Consensus Definition Research Articles

Considerations for the assessment of blast exposure in service members and veterans

IntroductionBlast exposure is an increasingly present occupational hazard for military service members, particularly in modern warfare scenarios. The study of blast exposure in humans is limited by the lack of a consensus definition for blast exposure and considerable variability in measurement. Research has clearly demonstrated a robust and reliable effect of blast exposure on brain structure and function in the absence of other injury mechanisms. However, the exact mechanisms underlying these outcomes remain unclear. Despite clear contributions from preclinical studies, this knowledge has been slow to translate to clinical applications. The present manuscript empirically demonstrates the consequences of variability in measurement and definition across studies through a re-analysis of previously published data from the Chronic Effects of Neurotrauma Study 34.MethodsDefinitions of blast exposure used in prior work were examined including Blast TBI, Primary Blast TBI, Pressure Severity, Distance, and Frequency of Exposure. Outcomes included both symptom report and cognitive testing.ResultsResults demonstrate significant differences in outcomes based on the definition of blast exposure used. In some cases the same definition was strongly related to one type of outcome, but unrelated to another.DiscussionThe implications of these results for the study of blast exposure are discussed and potential actions to address the major limitations in the field are recommended. These include the development of a consensus definition of blast exposure, further refinement of the assessment of blast exposure, continued work to identify relevant mechanisms leading to long-term negative outcomes in humans, and improved education efforts.

Current and emerging pharmacotherapies for cytokine release syndrome, neurotoxicity, and hemophagocytic lymphohistiocytosis-like syndrome due to CAR T cell therapy.

Chimeric antigen receptor (CAR) T cells have revolutionized treatment of multiple hematologic malignancies. Engineered cellular therapies now offer similar hope to transform management of solid tumors and autoimmune disease. However, toxicities can be serious and often require hospitalization. We review the two chief toxicities of CAR T therapy, cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS), and the rarer immune effector cell-associated hemophagocytic lymphohistiocytosis-like syndrome. We discuss treatment paradigms and promising future pharmacologic strategies. Literature and therapies reviewed were identified by PubMed search, cited references therein, and review of registered trials. Management of CRS and ICANS has improved, aided by consensus definitions and guidelines that facilitate recognition and timely intervention. Further data will define optimal timing of tocilizumab and corticosteroids, current foundations of management. Pathophysiologic understanding has inspired off-label use of IL-1 receptor antagonism, IFNγ and IL-6 neutralizing antibodies, and janus kinase inhibitors, with data emerging from ongoing clinical trials. Further strategies to reduce toxicities include novel pharmacologic targets and safety features engineered into CAR T cells themselves. As these potentially curative therapies are used earlier in oncologic therapy and even in non-oncologic indications, effective accessible strategies to manage toxicities are critical.

New consensus definition on defining and measuring care for children with paediatric feeding disorder.

This study addresses the absence of a definition of care for children with feeding disorders, limited agreement on key performance indicators (KPIs), and the lack of data linked to those KPIs. Clinicians, consumers and researchers involved in outpatient feeding care in New South Wales (NSW), Australia were invited to participate in a two-Phase study. In Phase 1, a modified Delphi method was used. Two rounds of voting resulted in a new consensus definition of a multidisciplinary paediatric feeding clinic. Three further rounds voting determined relevant KPIs. In Phase 2, the KPIs were piloted prospectively in 10 clinics. Twenty-six clinicians, consumers and researchers participated in Phase 1. Participation across five voting rounds declined from 92% to 60% and a valid definition and KPI set were created. In Phase 2, the definition and KPIs were piloted in 10 clinics over 6 weeks. Data for 110 patients were collected. The final KPI set of 28 measures proposed covers clinical features, patient demographics and medical issues, parent-child interaction and outcome measures. A new definition of a multidisciplinary paediatric feeding clinic is now available, linked to a standardised KPI set covering relevant performance measures. These proved viable in baseline data collection for 10 clinics across NSW. This sets a foundation for further data collection, systematic measurement of care provision and outcomes, and research needed to deliver care improvement for children with paediatric feeding disorder.

