Association Between Length of Buprenorphine or Methadone Use and Nonprescribed Opioid Use Among Individuals with Opioid Use Disorder: A Cohort Study.

BACKGROUND: Opioid use disorder (OUD) affects millions of individuals each year in the United States. Patient retention in medications for opioid use disorder (MOUD) treatment is suboptimal. This study examines and quantifies the associations between each additional month of buprenorphine or methadone use and nonprescribed opioid use. METHODS: Data were obtained from an 18-month longitudinal, observational cohort study of patients (age ≥ 18 years) treated for OUD. Patients completed a baseline self-reported questionnaire between March 2018 and December 2019 and were asked to complete follow-up questionnaires at approximately 3-, 6-, 12-, and 18-months post-baseline until May 2021. Patients treated with buprenorphine or methadone, without taking other MOUD at least 12 months prior to baseline, were included. Outcomes included past 30-day use of prescription opioids nonmedically, heroin, or illegally made fentanyl. A multivariable, multilevel regression model with a binomial distribution and a logit link was used to estimate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). RESULTS: This study included 353 patients taking buprenorphine (mean [standard deviation, SD] age 39 [11] years; 226 [64%] female), and 785 patients taking methadone (mean [SD] age 42 [12] years; 392 [50%] female). Each additional month of MOUD treatment was associated with a 25% decrease in the odds of past 30-day nonprescribed opioid use for patients taking buprenorphine (aOR [95% CI] = 0.75 [0.68-0.83]), and a 17% decrease for patients taking methadone (aOR = 0.83 [0.79-0.87]). The COVID-19 pandemic (aOR = 9.29 [2.96-29.17]; aOR = 3.19 [1.74-5.86]) and MOUD adverse reaction experiences (aOR = 3.07 [1.11-8.48]; aOR = 2.51 [1.01-6.22]) were significantly associated with higher odds of nonprescribed opioid use among buprenorphine and methadone groups. CONCLUSION: Among patients treated with buprenorphine or methadone, with each additional treatment month since baseline, those who continued with treatment appeared to be more likely to report 17% to 25% decreased odds of past 30-day nonprescribed opioid use. Our findings can be used by clinicians in the shared decision-making process with patients, emphasizing the value of sustained retention in MOUD.

Clinical Considerations for Healthcare Provider-Administered Lipid-Lowering Medications.

Atherosclerotic cardiovascular disease (ASCVD), a leading cause of mortality and morbidity, is associated with a substantial healthcare and economic burden. Reduction of low-density lipoprotein cholesterol (LDL-C) to guideline-recommended goals is crucial in the prevention or management of ASCVD, particularly in those at high risk. Despite the availability of several effective lipid-lowering therapies (LLTs), up to 80% of patients with ASCVD do not reach evidence-based LDL-C goals. This nonattainment may be due to poor adherence to, and lack of timely utilization of, LLTs driven by a range of variables, including polypharmacy, side effects, clinical inertia, costs, and access issues. Inclisiran was approved by the US Food and Drug Administration in 2021 as a novel, twice-yearly, healthcare provider (HCP)-administered LLT. In-office administration allows HCPs more control of drug acquisition, administration, and reimbursement, and may allow for more timely care and increased patient monitoring. In the USA, in-office administered drugs are considered a Medical Benefit and can be acquired and reimbursed using the "buy-and-bill" process. Buy-and-bill is a standard system for medication administration already established in multiple therapeutic areas, including oncology, vaccines, and allergy/immunology. Initiating in-office administration will involve new considerations for clinicians in the cardiovascular specialty, such as the implementation of new infrastructure and processes; however, it could ultimately increase treatment adherence and improve cardiovascular outcomes for patients with ASCVD. This article discusses the potential implications of buy-and-bill for the cardiology specialty and provides a practical guide to implementing HCP-administered specialty drugs in US clinical practice.

Machine Learning and Statistical Shape Modelling Methodologies to Assess Vascular Morphology before and after Aortic Valve Replacement.

