Reducing the Effects of Ageing on Cognition with Therapeutic Intervention of an Oral Multi-Nutrient: The REACTION Pilot Trial Study Design.

BACKGROUND: Clinical benefits have been reported with a specific multinutrient intervention (Souvenaid) in Alzheimer's disease and mild cognitive impairment due to Alzheimer's disease. The effects of Souvenaid in age-related cognitive decline are not established. OBJECTIVE: To assess the feasibility of using virtual assessments to study the effects of a multinutrient on cognitive ageing. DESIGN: This is a randomized, double-blind, placebo-controlled, parallel group virtual pilot trial performed over 6 months in a single-centre. Participants are randomly allocated (1:1) to receive the specific multinutrient (Souvenaid) or an isocaloric, same tasting, placebo. SETTING: Trial visits are done virtually using secure online video communication. PARTICIPANTS: English or Spanish speaking people aged 55-89 years from all ethnic groups and considered to have age-related cognitive decline are eligible. MEASUREMENTS: Neuropyschological tests are done at baseline and after 6 months of intervention. Participants are contacted monthly by telephone to monitor safety, assess motivation and promote compliance. The primary outcome is feasibility determined by assessing recruitment rate, recruitment time, adherence rate and retention rate. A comprehensive set of neuropyschological measures will provide a broad assessment of cognitive function, including verbal memory, processing speed, and attention and executive function. Self-reported questionnaires are used to assess quality of life. CONCLUSIONS: This pilot trial will provide data to guide inform selection of participants and outcome measures in future studies in age-related cognitive decline.

The effects of the DASH dietary pattern on clinical outcomes and quality of life in adults with uncontrolled asthma: Design and methods of the ALOHA Trial.

BACKGROUND: Poor diet quality is an important risk factor for increased asthma prevalence and poor asthma control. To address the question of whether adults with asthma can benefit from following a healthy diet, this trial will test the efficacy and mechanisms of action of a behavioral intervention promoting the Dietary Approaches to Stop Hypertension (DASH) dietary pattern with sodium reduction among patients with uncontrolled asthma. METHODS: In this 2-arm randomized clinical trial, 320 racially/ethnically and socioeconomically diverse adults with uncontrolled asthma on standard controller therapy will be randomized to either a control or an intervention group and assessed at baseline, 3, 6 and 12 months. Control and intervention participants will receive education on lung health, asthma, and other general health topics; additionally, the intervention group will receive DASH behavioral counseling over 12 months. The primary hypothesis is that the DASH behavioral intervention, compared with the education-only control, will lead to significantly more participants with minimum clinically important improvement (responders) in asthma-specific quality of life at 12 months. Secondary hypotheses will test the intervention effects on other asthma (e.g., asthma control, lung function) and non-asthma outcomes (e.g., quality of life). Additionally, therapeutic (e.g., short chain fatty acids, cytokines) and nutritional biomarkers (e.g., dietary inflammatory index, carotenoids) will be assessed to understand the mechanisms of the intervention effect. CONCLUSION: This trial can substantially advance asthma care by providing rigorous evidence on the benefits of a behavioral dietary intervention and mechanistic insights into the role of diet quality in asthma. CLINICALTRIALS: gov #: NCT05251402.

A study of the psychometric properties of the Brazilian...Portuguese version of Bronchiectasis Health Questionnaire.

INTRODUCTION AND OBJECTIVE: The Bronchiectasis Health Questionnaire (BHQ) is a simple, repeatable, and self-reporting health status questionnaire for bronchiectasis. This study aims to cross-culturally adapt the BHQ into Brazilian Portuguese and evaluate its measurement properties. METHODS: The participants answered the Saint George...s Respiratory Questionnaire (SGRQ) and the modified Medical Research Council (mMRC) scale for dyspnea. The Brazilian-Portuguese version of the Bronchiectasis Health Questionnaire (BHQ-Brazil) was used at baseline (test) and after 14 days (retest). The psychometric analyses included internal consistency, test-retest reliability, and construct validity: factorial validity, convergent validity, and discriminative validity, agreement, and ceiling and floor effects. RESULTS: The BHQ-Brazil demonstrated adequate internal consistency (Cronbach...s alpha...=...0.92) and substantial reliability (intraclass correlation coefficient...=...0.86; 95%CI: 0.79...0.90). The exploratory factorial analysis was considered suitable. All items presented a factorial load >0.40. The convergent validity of the BHQ-Brazil with mMRC was moderate (r...=......0.53, p...<...0.001), while concurrent validity with the SGRQ was strong (symptoms: r...=......0.72, activities: r...=......0.60, impact: r...=......0.60, total score: r...=......0.75, all p...<...0.001). The standard error of measurement was 4.81 points. The discriminative validity demonstrated that individuals with more pulmonary exacerbations, colonization by Pseudomonas aeruginosa, worst dyspnea, and a higher number of affected lung lobes presented the lowest quality of life. No floor or ceiling effects were observed. CONCLUSION: The BHQ-Brazil presents adequate measurement properties to evaluate the impact of bronchiectasis on health-related quality of life, and can be used in clinical and research settings.