Ageism and attitudes towards older people in the field of social work. A systematic review of operational definitions

ABSTRACT Combating ageism is a challenge for social workers, given that social work is directly intertwined with social justice. The conceptual definition of ageism varies due to different measurements and lack of definition consensus. The purpose of our study is the systematic review of operational definitions of ageism, which have been used by empirical research on ageism in the field of social work. Scopus, Pub Med, Taylor and Francis, and Springer were searched from 2000 to 2020. Inclusion- exclusion criteria were established concerning timespan, language, study type, and study focus. Finally, twelve peer review articles were included in the final review. Results suggest that the more prevalent forms of the operational definition of ageism include cognitive, other-directed, explicit negative, or positive components as well behavioural other-directed, explicit negative, or positive components. Our review reveals an absence of implicit and self-directed components. The findings highlight the need for an approach that covers all the dimensions of ageism. The exact dimension and manifestation of ageism in the various geriatric contexts of social work are necessary. Implications for social work research and practice are discussed.

Measuring the Impact of Primary Care Team Composition on Patient Activation Utilizing Electronic Health Record Big Data Analytics.

Team-based care has been linked to key outcomes associated with the Quadruple Aim and a key driver of high-value patient-centered care. Use of the electronic health record (EHR) and machine learning have significant potential to overcome previous barriers to studying the impact of teams, including delays in accessing data to improve teamwork and optimize patient outcomes. This study utilized a large EHR dataset (n=316,542) from an urban health system to explore the relationship between team composition and patient activation, a key driver of patient engagement. Teams were operationalized using consensus definitions of teamwork from the literature. Patient activation was measured using the Patient Activation Measure (PAM). Results from multilevel regression analyses were compared to machine learning analyses using multinomial logistic regression to calculate propensity scores for the effect of team composition on PAM scores. Under the machine learning approach, a causal inference model with generalized overlap weighting was used to calculate the average treatment effect of teamwork. Seventeen different team types were observed in the data from the analyzed sample (n=12,448). Team sizes ranged from 2 to 5 members. After controlling for confounding variables in both analyses, more diverse, multidisciplinary teams (team size of 4 or more) were observed to have improved patient activation scores. This is the first study to explore the relationship between team composition and patient activation using the EHR and big data analytics. Implications for further research using EHR data and machine learning to study teams and other patient-centered care are promising and could be used to advance team science.

Future directions for early detection of fracture related infections

IntroductionFracture related infection (FRI) refers to pathogens infecting a fracture site and hence impeding fracture healing. It is a significant complication that carries substantial disease burden and socio-economic costs, but has had limited scientific development. Hence, this paper will review the existing strategies for early detection of FRI, in the form of serum markers, molecular diagnostics and imaging modalities, and further discuss potential future directions for improved detection of FRI. Existing Strategies for Diagnosis of FRIThe Anti-infection Global Expert Committee (AIGEC) developed a consensus definition for FRI in 2017, which includes confirmatory and suggestive criteria for diagnosis of FRI. Existing strategies for diagnosis include clinical, laboratory, histopathological, microbiological and radiological investigations. Future Directions for Early Detection of FRIWith increasing recognition of FRI, early detection is crucial for early treatment to be enforced. We have identified potential areas for future development in diagnostics for early detection of FRI, which are discussed in this manuscript. They include inflammatory cytokines, serum calcium levels, platelet count, improved management of histopathological and microbiological specimens, metagenomics, wound biomarkers, gut microbiota analysis, and novel imaging technologies.

Defining remission in childhood-onset lupus: PReS-endorsed consensus definitions by an international task force

ObjectiveTo derive childhood-onset SLE (cSLE) specific remission definitions for future treat-to-target (T2T) trials, observational studies, and clinical practice. MethodsThe cSLE International T2T Task Force conducted Delphi surveys exploring paediatric perspectives on adult-onset SLE remission targets. A modified nominal group technique was used to discuss, refine, and agree on the cSLE remission target criteria. ResultsThe Task Force proposed two definitions of remission: ‘cSLE clinical remission on steroids (cCR)’ and ‘cSLE clinical remission off steroids (cCR-0)’. The common criteria are: (1) Clinical-SLEDAI-2 K = 0; (2) PGA score < 0.5 (0–3 scale); (4) stable antimalarials, immunosuppressive, and biologic therapy (changes due to side-effects, adherence, weight, or when building up to target dose allowed). Criterion (3) in cCR is the prednisolone dose ≤0.1 mg/kg/day (maximum 5 mg/day), whereas in cCR-0 it is zero. ConclusionscSLE definitions of remission have been proposed, maintaining sufficient alignment with the adult-SLE definition to facilitate life-course research.