Introduction: Statistical shape modelling (SSM) is used to analyse morphology, discover qualitatively and quantitatively unique shape features within a population, and generate mean shapes and shape modes that show morphological variability. Hierarchical agglomerative clustering is a machine learning analysis used to identify subgroups within a given population in relation to shape features. We tested the application of both methods in the clinically relevant scenario of patients undergoing aortic valve repair (AVR). Every year, around 5000 patients undergo surgical AVR in the UK. Aims: Evaluate aortic morphology and identify subgroups amongst patients who had undergone AVR, including Ozaki, Ross, and valve-sparing procedures using SSM and unsupervised hierarchical clustering analysis. This methodological framework can evaluate both pre- and post-surgical variability across subgroups undergoing different surgeries. Methods: Pre- (n = 47) and post- (n = 35) operative three-dimensional (3D) aortic models were reconstructed from computed tomography (CT) and cardiac magnetic resonance (CMR) images. Computational analyses for SSM and hierarchical clustering were run separately for the two subgroups, assessing (a) ascending aorta only and (b) the whole aorta. This allows for exploring possible variations in morphological classification related to the input shape. Results: Most patients in the Ross procedure subgroup exhibited differences in aortic morphology from other subgroups, including an elongated ascending and wide aortic arch pre-operatively, and an elongated ascending aorta with a slightly enlarged sinus post-operatively. In hierarchical clustering, the Ross aortas also appeared to cluster together compared to the other surgical procedures, both pre-operatively and post-operatively. There were significant differences between clusters in terms of clustering distance in the pre-operative analyses (p = 0.003 for ascending aortas, p = 0.016 for whole aortas). There were no significant differences between the clusters in post-operative analyses (p = 0.47 for ascending, p = 0.19 for whole aorta). Conclusions: We demonstrated the feasibility of evaluating aortic morphology before and after different aortic valve surgeries using SSM and hierarchical clustering. This framework could be used to further explore shape features associated with surgical decision-making pre-operatively and, importantly, to identify subgroups whose morphology is associated with poorer clinical outcomes post-operatively. Statistical shape modelling (SSM) and unsupervised hierarchical clustering are two statistical methods that can be used to assess morphology, show morphological variations, with the latter being able to identify subgroups within a population. These methods have been applied to the population of aortic valve replacement (AVR) patients since there are different surgical procedures (traditional AVR, Ozaki, Ross, and valve-sparing). The aim is to evaluate aortic morphology and identify subgroups within this population before and after surgery. Computed tomography and cardiac magnetic resonance images were reconstructed into 3D models of the ascending aorta and whole aorta, which were then input into SSM and hierarchical clustering. The results show that the Ross aortic morphology is quite different from the other aortas. The clustering did not classify the aortas based on the surgical procedures; however, most of the Ross group did cluster together, indicating low variability within this surgical group.

NOTCH1 fusions in pediatric T-cell lymphoblastic lymphoma: A high-risk subgroup with CCL17 (TARC) levels as diagnostic biomarker.

Twenty percent of children with T-cell lymphoblastic lymphoma (T-LBL) will relapse and have an extremely poor outcome. Currently, we can identify a genetically low-risk subgroup in pediatric T-LBL, yet these high-risk patients who need intensified or alternative treatment options remain undetected. Therefore, there is an urgent need to recognize these high-risk T-LBL patients through identification of molecular characteristics and biomarkers. By using RNA sequencing which was performed in 29/49 T-LBL patients who were diagnosed in the Princess Maxima Center for Pediatric Oncology between 2018 and 2023, we discovered a previously unknown high-risk biological subgroup of children with T-LBL. This subgroup is characterized by NOTCH1 gene fusions, found in 21% of our T-LBL cohort (6/29). All patients presented with a large mediastinal mass, pleural/pericardial effusions, and absence of blasts in the bone marrow, blood, and central nervous system. Blood CCL17 (C-C Motif Chemokine Ligand 17, TARC) levels were measured at diagnosis in 26/29 patients, and all six patients with NOTCH1 gene fusions patients exclusively expressed highly elevated blood CCL17 levels, defining a novel and previously not known clinically relevant biomarker for T-cell lymphoblastic lymphoma. Four out of these six patients relapsed during therapy, a fifth developed a therapy-related acute myeloid leukemia during maintenance therapy. These data indicate that T-LBL patients with a NOTCH1 fusion have a high risk of relapse which can be easily identified using a blood CCL17 screening at diagnosis. Further molecular characterization through NOTCH1 gene fusion analysis offers these patients the opportunity for treatment intensification or new treatment strategies.

Knowledge, Attitudes, and Practices of Antibiotic Use among Small-, Medium-, and Large-Scale Fish Farmers of the Stratum II of the Volta Lake of Ghana.

BACKGROUND: Antibiotic residue in food products and the resulting antibiotic-resistant bacteria represent a significant global public health threat. The misuse of antibiotics is a primary contributor to this issue. This study investigated the knowledge, attitudes, and practices (KAP) regarding antibiotic use among cage fish farmers on Ghana's Volta Lake. METHOD: We conducted a cross-sectional survey with 91 cage fish farmers across three scales: small, medium, and large. A semi-structured questionnaire complemented by personal observations provided comprehensive data. We used several statistical methods for analysis: Pearson Chi-Square and Spearman correlation tests to examine relationships and trends among variables, logistic regression to analyze variable interactions, and Cronbach's alpha to check internal consistency. Additionally, Kendall's coefficient was used to rank challenges, utilizing STATA and SPSS for these calculations. RESULTS: The survey revealed that 58.55% of cage fish farmers earn an average of 10,000 USD annually, with 35.16% having over 16 years of experience. From the survey, all sampled populations admitted to antibiotic applications in their farming operation. Knowledge of antibiotic types was mainly influenced by peers (46.15%), with tetracycline being the most recognized and used. There was a significant reliance on the empirical use of antibiotics, with 52.75% of farmers using them based on personal experience and 40.66% without a prescription. When initial treatments failed, 41.76% of the farmers would change or combine drugs. Older farmers (over 51 years) and those with tertiary education demonstrated significantly better KAP scores regarding antibiotic use. Strong correlations were also found among knowledge, attitudes, and practices in antibiotic usage. CONCLUSIONS: The findings indicate a need for improved education on antibiotic use among fish farmers to reduce misuse and enhance awareness of the potential consequences. This study provides foundational data for designing interventions to address these issues in the context of cage fish farming on Volta Lake.