The locked-in syndrome: The early French descriptions.

The classic 1966 description of locked-in syndrome was performed by Plum and Posner. Here, we revisit the world's first case report of this condition, which was presented in 1875 by Camille Darolles, an intern supervised by François Damaschino, at a monthly meeting of the Société Anatomique de Paris chaired by Jean-Martin Charcot. We also review the fascination of classic writers with this syndrome, including Alexandre Dumas, a genius of literature and known admirer of the medical sciences who, in the book "The Count of Monte Cristo" published in 1846, described a character with this condition.

Sherrington-Kirkpatrick model for spin glasses: Solution via the distributional zeta function method.

We discuss the Sherrington-Kirkpatrick mean-field version of a spin glass within the distributional zeta function method (DZFM). In the DZFM, since the dominant contribution to the average free energy is written as a series of moments of the partition function of the model, the spin-glass multivalley structure is obtained. Also, an exact expression for the saddle points corresponding to each valley and a global critical temperature showing the existence of many stables or at least metastable equilibrium states is presented. Near the critical point, we obtain analytical expressions of the order parameters that are in agreement with phenomenological results. We evaluate the linear and nonlinear susceptibility and we find the expected singular behavior at the spin-glass critical temperature. Furthermore, we obtain a positive definite expression for the entropy and we show that ground-state entropy tends to zero as the temperature goes to zero. We show that our solution is stable for each term in the expansion. Finally, we analyze the behavior of the overlap distribution, where we find a general expression for each moment of the partition function.

Critical points and potential pitfalls of outbreak of IMP-1-producing carbapenem-resistant Pseudomonas aeruginosa among kidney transplant recipients: a case-control study.

BACKGROUND: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) infection after kidney transplantation (KT) is associated with high mortality. AIM: To analyse an outbreak of infection/colonization with IMP-1-producing CRPA on a KT ward. METHODS: A case-control study was conducted. Cases were identified through routine surveillance culture and real-time polymerase chain reaction for carbapenemase performed directly from rectal swab samples. Controls were randomly selected from patients hospitalized on the same ward during the same period, at a ratio of 3:1. Strain clonality was analysed through pulsed-field gel electrophoresis (PFGE), and whole-genome sequencing was performed for additional strain characterization. FINDINGS: CRPA was identified in 37 patients, in 51.4% through surveillance cultures and in 49.6% through clinical cultures. The median persistence of culture positivity was 42.5 days. Thirteen patients (35.1%) presented a total of 15 infections, of which seven (46.7%) were in the urinary tract; among those, 30-day mortality rate was 46.2%. PFGE analysis showed that all of the strains shared the same pulsotype. Multilocus sequence typing analysis identified the sequence type as ST446. Risk factors for CRPA acquisition were hospital stay >10 days, retransplantation, urological surgical reintervention after KT, use of carbapenem or ciprofloxacin in the last three months and low median lymphocyte count in the last three months. CONCLUSION: KT recipients remain colonized by CRPA for long periods and could be a source of nosocomial outbreaks. In addition, a high proportion of such patients develop infection. During an outbreak, urine culture should be added to the screening protocol for KT recipients.

Maturation of nasal microbiota and antibiotic exposures during early childhood: a population-based cohort study.