Destructive fishing: An expert‐driven definition and exploration of this quasi‐concept

AbstractNumerous policy and international frameworks consider that “destructive fishing” hampers efforts to reach sustainability goals. Though ubiquitous, “destructive fishing” is undefined and therefore currently immeasurable. Here we propose a definition developed through expert consultation: “Destructive fishing is any fishing practice that causes irrecoverable habitat degradation, or which causes significant adverse environmental impacts, results in long‐term declines in target or nontarget species beyond biologically safe limits and has negative livelihood impacts.” We show strong stakeholder support for a definition, consensus on many biological and ecological dimensions, and no clustering of respondents from different sectors. Our consensus definition is a significant step toward defining sustainable fisheries goals and will help interpret and implement global political commitments which utilize the term “destructive fishing.” Our definition and results will help reinforce the Food and Agricultural Organization's Code of Conduct and meaningfully support member countries to prohibit destructive fishing practices.

A scoping review of vasculitis as an immune-related adverse event from checkpoint inhibitor therapy of cancer: Unraveling the complexities at the intersection of immunology and vascular pathology

Background/purposeVasculitis as an immune-related adverse event (irAE) from checkpoint inhibitor therapy (ICI) to treat cancer is a rare clinical event, and little is known regarding its nosology, clinical manifestations, or response to treatment and outcomes. MethodsTo address these gaps, we used the Preferred Reporting Items for Systemic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) framework to further define this complication. Two independent PUBMED searches in September and November of 2022 revealed 127 publications with 37 excluded from title by relevance, 43 excluded by article type, and 23 excluded due to lack of biopsy results, or biopsy negative for vasculitis. Twenty-nine documented cases from 24 publications were included for final analysis. Basic demographics, ICI details, timing of onset of vasculitis symptoms, irAE treatment and outcomes were collected. The vasculitides were classified using 2022 ACR/EULAR Vasculitis Classification Criteria as well as 2012 Revised Chapel-Hill Nomenclature. Adaptations from Naidoo et al. 2023 [1] consensus definitions for irAEs were used and efforts were made to classify steroid-responsive versus unresponsive irAEs. ResultsOf the 29 cases reviewed, the average age of patients was 62.1 ± 11.0, composed of 58.6 % (n = 17) male and 41.3 % (n = 12) female. Prominent cancer types were lung cancer (41.4 %; n = 12), melanoma (41.4 %; n = 12), and renal cancer (10.3 %; n = 3), with majority being stage 4 (75.9 %, n = 22) and stage 3 (10.3 %, n = 3). Only 8 cases met the ACR/EULAR criteria, and by Chapel-Hill Nomenclature, approximately a third were small-vessel vasculitis (31.0 %; n = 9) with n = 4 positive for ANCA. Most biopsies were taken from the skin (37.9 %, n = 11) and kidney (24.1 %, n = 7). Patients were either treated with single (65.5 %, n = 19), dual (17.2 %; n = 5), or sequential (17.2 %; n = 5) ICI regimen which included anti-PD-1 therapy in all but one case, with mean of 8.7 ± 10.5 cycles received. Mean time to onset of symptoms from start of ICI was 7.2 ± 7.8 months, with 55.2 % occurring >3 months since the initial immunotherapy. Vasculitis treatment included glucocorticoids in 96 % of cases and immunotherapy was often discontinued (44.8 %; n = 13). Clinical improvement of irAE was documented in 86.2 % (n = 25). Data were missing in terms of fate of ICI (34.5 %; n = 10) and tumor outcomes (41.4 %; n = 12). Cancer progressed in 20.7 % (n = 6), stable in 34.5 % (n = 10) cases, and 6 patients died of all-causes. ConclusionVasculitis as an irAE appears clinically heterogeneous and rare. Among reported cases with adequate documentation, vasculitis is of delayed onset following the initiation of immunotherapy. Outcomes of ICI-vasculitis were generally favorable, responding to glucocorticoids and immunotherapy withdrawal. There is an urgent need for more standardized reporting of rare irAEs such as vasculitis to clarify clinical risks, classification, relationship to immunotherapy and outcomes.

