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This paper delves into the intricate relationship between the evolving field of genomic medicine and healthcare providers' legal and ethical responsibilities, with a particular focus on the duty to warn in the context of genetic risks. Through a critical examination of landmark cases such as Pate v. Threlkel and Safer v. Estate of Pack, this study underscores the expanding scope of healthcare providers' duties to include not just the patient but potentially at-risk family members as well. It highlights the legal, ethical, and practical challenges that arise when balancing patient confidentiality with the need to prevent harm through the disclosure of genetic information. The descriptive portion of the paper outlines the current legal precedents and the ambiguity surrounding healthcare providers' responsibilities. The prescriptive portion proposes the establishment of comprehensive, clear guidelines to support healthcare providers, particularly genomic counselors, in navigating these complexities. This includes recommendations for policy changes and the development of protocols that respect patient autonomy while addressing the preventive potential of genomic medicine. Through an analysis of legal frameworks and ethical considerations, this paper argues for a nuanced approach that equitably balances individual rights with the collective good, ultimately advocating for a future where genomic medicine is integrated into patient care in an ethically responsible and legally sound manner.

INTRODUCTION: We aimed to investigate the impact of reduced contact prenatal care necessitated by the COVID-19 pandemic on meeting standards of care and perinatal outcomes. METHODS: This was a retrospective case-control study of patients in low-risk obstetrics clinic at a tertiary care county facility serving solely publicly insured patients comparing reduced in-person prenatal care (R) over 12 weeks with a control group (C) receiving traditional prenatal care who delivered prior. RESULTS: Total 90 patients in reduced contact (R) cohort were matched with controls (C). There were similar rates of standard prenatal care metrics between groups. Gestational age (GA) of anatomy ultrasound was later in R (p = 0.017). Triage visits and missed appointments were similar, though total number of visits (in-person and telehealth) was higher in R (p = 0.043). R group had higher GA at delivery (p = 0.001). Composite neonatal morbidity and length of stay were lower in R (p = 0.017, p = 0.048). Maternal and neonatal outcomes did not otherwise differ between groups. Using Kotelchuck Adequacy of Prenatal Care Utilization index, R had higher rates of adequate prenatal care (45.6% R vs. 24.4% C, p = 0.005). DISCUSSION: Our study demonstrates the non-inferiority of a hybrid, reduced schedule prenatal schedule to traditional prenatal scheduling. In a reduced contact prenatal care model, more patients met criteria for adequate prenatal care, likely due to higher attendance of telehealth visits. These findings raise the question of revising the prenatal care model to mitigate disparities in disadvantaged populations.

Objective: To evaluate the economic value of mepolizumab as an add-on therapy to the standard of care (SoC) for patients with severe eosinophilic asthma in China. Methods: A Markov model with three health conditions was constructed to calculate the incremental cost per quality-adjusted life year (QALY) in mepolizumab with SoC and SoC only groups from the perspective of the Chinese healthcare system throughout an entire lifespan. The model was populated with local costs, while efficacy parameters were obtained from the global Phase III MENSA trial and mortality was derived from two surveys. One-way and probabilistic sensitivity analyses were conducted. Additional scenario analysis was used to estimate the cost-effectiveness impact of changes in the price of mepolizumab. Results: Over the lifetime treatment horizon, the incremental cost-effectiveness ratio (ICER) of mepolizumab plus SoC compared to SoC alone was $170 648.73 per QALY. Sensitivity analyses focused on these results. Scenario analysis showed that mepolizumab would require a price reduction of at least 82% to reach the current willingness-to-pay (WTP=$38 223.34/QALY) threshold. Conclusion: Mepolizumab is not a cost-effective healthcare resource in China at its current pricing. [ABSTRACT FROM AUTHOR]

Introduction Military transport can induce whole-body vibrations, and combat almost always involves high impact between lower extremities and the ground. Therefore, robust splinting technology is necessary for lower extremity fractures in these settings. Our team compared a novel one-step spray-on foam splint (FastCast) to the current military standard structured aluminum malleable (SAM) splint. Materials and Methods Ten cadaveric specimens were subjected to complete tibia/fibula osteotomy. Specimens were fitted with custom accelerometer and gyroscope sensors superior and inferior to the fracture line. Each specimen underwent fracture and splinting from a standard of care SAM splint and an experimental FastCast spray foam splint in a randomized order. Each specimen was manually transported to an ambulance and then released from a 1 meter height to simulate impact. The custom sensors recorded accelerations and rotations throughout each event. Repeated-measures Friedman tests were used to assess differences between splint method within each event and between sensors within each splint method. Results During splinting, overall summation of change and difference of change between sensors for accelerations and rotations were greater for SAM splints than FastCast across all axes (P  ≤ 0.03). During transport, the range of acceleration along the linear superior/inferior axis was greater for SAM splint than FastCast (P  = 0.02), as was the range of rotation along the transverse plane (P  < 0.01). On impact, the summation of change observed was greater for SAM splint than FastCast with respect to acceleration and rotation on the posterior/anterior and superior/inferior axes (P  ≤ 0.03), and the cumulative difference between superior and inferior sensors was greater for SAM than FastCast with respect to anterior-axis rotation (P  < 0.05). Conclusion FastCast maintains stabilization of fractured lower extremities during transport and impacts to a significantly greater extent than SAM splints. Therefore, FastCast can potentially reduce the risk of fracture complications following physical stressors associated with combat and extraction. [ABSTRACT FROM AUTHOR]

Background Methods Results Conclusions 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.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.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.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. [ABSTRACT FROM AUTHOR]

Simple Summary: Glioblastoma is the most common and aggressive brain tumor in adults. Despite surgery, radiation, and chemotherapy, survival rates remain low, which emphasizes the urgent need for improved therapies. Current preclinical models use untreated tumors, which do not reflect the clinical scenario where patients already receive initial treatments. This review examines the effects of current treatments on the properties of recurrent tumors and evaluates preclinical models that incorporate these standard treatments to better mimic real patient conditions. Improving these models could help to identify more effective treatments, potentially leading to better outcomes for glioblastoma patients. 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. [ABSTRACT FROM AUTHOR]

Background We evaluated whether the addition of docetaxel (D) to a combination comprising 5-fluorouracil/leucovorin (5-FU/LV) or capecitabine (C) plus oxaliplatin (O) (DOF/DOX) improved overall survival (OS) compared with 6 months of 5-fluorouracil (5-FU) or capecitabine in combination with oxaliplatin (FOLFOX/CAPOX) alone in advanced HER2-negative gastroesophageal junction and gastric adenocarcinomas (G/GEJ). Methods This study was an investigator-initiated, open-label, multi-institutional, randomized phase III trial in adult patients with HER2-negative advanced G/GEJs. The primary endpoint of the study was a comparison of median OS by Kaplan-Meier method. Next-generation sequencing was performed on tissue. Results Of the 324 patients randomly assigned between July 2020 and November 2022, 305 patients were evaluable for analysis (FOLFOX/CAPOX: 156; DOF/DOX: 149). With a median follow-up time of 19.2 months (95% Confidence Interval [CI] = 16.5 months to 21.9 months) for the entire cohort, the median OS was 10.1 months (95% CI = 9.2 to 10.9) for FOLFOX/CAPOX and 8.9 months (95% CI = 7.3 to 10.5) for DOF/DOX, and this difference was not statistically significant (P  = .70). An increased proportion of grade 3 or grade 4 neutropenia (21% vs 3%; P  < .001) and grade 2/3 neuropathy (17% vs 7%; P  = .005) was seen in patients receiving DOF/DOX. Genomic profiling revealed a low incidence of microsatellite instability (1%) and a high incidence of BRCA1 (8.4%) and BRCA2 (7.5%) somatic alterations. Conclusion FOLFOX or CAPOX chemotherapy for 6 months remains one of the standards of care in advanced HER2-negative gastroesophageal junction and gastric adenocarcinomas, with no additional survival benefit seen with the addition of docetaxel. Genomic profiling of patients revealed a higher than previously known incidence of somatic BRCA alterations, which requires further evaluation. CTRI (Clinical Trial Registry of India: CTRI/2020/03/023944). [ABSTRACT FROM AUTHOR]

