initially experienced one of the highest death rates associated with COVID-19; however, the success and speed of the United Kingdom's vaccination programme has since improved the United Kingdom's performance in this respect. Principal health reforms in each country are focusing on facilitating cross-sectoral partnerships and promoting integration of services in a manner that improves the health and well-being of local populations. These include the establishment of integrated care systems in England, integrated joint boards in Scotland, regional partnership boards in Wales and integrated partnership boards in Northern Ireland. Policies are also being developed to align the social care funding model closer to the National Health Service funding model. These include a cap on costs over an individual's lifetime in England, and a national care service free at the point of need in Scotland and Wales. Currently, and for the future, significant investment is needed to address major challenges including a growing backlog of elective care, and staffing shortfalls exacerbated by Brexit.