Diagnostic and prognostic significance of apelin-13, APJ for sepsis in the emergency department: A prospective study

ObjectivesThis study aimed to assess the diagnostic, risk stratification, and prognostic capabilities of apelin-13 and APJ in comparison to procalcitonin (PCT) for septic patients presenting to the emergency department (ED). MethodsTwo hundred and thirty-eight patients meeting the Third International Consensus Definition (Sepsis-3) criteria were enrolled from Beijing Chaoyang Hospital's ED, along with a control group of forty healthy individuals. Patients were categorized into two groups based on disease severity: those with sepsis or septic shock. Plasma levels of apelin-13, CD4+ Th cells, and PCT were measured. The expression levels of plasma APJ mRNA were quantified using real-time fluorescence quantitative PCR (RT-qPCR) methodology. The Sequential Organ Failure Assessment (SOFA) score was determined at the time of enrollment. The prognostic values of apelin-13 and APJ was evaluated in comparison to that of PCT and the SOFA score. All patients were followed up for a duration of 28 days. ResultsThe plasma concentrations of apelin-13 and APJ exhibited a positive correlation with the severity of sepsis, while the number of CD4+ T cells decreased in septic patients. The areas under the receiver operating characteristic (AUC) curves for apelin-13 and APJ in the diagnosis and prediction of 28-day mortality were greater than that of PCT. In non-survivors at the 28-day follow-up, the plasma levels of apelin-13 and APJ were significantly higher compared to survivors. Furthermore, apelin-13 levels were notably higher in cases of sepsis-induced cardiomyopathy (SICM) than in those without SICM. Apelin-13 and APJ emerged as independent predictors of 28-day mortality among septic patients. ConclusionsApelin-13 and APJ demonstrate value in the assessment of risk stratification, early diagnosis, and prognosis of sepsis in the ED. Apelin-13 also proves to be an effective biomarker for assessing the prognosis of SICM in the ED. Sepsis may lead to immune function suppression.

Sleep factors were associated with a higher risk of MAFLD and significant fibrosis.

The relationships of sleep factors separately and jointly with metabolic associated fatty liver disease (MAFLD) and significant fibrosis remain unclear. We intended to explore the relationships in the United States. This cross-sectional study included 4477 individuals from the National Health and Nutrition Examination Survey from 2017 to 2018. Information regarding each sleep factor (sleep duration, trouble sleeping, snoring, excessive daytime sleep, and sleep apnea symptoms) was obtained through questionnaires. MAFLD was diagnosed by transient elastography according to the consensus definitions. Multivariable logistic regression models were employed to explore relationships of sleep factors separately and jointly with MAFLD and significant fibrosis. Participants having a poor sleep pattern was associated with higher MAFLD and significant fibrosis risk, and poor sleep pattern was related to about threefold (OR, 3.67; 95% CI, 1.82-7.37) increased risk of MAFLD remarkably. When examining specific factors of sleep patterns individually, trouble sleeping (OR, 1.53; 95% CI, 1.10-2.12), snoring (OR, 2.11; 95% CI, 1.40-3.19), excessive daytime sleep (OR, 1.57; 95% CI, 0.93-2.62), and sleep apnea symptoms (OR, 1.87; 95% CI, 1.13-3.10) were positively associated with the odds of MAFLD (all P < 0.05). However, sleep duration was not independently correlated with MAFLD or significant fibrosis. Sleep patterns showed similar relationships with MAFLD, regardless of all age, sex, physical activity, and shift work groups. Poor sleep pattern was linked with a considerably higher risk of MAFLD and significant fibrosis.