OBJECTIVES: Little is known about maturation of the airway microbiota during early childhood and the consequences of early-life antibiotic exposure. METHODS: In a population-based birth cohort of 902 healthy Finnish children, we applied deep neural network models to investigate the relationship between the nasal microbiota (measured by 16S rRNA gene sequencing at up to three time points) and child age during the first 24 months. We also performed stratified analyses according to antibiotic exposure during the age period 0-2 months. RESULTS: The dense deep neural network analysis successfully modelled the relationship between 232 bacterial genera and child age with a mean absolute error of 4.3 (95%CI 4.0-4.7) months. Similarly, the recurrent neural network analysis also successfully modelled the relationship between 215 genera and child age with a mean absolute error of 0.45 (95%CI 0.42-0.47) months. Among the genera, Staphylococcus spp. and members of the Corynebacteriaceae decreased with age, while Dolosigranulum and Moraxella increased with age in the first 2 years of life (all false discovery rate (FDR) = 0.001). In children without early-life antibiotic exposure, Dolosigranulum increased with age (FDR = 0.001). By contrast, in those with early-life antibiotic exposure, Haemophilus increased with age (FDR = 0.002). CONCLUSIONS: In this prospective birth cohort of healthy children, we demonstrated the development of the nasal microbiota, with shifts in specific genera constituting maturation, in the first 2 years of life. Antibiotic exposures during early infancy were related to different age-discriminatory bacteria.

Castleman disease. Interaction with dermatopathy: Case report.

INTRODUCTION: Castleman disease (CD) is a lymphoproliferative disorder with lymph node hypertrophy. In the unicentric form (UCD), it affects one lymph node or chain of lymph nodes. In the multicentric form (DCM), there is hypertrophy of several lymph node chains with the formation of tumor masses, causing compressive symptoms. This case report showed a case of CD in a different location(inguinal region) associated to a multiple skin lesions. PRESENTATION OF THE CASE: We reported a UCD in a 43-year-old female patient with no previous comorbidities. Since January 2016, this patient developed erysipelas lesions of the left leg (LL) from the thigh root to the foot. Concomitantly, a tumor mass appeared in the inguinal region. In 2019 we performed a biopsy that revealed changes characteristic of CD. Due to extremely poor trophic conditions, the skin area with erysipelas was resected, and the raw surface was grafted. DISCUSSION: As an inference, the erysipelas may have been responsible for the subsequent lymphangitis, lymphedema and lymph node hypertrophy. CONCLUSION: Resection of the diseased skin and lymph node excision constitute the treatment of UCD and result in improvement of the clinical picture. Nevertheless, further study of the inflammatory reaction and of markers such as interleukin-6 and the presence of skin disorders in DC is needed.

Study of the Effect of Hyperbaric Oxygen Therapy on the Viability of Dorsal Cutaneous Flaps in Tobacco-Exposed Rats.

BACKGROUND: Smoking causes a threefold increase in the risk of surgical complications in flaps. Hyperbaric oxygen therapy (HBOT) increases the viability of chronic wounds. However, there are few studies concerning the effects of HBOT on surgical flaps in patients who smoke. This study aimed to analyze the effect of HBOT on the viability of cutaneous flaps in tobacco-exposed rats. METHODS: Twenty Wistar rats were exposed to tobacco smoke for two months. Following this period, all animals underwent a dorsal cutaneous flap (3 × 10 cm) surgery and were divided into two groups: control (n = 10) and HBOT (n = 10). HBOT was performed in seven daily sessions (2 ATA, 90 min). After seven days, the animals were euthanized. The outcomes were total area, viable area, viable area/total area rate, analysis of dermal appendages and angiogenesis (hematoxylin-eosin), and gene expression analysis of iNOS and VEGF-a biomarkers. RESULTS: The HBOT group showed an increase in viable area compared with the control group (84% versus 47%, p = 0.009, respectively). The HBOT group also showed an increase in appendage units (1.69 ± 0.54 versus 1.87 ± 0.58, p = 0.04) and angiogenesis density (1.29 ± 0.45 versus 1.82 ± 0.64, p < 0.001) compared to the control group. There was a difference between the control and HBOT groups in iNOS levels (0.926 ± 1.4 versus 0.04 ± 0.1 p = 0.002, respectively). However, this study did not show a difference between the groups concerning the gene expression of VEGF-a. CONCLUSION: The use of hyperbaric oxygen therapy increased the viability of cutaneous flaps in tobacco-exposed rats and decreased iNOS mRNA levels; however, it did not change VEGF-a levels. Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

The mule (Equus mulus) as a recipient of horse (Equus caballus) embryos: Comparative aspects of early pregnancy with mares.