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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. [ABSTRACT FROM AUTHOR]

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 benefitwith 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective Materials and Methods Results Conclusions Clinical Significance This study evaluated the completeness and accuracy of information in LCU instruction manuals from 40 manufacturers.Instruction manuals from 40 LCUs (20 from leading manufacturers and 20 budget units) were reviewed. Twenty‐eight parameters across five categories were assessed using a binary scale (0=incorrect/missing, 1=correct). The categories and their respective evaluation scores were: LCU characteristics (43%), instructions for use (7%), safety precautions (14%), maintenance recommendations (29%), and regulatory certification (7%). These scores were combined to produce a final score.Scores from leading manufacturers ranged between 46‐86%, while the budget category ranged from 18‐68%. All manuals provided information about the wavelength/spectrum of the LCU. Only Valo X and Valo Cordless reported power values and used the term “irradiance” instead of “intensity.” Details such as LED type and active tip emission area were often missing. Instructions on how to use the LCU to photo‐cure resins were frequently limited. Although most manuals addressed safety precautions, several lacked details on heat issues and general health precautions. All manuals included maintenance instructions, though information on replacement parts was often missing. Among the LCUs, 85% stated they were CE certified, 32% held both FDA and CE certification, and 63% claimed compliance with ISO and/or IEC standards.There were notable differences in the completeness and accuracy of the instruction manuals. Manuals from major manufacturers generally provided more comprehensive information than their budget counterparts.Instruction manuals should contain accurate information to help clinicians deliver the highest standard of care. The lack of important information about the LCUs in the manuals is concerning. [ABSTRACT FROM AUTHOR]

AbstractTo 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. [ABSTRACT FROM AUTHOR]

Objective: To describe treatment patterns and direct healthcare costs over 3 years following initiation of standard of care acute and preventive migraine medications in patients with migraine in the United States. Background: There are limited data on long‐term (>1 year) migraine treatments patterns and associated outcomes. Methods: This was a retrospective, observational cohort study using US claims data from the IBM® MarketScan® Research Database (January 2010–December 2017). Adults were included if they had a prescription claim for acute migraine treatments (AMT) or preventive migraine treatments (PMT) in the index period (January 2011–December 2014). The AMT cohort was categorized as persistent, cycled, or added‐on subgroups; the PMT cohort was categorized PMT‐persistent, switched without gaps, or cycled with gaps. Migraine‐specific annual direct costs (2017 US$) across AMT and PMT cohort subgroups were summarized at baseline through 3 years from index (follow‐up). Results: During the index period, 20,778 and 42,259 patients initiated an AMT and a PMT, respectively. At the 3‐year follow‐up, migraine‐specific direct costs were lower in the persistent subgroup relative to the non‐persistent subgroups in both AMT (mean [SD]: $789 [$1741] vs. $2847 [$8149] in the added‐on subgroup and $862 [$5426] for the cycled subgroup) and PMT cohorts (mean [SD]: $1817 [$5892] in the persistent subgroup vs. $4257 [$11,392] in the switched without gaps subgroup and $3269 [$18,540] in the cycled with gaps subgroup). Acute medication overuse was lower in the persistent subgroup (1025/6504 [27.2%]) vs. non‐persistent subgroups (11,236/58,863 [32.2%] in cycled with gaps subgroup and 1431/6504 [39.4%] in the switched without gaps subgroup). Most patients used multiple acute (19,717/20,778 [94.9%]) or preventive (38,494/42,259 [91.1%]) pharmacological therapies over 3 years following treatment initiation. Gaps in preventive therapy were common; an average gap ranged from 85 to 211 days (~3–7 months). Conclusion: Migraine‐specific annual healthcare costs and acute migraine medication overuse remained lowest among patients with persistent AMT and PMT versus non‐persistent treatment. Study findings are limited to the US population. Future studies should compare costs and associated outcomes between newer preventive migraine medications in patients with migraine. Plain Language Summary: Little is known about how patients use medications to acutely treat or prevent migraine over longer periods of time and their associated costs. This study used information from medical and pharmacy claims to understand costs over time for three groups of patients with migraine: (1) those who remained on the same medication for 3 years, (2) those who changed medications, or (3) those who stopped treatment and then changed medications. Results showed that fewer than one in 10 patients stayed on the same medication to treat or prevent migraine over 3 years, but migraine costs and acute migraine medication overuse were lowest in these patients. [ABSTRACT FROM AUTHOR]

The article discusses the Epicensus program, a pan-European initiative aimed at improving the standard of care for patients with psoriasis. The program identified gaps in care and developed Calls to Action (CTAs) across various themes, including improving healthcare systems, real-world data generation, patient access, and patient-centered care. The article highlights several initiatives across Europe that align with the CTAs, such as the implementation of electronic patient databases, the inclusion of disease severity tools, and the expansion of regional care networks. Education and awareness activities, including webinars and conferences, are also being conducted to improve patient outcomes and tackle the stigma associated with psoriasis. The authors emphasize the need for continued collaboration and efforts to elevate the standard of care for patients with psoriasis. [Extracted from the article]

Brain injuries (BI) are highly disruptive, often having long lasting effects. Inadequate standard of care (SOC) energy support in the hospital leads to dietary energy deficiencies in BI patients. However, it is unclear how underfeeding (UF) affects protein synthesis post-BI. Therefore, in a rat model, we addressed the issue of UF on the protein fractional synthesis rate (fSR) post-BI. Compared to ad libitum (AL)-fed animals, we found that UF decreased protein synthesis in hind-limb skeletal muscle and cortical mitochondrial and structural proteins (p ≤ 0.05). BI significantly increased protein synthesis in the left and right cortices (p ≤ 0.05), but suppressed protein synthesis in the cerebellum (p ≤ 0.05) as compared to non-injured sham animals. Compared to underfeeding alone, UF in conjunction with BI (UF+BI) caused increased protein synthesis rates in mitochondrial, cytosolic, and whole-tissue proteins of the cortical brain regions. The increased rates of protein synthesis found in the UF+BI group were mitigated by AL feeding, demonstrating that caloric adequacy alleviates the effects of BI on protein dynamics in cortical and cerebellar brain regions. This research provides evidence that underfeeding has a negative impact on brain healing post-BI and that protein reserves in uninjured tissues are mobilized to support cortical tissue repair following BI.

