Temporomandibular disorders: INfORM/IADR key points for good clinical practice based on standard of care.

OBJECTIVE: To present a list of key points for good Temporomandibular Disorders (TMDs) clinical practice on behalf of the International Network for Orofacial Pain and Related Disorders Methodology (INfORM) group of the International Association for Dental, Oral and Craniofacial Research (IADR). METHODS: An open working group discussion was held at the IADR General Session in New Orleans (March 2024), where members of the INfORM group finalized the proposal of a list of 10 key points. RESULTS: The key points covered knowledge on the etiology, diagnosis, and treatment. They represent a summary of the current standard of care for management of TMD patients. They are in line with the current need to assist general dental practitioners advance their understanding and prevent inappropriate treatment. CONCLUSIONS: The key points can be viewed as a guiding template for other national and international associations to prepare guidelines and recommendations on management of TMDs adapted to the different cultural, social, educational, and healthcare requirements.

Enhancing pharmacist intervention targeting based on patient clustering with unsupervised machine learning.

OBJECTIVES: Adherence to the American Diabetes Association (ADA) Standards of Medical Care is low. This study aimed to assist pharmacists in identifying patients for diabetes control interventions using unsupervised machine learning. METHODS: This study analyzed the 2021 Medical Expenditure Panel Survey and used a k-mode cluster analysis. Patient features analyzed were adherence to a select set of preventive measures from the ADA Standards of Medical Care (HbA1c test, foot examination, blood cholesterol test, dilated eye examination, and influenza vaccination) and some patient characteristics (age, gender, health insurance, insulin use, and diabetes-related complications). RESULTS: The study included 1,219 patients with self-reported diabetes, and the adherence rate to the ADA standards was 33.72%. Five distinct clusters emerged: (A) moderate-complexity, privately insured male; (B) moderate-complexity, publicly insured female; (C) low-complexity, privately insured female; (D) high-complexity, publicly insured female; (E) moderate-complexity, publicly insured male. Groups B, C, and E exhibited nonadherence. CONCLUSIONS: Pharmacists can target publicly insured elderly (Groups B and E) and privately insured middle-aged females (Group C) for interventions. For instance, pharmacists may help patients in Groups B and E locate existing resources in their insurance program and remind those in Group C of the importance of adequate diabetes care.

The American Cancer Society National Lung Cancer Roundtable strategic plan: Introduction.

Lung cancer is the leading cause of cancer death in the United States and across the world. The American Cancer Society National Lung Cancer Roundtable (ACS NLCRT) was established in 2017 as a consortium of public, private, and voluntary organizations with a mission to lower the impact of lung cancer via prevention, early detection, and optimal therapy. The ACS NLCRT supports a comprehensive scope of work that covers the lung cancer continuum, from risk reduction, tobacco prevention and control, and early detection (screening and incidental lung nodule management) to guideline-based staging, biomarker testing, treatment, and survivorship and overarching issues such as stigma and nihilism, health equity, and tactical approaches such as state coalition efforts and policy initiatives. Applying a multidimensional and multisector approach, over 220 public, private, and government agency member organizations and 250 volunteer experts, patients, and caregiver advocate representatives collaborate to address challenges across the lung cancer continuum by catalyzing action to conceive, build, and strengthen innovative solutions. The wide-ranging membership allows the ACS NLCRT to harness the collective power and expertise of the entire lung cancer community by connecting leaders, communities, and systems to improve equity and access. These national, state, and local relationships provide partnerships for the dissemination of ACS NLCRT-developed tools and resources. This article describes the ACS NLCRT and introduces the series of accompanying and future articles that together make up the ACS NLCRT strategic plan, which provides a roadmap for future research, investment, and collaboration to reduce lung cancer mortality and lung cancer-related stigma and enhance survivorship.

The American Cancer Society National Lung Cancer Roundtable strategic plan: Implementation of high-quality lung cancer screening.