The aim of this study was to compare the embryonic and early fetal development of horse embryos between recipient mules and mares from day 10-60 of pregnancy, in addition to hormonal (eCG and progesterone), ovarian, and uterine characteristics for approximately 4 months. Embryo donor mares (n = 5) and two groups of recipients (acyclic mules, n = 7; cyclic mares, n = 7) were used. Donor mares were monitored daily by transrectal ultrasonography and inseminated using fresh semen. Cyclic recipient mares were synchronized with the donor's ovulation using PGF2α and deslorelin acetate. Mules were prepared for the embryo transfers with estrogen and progestagen. Embryo collection and transfer were performed 8 days after ovulation of the donor mares. Pregnancy diagnosis with ultrasonography began 1 day after embryo transfer. After pregnancy confirmation, the recipient mules received long-acting progesterone once weekly for at least 120 days. The first day of detection (day 10) of an embryonic vesicle (EV) was similar between mules and mares. A period of extensive intrauterine mobility of the embryonic vesicle was observed similarly in mules and mares from days 10-17. The day of fixation of the EV in mules tended to be 1-day earlier than in mares; however, the diameter and growth rate of the EV did not differ between the two species. The embryo proper was first detected at day 20, and the crown-rump, width, and diameter were similar between the two recipient types. The heartbeat and allantoic sac tended to be detected 1 day later in mules than in mares, while the umbilical cord was first observed around day 40 in both species. Besides the expected differences found in ovarian aspects and eCG production, similar endometrial diameter, uterine tone and echotexture, and progesterone levels were seen between the two types of recipients. In conclusion, striking ultrasound similarities in equine embryo and fetal development, and uterine characteristics were seen between mules and mares used as recipients of horse embryos.

Risk factors for reporting adverse events and for study withdrawal in a population-based trial of vitamin D supplementation.

With increasing numbers of randomized controlled trials (RCTs) investigating potential health events of vitamin D supplementation, a better understanding is required of the risk factors for adverse events and for study withdrawals. This analysis aimed to identify baseline risk factors of reporting an adverse event in a multi-year randomized double-blinded placebo-controlled trial of vitamin D supplementation. The secondary aim was to investigate if adverse events were associated with study withdrawals. We analyzed data from the Vitamin D Assessment (ViDA) study: 5110 adults, aged 50-84 years, living in Auckland, New Zealand. Monthly doses of 100,000 IU vitamin D3 or placebo were mailed to participants homes, with a questionnaire to collect data on adverse events and adherence to the study capsule (initially monthly, then 4-monthly). Median follow-up was 3.3 years. Data were analysed using multivariable log-binomial regression and Cox-regression. During the follow-up period, 818 people reported adverse events and 412 withdrew or stopped returning questionnaires. Vitamin D was not associated with reporting of adverse events. Of sociodemographic factors, ethnicity was associated with reporting adverse events: compared to European participants, Maori and Pacific Islander people were more likely to report an adverse event. Non-smokers were more likely to report an adverse event, compared to smokers (adjusted hazard ratio (HR) = 1.80; 95%CI = 1.24, 2.62); as were those who had reported a history of depression (adjusted HR = 1.27; 95%CI = 1.01, 1.60) or a recent cough or cold (adjusted HR = 1.22; 95%CI = 1.03, 1.44) at baseline. Reporting of adverse events was not associated with withdrawals (adjusted HR = 1.12; 95%CI = 0.86, 1.46). These data did not identify any clear pattern in the factors associated with self-reported adverse events, which themselves did not increase risk of withdrawals.

Vitamin D status in pregnant women with asthma and its association with adverse respiratory outcomes during infancy.

BACKGROUND: Vitamin D may influence pregnancy and infant outcomes, especially infant respiratory health. This study aimed to examine vitamin D status in pregnant women with asthma, and whether higher vitamin D levels are associated with fewer adverse respiratory outcomes in their infants. METHODS: Pregnant women with asthma, recruited from John Hunter Hospital Newcastle Australia (latitude 33°S), had serum total 25-hydroxyvitamin-D (25(OH)D) measured at 16 and 35 weeks gestation. Infant respiratory outcomes were collected at 12 months by parent-report questionnaire. Mother-infant dyads were grouped by serum 25(OH)D during pregnancy: 25(OH)D < 75 nmol/L (at both time-points) versus 25(OH)D ≥ 75 nmol/L (at one or both time-points). RESULTS: In 52 pregnant women with asthma, mean serum 25(OH)D levels were 61 (range 26-110) nmol/L at 16 weeks, and 65 (range 32-116) nmol/L at 35 weeks, gestation. Thirty-one (60%) women had 25(OH)D < 75 nmol/L at both time-points; 21 (40%) had 25(OH)D ≥ 75 nmol/L at one or both time-points. Maternal 25(OH)D < 75 nmol/L during pregnancy was associated with a higher proportion of infants with "wheeze ever" at 12 months, compared with 25(OH)D ≥ 75 nmol/L (71 versus 43%, p = .04). Infant acute-care presentations (45 versus 13%, p = .02) and oral corticosteroid use (26 versus 4%, p = .03) due to "asthma/wheezing" were higher in the maternal group with 25(OH)D < 75 nmol/L, versus ≥75 nmol/L. CONCLUSIONS: Most pregnant women with asthma had low vitamin D status, which persisted across gestation. Low maternal vitamin D status was associated with greater risk of adverse respiratory outcomes in their infants, a group at high risk of developing childhood asthma.