BACKGROUND: These clinical standards aim to provide guidance for diagnosis, treatment, and management of drug-susceptible TB in children and adolescents.METHODS: Fifty-two global experts in paediatric TB participated in a Delphi consensus process. After eight rounds of revisions, 51/52 (98%) participants endorsed the final document.RESULTS: Eight standards were identified: Standard 1, Age and developmental stage are critical considerations in the assessment and management of TB; Standard 2, Children and adolescents with symptoms and signs of TB disease should undergo prompt evaluation, and diagnosis and treatment initiation should not depend on microbiological confirmation; Standard 3, Treatment initiation is particularly urgent in children and adolescents with presumptive TB meningitis and disseminated (miliary) TB; Standard 4, Children and adolescents should be treated with an appropriate weight-based regimen; Standard 5, Treating TB infection (TBI) is important to prevent disease; Standard 6, Children and adolescents should receive home-based/community-based treatment support whenever possible; Standard 7, Children, adolescents, and their families should be provided age-appropriate support to optimise engagement in care and clinical outcomes; and Standard 8, Case reporting and contact tracing should be conducted for each child and adolescent.CONCLUSION: These consensus-based clinical standards, which should be adapted to local contexts, will improve the care of children and adolescents affected by TB.

Abstract Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is a predominant chronic liver condition globally and is strongly associated with obesity, diabetes mellitus, and dyslipidemia. Essential phospholipids (EPL) are recommended as supportive treatment for managing liver conditions, including MASLD or metabolic dysfunction-associated steatohepatitis, cirrhosis, and viral hepatitis. While efficacy of EPL as an adjunctive therapy in MASLD treatment has been established earlier, certain aspects of its usage such as the impact of standard-of-care parameters, effect of EPL on quality of life (QoL) and change in symptoms evaluation in patients with MASLD remain unexplored. The proposed trial aims to assess the efficacy and safety of EPL and the subsequent QoL of patients with MASLD associated with type 2 diabetes mellitus (T2DM) and/or hyperlipidemia and/or obesity. Methods This is a multicenter, multinational, double-blind, randomized, two-arm, placebo-controlled, parallel-group, phase IV clinical trial. The trial is being conducted in approximately 190 patients who are randomized on a 1:1 basis either to the EPL arm (Essentiale® 1800 mg/day orally + standard of care) or placebo arm (placebo + standard of care). The primary outcome is to assess the efficacy of EPL on hepatic steatosis, as measured by transient elastography, from baseline to 6 months. The secondary outcomes include change in QoL parameters, as measured by the Chronic Liver Disease Questionnaire–metabolic dysfunction-associated steatotic liver disease/ metabolic dysfunction-associated steatohepatitis and change in symptom evaluation (using the Global Overall Symptom scale) from baseline to 6 months for symptoms, including asthenia, feeling depressed, abdominal pain/discomfort, or fatigue. Discussion The current protocol design will allow to comprehensively explore the efficacy of EPL added to the standard of care on hepatic steatosis and QoL and its safety in patients with MASLD associated with T2DM and/or hyperlipidemia and/or obesity by assessing various outcome measures. Trial registration European Union Clinical Trials Register, EudraCT, 2021–006069-39. Registered on March 13, 2022.

Abstract Background Self-monitoring of glucose is an essential component of type 1 diabetes (T1D) management. In recent years, continuous glucose monitoring (CGM) has provided an alternative to daily fingerstick testing for the optimisation of insulin dosing and general glucose management in people with T1D. While studies have been conducted to evaluate the impact of CGM on clinical outcomes in the US, Europe and Australia, there are limited data available for low- and middle-income countries (LMICs) and further empirical evidence is needed to inform policy decision around their use in these countries. Methods This trial was designed as a pragmatic, parallel-group, open-label, multicentre, three-arm, randomised (1:1:1) controlled trial of continuous or periodic CGM device use versus standard of care in people with T1D in South Africa and Kenya. The primary objective of this trial will be to assess the impact of continuous or periodic CGM device use on glycaemic control as measured by change from baseline glycosylated haemoglobin (HbA1c). Additional assessments will include clinical outcomes (glucose variation, time in/below/above range), safety (adverse events, hospitalisations), quality of life (EQ-5D, T1D distress score, Glucose Monitoring Satisfaction Survey for T1D), and health economic measures (incremental cost-effectiveness ratios, quality adjusted life years). Discussion This trial aims to address the substantial evidence gap on the impact of CGM device use on clinical outcomes in LMICs, specifically South Africa and Kenya. The trial results will provide evidence to inform policy and treatment decisions in these countries. Trial registration NCT05944731 (Kenya), July 6, 2023; NCT05944718 (South Africa), July 13, 2023.

Abstract Introduction Psoriatic arthritis (PsA) is a complex, progressive, and often debilitating disease. Despite recent advances in treatment, numerous unmet needs in patient care persist. Rheumacensus is a multistakeholder, pan-European initiative designed to identify ways to elevate the standard of care (SoC) and treatment ambition for patients with PsA, using the perspectives of three key stakeholder groups: patients, healthcare professionals (HCPs) and payors. Methods Rheumacensus followed three phases: an insights-gathering workshop to identify current unmet needs in PsA and an area of focus for the project, a modified Delphi process to gain consensus on improvements within the agreed area of focus, and a Consensus Council (CC) meeting which used consensus statements as inspiration to generate ‘Calls to Action’ (CTA)—practical measures which, if implemented, could elevate the SoC for patients with PsA. Results The Rheumacensus CC consisted of four patient representatives, four HCPs and four payors. All 12 members completed all three Delphi e-consultations. The shared area of focus that informed the Delphi process was “patient empowerment through education on the disease and treatment options available, to enable patient involvement in management”. Four key themes emerged from the Delphi process: patient empowerment, patient knowledge and sources of education, patient–HCP consultations, and optimal initial treatment. Statements within these themes informed 12 overarching CTA, which focus on the need for a multistakeholder approach to implementing a paradigm shift towards patient-centred care and improved outcomes for patients with PsA. Conclusion Rheumacensus has identified shortcomings in the current SoC for patients with PsA and provides a foundation for change through practical CTA. It is hoped that all stakeholders will now take practical steps towards implementing these CTA across Europe to elevate the SoC for patients with PsA.

Abstract Introduction Several barriers to optimal care in axial spondyloarthritis (axSpA) exist, which is detrimental to patient outcomes. The Rheumacensus programme aimed to identify how the standard of care (SoC) and treatment ambition for patients with axSpA could be elevated, from the unique perspective of three key stakeholders from across Europe: patients, healthcare professionals (HCPs) and payors. Methods Rheumacensus followed three phases: an insights-gathering workshop to identify current unmet needs in axSpA and an area of focus, a modified Delphi process to gain consensus on improvements within the agreed area of focus, and a Consensus Council (CC) meeting to generate ‘Calls to Action’ (CTA) to highlight the changes needed to elevate the SoC for patients with axSpA. Results The Rheumacensus CC consisted of four patient representatives, four HCPs and four payors. All 12 members completed all three Delphi e-consultations. The shared area of focus that informed the Delphi process was patient empowerment through education on the disease and treatment options available, to enable patient involvement in management and ultimately increase treatment adherence. Four key themes emerged from the Delphi process: patient empowerment, patient knowledge, patient–HCP consultations and optimal initial treatment. These themes informed 11 overarching CTA, which demonstrate the need for a multistakeholder approach to implement a paradigm shift towards patient-centred care to elevate health outcomes in patients with axSpA. Conclusion Rheumacensus identified CTA to help bridge the disparities observed in axSpA care. It is now imperative for all stakeholders to take practical steps towards addressing these CTA to elevate the SoC and treatment ambition in patients with axSpA.