Soft tissue tumor imaging in adults: whole-body staging in sarcoma, non-malignant entities requiring special algorithms, pitfalls and special imaging aspects. Guidelines 2024 from the European Society of Musculoskeletal Radiology (ESSR).

OBJECTIVES: The revised European Society of Musculoskeletal Radiology (ESSR) consensus guidelines on soft tissue tumor imaging represent an update of 2015 after technical advancements, further insights into specific entities, and revised World Health Organization (2020) and AJCC (2017) classifications. This second of three papers covers algorithms once histology is confirmed: (1) standardized whole-body staging, (2) special algorithms for non-malignant entities, and (3) multiplicity, genetic tumor syndromes, and pitfalls. MATERIALS AND METHODS: A validated Delphi method based on peer-reviewed literature was used to derive consensus among a panel of 46 specialized musculoskeletal radiologists from 12 European countries. Statements that had undergone interdisciplinary revision were scored online by the level of agreement (0 to 10) during two iterative rounds, that could result in 'group consensus', 'group agreement', or 'lack of agreement'. RESULTS: The three sections contain 24 statements with comments. Group consensus was reached in 95.8% and group agreement in 4.2%. For whole-body staging, pulmonary MDCT should be performed in all high-grade sarcomas. Whole-body MRI is preferred for staging bone metastasis, with [18F]FDG-PET/CT as an alternative modality in PET-avid tumors. Patients with alveolar soft part sarcoma, clear cell sarcoma, and angiosarcoma should be screened for brain metastases. Special algorithms are recommended for entities such as rhabdomyosarcoma, extraskeletal Ewing sarcoma, myxoid liposarcoma, and neurofibromatosis type 1 associated malignant peripheral nerve sheath tumors. Satisfaction of search should be avoided in potential multiplicity. CONCLUSION: Standardized whole-body staging includes pulmonary MDCT in all high-grade sarcomas; entity-dependent modifications and specific algorithms are recommended for sarcomas and non-malignant soft tissue tumors. CLINICAL RELEVANCE STATEMENT: These updated ESSR soft tissue tumor imaging guidelines aim to provide support in decision-making, helping to avoid common pitfalls, by providing general and entity-specific algorithms, techniques, and reporting recommendations for whole-body staging in sarcoma and non-malignant soft tissue tumors. KEY POINTS: An early, accurate, diagnosis is crucial for the prognosis of patients with soft tissue tumors. These updated guidelines provide best practice expert consensus for standardized imaging algorithms, techniques, and reporting. Standardization can improve the comparability examinations and provide databases for large data analysis.

The BMP2 prodomain promotes dimerization and cleavage of BMP6 homodimers and BMP2/6 heterodimers in vivo.

Bone morphogenetic protein 2 (BMP2) and BMP6 are key regulators of systemic iron homeostasis. All BMPs are generated as inactive precursor proteins that dimerize and are cleaved to generate the bioactive ligand and inactive prodomain fragments, but nothing is known about how BMP2 or BMP6 homodimeric or heterodimeric precursor proteins are proteolytically activated. Here, we conducted in vitro cleavage assays, which revealed that BMP2 is sequentially cleaved by furin at two sites, initially at a site upstream of the mature ligand, and then at a site adjacent to the ligand domain, while BMP6 is cleaved at a single furin motif. Cleavage of both sites of BMP2 is required to generate fully active BMP2 homodimers when expressed in Xenopus embryos or liver endothelial cells, and fully active BMP2/6 heterodimers in Xenopus . We analyzed BMP activity in Xenopus embryos expressing chimeric proteins consisting of the BMP2 prodomain and BMP6 ligand domain, or vice versa. We show that the prodomain of BMP2 is necessary and sufficient to generate active BMP6 homodimers and BMP2/6 heterodimers, whereas the BMP6 prodomain cannot generate active BMP2 homodimers or BMP2/6 heterodimers. We examined BMP2 and BMP6 homodimeric and heterodimeric ligands generated from native and chimeric precursor proteins expressed in Xenopus embryos. Whereas native BMP6 is not cleaved when expressed alone, it is cleaved to generate BMP2/6 heterodimers when co-expressed with BMP2. Furthermore, BMP2-6 chimeras are cleaved to generate BMP6 homodimers. Our findings reveal an important role for the BMP2 prodomain in dimerization and proteolytic activation of BMP6.

Patients' Needs Regarding Work-Focused Healthcare: A Qualitative Evidence Synthesis.

