The Eczema Area and Severity Index: An update of progress and challenges in its measurement of atopic dermatitis after 20 years of use.

The Eczema Area and Severity Index is an investigator-assessed instrument reporting clinical signs of atopic dermatitis. The instrument is extensively validated in both adult and paediatric populations and recommended as a core outcome measure to assess clinical signs by the Harmonising Outcome Measures for Eczema initiative in clinical trials and was recently recommended as an option to measure signs in clinical practice. Here, we review the validation of the instrument using standard assessment criteria, explore controversies and challenges to its universal applicability and highlight future electronic adaptations. We find that the instrument demonstrates adequate performance in the measurement properties recommended by the COnsensus-based Standards for the selection of health Measurement INstruments initiative for instruments reporting clinical signs, is clinically interpretable, and is suitable for all atopic dermatitis severities. Some validation gaps remain. Information reporting on its performance in diverse populations, with emphasis on deeply pigmented skin, is promising though limited. Technological adaptations are demonstrating promising initial validation results and may facilitate remote and/or automated assessments assisting clinical care and decentralized clinical trials in the future. We find no strong evidence limiting its use in trials or clinical practice although questions pertaining to the effect of investigator training remain. We recommend that the Eczema Area and Severity Index be used in all interventional atopic dermatitis trials and be considered alongside other recommended clinical practice severity instruments.

Clay Tailings Flocculated in Seawater and Industrial Water: Analysis of Aggregates, Sedimentation, and Supernatant Quality.

High-molecular-weight anionic polyacrylamide was used to analyze the effect of kaolin on the structure of particle aggregates formed in freshwater and seawater. Batch flocculation experiments were performed to determine the size of the flocculated aggregates over time by using focused beam reflectance measurements. Sedimentation tests were performed to analyze the settling rate of the solid-liquid interface and the turbidity of the supernatant. Subsequently, a model that relates the hindered settling rate to the aggregate size was used to determine the mass fractal dimension (Df). Flocculation kinetics revealed that greater amounts of kaolin generated larger aggregates because of its lamellar morphology. The maximum size was between 10 and 20 s of flocculation under all conditions. However, the presence of kaolin reduced the settling rate. The fractal dimension decreased with the increase in the kaolin content, resulting in the formation of irregular and porous aggregates. By contrast, factors such as the flocculation time, water quality, and quartz size had limited influences on the fractal dimension. Seawater produced a clearer supernatant because of its higher ionic strength and precoagulation of particles. Notably, the harmful effect of clays in seawater was reduced.

ALLIANCE A022104/NRG-GI010: The Janus Rectal Cancer Trial: a randomized phase II/III trial testing the efficacy of triplet versus doublet chemotherapy regarding clinical complete response and disease-free survival in patients with locally advanced rectal cancer.