Abstract Background Since the last guidance was published by the Canadian Thoracic Society, there have been several advances in the clinical management of severe asthma. To gain a better understanding of the current standards of care and treatment patterns of patients, the CASCADE practice reflective program was established to conduct a real-world analysis of severe asthma management among specialists in Canada with a goal of identifying areas of opportunity to enhance patient management and outcomes. Methods The CASCADE program was a two-part practice reflective and assessment program delivered through an on-line portal for selected specialists (Respirologists and Allergists) in Canada. The program consisted of a one-time overview survey of physician practice to establish overall practice parameters, followed by a review of at least 5 severe asthma patients to establish the current landscape of severe asthma management. Results The program collected practice overview surveys from 78 specialists (52 Respirologists, 24 Allergists, and 2 General practice physicians with an interest in respiratory disease) in 8 provinces. Practices included a variety of types in both large metropolitan centres and smaller regional settings. There were 503 patients reviewed and included in the program. Most (65%) patients were currently using a biologic treatment, 30% were biologic naive, and 5% had used a biologic treatment in the past. Most patients (53%) were reported to have mixed allergic and eosinophilic phenotypes, despite a perception that allergic, eosinophilic and mixed phenotypes were evenly balanced in the physician practice. Overall, patients currently treated with biologic agents had parameters suggesting higher control and were more satisfied with treatment. However, there was less than optimal treatment satisfaction for more than half of all patients, particularly for those patients not treated with a biologic agent. Conclusions Phenotyping is hampered by poor availability for several assessments, and the full range of treatments are not currently fully utilized, partly due to physician familiarity with the agents and partly due to prescribing restrictions. Even when treated with biologic agents, patient satisfaction can still be improved.

Access to treatment and healthcare services for people with haemophilia in the United Kingdom (UK) and Republic of Ireland ranks highly by international standards for contemporary haemophilia management. Collaborate & Address Treatment Challenges in Haemophilia (CATCH) is an annual Sobi™ medical education meeting which brings together multidisciplinary haemophilia treaters throughout the UK and Ireland to discuss all aspects of haemophilia management, including associated challenges and unmet need. This report summarises key issues explored and discussed during CATCH 2023, including ‘raising the bar’ in haemophilia care; haemophilia care for women and girls; changing haemophilia treatment paradigms to consider disease impact as well disease severity; bone health and haemophilia; and shared decision-making.

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a predominant chronic liver condition globally and is strongly associated with obesity, diabetes mellitus, and dyslipidemia. Essential phospholipids (EPL) are recommended as supportive treatment for managing liver conditions, including MASLD or metabolic dysfunction-associated steatohepatitis, cirrhosis, and viral hepatitis. While efficacy of EPL as an adjunctive therapy in MASLD treatment has been established earlier, certain aspects of its usage such as the impact of standard-of-care parameters, effect of EPL on quality of life (QoL) and change in symptoms evaluation in patients with MASLD remain unexplored. The proposed trial aims to assess the efficacy and safety of EPL and the subsequent QoL of patients with MASLD associated with type 2 diabetes mellitus (T2DM) and/or hyperlipidemia and/or obesity. Methods: This is a multicenter, multinational, double-blind, randomized, two-arm, placebo-controlled, parallel-group, phase IV clinical trial. The trial is being conducted in approximately 190 patients who are randomized on a 1:1 basis either to the EPL arm (Essentiale® 1800 mg/day orally + standard of care) or placebo arm (placebo + standard of care). The primary outcome is to assess the efficacy of EPL on hepatic steatosis, as measured by transient elastography, from baseline to 6 months. The secondary outcomes include change in QoL parameters, as measured by the Chronic Liver Disease Questionnaire–metabolic dysfunction-associated steatotic liver disease/ metabolic dysfunction-associated steatohepatitis and change in symptom evaluation (using the Global Overall Symptom scale) from baseline to 6 months for symptoms, including asthenia, feeling depressed, abdominal pain/discomfort, or fatigue. Discussion: The current protocol design will allow to comprehensively explore the efficacy of EPL added to the standard of care on hepatic steatosis and QoL and its safety in patients with MASLD associated with T2DM and/or hyperlipidemia and/or obesity by assessing various outcome measures. Trial registration: European Union Clinical Trials Register, EudraCT, 2021–006069-39. Registered on March 13, 2022. [ABSTRACT FROM AUTHOR]

AbstractSince 1980’s, the established/standard treatment of acute myeloid leukemia (AML) is cytarabine infusion with anthracycline (7 + 3 regimen). We compared the 7 + 3 regimen in older secondary/high-risk AML patientsfrom a clinical trial with a matched population from the Swedish AML Registrytreated withan increased cytarabine dose in induction and consolidation as recommended in the Swedish National Guidelines since 2005. After successfulpropensity score matching, 104 patients per group were included. The primary outcome was overall survival (OS), and standard dosed patients had a median OS of 6.4 versus 10.7 months with increased dose intensity (hazard ratio:0.69, p = 0.012), with 5-year OS of 8.7% and 18.1%, andremission rates of 36% and 60%, respectively (p < 0.001). Median OS after allogeneic hematopoietic cell transplantation (in 27.9% per group) was 10.4 and 20.7 months, respectively. We conclude that the more intensive cytarabine schedule seems to provide improved outcomes inthe investigated AML patient group. [ABSTRACT FROM AUTHOR]

Introduction: Psoriatic arthritis (PsA) is a complex, progressive, and often debilitating disease. Despite recent advances in treatment, numerous unmet needs in patient care persist. Rheumacensus is a multistakeholder, pan-European initiative designed to identify ways to elevate the standard of care (SoC) and treatment ambition for patients with PsA, using the perspectives of three key stakeholder groups: patients, healthcare professionals (HCPs) and payors. Methods: Rheumacensus followed three phases: an insights-gathering workshop to identify current unmet needs in PsA and an area of focus for the project, a modified Delphi process to gain consensus on improvements within the agreed area of focus, and a Consensus Council (CC) meeting which used consensus statements as inspiration to generate 'Calls to Action' (CTA)—practical measures which, if implemented, could elevate the SoC for patients with PsA. Results: The Rheumacensus CC consisted of four patient representatives, four HCPs and four payors. All 12 members completed all three Delphi e-consultations. The shared area of focus that informed the Delphi process was "patient empowerment through education on the disease and treatment options available, to enable patient involvement in management". Four key themes emerged from the Delphi process: patient empowerment, patient knowledge and sources of education, patient–HCP consultations, and optimal initial treatment. Statements within these themes informed 12 overarching CTA, which focus on the need for a multistakeholder approach to implementing a paradigm shift towards patient-centred care and improved outcomes for patients with PsA. Conclusion: Rheumacensus has identified shortcomings in the current SoC for patients with PsA and provides a foundation for change through practical CTA. It is hoped that all stakeholders will now take practical steps towards implementing these CTA across Europe to elevate the SoC for patients with PsA. Plain Language Summary: Inequalities in the care patients with psoriatic arthritis (PsA) receive can be mainly explained by poorly coordinated management due to a lack of disease and treatment knowledge. This report is about a programme called Rheumacensus which has the overall aim of improving the standard of care (SoC) for patients with PsA. Rheumacensus brings together the points of view of three key groups involved in the care of people with PsA: patients, payors and healthcare professionals (HCPs) from across Europe. Together, these three groups agreed to focus on patient empowerment through education on the disease and treatment options as a way to raise the SoC. Through a series of exercises—to agree on the current SoC and what needs to be improved—and group discussions, four themes were established which were used by the groups to help them suggest 'Calls to action' (CTA). The CTAs were ideas of how improvements could be made or what needs to be done to improve the care patients receive. The four themes were (1) patient empowerment, (2) patient knowledge, (3) patient–HCP consultation and (4) optimal initial treatment. In total, 12 CTAs were developed across these themes that provide direction and practical next steps which patients, payors and HCPs could take to drive change and make a real difference to patients by improving their care. [ABSTRACT FROM AUTHOR]