More than a decade has passed since researchers in the Early Lung Cancer Action Project and the National Lung Screening Trial demonstrated the ability to save lives of high-risk individuals from lung cancer through regular screening by low dose computed tomography scan. The emergence of the most recent findings in the Dutch-Belgian lung-cancer screening trial (Nederlands-Leuvens Longkanker Screenings Onderzoek [NELSON]) further strengthens and expands on this evidence. These studies demonstrate the benefit of integrating lung cancer screening into clinical practice, yet lung cancer continues to lead cancer mortality rates in the United States. Fewer than 20% of screen eligible individuals are enrolled in lung cancer screening, leaving millions of qualified individuals without the standard of care and benefit they deserve. This article, part of the American Cancer Society National Lung Cancer Roundtable (ACS NLCRT) strategic plan, examines the impediments to successful adoption, dissemination, and implementation of lung cancer screening. Proposed solutions identified by the ACS NLCRT Implementation Strategies Task Group and work currently underway to address these challenges to improve uptake of lung cancer screening are discussed. PLAIN LANGUAGE SUMMARY: The evidence supporting the benefit of lung cancer screening in adults who previously or currently smoke has led to widespread endorsement and coverage by health plans. Lung cancer screening programs should be designed to promote high uptake rates of screening among eligible adults, and to deliver high-quality screening and follow-up care.

Feeding cessation and antibiotics improve clinical symptoms and alleviate gut and systemic inflammation in preterm pigs sensitive to necrotizing enterocolitis.

Necrotizing enterocolitis (NEC) is a microbiota- and feeding-related gut inflammatory disease in preterm infants. The standard of care (SOC) treatment for suspected NEC is antibiotic treatment and reduced enteral feeding, but how SOC treatment mitigates NEC remains unclear. We explored whether SOC treatment alone or combined with an anti-inflammatory protein (inter-alpha inhibitor protein, IAIP) supplementation improves outcomes in a preterm piglet model of formula-induced NEC. Seventy-one cesarean-delivered preterm piglets were initially fed formula, developing NEC symptoms by day 3, and then randomized into CON (continued feeding) or SOC groups (feeding cessation and antibiotics), each with or without human IAIP (2×2 factorial design). By day 5, IAIP treatment did not significantly influence outcomes, whereas SOC treatment effectively reduced NEC lesions, diarrhea, and bloody stools. Notably, SOC treatment improved gut morphology and function, dampened gut inflammatory responses, altered the colonic microbiota composition, and modulated systemic immune responses. Plasma proteomic analysis revealed the effects of SOC treatment on organ development and systemic inflammatory responses. Collectively, these findings suggest that SOC treatment significantly prevents NEC progression in preterm piglets via effects on gut structure, function, and microbiota, as well as systemic immune and inflammatory responses. Timely feeding cessation and antibiotics are critical factors in preventing NEC progression in preterm infants, while the benefits of additional human IAIP treatment remain to be established.

Treatment patterns, healthcare resource utilization, and costs in Medicare patients with diffuse large B-cell lymphoma: a retrospective claims analysis (2015-2020).

AIMS: To understand treatment patterns, healthcare resource utilization (HCRU), and the economic burden of diffuse large B-cell lymphoma (DLBCL) in elderly adults in the US. MATERIALS AND METHODS: This retrospective database analysis utilized US Centers for Medicare and Medicaid Services Medicare fee-for-service administrative claims data from 2015 to 2020 to describe DLBCL patient characteristics, treatment patterns, HCRU, and costs among patients aged ≥66 years. Patients were indexed at DLBCL diagnosis and required to have continuous enrollment from 12 months pre-index until 3 months post-index. HCRU and costs (USD 2022) are reported as per-patient per-month (PPPM) estimates. RESULTS: A total of 11,893 patients received ≥1-line (L) therapy; 1,633 and 391 received ≥2 L and ≥3 L therapies, respectively. Median (Q1, Q3) age at 1 L, 2 L, and 3 L initiation, respectively, was 76 (71, 81), 77 (72, 82), and 77 (72, 82) years. The most common therapy was R-CHOP (70.9%) for 1 L and bendamustine ± rituximab for 2 L (18.7%) and 3 L (17.4%). CAR T was used by 14.8% of patients in 3 L. Overall, 39.6% (1 L), 42.1% (2 L), and 47.8% (3 L) of patients had all-cause hospitalizations. All-cause mean (median [Q1-Q3]) costs PPPM during each line were $22,060 ($20,121 [$16,676-$24,597]) in 1 L, $30,027 ($20,868 [$13,416-$31,016]) in 2 L, and $47,064 ($25,689 [$15,555-$44,149]) in 3 L, with increasing costs driven primarily by inpatient expenses. Total all-cause 3 L mean (median [Q1-Q3]) costs PPPM for patients with and without CAR T were $153,847 ($100,768 [$26,534-$253,630]) and $28,466 ($23,696 [$15,466-$39,107]), respectively. CONCLUSIONS: No clear standard of care exists in 3 L therapy for older adults with relapsed/refractory DLBCL. The economic burden of DLBCL intensifies with each progressing line of therapy, thus underscoring the need for additional therapeutic options.