PURPOSE: To identify, appraise, and synthesize qualitative research evidence exploring patients' needs regarding work-focused healthcare. METHODS: A systematic review was conducted in accordance with the PRISMA statement guidelines to identify studies reporting patients' needs regarding work-focused healthcare. Four databases (MEDLINE, Embase, PsychInfo and Web of Science) were systematically searched from January 2000 until May 2023 and screened in duplicate by pairs of two reviewers. Inclusion criteria were qualitative data collection method, and patients' perspectives regarding healthcare focusing on work when experiencing work-related problems due to chronic medical conditions. Data extraction and synthesis was executed by means of an inductive thematic analysis approach. The quality of the included studies was assessed using the CASP Qualitative Study checklist. Confidence in the review findings was assessed through the Confidence in the Evidence from Reviews of Qualitative research (CERQual) approach. RESULTS: Out of 23,677 records, 97 qualitative studies were included. Needs regarding four main themes were identified: (1) Substantive guidance, which comprises the specific content of work-focused healthcare; (2) Clear and continuous process, which comprises clarification and optimization of the work-focused healthcare process; (3) Supportive attitude and behavior, which comprises a positive and supportive attitude and behavior from professionals towards the patients; and (4) Tailored approach, which comprises the delivery of tailored care to the individuals' needs. 17 subthemes were identified. CONCLUSION: The broader insight in patients' needs in work-focused healthcare can help (occupational) healthcare professionals adopt a more patient-centred approach in practice.

Cancel culture in a developing country: A belief in a just world behavioral analysis among generation Z.

Cancel culture is a prevalent boycotting practice used to exert pressure, express disapproval, and enforce consequences online. While multiple studies have been done on cancel culture's history, evolution, and effects, none of them were focused on Cancel Culture for Gen Z, the most socially aware and digitally inclined generation. The study aimed to uncover the factors that influence Gen Z's intention to participate and actual participation in cancel culture by utilizing a newly established integrated framework of Belief in a Just World (BJW) and the Theory of Planned Behavior (TPB). A total of 677 valid survey responses from Gen Z respondents were collected to thoroughly evaluate the belief and behavioral dimensions of cancel culture through the utilization of Structural Equation Modeling (SEM). The study's results showed that attitude towards cancel culture, the subjective norm of cancel culture, and perceived behavioral control, are strong facilitating conditions that drive Gen Z's intent and actual participation in canceling behavior. It was seen that BJW has no effect on actual canceling behavior and a reverse effect on the intention to participate in canceling behavior. For the canceling methods, 97 % will unsubscribe or unfollow accounts and 94.68 % will block or mute accounts. It was also discovered that Facebook, Instagram, and YouTube are the top social media platforms used by Gen Zs in the Philippines with at least a 94 % usage rate. The findings of this study may be utilized by businesses and policymakers on how to reduce the incidence and impact of cancel culture.

Symptom-Free Intervals Following Laser Wedge Excision for Recurrent Idiopathic Subglottic Stenosis.

OBJECTIVE: Analyze the duration of symptom-free intervals following laser wedge excision (LWE) for recurrent idiopathic subglottic stenosis (iSGS). Secondary aim includes evaluating the influence of patient-related or disease factors. STUDY DESIGN: Retrospective review. SETTING: Tertiary center. METHODS: Review of iSGS patients who underwent LWE between 2002 and 2021. LWE patients without prior airway surgery were labeled LWE primary (LWEP) and those with prior history of dilation were labeled LWE secondary (LWES). A conditional frailty repeated events model was used to analyze the median time to recurrence (MTR) for each nth recurrence. Secondary analysis included stratification by use of medical therapy and initial preoperative characteristics of scar (Myer-Cotton grade, distance between the glottis and superior-most aspect of scar, DGS; length of scar, DL). RESULTS: Two hundred and ten iSGS patients underwent LWE (131 LWEP, 79 LWES). The proportion of patients experiencing at least 1, 3, 6, and 12 recurrences, respectively, was 68.0% (n = 143), 40.7% (n = 85), 20.0% (n = 42), and 5.2% (n = 11). There was exponential time-shortening from the 1st to 12th recurrence (P < .0001). While MTR was 4.1 years after the first LWE, this fell to 2.8, 1.7, 1.0, and 0.7 years for the 2nd, 3rd, 6th, and 12th recurrences. Furthermore, LWEP patients experienced longer MTR than LWES counterparts within the first 6 recurrences (P < .01). There was no significant relationship between intersurgical interval and medication adherence, DL, DGS, or grade for recurrences beyond the first (P = .207, P = .20, P = .43, P = .16). CONCLUSION: Symptom-free intervals in iSGS shorten with each subsequent recurrence and LWE. The difference in MTR between LWEP and LWES groups was significant within the first 6 recurrences with LWEP having longer MTR.

Overdose, Behavioral Health Services, and Medications for Opioid Use Disorder After a Nonfatal Overdose.