Introduction: Several barriers to optimal care in axial spondyloarthritis (axSpA) exist, which is detrimental to patient outcomes. The Rheumacensus programme aimed to identify how the standard of care (SoC) and treatment ambition for patients with axSpA could be elevated, from the unique perspective of three key stakeholders from across Europe: patients, healthcare professionals (HCPs) and payors. Methods: Rheumacensus followed three phases: an insights-gathering workshop to identify current unmet needs in axSpA and an area of focus, a modified Delphi process to gain consensus on improvements within the agreed area of focus, and a Consensus Council (CC) meeting to generate 'Calls to Action' (CTA) to highlight the changes needed to elevate the SoC for patients with axSpA. Results: The Rheumacensus CC consisted of four patient representatives, four HCPs and four payors. All 12 members completed all three Delphi e-consultations. The shared area of focus that informed the Delphi process was patient empowerment through education on the disease and treatment options available, to enable patient involvement in management and ultimately increase treatment adherence. Four key themes emerged from the Delphi process: patient empowerment, patient knowledge, patient–HCP consultations and optimal initial treatment. These themes informed 11 overarching CTA, which demonstrate the need for a multistakeholder approach to implement a paradigm shift towards patient-centred care to elevate health outcomes in patients with axSpA. Conclusion: Rheumacensus identified CTA to help bridge the disparities observed in axSpA care. It is now imperative for all stakeholders to take practical steps towards addressing these CTA to elevate the SoC and treatment ambition in patients with axSpA. Plain Language Summary: Axial spondyloarthritis (axSpA) is a long-term inflammatory disease involving the spine and other joints of the body as well as where tendons and ligaments attach to bone. AxSpA is associated with a significant burden to patients which can be worsened by delays in diagnosis and poor disease management. This report is about a programme called Rheumacensus which has the overall aim of improving the standard of care (SoC) for patients with axSpA. Rheumacensus brings together the points of view of three key groups involved in the care of people with axSpA: patients, payors and healthcare professionals (HCPs) from across Europe. Together, these three groups agreed to focus on patient empowerment through education on the disease and treatment options to effectively enhance treatment adherence, as a way to raise the SoC. Through a series of exercises—to agree on the current SoC and what needs to be improved—and group discussions, four themes were established which were used by the groups to help them suggest 'Calls to action' (CTA). The CTAs were ideas of how improvements could be made or what needs to be done to improve the care patients receive. The four themes were (1) patient empowerment, (2) patient knowledge, (3) patient–HCP consultation and (4) optimal initial treatment. In total, 11 CTAs were developed across these themes that provide direction and practical next steps which patients, payors and HCPs could take to drive change and make a real difference to patients by improving their care. [ABSTRACT FROM AUTHOR]

Background: Prematurity represents a critical health disparity. It is important to note that late preterm (LPT) infants comprise the majority of preterm births, yet they are the least studied within the premature population. Evidencebased practice guidelines are now a decade old, indicating the potential need for review and revision. Objectives: This systematic review proposed the assessment of sociodemographic characteristics of LPT infants, clinical practice standards, and associated hospital readmission rates, mortality, and morbidity to determine the need for revision of evidence-based practice guidelines for these infants. Data Sources: The Preferred Reporting System Items for Systematic Reviews and Meta Analysis methodology provided the framework for the completion of this review. Literature searches of PubMed/Medline (Ovid), Web of Science, Cumulative Index of Nursing, and Allied Health Literature Plus databases and citation searches included articles published after 2012 using the search terms "late preterm infants," "readmissions," and "readmission rates." Conclusions: The literature search identified 11 studies meeting search criteria. These studies included quasi experimental, retrospective, and prospective cohort studies. These studies highlighted the characteristics of LPT infants that potentially contribute to increased readmission rates, morbidity and mortality rates, health care costs, and longterm health inequities. Overall findings indicate the need for review and revision of evidence-based practice guidelines for these infants. [ABSTRACT FROM AUTHOR]

Over the last decade, Singapore has grappled with substantial healthcare challenges, chiefly a bourgeoning aging population and a mounting burden of chronic diseases. The oral health landscape has also changed, with the Ministry of Health placing a greater focus on a life‐course approach supported by policies that facilitate Singaporeans to receive dental care appropriately and affordably. A pivotal oral health policy is the National Dental Strategy, a comprehensive framework governing dental services in the public sector. This strategy encompasses aspects such as financing, workforce management, and capacity considerations. To facilitate affordability and accessibility to dental services in the public sector, the government extends subsidies to reduce out‐of‐pocket costs. Those attending private dental clinics also benefit from the Community Health Assist Scheme, introduced in 2012, which alleviates treatment costs for enrolled Singaporeans. Furthermore, additional age‐banded subsidies have been introduced for older Singaporeans born before 1960, enhancing financial support when accessing dental services in both private and public sectors. In 2019, a national adult oral health survey was commissioned to gauge the oral health status of Singaporeans aged 21 and above. The findings reported 34.8% having untreated dental caries, and 15.7% and 41.2% experiencing moderate and severe periodontitis, respectively. While over half (53.9%) of respondents visited the dentist at least annually, about 60% of eligible individuals did not utilize their government dental subsidies. In response, the Ministry of Health is committed to strengthening oral disease prevention, integrating oral health into general healthcare services, expanding dental financing schemes to enhance service utilization, improving the quality and transparency of dental care, and leveraging advancements in tele‐dentistry and other modes of dental services. It is imperative to adapt Singapore's oral health policies and service delivery models to meet the evolving needs of the population and ensure a sustainable, equitable and resilient oral healthcare system. [ABSTRACT FROM AUTHOR]

Objectives: Lymph node metastasis (LNM) is the most significant parameter affecting overall survival in patients with oral cavity squamous cell carcinomas (OCSCC). Elective neck dissection (END) is the standard of care in the early management of OCSCC with a depth of invasion (DOI) greater than 2-4 mm. However, most patients show no LNM in the final pathologic report, indicating overtreatment. Thus, more detailed indicators are needed to predict LNM in patients with OCSCC. In this study, we critically evaluate the existing literature about the risk of different histological parameters in estimating LNM. Methods: A systematic review was conducted using PRISMA guidelines. PubMed, Web of Science, Cochrane, and Scopus were searched from inception to December 2023 to collect all relevant studies. Eligibility screening of records was performed, and data extraction from the selected studies was carried out independently. Inclusion in our systematic review necessitated the following prerequisites: Involvement of patients diagnosed with OCSCC, and examination of histological parameters related to lymph node metastasis in these studies. Exclusion criteria included animal studies, non-English articles, non-availability of full text, and unpublished data. Results: We included 217 studies in our systematic review, of which 142 were eligible for the meta-analysis. DOI exceeding 4 mm exhibited higher risk for LNM [Risk ratio (RR) 2.18 (1.91-2.48), p<0.00001], as did perineural invasion (PNI) [RR 2.04 (1.77-2.34), p<0.00001], poorly differentiated tumors [RR 1.97 (1.61-2.42), p<0.00001], lymphovascular invasion (LVI) [RR 2.43 (2.12-2.78), p<0.00001], groups and single pattern of invasion [RR 2.47 (2.11-2.89), p<0.00001], high tumor budding [RR 2.65 (1.99-3.52), p<0.00001], tumor size over 4 cm [RR 1.76 (1.43-2.18), p<0.00001], tumor thickness beyond 4 mm [RR 2.72 (1.91-3.87), p<0.00001], involved or close margin [RR 1.73 (1.29-2.33), p = 0.0003], and T3 and T4 disease [RR 1.98 (1.62-2.41), p <0.00001]. Conclusion: Our results confirm the potential usefulness of many histopathological features in predicting LNM and highlight the promising results of others. Many of these parameters are not routinely incorporated into pathologic reports. Future studies must focus on applying these parameters to examine their validity in predicting the need for elective neck treatment. [ABSTRACT FROM AUTHOR]