Independent and joint association of physical activity and adequate weekday sleep duration with metabolic dysfunction-associated steatotic liver disease

BackgroundThe independent and joint association of physical activity (PA) and weekday sleep duration with metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear. Aims: We intended to explore this association in the United States. MethodsThis cross-sectional study recruited 4974 individuals from the National Health and Nutrition Examination Survey between 2017 and 2018. Information regarding PA and weekday sleep duration was obtained through questionnaires. Metabolic associated fatty liver disease (MAFLD) was diagnosed by transient elastography based on the consensus definitions. Multivariable logistic regression models were employed to investigate the independent and joint association of PA and weekday sleep duration with MAFLD. ResultsOf the 4974 subjects, engaging in active PA or sustaining adequate sleep duration was associated with decreased the odds of MAFLD (p < 0.05). Specifically, active leisure-time PA was linked to lower 37 % odds of MAFLD (OR, 0.63; 95 % CI, 0.55–0.73). Individuals who had one to twice times (150–299 min/week) or more than twice (≥300 min/week) the recommended amount of leisure-time PA by PA Guidelines had 19 % (OR, 0.81; 95 % CI, 0.67–0.99) and 45 % (OR, 0.55; 95 % CI, 0.47–0.65) lower odds of MAFLD, respectively (P for trend <0.001). Individuals with adequate weekday sleep duration was associated with 24 % lower odds of MAFLD (OR, 0.76;95 % CI,0.67–0.88). Notably, active PA combined with adequate weekday sleep duration significantly decreased the odds ratios for MAFLD by 35 % (OR: 0.65, 95 % CI, 0.52–0.80). However, in individuals with significant alcohol use, the joint effect of total PA and weekday sleep duration on MAFLD was not statistically significant. ConclusionsBoth active PA and adequate weekday sleep duration were inversely associated with the risk of MASLD independently, while combining them could further lower the risk of MASLD.

Intravenous Vitamin C as an Add-on Therapy for the Treatment of Sepsis in an Intensive Care Unit: A Prospective Cohort Study.

Background and Objectives: According to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3), sepsis is defined as "life-threatening organ dysfunction caused by a dysregulated host response to infection". The increased presence of free radicals causes an increase in oxidative stress. Vitamin C is an essential water-soluble vitamin with antioxidant activity and immunoregulatory effects that plays a potential role in the treatment of bacterial infections. Our aim was to evaluate the effectiveness of adding vitamin C to the conventional treatment of sepsis to decrease its mortality rate. Materials and Methods: In a prospective cohort study, we included patients with a diagnosis of sepsis and a SOFA score ≥ 9 who were evaluated in an Intensive Care Unit at a secondary-care hospital. According to the intensive care specialist, they were treated using two different strategies: Group 1-patients with sepsis treated with conventional treatment without vitamin C; Group 2-patients with sepsis with the addition of vitamin C to conventional treatment. Results: We included 34 patients with sepsis. The incidence of mortality was 38%, and 47% of patients used vitamin C as an adjuvant to the basic treatment of sepsis. In the basal analyses, patients treated with use of vitamin C compared to patients treated without vitamin C required less use of glucocorticoids (75% vs. 100%, p = 0.039). At follow-up, patients treated without vitamin C had higher mortality than patients treated with vitamin C as an adjuvant for the treatment of sepsis (55.6% vs. 18.8%, p = 0.03). We observed that the use of vitamin C was a protective factor for mortality in patients with sepsis (RR: 0.54, 95% CI: 0.31-0.96, p = 0.03). Conclusions: The use of vitamin C as an adjuvant to treatment decreases the risk of mortality by 46% in patients with sepsis and SOFA ≥ 9 compared to patients treated without vitamin C as an adjuvant to sepsis.