Importance: Recognizing and providing services to individuals at highest risk for drug overdose are paramount to addressing the drug overdose crisis. Objective: To examine receipt of medications for opioid use disorder (MOUD), naloxone, and behavioral health services in the 12 months after an index nonfatal drug overdose and the association between receipt of these interventions and fatal drug overdose. Design, Setting, and Participants: This cohort study was conducted in the US from January 2020 to December 2021 using claims, demographic, mortality, and other data from the Centers for Medicare & Medicaid Services, the Centers for Disease Control and Prevention, and other sources. The cohort comprised Medicare fee-for-service beneficiaries aged 18 years or older with International Statistical Classification of Diseases, Tenth Revision, Clinical Modification codes for a nonfatal drug overdose. Data analysis was performed from February to November 2023. Exposures: Demographic and clinical characteristics, substance use disorder, and psychiatric comorbidities. Main Outcomes and Measures: Receipt of MOUD, naloxone, and behavioral health services as well as subsequent nonfatal and fatal drug overdoses. Results: The cohort consisted of 136 762 Medicare beneficiaries (80 140 females [58.6%]; mean (SD) age of 68.2 [15.0] years) who experienced an index nonfatal drug overdose in 2020. The majority of individuals had Hispanic (5.8%), non-Hispanic Black (10.9%), and non-Hispanic White (78.8%) race and ethnicity and lived in metropolitan areas (78.9%). In the 12 months after their index nonfatal drug overdose, 23 815 beneficiaries (17.4%) experienced at least 1 subsequent nonfatal drug overdose and 1323 (1.0%) died of a fatal drug overdose. Opioids were involved in 72.2% of fatal drug overdoses. Among the cohort, 5556 (4.1%) received any MOUD and 8530 (6.2%) filled a naloxone prescription in the 12 months after the index nonfatal drug overdose. Filling a naloxone prescription (adjusted odds ratio [AOR], 0.70; 95% CI, 0.56-0.89), each percentage of days receiving methadone (AOR, 0.98; 95% CI, 0.98-0.99) or buprenorphine (AOR, 0.99; 95% CI, 0.98-0.99), and receiving behavioral health assessment or crisis services (AOR, 0.25; 95% CI, 0.22-0.28) were all associated with reduced adjusted odds of fatal drug overdose in the 12 months after the index nonfatal drug overdose. Conclusions and Relevance: This cohort study found that, despite their known association with reduced risk of a fatal drug overdose, only a small percentage of Medicare beneficiaries received MOUD or filled a naloxone prescription in the 12 months after a nonfatal drug overdose. Efforts to improve access to behavioral health services; MOUD; and overdose-prevention strategies, such as prescribing naloxone and linking individuals to community-based health care settings for ongoing care, are needed.

ATM germline pathogenic variants affect outcomes in children with ataxia-telangiectasia and hematological malignancies.

Ataxia-telangiectasia (A-T) is an autosomal-recessive disorder caused by pathogenic variants (PVs) of the ATM gene. Children with A-T are predisposed to hematological malignancies. We aimed to investigate their characteristics and outcomes in order to generate data-based treatment recommendations. In this multinational, observational study we report 202 patients aged ≤25 years with A-T and hematological malignancies from 25 countries. Ninety-one patients (45%) presented with mature B-cell lymphomas, 82 (41%) with acute lymphoblastic leukemia/lymphoma, 21(10%) with Hodgkin lymphoma and eight (4%) with other hematological malignancies. Four-year overall survival and event-free survival (EFS) were 50.8% (95% CI 43.6-59.1) and 47.9% (95% CI 40.8-56.2), respectively. Cure rates have not significantly improved over the last four decades (p=.76). The major cause of treatment failure was treatment-related mortality (TRM) with a four-year cumulative incidence of 25.9% (95% CI 19.5-32.4). Germline ATM PVs were categorized as null or hypomorphic and patients with available genetic data (n=110) were classified as having absent (n=81) or residual (n=29) ATM kinase activity. Four-year EFS was 39.4% (95% CI 29-53.3) vs 78.7% (95% CI 63.7-97.2), (p<.001), and TRM rates were 37.6% (95% CI 26.4-48.7) vs 4.0% (95% CI 0-11.8), (p=.017), for those with absent and residual ATM kinase activity, respectively. Absence of ATM kinase activity was independently associated with decreased EFS (HR=0.362, 95% CI 0.16-0.82; p=.009) and increased TRM (HR=14.11, 95% CI 1.36-146.31; p=.029). Patients with A-T and leukemia/lymphoma may benefit from de-escalated therapy for patients with absent ATM kinase activity and near-standard therapy regimens for those with residual kinase activity.

World Allergy Organization (WAO) Diagnosis and Rationale for Action against Cow's Milk Allergy (DRACMA) guideline update - XII - Recommendations on milk formula supplements with and without probiotics for infants and toddlers with CMA.