Background: Recent data have demonstrated that in locally advanced rectal cancer (LARC), a total neoadjuvant therapy (TNT) approach improves compliance with chemotherapy and increases rates of tumor response compared to neoadjuvant chemoradiation (CRT) alone. They further indicate that the optimal sequencing of TNT involves consolidation (rather than induction) chemotherapy to optimize complete response rates. Data, largely from retrospective studies, have also shown that patients with clinical complete response (cCR) after neoadjuvant therapy may be managed safely with the watch and wait approach (WW) instead of preemptive total mesorectal resection (TME). However, the optimal consolidation chemotherapy regimen to achieve cCR has not been established, and a randomized clinical trial has not robustly evaluated cCR as a primary endpoint. Collaborating with a multidisciplinary oncology team and patient groups, we designed this NCI-sponsored study of chemotherapy intensification to address these issues and to drive up cCR rates, to provide opportunity for organ preservation, improve quality of life for patients and improve survival outcomes. Methods: In this NCI-sponsored multi-group randomized, seamless phase II/III trial (1:1), up to 760 patients with LARC, T4N0, any T with node positive disease (any T, N+) or T3N0 requiring abdominoperineal resection or coloanal anastomosis and distal margin within 12 cm of anal verge will be enrolled. Stratification factors include tumor stage (T4 vs T1-3), nodal stage (N+ vs N0) and distance from anal verge (0-4; 4-8; 8-12 cm). Patients will be randomized to receive neoadjuvant long course chemoradiation (LCRT) followed by consolidation doublet (mFOLFOX6 or CAPOX) or triplet chemotherapy (mFOLFIRINOX) for 3-4 months. LCRT in both arms involves 4500 cGy in 25 fractions over 5 weeks + 900 cGy boost in 5 fractions with a fluoropyrimidine (capecitabine preferred). Patients will undergo assessment 8-12 (+/- 4) weeks post-TNT completion. The primary endpoint for the phase II portion will compare cCR between treatment arms. A total number of 296 evaluable patients (148 per arm) will provide statistical power of 90.5% to detect an 17% increase in cCR rate, at a one-sided alpha=0.048. The primary endpoint for the phase III portion will compare disease-free survival (DFS) between treatment arms. A total of 285 DFS events will provide 85% power to detect an effect size of hazard ratio 0.70 at a one-sided alpha of 0.025, requiring enrollment of 760 patients (380 per arm). Secondary objectives include time-to event outcomes (overall survival, organ preservation time and time to distant metastasis) and adverse effects. Biospecimens including archival tumor tissue, plasma and buffy coat in EDTA tubes, and serial rectal MRIs will be collected for exploratory correlative research. This study, activated in late 2022, is open across the NCTN and has a current accrual of 312. Support: U10CA180821, U10CA180882, U24 CA196171; https://acknowledgments.alliancefound.org . Discussion: Building off of data from modern day rectal cancer trials and patient input from national advocacy groups, we have designed the current trial studying chemotherapy intensification via a consolidation chemotherapy approach with the intent to enhance cCR and DFS rates, increase organ preservation rates, and improve quality of life for patients with rectal cancer. Trial Registration: Clinicaltrials.gov ID: NCT05610163 ; Support includes U10CA180868 (NRG) and U10CA180888 (SWOG).

Assessing periparturient ewe characteristics and nemabiome composition to guide targeted selective treatment for sustainable gastrointestinal nematodes control in sheep.

Gastrointestinal nematodes (GINs) are a significant threat to the sustainability of global sheep production. Periparturient ewes play a key role in GIN epidemiology, with increased GIN faecal egg counts (FECs) in these ewes resulting in heavy pasture contamination that facilitates parasitic gastroenteritis in immunologically naïve lambs later during the grazing period. Traditionally, blanket anthelmintic treatment would suppress GIN egg outputs in these ewes and subsequent pasture contamination. However, farmers are now advised to implement targeted selective treatment (TST) to reduce anthelmintic use and subsequent anthelmintic resistance development, yet, there is currently limited evidence to determine optimal TST strategies in ewes. In this study, the characteristics of 226 ewes on seven Welsh farms were assessed postlambing to identify factors associated with their individual strongyle FECs using negative binomial mixed model analysis. Nemabiome analysis was conducted on 34 ewes across two study farms using the Oxford Nanopore MinIon platform with an aim of identifying factors associated with variations in ewe nemabiome composition within flocks. The best-fitted model of ewe FEC incorporated ewe body condition score, dag score, breed, and an interaction effect between ewe age and litter size as fixed factors. The addition of a mean FEC value for ewes of a specific litter size on each farm further improved model fit and reduced between-farm variance in the model. Nemabiome analysis revealed significant variation in within flock nemabiome diversity on individual farms, with significantly reduced nemabiome diversity recorded in ewes exhibiting dags and in twin-bearing ewes on respective farms, whilst T. circumcincta was present as a significantly higher proportion of the nemabiome in Suffolk ewes and twin bearing ewes (P < 0.05) in respective flocks. Our data demonstrate that commonly recorded ewe characteristics can be exploited to predict individual periparturient ewe FEC and subsequently may be used as a guide for TST strategies on sheep farms once specific TST thresholds are identified to deliver the optimal balance between minimal pasture contamination and maximal GIN refugia. This study is the first to utilise Oxford Nanopore MinIon sequencing to evaluate the nemabiome of sheep, and to molecularly assess the nemabiome of individual ruminants within a flock/herd, with results indicating that significant within flock variations in nemabiome composition which may have implications for TST and flock management strategies.

The use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection and other potential indications: second edition of joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines.