A cross-sectional study on serum uric acid as an early marker in predicting the mortality and morbidity in patients with sepsis

Introduction Sepsis is a critical medical condition characterized by a dysregulated host response to infection, often resulting in acute organ dysfunction. Early diagnosis and timely intervention are essential for improving outcomes in sepsis patients. This study protocol outlines a cross-sectional investigation into the potential prognostic value of serum uric acid levels in sepsis cases, aiming to contribute to the early identification and management of this life-threatening condition. Methods The study will be conducted at the Acharya Vinoba Bhave Rural Hospital, a tertiary care teaching hospital in Wardha District. Patients aged 18 years and above, diagnosed with sepsis or septic shock according to the Third International Consensus definition, will be included. Detailed clinical data will be collected, including comorbidities, vital signs, and organ dysfunction scores. Serum uric acid levels will be measured upon admission and at recovery from sepsis or seven days of non-recovery. Expected outcomes The primary outcome is assessing whether serum uric acid levels can be an early marker for sepsis diagnosis and prognosis. Secondary outcomes include evaluating the correlation between uric acid levels and mortality rates, organ dysfunction severity, inflammatory response, treatment response, and hospital length of stay. Additionally, serum uric acid’s prognostic value will be compared with established biomarkers for sepsis.

How to define failure of intradetrusor injections of botulinum toxin A for neurogenic detrusor overactivity.

Neurogenic detrusor overactivity (NDO) has a major impact on patients' quality of life and can lead to upper urinary tract complications. Intradetrusor botulinum toxin type A injections are administered as second-line treatment to these patients following the failure of anticholinergic agents. The aim of the DETOX 2 study is to propose a consensus definition of the failure of intradetrusor botulinum toxin injections for NDO in patients presenting spinal cord injury, spina bifida, or multiple sclerosis (MS) with self-catheterization. This study followed the method adopted by the French National Authority for Health for recommendations by consensus. Based on a review of the literature and a preliminary survey, a steering committee compiled a questionnaire and selected a rating group comprising 16 experts from the Neuro-Urology Committee of the French Urology Association (cnuAFU) and Genulf. The experts were asked to complete the online questionnaire. At the end of the first round, all participants came together to discuss any disagreements and a second-round online questionnaire was completed to reach a consensus. Thirteen of the 16 experts approached completed both rounds of questionnaires. A strong consensus was reached for two proposals (median score = 9/10) which were therefore included in the definition from the first round: at least one repeat injection of the same botulinum toxin at the same dose must be given to rule out failure on technical grounds and a duration of efficacy <3 months must be considered a failure. At the end of round 2, a relative consensus was reached regarding the clinical criterion defining failure (median score = 7/10) and the urodynamic criterion of failure (median score = 8/10). An additional proposal was selected during this second round on the need for a voiding diary (median score = 8/10). The first consensus definition of failure of an intradetrusor injection of TB-A for NDO has been achieved with this study: persistence of detrusor overactivity with maximum detrusor pressures >40 cm H2 O and/or a compliance issue and/or persistence of urinary incontinence and/or urgency and/or a number of daily self-catheterizations >8/day and/or efficacy <3 months. This study will help to standardize research on the failure of the intradetrusor botulinum toxin for NDO in clinical practice and clinical research.

A coming-of-age story: adult neurogenesis or adolescent neurogenesis in rodents?

It is surprising that after more than a century using rodents for scientific research, there are no clear, consensual, or consistent definitions for when a mouse or a rat becomes adult. Specifically, in the field of adult hippocampal neurogenesis, where this concept is central, there is a trend to consider that puberty marks the start of adulthood and is not uncommon to find 30-day-old mice being described as adults. However, as others discussed earlier, this implies an important bias in the perceived importance of this trait because functional studies are normally done at very young ages, when neurogenesis is at its peak, disregarding middle aged and old animals that exhibit very little generation of new neurons. In this feature article we elaborate on those issues and argue that research on the postnatal development of mice and rats in the last 3 decades allows to establish an adolescence period that marks the transition to adulthood, as occurs in other mammals. Adolescence in both rat and mice ends around postnatal day 60 and therefore this age can be considered the onset of adulthood in both species. Nonetheless, to account for inter-individual, inter-strain differences in maturation and for possible delays due to environmental and social conditions, 3 months of age might be a safer option to consider mice and rats bona fide adults, as suggested by The Jackson Labs.