Follicular lymphoma (FL) is often considered a chronic disease with frequent relapses, shortening both response duration and survival after every relapse. Selecting the most appropriate therapy at the right time within the treatment timeline is key to optimize outcomes. The aim of this vodcast, featuring Dr. Kai Hübel, is to outline the severity of FL by referring to a patient case as well as highlight chimeric antigen receptor (CAR)-T cells as an effective therapy in relapsed/refractory (r/r) FL. The patient was in their early 50s, diagnosed with FL in the early 2010s and presented with a third relapse. The patient complained of night sweats and fatigue but was still capable of self-care (Eastern Cooperative Oncology Group Performance Status Scale 2). The patient received eight cycles of rituximab-cyclophosphamide-doxorubicin-vincristine-prednisolone (R-CHOP), followed by irradiation and rituximab maintenance (first-line) and then received rituximab 4 × weekly, followed by rituximab maintenance (second-line). The patient relapsed during rituximab maintenance; the patient was rituximab refractory. The patient received six cycles of bendamustine/obinutuzumab followed by obinutuzumab maintenance. The patient relapsed during obinutuzumab maintenance, achieved a partial remission after irradiation and was switched to R/lenalidomide. Due to several high-risk features, CAR-T cell therapy was initiated. Dr. Hubel underlines how earlier treatment with CAR-T cell therapy would have been beneficial for this patient. Results of the ELARA trial as well as comparative studies have shown tisagenlecleucel to be more effective than standard of care in extensively pretreated r/r FL, including high-risk patients. In conclusion, CAR-T cell therapy is a promising therapy option for patients with multiply r/r FL. A vodcast feature is available for this article. [ABSTRACT FROM AUTHOR]

Background: Self-monitoring of glucose is an essential component of type 1 diabetes (T1D) management. In recent years, continuous glucose monitoring (CGM) has provided an alternative to daily fingerstick testing for the optimisation of insulin dosing and general glucose management in people with T1D. While studies have been conducted to evaluate the impact of CGM on clinical outcomes in the US, Europe and Australia, there are limited data available for low- and middle-income countries (LMICs) and further empirical evidence is needed to inform policy decision around their use in these countries. Methods: This trial was designed as a pragmatic, parallel-group, open-label, multicentre, three-arm, randomised (1:1:1) controlled trial of continuous or periodic CGM device use versus standard of care in people with T1D in South Africa and Kenya. The primary objective of this trial will be to assess the impact of continuous or periodic CGM device use on glycaemic control as measured by change from baseline glycosylated haemoglobin (HbA1c). Additional assessments will include clinical outcomes (glucose variation, time in/below/above range), safety (adverse events, hospitalisations), quality of life (EQ-5D, T1D distress score, Glucose Monitoring Satisfaction Survey for T1D), and health economic measures (incremental cost-effectiveness ratios, quality adjusted life years). Discussion: This trial aims to address the substantial evidence gap on the impact of CGM device use on clinical outcomes in LMICs, specifically South Africa and Kenya. The trial results will provide evidence to inform policy and treatment decisions in these countries. Trial registration: NCT05944731 (Kenya), July 6, 2023; NCT05944718 (South Africa), July 13, 2023. [ABSTRACT FROM AUTHOR]

Due to the location and toxicity of treatments, head and neck cancer (HNC) has a major impact on quality of life (QoL). Objective: to assess the effects of geriatric-assessment (GA)-driven interventions on QoL over 2 years in older adults with HNC. EGeSOR was a randomized study of HNC patients aged ≥65, receiving a pretreatment GA, a geriatric intervention and follow-up (intervention) or standard of care (control). The primary endpoint was QoL score using the European Organisation for Research and Treatment of Cancer's (EORTC QLQ-C30) and HNC (QLQ-HN35) QoL questionnaires over 24 months. In total, 475 patients were included (median age: 75.3; women: 31%; oral cancer: 44%). QoL scores improved over 24 months with various trajectories, without significant differences between the groups. A total of 74% of patients (interventional group) did not receive the complete intervention. Cancer characteristics, functional status, and risk of frailty were associated with change in the Global Health Status QoL score. There is a need to develop an alternative model of implementation such as patient-centered health-care pathways. Trial registration NCT02025062. [ABSTRACT FROM AUTHOR]

This research aimed to develop best-practice recommendations for identifying the "standard of care" (SoC) and integrate it when it is the comparator in diagnostic economic models (SoC comparator). A multi-methods approach comprising 2 pragmatic literature reviews and 9 expert interviews was used. Experts rated their agreement with draft recommendations based on the authors' analysis of the reviews. These were refined iteratively to produce final recommendations. Fourteen best-practice recommendations are provided. Care pathway mapping (using quantitative, qualitative, or mixed-methods approaches) should be used for identifying the SoC comparator. Guidelines analysis can be integrated with expert opinion to identify pathway variability and discrepancies from clinical practice. For integrating the SoC comparator into the model, recommendations around structure, input sourcing, data aggregation and reporting, input uncertainty, and model variability are presented. For example, modelers should consider that the reference standard is not synonymous with the SoC, and the SoC may not be the only comparator. The comparator limitations should be discussed with clinical experts, but elicitation of its diagnostic accuracy is not recommended. Probabilistic sensitivity analysis is recommended when evaluating the overall input uncertainty, and deterministic sensitivity analysis is useful when there is high model uncertainty or SoC variability. Consensus could not be reached for some topics (eg, the role of real-world data, model averaging, and alternative model structures), but the reported discussions provide points for consideration. To our knowledge, this is the first guidance to support modelers when identifying and operationalizing the SoC comparator in diagnostic cost-effectiveness models. • Modeling the cost-effectiveness requires a comparison of the new diagnostic and patient management strategy with a comparator, often a complex standard of care (SoC) pathway. The new diagnostic test can replace or, more commonly, be integrated with the diagnostic SoC pathway. This presents 2 main challenges in obtaining useful estimates of cost-effectiveness: (1) identifying the diagnostic SoC pathway to define the comparator and (2) integrating it into the model. • We identified possible methodological approaches through pragmatic literature reviews and expert interviews. Some examples are to identify the SoC comparator via mapping the care pathway through qualitative, quantitative, or mixed-methods approaches; to select data on the diagnostic accuracy of the SoC comparator from studies in which the reference standard is the one used for the new test and report detailed information of the data source; and to assess the impact of the SoC pathway variability through scenario analysis. • We provide 14 recommendations that can support modelers to minimize the risk of a misrepresentation of the incremental clinical utility of the new diagnostic test because of the uncertainty and variability of the SoC comparator. We identified practice recommendations, gaps in knowledge, and areas where further research would advance the field. [ABSTRACT FROM AUTHOR]