Background: Cow's milk allergy (CMA) is the most common food allergy in infants. The replacement with specialized formulas is an established clinical approach to ensure adequate growth and minimize the risk of severe allergic reactions when breastfeeding is not possible. Still, given the availability of multiple options, such as extensively hydrolyzed cow's milk protein formula (eHF-CM), amino acid formula (AAF), hydrolyzed rice formula (HRF) and soy formulas (SF), there is some uncertainty as to the most suitable choice with respect to health outcomes. Furthermore, the addition of probiotics to a formula has been proposed as a potential approach to maximize benefit. Objective: These evidence-based guidelines from the World Allergy Organization (WAO) intend to support patients, clinicians, and others in decisions about the use of milk specialized formulas, with and without probiotics, for individuals with CMA. Methods: WAO formed a multidisciplinary guideline panel balanced to include the views of all stakeholders and to minimize potential biases from competing interests. The McMaster University GRADE Centre supported the guideline-development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used, including GRADE Evidence-to-Decision frameworks, which were subject to review by stakeholders. Results: After reviewing the summarized evidence and thoroughly discussing the different management options, the WAO guideline panel suggests: a) using an extensively hydrolyzed (cow's milk) formula or a hydrolyzed rice formula as the first option for managing infants with immunoglobulin E (IgE) and non-IgE-mediated CMA who are not being breastfed. An amino-acid formula or a soy formula could be regarded as second and third options respectively; b) using either a formula without a probiotic or a casein-based extensively hydrolyzed formula containing Lacticaseibacillus rhamnosus GG (LGG) for infants with either IgE or non-IgE-mediated CMA.The issued recommendations are labeled as "conditional" following the GRADE approach due to the very low certainty about the health effects based on the available evidence. Conclusions: If breastfeeding is not available, clinicians, patients, and their family members might want to discuss all the potential desirable and undesirable consequences of each formula in infants with CMA, integrating them with the patients' and caregivers' values and preferences, local availability, and cost, before deciding on a treatment option. We also suggest what research is needed to determine with greater certainty which formulas are likely to be the most beneficial, cost-effective, and equitable.

New approach methods to assess developmental and adult neurotoxicity for regulatory use: a PARC work package 5 project.

In the European regulatory context, rodent in vivo studies are the predominant source of neurotoxicity information. Although they form a cornerstone of neurotoxicological assessments, they are costly and the topic of ethical debate. While the public expects chemicals and products to be safe for the developing and mature nervous systems, considerable numbers of chemicals in commerce have not, or only to a limited extent, been assessed for their potential to cause neurotoxicity. As such, there is a societal push toward the replacement of animal models with in vitro or alternative methods. New approach methods (NAMs) can contribute to the regulatory knowledge base, increase chemical safety, and modernize chemical hazard and risk assessment. Provided they reach an acceptable level of regulatory relevance and reliability, NAMs may be considered as replacements for specific in vivo studies. The European Partnership for the Assessment of Risks from Chemicals (PARC) addresses challenges to the development and implementation of NAMs in chemical risk assessment. In collaboration with regulatory agencies, Project 5.2.1e (Neurotoxicity) aims to develop and evaluate NAMs for developmental neurotoxicity (DNT) and adult neurotoxicity (ANT) and to understand the applicability domain of specific NAMs for the detection of endocrine disruption and epigenetic perturbation. To speed up assay time and reduce costs, we identify early indicators of later-onset effects. Ultimately, we will assemble second-generation developmental neurotoxicity and first-generation adult neurotoxicity test batteries, both of which aim to provide regulatory hazard and risk assessors and industry stakeholders with robust, speedy, lower-cost, and informative next-generation hazard and risk assessment tools.

Aortic geometry and long-term outcome in patients with a repaired coarctation.

OBJECTIVE: This study aims to compare aortic morphology between repaired coarctation patients and controls, and to identify aortic morphological risk factors for hypertension and cardiovascular events (CVEs) in coarctation patients. METHODS: Repaired coarctation patients with computed tomography angiography (CTA) or magnetic resonance angiography (MRA) were included, followed-up and compared with sex-matched and age-matched controls. Three-dimensional aortic shape was reconstructed using patients' CTA or MRA, or four-dimensional flow cardiovascular magnetic resonance in controls, and advanced geometrical characteristics were calculated and visualised using statistical shape modelling. In patients, we examined the association of geometrical characteristics with (1) baseline hypertension, using multivariable logistic regression; and (2) cardiovascular events (CVE, composite of aortic complications, coronary artery disease, ventricular arrhythmias, heart failure hospitalisation, stroke, transient ischaemic attacks and cardiovascular death), using multivariable Cox regression. The least absolute shrinkage and selection operator (LASSO) method selected the most informative multivariable model. RESULTS: Sixty-five repaired coarctation patients (23 years (IQR 19-38)) were included, of which 44 (68%) patients were hypertensive at baseline. After a median follow-up of 8.7 years (IQR 4.8-15.4), 27 CVEs occurred in 20 patients. Aortic arch dimensions were smaller in patients compared with controls (diameter p<0.001, wall surface area p=0.026, volume p=0.007). Patients had more aortic arch torsion (p<0.001) and a higher curvature (p<0.001). No geometrical characteristics were associated with hypertension. LASSO selected left ventricular mass, male sex, tortuosity and age for the multivariable model. Left ventricular mass (p=0.014) was independently associated with CVE, and aortic tortuosity showed a trend towards significance (p=0.070). CONCLUSION: Repaired coarctation patients have a smaller aortic arch and a more tortuous course of the aorta compared with controls. Besides left ventricular mass index, geometrical features might be of importance in long-term risk assessment in coarctation patients.