Establishing a research agenda for the study and assessment of opioid withdrawal.

The opioid crisis is an international public health concern. Treatments for opioid use disorder centre largely on the management of opioid withdrawal, an aversive collection of signs and symptoms that contribute to opioid use disorder. Whereas in the past 50 years more than 90 medications have been developed for depression, only five medications have been developed for opioid use disorder during this period. We posit that underinvestment has occurred in part due to an underdeveloped understanding of opioid withdrawal syndrome. This Personal View summarises substantial gaps in our understanding of opioid withdrawal that are likely to continue to limit major advancements in its treatment. There is no firm consensus in the field as to how withdrawal should be precisely defined; 10-550 symptoms of withdrawal can be measured on 18 scales. The imprecise understanding of withdrawal is likely to result in overestimating or underestimating the severity of an individual's withdrawal syndrome or potential therapeutic effects of different candidate medications. The severity of the opioid crisis is not remitting, and an international research agenda for the study and assessment of opioid withdrawal is necessary to support transformational changes in withdrawal management and treatment of opioid use disorder. Nine actionable targets are delineated here: develop a consensus definition of opioid withdrawal; understand withdrawal symptomatology after exposure to different opioids (particularly fentanyl); understand precipitated opioid withdrawal; understand how co-exposure of other drugs (eg, xylazine and stimulants) influences withdrawal expression; examine individual variation in withdrawal phenotypes; precisely characterise the protracted withdrawal syndrome; identify biomarkers of opioid withdrawal severity; identify predictors of opioid withdrawal severity; and understand which symptoms are most closely associated with treatment attrition or relapse. The US Food and Drug Administration recently established a formal indication for opioid withdrawal that has invigorated interest in drug development for opioid withdrawal management. Action is now needed to support these interests and help industry identify new classes of medications so that real change can be achieved for people with opioid use disorder.

Baseline chest computed tomography for diagnosis of invasive aspergillosis in patients with acute myeloid leukaemia treated with intensive chemotherapy: A retrospective single-centre cohort study.

Invasive pulmonary aspergillosis (IPA) is a relatively common infection in patients with acute myeloid leukaemia (AML), and is associated with high mortality rates. Optimising early detection is key to reduce the burden of IPA in this population. In this retrospective cohort study, we evaluated the added value of baseline chest CT before start of classical induction chemotherapy. Adult patients receiving first-line intensive chemotherapy for AML were included if a baseline chest CT scan was available (±7 days). Data were collected from the electronic health record. IPA was classified using the EORTC/MSGERC 2020 consensus definitions. Between 2015 and 2019, 99 patients were included. During first-line treatment, 29/99 (30%) patients developed a probable IPA. Baseline chest CT was abnormal in 61/99 (62%) and 14/61 (23%) patients had typical radiological signs for IPA. An abnormal scan showed a trend towards higher risk for IPA (hazard ratio (HR): 2.12; 95% CI 0.95-4.84). Ground glass opacities were a strong predictor for developing IPA (HR 3.35: 95% CI 1.61-7.00). No probable/proven IPA was diagnosed at baseline; however, a bronchoalveolar lavage (BAL) at baseline was only performed in seven patients. Twelve-week mortality was higher in patients with IPA (7/26, 27% vs. 5/59, 8%; p = .024). Baseline chest CT scan could be an asset in the early diagnosis of IPA and contribute to risk estimation for IPA. In patients with an abnormal baseline CT, performing a BAL should be considered more frequently, and not only in patients with radiological findings typical for IPA.