A substantial evidence base supports the use of sodium-glucose cotransporter-2 inhibitors (SGLT2is) in the treatment of type 2 diabetes mellitus (T2DM). This class of medicines has demonstrated important benefits that extend beyond glucose-lowering efficacy to protective mechanisms capable of slowing or preventing the onset of long-term cardiovascular, renal and metabolic (CVRM) complications, making their use highly applicable for organ protection and the maintenance of long-term health outcomes. SGLT2is have shown cost-effectiveness in T2DM management and economic savings over other glucose-lowering therapies due to reduced incidence of cardiovascular and renal events. National and international guidelines advocate SGLT2i use early in the T2DM management pathway, based upon a plethora of supporting data from large-scale cardiovascular outcome trials, renal outcomes trials and real-world studies. While most people with T2DM would benefit from CVRM protection through SGLT2i use, prescribing hesitancy remains, potentially due to confusion concerning their place in the complex therapeutic paradigm, variation in licensed indications or safety perceptions/misunderstandings associated with historical data that have since been superseded by robust clinical evidence and long-term pharmacovigilance reporting. This latest narrative review developed by the Improving Diabetes Steering Committee (IDSC) outlines the place of SGLT2is within current evidence-informed guidelines, examines their potential as the standard of care for the majority of newly diagnosed people with T2DM and sets into context the perceived risks and proven advantages of SGLT2is in terms of sustained health outcomes. The authors discuss the cost-effectiveness case for SGLT2is and provide user-friendly tools to support healthcare professionals in the correct application of these medicines in T2DM management. The previously published IDSC SGLT2i Prescribing Tool for T2DM Management has undergone updates and reformatting and is now available as a Decision Tool in an interactive pdf format as well as an abbreviated printable A4 poster/wall chart. [ABSTRACT FROM AUTHOR]

A central feature of experimental development economics is the use of randomized controlled trials (RCTs) to evaluate the effectiveness of prospective socioeconomic interventions. The use of RCTs in development economics raises a host of ethical issues which are just beginning to be explored. In this article, I address one ethical issue in particular: the routine use of the status quo as a control when designing and conducting a development RCT. Drawing on the literature on the principle of standard care in medical research ethics, as well as considerations of distributive justice in non-ideal circumstances, I argue that the practice of using the status quo as a control is ethically justifiable. However, I add an important qualification based on the natural duty of rescue to address the concern that my account is overly permissive. [ABSTRACT FROM AUTHOR]

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Background: Since the last guidance was published by the Canadian Thoracic Society, there have been several advances in the clinical management of severe asthma. To gain a better understanding of the current standards of care and treatment patterns of patients, the CASCADE practice reflective program was established to conduct a real-world analysis of severe asthma management among specialists in Canada with a goal of identifying areas of opportunity to enhance patient management and outcomes. Methods: The CASCADE program was a two-part practice reflective and assessment program delivered through an on-line portal for selected specialists (Respirologists and Allergists) in Canada. The program consisted of a one-time overview survey of physician practice to establish overall practice parameters, followed by a review of at least 5 severe asthma patients to establish the current landscape of severe asthma management. Results: The program collected practice overview surveys from 78 specialists (52 Respirologists, 24 Allergists, and 2 General practice physicians with an interest in respiratory disease) in 8 provinces. Practices included a variety of types in both large metropolitan centres and smaller regional settings. There were 503 patients reviewed and included in the program. Most (65%) patients were currently using a biologic treatment, 30% were biologic naive, and 5% had used a biologic treatment in the past. Most patients (53%) were reported to have mixed allergic and eosinophilic phenotypes, despite a perception that allergic, eosinophilic and mixed phenotypes were evenly balanced in the physician practice. Overall, patients currently treated with biologic agents had parameters suggesting higher control and were more satisfied with treatment. However, there was less than optimal treatment satisfaction for more than half of all patients, particularly for those patients not treated with a biologic agent. Conclusions: Phenotyping is hampered by poor availability for several assessments, and the full range of treatments are not currently fully utilized, partly due to physician familiarity with the agents and partly due to prescribing restrictions. Even when treated with biologic agents, patient satisfaction can still be improved. [ABSTRACT FROM AUTHOR]

Cystic fibrosis (CF) care in Denmark has been characterized by close monitoring and pre‐emptive treatment of lung disease and other CF‐related complications. Continuous evaluation through data collection and commitment to clinical research has incrementally improved outcomes. This approach has been in line with best practices set forth by European Standards of Care but has also gone beyond Society standards particularly pertaining to early treatment with high‐dose combination antimicrobial therapy. Despite a high prevalence of severe CF variants, lung function has been among the best in Europe. In this review, the Danish approach to management of CF prior to the introduction of new CF modulator treatment is explained and benchmarked. Downsides to the Danish approach are discussed and include increased burden of treatment, risk of antimicrobial resistance, side‐effects and costs. [ABSTRACT FROM AUTHOR]

To examine the cost-effectiveness of an enhanced postdischarge home-based care program for stroke survivors compared with usual care. This was a trial-based economic evaluation study. One hundred and sixteen patients with ischemic stroke were recruited from neurology units in a Chinese hospital and randomized into intervention (n = 58) or usual care groups (n = 58). The intervention commenced with predischarge planning and transitioned to home follow-up postdischarge. Trained nurse case managers supported by an interdisciplinary team provided comprehensive assessment, individualized goal setting, and skill training to support home-based rehabilitation for intervention group participants. Standard care was provided to usual care group participants. Total cost and quality-adjusted life-years gained at 3-month (T1), 6-month (T2), and 12-month (T3) follow-ups were calculated. The incremental cost-effectiveness ratios between the groups were obtained. The intervention group showed a significant increase in utility compared with the usual care group at T1 (P =.003), T2 (P =.007), and T3 (P <.001). The average total QALY gain from baseline for the intervention group was higher than for the usual care group at all time points. The likelihood of being cost-effective ranged from 61.9% to 67.2% from the provider perspective, and from 59.7% to 66.8% from the societal perspective. The results showed that the intervention program was cost-effective with significantly higher quality-adjusted life-years for stroke survivors when compared with usual care. It provides economic evidence to support the development of home-based stroke rehabilitation program, especially in the low- and middle-income countries. • Cost-effective postdischarge care is crucial to relieving the global stroke burden. • Lack of health economic studies evaluating care programs on stroke patients. • Program that delivered by a nurse and a multidisciplinary team is cost-effective. [ABSTRACT FROM AUTHOR]

Objective: Little guidance exists on the conduct of randomised clinical trials (RCT) that seek to randomise patients away from standard of care. We sought to test the technique of network meta‐analysis (NMA) to ascertain best available evidence for the purposes of informing the ethical evaluation of RCTs under these circumstances. We used the example of RCTs for patients with symptomatic, moderate to severe carotid stenosis that seek to compare surgical intervention plus medical therapy (standard of care) versus medical therapy (less than standard of care). Study Design and Setting: Network meta‐analysis of RCTs of adults with symptomatic carotid artery stenosis of 50%–99% who were treated with carotid endarterectomy (CEA), carotid artery stenting (CAS), or medical therapy (MT). The primary outcome was any stroke or death until end of follow‐up, and secondary outcome was 30‐day risk of ipsilateral stroke/death. Results: We analysed eight studies, with 7187 subjects with symptomatic moderate/severe stenosis (50%–99%). CEA was more efficacious than MT (HR = 0.82, 95% credible intervals [95% CrI] = 0.73–0.92) and CAS (HR 0.73, 95% CrI = 0.62–0.85) for the prevention of any stroke/death. At 30 days, the odds of experiencing an ipsilateral stroke/death were significantly lower in the CEA group compared to both MT (OR = 0.58, 95% CrI = 0.47–0.72) and CAS (OR = 0.68, 95% CrI = 0.55–0.83). Conclusion: Our results support the feasibility of using NMA to assess best available evidence to inform the ethical evaluation of RCTs seeking to randomise patients away from standard of care. Our results suggest that a strong argument is required to ethically justify the conduct of RCTs that seek to randomise patients away from standard of care in the setting of symptomatic moderate to severe carotid stenosis. [ABSTRACT FROM AUTHOR]