Extracorporeal shock wave therapy (ESWT) favors healing of diabetic foot ulcers: A systematic review and meta-analysis.

AIMS: To investigate the efficacy and safety of extracorporeal shockwave therapy(ESWT) for diabetic foot ulcers(DFUs). METHODS: Search in PubMed, EMBASE, the Cochrane Controlled Register of Trials (CENTAL), and Web of Science for randomized controlled trials (RCTs) published before August 8, 2023. All identified studies were screened following the selection criteria. Finally, we employed the STATA 14.0 software for conducting a meta-analysis to evaluate the efficacy and safety of ESWT. RESULTS: A total of ten RCTs with moderate methodological quality were included for data analysis. The findings showed that ESWT was significantly associated with significantly complete healed ulcers (risk ratio [RR]: 1.57, 95 % confidence interval [CI]:1.26 to 1.95) and lower rate of unchanged ulcers (RR: 0.25, 95 %CI: 0.14 to 0.42) compared to controls. Subgroup analysis further revealed that ESWT was better than both hyperbaric oxygen therapy (HOT) and the standard of care (SOC). Moreover, ESWT also significantly improved the average transcutaneous partial oxygen pressure (TcPO2) (mean difference[MD]: 1.71, 95 %CI: 1.22 to 2.19, p < 0.001). However, the rate of ≥ 50 % improved ulcers and treatment-emergent adverse events (TEAEs) were not significantly different between the ESWT and controls. CONCLUSIONS: ESWT has shown promising efficacy and a favorable safety profile in the treatment of DFUs.

Glioblastoma Standard of Care: Effects on Tumor Evolution and Reverse Translation in Preclinical Models.

Glioblastoma (GBM) presents a significant public health challenge as the deadliest and most common malignant brain tumor in adults. Despite standard-of-care treatment, which includes surgery, radiation, and chemotherapy, mortality rates are high, underscoring the critical need for advancing GBM therapy. Over the past two decades, numerous clinical trials have been performed, yet only a small fraction demonstrated a benefit, raising concerns about the predictability of current preclinical models. Traditionally, preclinical studies utilize treatment-naïve tumors, failing to model the clinical scenario where patients undergo standard-of-care treatment prior to recurrence. Recurrent GBM generally exhibits distinct molecular alterations influenced by treatment selection pressures. In this review, we discuss the impact of treatment-surgery, radiation, and chemotherapy-on GBM. We also provide a summary of treatments used in preclinical models, advocating for their integration to enhance the translation of novel strategies to improve therapeutic outcomes in GBM.

Conscience, Disobedience, and Standard of Care.

In the article "Principled Conscientious Provision: Referral Symmetry and Its Implications for Protecting Secular Conscience," Abram L. Brummett, Tanner Hafen, and Mark C. Navin reject what they call the "referral asymmetry" in U.S. conscientious objection law in medicine, which recognizes rights of conscientiously objecting physicians to withhold referrals for medical interventions but does not (yet) recognize rights of physicians to make referrals for medical interventions to which they are morally committed but to which their health care institutions are morally opposed. This commentary concentrates on a second asymmetry, namely, the relationship of a health care provider's referral or nonreferral to the medical standard of care. The commentary argues that this second asymmetry seems to require action more appropriately recognized as civil disobedience than conscientious provision of referral.

A systematic review and meta-analysis on utilizing anti-CD19 chimeric antigen receptor T-cell therapy as a second-line treatment for relapsed and refractory diffuse large B-cell lymphoma.