Diagnosis validation and clinical characterization of atopic dermatitis in Nurses' Health Study 2.

BACKGROUND: Epidemiologic studies of atopic dermatitis (AD) are often limited by case definitions that have not been validated. OBJECTIVE: In this study, we assessed the accuracy of self-report of AD in a large cohort of US female nurses, the Nurses' Health Study 2 (NHS2). We also provide clinical characteristics of AD in the cohort. METHODS: We sent an electronic questionnaire to NHS2 participants who previously reported ever having a diagnosis of AD. This questionnaire was designed to confirm cases of AD using previously validated algorithms with >85% specificity. We assessed the association of AD with asthma, comparing the results when different definitions of AD were applied. We also inquired about various aspects of participants' AD. RESULTS: Responses were received from 2509 of 5126 (49%) nurses who were sent the questionnaire, with an average age of 62. Most participants (1996/2509, 80%) reiterated their previously reported clinician diagnosis of AD. Application of the two diagnostic algorithms yielded confirmation of 1538 and 1293 prevalent cases, respectively. The association of AD with asthma was stronger when more stringent AD case definitions were applied. Participants generally reported mild disease (92% with ≤10% maximal body surface area involved) and a high proportion (57%) reported adult-onset disease. CONCLUSIONS: Self-report of AD diagnosis has good reliability, and future analyses will be strengthened by our ability to conduct sensitivity analyses with refined confirmed AD subgroups.

Diarrhoeagenic Escherichia coli and Escherichia albertii in Brazil: pathotypes and serotypes over a 6-year period of surveillance.

Diarrhoeagenic Escherichia coli (DEC) is a leading cause of infectious diarrhoea worldwide. In recent years, Escherichia albertii has also been implicated as a cause of human enteric diseases. This study describes the occurrence of E. coli pathotypes and serotypes associated with enteric illness and haemolytic uremic syndrome (HUS) isolated in Brazil from 2011 to 2016. Pathotypes isolated included enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAEC), enterotoxigenic E. coli (ETEC), enteroinvasive E. coli (EIEC) and Shiga toxin-producing E. coli (STEC). PCR of stool enrichments for DEC pathotypes was employed, and E. albertii was also sought. O:H serotyping was performed on all DEC isolates. A total of 683 DEC and 10 E. albertii strains were isolated from 5047 clinical samples. The frequencies of DEC pathotypes were 52.6% (359/683) for EPEC, 32.5% for EAEC, 6.3% for ETEC, 4.4% for EIEC and 4.2% for STEC. DEC strains occurred in patients from 3 months to 96 years old, but EPEC, EAEC and STEC were most prevalent among children. Both typical and atypical isolates of EPEC and EAEC were recovered and presented great serotype heterogeneity. HUS cases were only associated with STEC serotype O157:H7. Two E. albertii isolates belonged to serogroup O113 and one had the stx2f gene. The higher prevalence of atypical EPEC in relation to EAEC in community-acquired diarrhoea in Brazil suggests a shift in the trend of DEC pathotypes circulation as previously EAEC predominated. This is the first report of E. albertii isolation from active surveillance. These results highlight the need of continuing DEC and E. albertii surveillance, as a mean to detect changes in the pattern of pathotypes and serotypes circulation and provide useful information for intervention and control strategies.

Molecular epidemiology of methicillin-susceptible Staphylococcus aureus (MSSA) isolated from milk of cows with subclinical mastitis.