An evaluation of treatment response and remission definitions in adult obsessive-compulsive disorder: A systematic review and individual-patient data meta-analysis

IntroductionExpert consensus operationalized treatment response and remission in obsessive-compulsive disorder (OCD) as a Yale-Brown Obsessive-Compulsive Scale (Y-BOCS) reduction ≥35% and score ≤12 with ≤2 on Clinical Global Impressions Improvement (CGI-I) and Severity (CGI-S) scales, respectively. However, there has been scant empirical evidence supporting these definitions. MethodsWe conducted a systematic review and an individual participant data meta-analysis of randomized-controlled trials (RCTs) in adults with OCD to determine optimal Y-BOCS thresholds for response and remission. We estimated pooled sensitivity/specificity for each percent reduction threshold (response) or posttreatment score (remission) to determine response and remission defined by a CGI-I and CGI-S ≤ 2, respectively. ResultsIndividual participant data from 25 of 94 eligible RCTs (1235 participants) were included. The optimal threshold for response was ≥30% Y-BOCS reduction and for remission was ≤15 posttreatment Y-BOCS. However, differences in sensitivity and specificity between the optimal and nearby thresholds for response and remission were small with some uncertainty demonstrated by the confidence ellipses. ConclusionWhile the empirically derived Y-BOCS thresholds in our meta-analysis differ from expert consensus, given the predominance of data from more recent trials of OCD, which involved more refractory participants and novel treatment modalities as opposed to first-line therapies, we recommend the continued use of the consensus definitions.

Whole-genome characterisation of Escherichia coli isolates from patients with bacteraemia presenting with sepsis or septic shock in Spain: a multicentre cross-sectional study

Escherichia coli is the most frequent cause of bloodstream infections (BSIs). About one-third of patients with BSIs due to E coli develop sepsis or shock. The objective of this study is to characterise the microbiological features of E coli blood isolates causing sepsis or septic shock to provide exploratory information for future diagnostic, preventive, or therapeutic interventions. E coli blood isolates from a multicentre cross-sectional study of patients older than 14 years presenting with sepsis or septic shock (according to the Third International Consensus Definitions for Sepsis and Septic Shockcriteria) from hospitals in Spain between Oct 4, 2016, and Oct 15, 2017, were studied by whole-genome sequencing. Phylogroups, sequence types (STs), serotype, FimH types, antimicrobial resistance (AMR) genes, pathogenicity islands, and virulence factors were identified. Susceptibility testing was performed by broth microdilution. The main outcome of this study was the characterisation of the E coli blood isolates in terms of population structure by phylogroups, groups (group 1: phylogroups B2, F, and G; group 2: A,B1, and C; group 3: D), and STs and distribution by geographical location and bloodstream infection source. Other outcomes were virulence score and prevalence of virulence-associated genes, pathogenicity islands, AMR, and AMR-associated genes. Frequencies were compared using χ² or Fisher's exact tests, and continuous variables using the Mann-Whitney test, with Bonferroni correction for multiple comparisons. We analysed 224 isolates: 140 isolates (63%) were included in phylogenetic group 1, 52 (23%) in group 2, and 32 (14%) in group 3. 85 STs were identified, with four comprising 44% (n=98) of the isolates: ST131 (38 [17%]), ST73 (25 [11%]), ST69 (23 [10%]), and ST95 (12 [5%]). No significant differences in phylogroup or ST distribution were found according to geographical areas or source of bloodstream infection, except for ST95, which was more frequent in urinary tract infections than in other sources (11 [9%] of 116 vs 1 [1%] of 108, p=0·0045). Median virulence score was higher in group 1 (median 25·0 [IQR 20·5-29·0) than in group 2 (median 14·5 [9·0-20·0]; p<0·0001) and group 3 (median 21 [16·5-23·0]; p<0·0001); prevalence of several pathogenicity islands was higher in group 1. No significant differences were found between phylogenetic groups in proportions of resistance to antibiotics. ST73 had higher median virulence score (32 [IQR 29-35]) than the other predominant clones (median range 21-28). Some virulence genes and pathogenicity islands were significantly associated with each ST. ST131 isolates had higher prevalence of AMR and a higher proportion of AMR genes, notably blaCTX-M-15 and blaOXA-1. In this exploratory study, the population structure of E coli causing sepsis or shock was similar to previous studies that included all bacteraemic isolates. Virulence genes, pathogenicity islands, and AMR genes were not randomly distributed among phylogroups or STs. These results provide a comprehensive characterisation of invasive E coli isolates causing severe response syndrome. Future studies are required to determine the contribution of these microbiological factors to severe clinical presentation and worse outcomes in patients with E coli bloodstream infection. Instituto de Salud Carlos III.