Introduction: Inconsistent results observed in recent phase III trials assessing chimeric antigenic receptor T (CAR-T) cell therapy as a second-line treatment compared to standard of care (SOC) in patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) prompted a meta-analysis to assess the effectiveness of CAR-T cell therapy in this setting. Methods: Random-effects meta-analysis was conducted to pool effect estimates for comparison between CAR-T cell therapy and SOC. Mixed treatment comparisons were made using a frequentist network meta-analysis approach. Results: Meta-analysis of three trials with 865 patients showed significant improvement in event-free survival (EFS: HR: 0.51; 95% CI: 0.27-0.97; I2: 92%), progression-free survival (PFS: HR: 0.47; 95% CI: 0.37-0.60; I2: 0%) with CAR-T cell therapy compared to SOC. Although there was a signal of potential overall survival (OS) improvement with CAR-T cell therapy, the difference was not statistically significant between the two groups (HR 0.76; 95% CI: 0.56 to 1.03; I2: 29%). Mixed treatment comparisons showed significant EFS benefit with liso-cel (HR: 0.37; 95% CI: 0.22-0.61) and axi-cel (HR: 0.42; 95% CI: 0.29-0.61) compared to tisa-cel. Discussion: CAR-T cell therapy, as a second-line treatment, appears to be effective in achieving higher response rates and delaying the disease progression compared to SOC in R/R DLBCL.

"One blade, two cuts?" A multidisciplinary survey investigating practice variability of scalpel blade change for simultaneous excision of multiple skin lesions in the same patient.

BACKGROUND: Skin cancer incidence increases globally, requiring effective preventive measures and evidence-based treatment strategies. Current guidelines advocate for surgical excision as a first-line treatment for most early skin cancers. The study investigated practices regarding changing scalpel blades when excising multiple skin lesions in the same patient during the same visit (CSB) and explored how beliefs about iatrogenic seeding influence individual norms of practice. METHODS: A multidisciplinary survey was conducted among 173 medical specialists involved in skin cancer care. Participants provided demographic information, years of experience, and practices regarding CSB in four clinical scenarios (first excised tumor: basal cell carcinoma, squamous cell carcinoma, melanoma suspect, and evident melanoma). Practice variations based on specialty, experience, and beliefs about seeding risk were statistically assessed. RESULTS: Surgeons exhibited a significantly higher tendency to change blades compared to non-surgeons across all diagnoses. Iatrogenic seeding (56.52%) and clinical training (18.84%) were the main reasons provided for CSB. Beliefs about seeding risk did not differ significantly between specialties. CONCLUSIONS: Although the practice of CSB lacks strong scientific rationale, the approach to this practice significantly varies among different medical specialties. Healthcare professionals should critically evaluate and standardize evidence-based practices to ensure optimal patient care and mitigate potential harm.

Micro-costing of genetic diagnostics in acute leukemia in Sweden: from standard-of-care to whole-genome sequencing.

AIMS AND BACKGROUND: Whole-genome sequencing (WGS) is increasingly applied in clinical practice and expected to replace standard-of-care (SoC) genetic diagnostics in hematological malignancies. This study aims to assess and compare the fully burdened cost ('micro-costing') per patient for Swedish laboratories using WGS and SoC, respectively, in pediatric and adult patients with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). METHODS: The resource use and cost details associated with SoC, e.g. chromosome banding analysis, fluorescent in situ hybridization, and targeted sequencing analysis, were collected via activity-based costing methods from four diagnostic laboratories. For WGS, corresponding data was collected from two of the centers. A simulation-based scenario model was developed for analyzing the WGS cost based on different annual sample throughput to evaluate economy of scale. RESULTS: The average SoC total cost per patient was €2,465 for pediatric AML and €2,201 for pediatric ALL, while in adults, the corresponding cost was €2,458 for AML and €1,207 for ALL. The average WGS cost (90x tumor/30x normal; sequenced on the Illumina NovaSeq 6000 platform) was estimated to €3,472 based on an annual throughput of 2,500 analyses, however, with an annual volume of 7,500 analyses the average cost would decrease by 23% to €2,671. CONCLUSION: In summary, WGS is currently more costly than SoC, however the cost can be reduced by utilizing laboratories with higher throughput and by the expected decline in cost of reagents. Our data provides guidance to decision-makers for the resource allocation needed when implementing WGS in diagnostics of hematological malignancies.