Personal protective equipment for preventing asbestos exposure in workers.

BACKGROUND: Asbestos exposure can lead to asbestos-related diseases. The European Union (EU) has adopted regulations for workplaces where asbestos is present. The EU occupational exposure limit (OEL) for asbestos is 0.1 fibres per cubic centimetre of air (f/cm3) as an eight-hour average. Different types of personal protective equipment (PPE) are available to provide protection and minimise exposure; however, their effectiveness is unclear. OBJECTIVES: To assess the effects of personal protective equipment (PPE), including donning and doffing procedures and individual hygienic behaviour, compared to no availability and use of such equipment or alternative equipment, on asbestos exposure in workers in asbestos demolition and repair work. SEARCH METHODS: We searched MEDLINE, Embase, CENTRAL, and Scopus (September 2022), and we checked the reference lists of included studies. SELECTION CRITERIA: We included studies that measured asbestos concentration outside and inside PPE (considering outside concentration a surrogate for no PPE), exposure to asbestos after doffing PPE, donning and doffing errors, nonadherence to regulations, and adverse effects of PPE. DATA COLLECTION AND ANALYSIS: Two review authors selected studies, extracted data, and assessed risk of bias using ROBINS-I. We categorised PPE as full-face filtering masks, supplied air respirators (SARs), and powered air-purifying respirators (PAPRs). Values for asbestos outside and inside PPE were transformed to logarithmic values for random-effects meta-analysis. Pooled logarithmic mean differences (MDs) were exponentiated to obtain the ratio of means (RoM) and 95% confidence interval (95% CI). The RoM shows the degree of protection provided by the respirators (workplace protection factor). Since the RoM is likely to be much higher at higher outside concentrations, we presented separate results according to the outside asbestos concentration, as follows. • Below 0.01 f/cm3 (band 1) • 0.01 f/cm3 to below 0.1 f/cm3 (band 2) • 0.1 f/cm3 to below 1 f/cm3 (band 3) • 1 f/cm3 to below 10 f/cm3 (band 4) • 10 f/cm3 to below 100 f/cm3 (band 5) • 100 f/cm3 to below 1000 f/cm3 (band 6) Additionally, we determined whether the inside concentrations per respirator and concentration band complied with the current EU OEL (0.1 f/cm3) and proposed EU OEL (0.01 f/cm3). MAIN RESULTS: We identified six studies that measured asbestos concentrations outside and inside respiratory protective equipment (RPE) and one cross-over study that compared the effect of two different coveralls on body temperature. No studies evaluated the remaining predefined outcomes. Most studies were at overall moderate risk of bias due to insufficient reporting. The cross-over study was at high risk of bias. Full-face filtering masks Two studies evaluated full-face filtering masks. They provided insufficient data for band 1 and band 6. The results for the remaining bands were as follows. • Band 2: RoM 19 (95% CI 17.6 to 20.1; 1 study, 3 measurements; moderate certainty) • Band 3: RoM 69 (95% CI 26.6 to 175.9; 2 studies, 17 measurements; very low certainty) • Band 4: RoM 455 (95% CI 270.4 to 765.1; 1 study, 16 measurements; low certainty) • Band 5: RoM 2752 (95% CI 1236.5 to 6063.2;1 study, 3 measurements; low certainty) The inside measurements in band 5 did not comply with the EU OEL of 0.1 f/cm3, and no inside measurements complied with the proposed EU OEL of 0.01 f/cm3. Supplied air respirators Two studies evaluated supplied air respirators. They provided no data for band 6. The results for the remaining bands were as follows. • Band 1: RoM 11 (95% CI 7.6 to 14.9; 1 study, 134 measurements; moderate certainty) • Band 2: RoM 63 (95% CI 43.8 to 90.9; 1 study, 17 measurements; moderate certainty) • Band 3: RoM 528 (95% CI 368.7 to 757.5; 1 study, 38 measurements; moderate certainty) • Band 4: RoM 4638 (95% CI 3071.7 to 7044.5; 1 study, 49 measurements; moderate certainty) • Band 5: RoM 26,134 (16,647.2 to 41,357.1; 1 study, 22 measurements; moderate certainty) All inside measurements complied with the current OEL of 0.1 f/cm3 and the proposed OEL of 0.01 f/cm3. Powered air-purifying respirators Three studies evaluated PAPRs. The results per band were as follows. • Band 1: RoM 8 (95% CI 3.7 to 19.1; 1 study, 23 measurements; moderate certainty) • Band 2: RoM 90 (95% CI 64.7 to 126.5; 1 study, 17 measurements; moderate certainty) • Band 3: RoM 104 (95% CI 23.1 to 464.1; 3 studies, 14 measurements; very low certainty) • Band 4: RoM 706 (95% CI 219.2 to 2253.0; 2 studies, 43 measurements; very low certainty) • Band 5: RoM 1366 (544.6 to 3428.9; 2 studies, 8 measurements; low certainty) • Band 6: RoM 18,958 (95% CI 4023.9 to 90,219.4; 2 studies, 13 measurements; very low certainty) All inside measurements complied with the 0.1 f/cm3 OEL when the outside concentration was below 10 f/cm3 (band 1 to band 4). From band 3, no measurements complied with the proposed OEL of 0.01 f/cm3. Different types of coveralls One study reported the adverse effects of coveralls. A polyethylene suit may increase the body temperature more than a ventilated impermeable polyvinyl (PVC) coverall, but the evidence is very uncertain (MD 0.17 °C, 95% CI -0.08 to 0.42; 1 study, 11 participants; very low certainty). AUTHORS' CONCLUSIONS: Where the outside asbestos concentration is below 0.1 f/cm3, SARS and PAPRs likely reduce exposure to below the proposed OEL of 0.01 f/cm3. For outside concentrations up to 10 f/cm3, all respirators may reduce exposure below the current OEL, but only SAR also below the proposed OEL. In band 5 (10 to < 100 f/cm3), full-face filtering masks may not reduce asbestos exposure below either OEL, SARs likely reduce exposure below both OELs, and there were no data for PAPRs. In band 6 (100 f/cm3 to < 1000 f/cm3), PAPRs may not reduce exposure below either OEL, and there were no data for full-face filtering masks or SARs. Some coveralls may increase body temperature more than others. Randomised studies are needed to directly compare PAPRs and SARs at higher asbestos concentrations and to assess adverse effects. Future studies should assess the effects of doffing procedures.