As the incidence of diabetic foot ulcers (DFU) increases, better treatments that improve healing should reduce complications of these ulcers including infections and amputations. We conducted a randomized controlled trial comparing outcomes between a novel purified reconstituted bilayer membrane (PRBM) to the standard of care (SOC) in the treatment of non‐healing DFUs. This study included 105 patients who were randomized to either of two treatment groups (n = 54 PRBM; n = 51 SOC) in the intent to treat (ITT) group and 80 who completed the study per protocol (PP) (n = 47 PRBM; n = 33 SOC). The primary endpoint was the percentage of wounds closed after 12 weeks. Secondary outcomes included percent area reduction, time to healing, quality of life, and cost to closure. The DFUs that had been treated with PRBM healed at a higher rate than those treated with SOC (ITT: 83% vs. 45%, p = 0.00004, PP: 92% vs. 67%, p = 0.005). Wounds treated with PRBM also healed significantly faster than those treated with SOC with a mean of 42 versus 62 days for SOC (p = 0.00074) and achieved a mean wound area reduction within 12 weeks of 94% versus 51% for SOC (p = 0.0023). There were no adverse events or serious adverse events that were related to either the PRBM or the SOC. In comparison to the SOC, DFUs healed faster when treated with PRBM. Thus, the use of this PRBM is an effective option for the treatment of chronic DFUs. [ABSTRACT FROM AUTHOR]

The purpose of the meta‐analysis was to evaluate and compare the effects of prolonged antibiotic prophylaxis on the occurrence of surgical site wound infection after instant breast reconstruction. The results of this meta‐analysis were analysed, and the odds ratio (OR) and mean difference with 95% confidence intervals (CIs) were calculated using dichotomous or contentious random‐ or fixed‐effect models. For the current meta‐analysis, 18 examinations spanning from 2009 to 2023 were included, encompassing 19 301 females with instant breast reconstruction. Systemic antibiotic prophylaxis had a significantly lower surgical site wound infection rate (OR, 0.85; 95% CI, 0.75–0.98, p = 0.02) compared with the standard of care after instant breast reconstruction in females. Topical antibiotic prophylaxis had a significantly lower surgical site wound infection rate (OR, 0.26; 95% CI, 0.13–0.52, p < 0.001) compared with the standard of care after instant breast reconstruction in females. The examined data revealed that systemic and topical antibiotic prophylaxis had a significantly lower surgical site wound infection rate compared with the standard of care after instant breast reconstruction in females. However, given that several examinations had a small sample size, consideration should be given to their values. [ABSTRACT FROM AUTHOR]

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BACKGROUND: In VISION, the prostate-specific membrane antigen (PSMA)-targeted radioligand therapy lutetium-177 [177Lu]Lu-PSMA-617 (vipivotide tetraxetan) improved radiographic progression-free survival and overall survival when added to protocol-permitted standard of care in patients with metastatic castration-resistant prostate cancer. Here, we report additional health-related quality of life (HRQOL), pain, and symptomatic skeletal event results. METHODS: This multicentre, open-label, randomised, phase 3 trial was conducted at 84 cancer centres in nine countries in North America and Europe. Eligible patients were aged 18 years or older; had progressive PSMA-positive metastatic castration-resistant prostate cancer; an Eastern Cooperative Oncology Group (ECOG) performance status score of 0-2; and had previously received of at least one androgen receptor pathway inhibitor and one or two taxane-containing regimens. Patients were randomly assigned (2:1) to receive either [177Lu]Lu-PSMA-617 plus protocol-permitted standard of care ([177Lu]Lu-PSMA-617 group) or standard of care alone (control group) using permuted blocks. Randomisation was stratified by baseline lactate dehydrogenase concentration, liver metastases, ECOG performance status, and androgen receptor pathway inhibitor inclusion in standard of care. Patients in the [177Lu]Lu-PSMA-617 group received intravenous infusions of 7·4 gigabecquerel (GBq; 200 millicurie [mCi]) [177Lu]Lu-PSMA-617 every 6 weeks for four cycles plus two optional additional cycles. Standard of care included approved hormonal treatments, bisphosphonates, and radiotherapy. The alternate primary endpoints were radiographic progression-free survival and overall survival, which have been reported. Here we report the key secondary endpoint of time to first symptomatic skeletal event, and other secondary endpoints of HRQOL assessed with the Functional Assessment of Cancer Therapy-Prostate (FACT-P) and EQ-5D-5L, and pain assessed with the Brief Pain Inventory-Short Form (BPI-SF). Patient-reported outcomes and symptomatic skeletal events were analysed in all patients who were randomly assigned after implementation of measures designed to reduce the dropout rate in the control group (on or after March 5, 2019), and safety was analysed according to treatment received in all patients who received at least one dose of treatment. This trial is registered with ClinicalTrials.gov, NCT03511664, and is active but not recruiting. FINDINGS: Between June 4, 2018, and Oct 23, 2019, 831 patients were enrolled, of whom 581 were randomly assigned to the [177Lu]Lu-PSMA-617 group (n=385) or control group (n=196) on or after March 5, 2019, and were included in analyses of HRQOL, pain, and time to first symptomatic skeletal event. The median age of patients was 71 years (IQR 65-75) in the [177Lu]Lu-PSMA-617 group and 72·0 years (66-76) in the control group. Median time to first symptomatic skeletal event or death was 11·5 months (95% CI 10·3-13·2) in the [177Lu]Lu-PSMA-617 group and 6·8 months (5·2-8·5) in the control group (hazard ratio [HR] 0·50, 95% CI 0·40-0·62). Time to worsening was delayed in the [177Lu]Lu-PSMA-617 group versus the control group for FACT-P score (HR 0·54, 0·45-0·66) and subdomains, BPI-SF pain intensity score (0·52, 0·42-0·63), and EQ-5D-5L utility score (0·65, 0·54-0·78). Grade 3 or 4 haematological adverse events included decreased haemoglobin (80 [15%] of 529 assessable patients who received [177Lu]Lu-PSMA-617 plus standard of care vs 13 [6%] of 205 who received standard of care only), lymphocyte concentrations (269 [51%] vs 39 [19%]), and platelet counts (49 [9%] vs five [2%]). Treatment-related adverse events leading to death occurred in five (1%) patients who received [177Lu]Lu-PSMA-617 plus standard of care (pancytopenia [n=2], bone marrow failure [n=1], subdural haematoma [n=1], and intracranial haemorrhage [n=1]) and no patients who received standard of care only. INTERPRETATION: [177Lu]Lu-PSMA-617 plus standard of care delayed time to worsening in HRQOL and time to skeletal events compared with standard of care alone. These findings support the use of [177Lu]Lu-PSMA-617 in patients with metastatic castration-resistant prostate cancer who received previous androgen receptor pathway inhibitor and taxane treatment. FUNDING: Advanced Accelerator Applications (Novartis).