Individualized clinical decisions within standard-of-care pragmatic clinical trials: Implications for consent.

Pragmatic clinical trials of standard-of-care interventions compare the relative merits of medical treatments already in use. Traditional research informed consent processes pose significant obstacles to these trials, raising the question of whether they may be conducted with alteration or waiver of informed consent. However, to even be eligible, such a trial in the United States must have no more than minimal research risk. We argue that standard-of-care pragmatic clinical trials can be designed to ensure that they are minimal research risk if the random assignment of an intervention in a pragmatic clinical trial can accommodate individualized, clinically motivated decision-making for each participant. Such a design will ensure that the patient-participants are not exposed to any risks beyond the clinical risks of the interventions, and thus, the trial will have minimal research risk. We explain the logic of this view by comparing three scenarios of standard-of-care pragmatic clinical trials: one with informed consent, one without informed consent, and one recently proposed design called Decision Architecture Randomization Trial. We then conclude by briefly showing that our proposal suggests a natural way to determine when to use an alteration versus a waiver of informed consent.

Optimising patient care: comprehensive evaluation of inpatient hypokalaemia.

Hypokalaemia is a common electrolyte disorder affecting hospitalised patients. It is associated with adverse outcomes including increased mortality. Inpatients with hypokalaemia need a different approach to workup and management as the aetiologies and progression of the hypokalaemia are distinct to outpatients. Potassium homeostasis is predominantly maintained by renal potassium handling. The clinical manifestations of hypokalaemia depend on the severity of hypokalaemia, however, most of the findings are non-specific. The approach to management is guided by the severity of the hypokalaemia and the underlying aetiology. Oral potassium replacement can be used in many cases of mild hypokalaemia. Intravenous replacement of potassium is necessary for many inpatients. Close monitoring is essential to ensure adequacy and to prevent adverse outcomes. An interdisciplinary approach with critical care input is needed in severe cases, and in patients where routine intravenous replacement may not be feasible (e.g., patients with heart failure). In addition to replacement, the cornerstone of management is a comprehensive review of the patient to identify the underlying cause of the hypokalaemia and the factors sustaining it. In patients in whom the cause is not apparent, or the potassium does not improve as anticipated, a referral to nephrology or endocrinology should be considered. This paper reviews the assessment of hypokalaemia in a hospital setting. It is aimed at early career doctors on the wards to help carry out a thorough evaluation. It also provides a useful framework for management.

Impact of fecal microbiota transplantation in severe alcoholic hepatitis: A systematic review and meta-analysis.

Background and Aim: Severe alcoholic hepatitis (SAH) is a serious condition with few treatments. By modifying the gut-liver axis, fecal microbiota transplantation (FMT) was proposed as a treatment for SAH. The purpose of this meta-analysis was to evaluate the efficacy of FMT versus the standard of care (SOC) in improving SAH patient survival rates. Methods: A thorough search of electronic databases was conducted till September 2023. The survival rates of SAH patients undergoing FMT versus SOC were compared. Using Review Manager 5.4, odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Results: The meta-analysis consisted of six studies with a total of 371 patients with SAH. Patients who received FMT had significantly higher survival rates at 1 and 3 months compared to those who received SOC, with pooled OR of 2.91 (95% CI: 1.56-5.42, P = 0.0008) and 3.07 (95% CI: 1.81-5.20, P < 0.0001), respectively. However, the survival advantage disappeared after 6 months (OR: 2.96, 95% CI: 0.99-8.85, P = 0.05) and 1 year of follow-up (OR: 1.81, 95% CI: 0.44-7.46, P = 0.41). Conclusion: This meta-analysis highlights the potential of FMT to significantly improve short-term survival rates in SAH patients. However, the survival benefit did not last 6-12 months. These findings call for additional research into the effectiveness of FMT over the long term, along with strategies for extending the survival benefit.

Antiemetic prophylaxis regimens in haematologic malignancies patients undergoing a hematopoietic stem cell transplantation. Which is the best standard of care? A systematic review.