Bovine mastitis has been a concern for dairy herd for decades. The adaptation capacity of one of the main species responsible for this disease, Staphylococcus aureus (S. aureus), plays a pivotal role in this issue. The aim of this study was to establish a molecular and phenotypic profile of 285 S. aureus strains isolated from milk of subclinical mastitis cows from 18 different farms in São Paulo State using spa typing, multilocus sequence typing (MLST), pulsed field gel electrophoresis (PFGE), agr cluster (I, II, III and IV) typing, PCR for genes including enterotoxins (sea, seb, sec, sed, see, seg, seh, sei), toxic shock syndrome toxin (tsst-1), and Panton-Valentine leucocidin (pvl), as well as in vitro resistance assays for 12 antibiotics. The results showed a wide variety of strains with a high toxigenic potential; concomitantly, sec, seg and seh were prevalent. In addition, we observed a predominance of the spa types t605 (ST 126, CC126) and t127 (ST1, CC1) and the unusual presence of t321 causing bovine mastitis, which has been previously reported only in swine. The most frequent ST were ST126 (70.5%) and ST1 (10.5%). Regarding PFGE, we observed four major groups and six profile patterns. The highest resistance was observed for streptomycin (9.5%), followed by tetracycline (3.5%), clindamycin (9.3%), and erythromycin (2.8%). The tsst-1 gene was detected in 36.8% of isolates and pvl was not observed. One hundred and thirty-six (47.7%) isolates possessed agr type II, followed by types III (20%) and I (8.1%), with type IV not being detected. We observed that the same spa type could result in different PFGE profiles, so the exclusive use of spa type sequences can lead to incorrect interpretations regarding the spread of clones in an epidemiological context.

Multiple drug intolerance syndrome and multiple drug allergy syndrome: Epidemiology and associations with anxiety and depression.

BACKGROUND: The epidemiology of multiple drug intolerance syndrome (MDIS) and multiple drug allergy syndrome (MDAS) is poorly characterized. We used electronic health record (EHR) data to describe prevalences of MDIS and MDAS and to examine associations with anxiety and depression. METHODS: Patients with ≥3 outpatient encounters at Partners HealthCare System from 2008 to 2015 were included. Patients with MDIS had intolerances to ≥3 drug classes, and patients with MDAS had hypersensitivities to ≥2 drug classes. Psychiatric conditions and comorbidities were defined from the EHR and used in multivariable logistic regression models to assess the relation between anxiety/depression and MDIS/MDAS. RESULTS: Of 746 888 patients, 47 634 (6.4%) had MDIS and 8615 (1.2%) had MDAS; 3171 (0.4%) had both. Anxiety (adjusted odds ratio [aOR] 1.72 [1.65, 1.80]), depression (aOR 1.46 [1.41, 1.52]), and both anxiety and depression (aOR 1.97 [1.86, 2.08]) were associated with increased odds of MDIS. Depression was associated with increased odds of MDAS (aOR 1.41 [1.28, 1.56]), but there were no clear associations with anxiety (aOR 1.13 [0.99, 1.30]) nor both depression and anxiety (aOR 1.13 [0.92, 1.38]). CONCLUSION: While 6% of patients had MDIS, only 1% had MDAS. MDIS was associated with both anxiety and depression; patients with both anxiety and depression had an almost twofold increased odds of MDIS. MDAS was associated with a 40% increased odds of depression, but there was no significant association with anxiety. Psychological assessments may be useful in the evaluation and treatment of patients with MDIS and MDAS; physiologic causes for MDAS warrant further investigation.

The urgent need for a harmonized severity scoring system for acute allergic reactions.

The accurate assessment and communication of the severity of acute allergic reactions are important to patients, clinicians, researchers, the food industry, and public health and regulatory authorities. Severity has different meanings to different stakeholders with patients and clinicians rating the significance of particular symptoms very differently. Many severity scoring systems have been generated, most focusing on the severity of reactions following exposure to a limited group of allergens. They are heterogeneous in format, none has used an accepted developmental approach, and none has been validated. Their wide range of outcome formats has led to difficulties with interpretation and application. Therefore, there is a persisting need for an appropriately developed and validated severity scoring system for allergic reactions that work across the range of allergenic triggers and address the needs of different stakeholder groups. We propose a novel approach to develop and then validate a harmonized scoring system for acute allergic reactions, based on a data-driven method that is informed by clinical and patient experience and other stakeholders' perspectives. We envisage two formats: (i) a numerical score giving a continuum from mild to severe reactions that are clinically meaningful and are useful for allergy healthcare professionals and researchers, and (ii) a three-grade-based ordinal format that is simple enough to be used and understood by other professionals and patients. Testing of reliability and validity of the new approach in a range of settings and populations will allow eventual implementation of a standardized scoring system in clinical studies and routine practice.