Towards person-centred work-focused healthcare for people with cardiovascular disease: a qualitative exploration of patients' experiences and needs.

PURPOSE: To explore the experiences and needs concerning work-focused healthcare of patients experiencing problems with work participation due to cardiovascular disease based on all facets of person-centred care. METHODS: Nineteen patients who experienced or continue to experience problems with work participation due to cardiovascular disease participated in semi-structured interviews preceded by preparatory written assignments. The transcripts were analysed by means of directed qualitative content analysis. Adapted principles of the Picker Institute for Person-Centred Care provided a template for the analysis. RESULTS: 28 experiences and needs emerged and were grouped into the eight principles for person-centred work-focused healthcare. Randomly presenting one theme for each of the eight principles, the themes included: (1) frequent encounters with occupational healthcare professionals; (2) substantive work-related advice; (3) transparency in communication; (4) support for family; (5) information provision on the work-focused healthcare process; (6) personal control during the process; (7) empathy for the personal situation; and (8) tailored work-focused support. CONCLUSIONS: The identified experiences and needs for work-focused healthcare of patients experiencing problems with work participation due to cardiovascular disease clearly indicate the need to improve the delivery of person-centred work-focused healthcare to better meet the individual needs of patients.

Provided work-focused healthcare services do not always align with the patient's needs when experiencing disease-related sick leave, potentially impacting their ability to stay in or return to work.This overview of patients' experiences and needs for work-focused healthcare may provide professionals with better insight into the patients' needs and aids to adapt the healthcare provision to these needs.When professionals target the patient's needs, it may facilitate better provision of person-centred work-focused healthcare.

Associations among COVID-19 Family Stress, Family Functioning, and Child Health-Related Quality of Life through Lifestyle Behaviors in Children.

The COVID-19 pandemic has resulted in lasting effects on children, necessitating a thorough understanding of its impact for effective recovery planning. This study investigated the associations among COVID-19 family stress, family functioning, children's lifestyle behaviors (i.e., healthy food intake, unhealthy food intake, physical activity, and screen time), and their health-related quality of life (HRQOL). Data from a 2022 survey of parents with children aged 5 to 12 (mean age of boys: 8.36, mean age of girls: 7.76) in the United States through the online Prolific platform were analyzed using path analysis and gender-based multi-group analysis. The results showed an inverse relationship between family stressors and functioning (ß = -0.39, p < 0.05). COVID-19 family stress was negatively related to child physical HRQOL (ß = -0.20, p < 0.05) but not psychosocial HRQOL. Family functioning showed a positive relation with child healthy food intake (ß = 0.26, p < 0.05) and a negative relation with unhealthy diet consumption (ß = -0.27, p < 0.05), while no significant associations were found with child physical activity and screen time. Family functioning was indirectly associated with both types of HRQOL through the child's eating patterns. These relationships were more pronounced for girls. The findings point to a complex interplay between family stress and functioning, dietary habits, and the HRQOL of children during the COVID-19 pandemic, particularly concerning girls' food intake and well-being.