INTRODUCTION: This systematic review, adhering to PRISMA guidelines, aimed to evaluate the efficacy and safety of antiemetic prophylaxis in haematological patients undergoing high-dose chemotherapy as part of their hematopoietic stem cell transplantation (HSCT) conditioning regimens. METHODS: We performed a comprehensive search in PubMed, EMBASE, ClinicalTrials.gov and the Cochrane database to identify randomised controlled trials (RCTs) and systematic reviews of antiemetic prophylaxis. Studies in English, French, Italian or Spanish were included. This review is registered with PROSPERO, ID CRD42023406380. RESULTS: Eight RCTs were analysed. The antiemetic regimens evaluated ranged from monotherapy with 5-Hydroxytryptamine Receptor 3 antagonists (5-HT3RAs) to complex combinations including olanzapine, neurokinin-1 receptor antagonists, 5-HT3RAs and corticosteroids. Complete response rates for triplet or quadruple regimens varied between 23.5% and 81.9%. Although no significant adverse effects were observed, minor symptoms such as diarrhoea, constipation, sedation and headaches were reported. CONCLUSION: Existing evidence on HSCT antiemetic therapy highlights its benefits but fails to provide clear clinical directions. The choice between triplet and quadruplet therapies for different patient scenarios is still uncertain. Until more detailed research is available, healthcare providers must rely on the latest guidelines and their judgement to customise antiemetic care for each patient's specific needs and risks.

Unmet needs in relapsed/refractory mantle cell lymphoma (r/r MCL) post-covalent Bruton tyrosine kinase inhibitor (BTKi): a systematic literature review and meta-analysis.

To quantify the clinical unmet need of r/r MCL patients who progress on a covalent Bruton tyrosine kinase inhibitor (BTKi), we conducted a systematic review to identify studies that reported overall survival (OS), progression-free survival (PFS), or response outcomes of patients who received a chemo(immunotherapy) ± targeted agent standard therapy (STx) or brexucabtagene autoleucel (brexu-cel) in the post-BTKi setting. Twenty-six studies (23 observational; three trials) reporting outcomes from 2005 to 2022 were included. Using two-stage frequentist meta-analyses, the estimated median PFS/OS for patients treated with an STx was 7.6 months (95% CI: 3.9-14.6) and 9.1 months (95% CI: 7.3-11.3), respectively. The estimated objective response rate (ORR) was 45% (95% CI: 34-57%). For patients treated with brexu-cel, the estimated median PFS/OS was 14.9 months (95% CI: 10.5-21.0) and 32.1 months (95% CI: 25.2-41.2), with a pooled ORR of 89% (95% CI: 86-91%). Our findings highlight a significant unmet need for patients whose disease progresses on a covalent BTKi.

FDG-PET/MRI in colorectal cancer care: an updated systematic review.

PURPOSE: Since its introduction in 2011, FDG-PET/MRI has been advocated as a useful adjunct in colorectal cancer care. However, gaps and limitations in current research remain. This systematic review aims to review the current literature to quantify the utility of FDG-PET/MRI in colorectal cancer care. METHODS: An up-to-date review was performed on the available literature between 2000 and 2023 on PubMed, EMBASE, Medline, databases. All studies reporting on the use of FDG-PET/MRI in colorectal cancer care were analyzed. The main outcome measures were accuracy in initial staging, restaging, and detection of metastatic disease in both rectal as well as colon cancers. The secondary outcome was comparing the performance of FDG-PET/MRI versus Standard of Care Imaging (SCI). Finally, the clinical significance of FDG-PET/MRI was measured in the change in management resulting from imaging findings. RESULTS: A total of 22 observational studies were included, accounting for 988 patients. When individually compared to current Standard of Care Imaging (SCI)-MRI pelvis for rectal cancer and thoraco-abdominal contrast CT, PET/MRI proved superior in terms of distant metastatic disease detection. This led to as much as 21.0% change in management. However, the technological limitations of PET/MRI were once again highlighted, suggesting SCI should retain its place as first-line imaging. CONCLUSION: FDG-PET/MRI appears to be a promising adjunct in staging and restaging of colorectal cancer in carefully selected patients.