The first British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS)-endorsed faecal microbiota transplant (FMT) guidelines were published in 2018. Over the past 5 years, there has been considerable growth in the evidence base (including publication of outcomes from large national FMT registries), necessitating an updated critical review of the literature and a second edition of the BSG/HIS FMT guidelines. These have been produced in accordance with National Institute for Health and Care Excellence-accredited methodology, thus have particular relevance for UK-based clinicians, but are intended to be of pertinence internationally. This second edition of the guidelines have been divided into recommendations, good practice points and recommendations against certain practices. With respect to FMT for Clostridioides difficile infection (CDI), key focus areas centred around timing of administration, increasing clinical experience of encapsulated FMT preparations and optimising donor screening. The latter topic is of particular relevance given the COVID-19 pandemic, and cases of patient morbidity and mortality resulting from FMT-related pathogen transmission. The guidelines also considered emergent literature on the use of FMT in non-CDI settings (including both gastrointestinal and non-gastrointestinal indications), reviewing relevant randomised controlled trials. Recommendations are provided regarding special areas (including compassionate FMT use), and considerations regarding the evolving landscape of FMT and microbiome therapeutics.

John R. Ward, MD: Pioneer-Clinical Trials in Rheumatology.

John Robert Ward was one of the early academic rheumatologists in the United States. He was the founding father of rheumatology in the Intermountain West, the first Chief of the Division of Rheumatology in the Department of Internal Medicine at the University of Utah. Dr Ward became a national leader in the understanding and treatment of rheumatic disease. His foundational work established gold-standard techniques for the successful investigation of anti-rheumatic drugs. His leadership and scientific contributions clearly qualify him as a "giant in rheumatology."

Ivermectin treatment response in two rural villages with a high prevalence of onchocerciasis and epilepsy, Mahenge Tanzania

Background: Despite 20 years of ivermectin mass distribution in the Mahenge area, Tanzania, the prevalence of onchocerciasis and epilepsy has remained high in rural villages. Objectives: We investigated the efficacy of ivermectin in reducing Onchocerca volvulus microfilariae and predictors for parasitic load following ivermectin treatment in persons with (PWE) and without epilepsy (PWOE). Methods: Between April and September 2019, 50 PWE and 160 randomly selected PWOE from Msogezi and Mdindo villages participated in a follow-up study. Skin snips were obtained pre (baseline) and three months post-ivermectin treatment. Results: The overall prevalence of O. volvulus positive skin snips at baseline was 49% (103/210), with no significant difference between PWE (58.0%) and PWOE (46.3%); p=0.197. The overall mean micro filarial density was significantly higher at baseline 1.45(95%CI:0.98-2.04)) than three-month post-ivermectin treatment (0.23(95%CI:0.11-0.37), p<0.001. Three months after ivermectin, the micro filarial density had decreased by ≥80% in 54 (81.8%, 95%CI: 72.3-91.4) of the 66 individuals with positive skin snips at baseline. High micro filarial density at baseline was the only significant predictor associated with higher micro filarial density in the post-ivermectin skin snips. Conclusion: Our study reports a decrease in micro filarial density following ivermectin treatment in most individuals. Optimizing ivermectin coverage will address the ongoing onchocerciasis transmission in Mahenge

Opiniones y creencias de embarazadas encontrol prenatal relacionadas con salud oral y embarazo / Opinion and beliefs of pregnancy women in prenatal control related to oral health and pregnant

Los procesos vitales son motivo de preguntas para la humanidad. La cultura popular da respuestas a éstas, no siempre científicamente, transformando las creencias en mitos. En salud oral, se cree que las embarazadas desarrollarían caries más fácilmente que la población general, considerándose normal que “por cada hijo se pierda un diente”, y mujeres embarazadas no desean recibir atención odontológica por el daño que podría producir al feto el uso de anestésicos locales, hecho importante ante la carencia de información del bajo riesgo que poseen para el paciente éstos procedimientos por algunos médicos, quienes rehusan someter a embarazadas a tratamientos dentales. La cultura tiene una profunda relación en el estilo de vida, sociabilización y autoayuda, mecanismos de intervención que serían cimientos que basan la promoción en salud. La investigación busca conocer las ideas que posee un grupo de embarazadas en control prenatal, en torno a la salud oral y el embarazo. Fue confeccionada una encuesta con 5 preguntas cerradas, aplicándose a 65 embarazadas seleccionadas aleatoriamente. La muestra fue obtenida por conveniencia. El 98% de las encuestadas cree que durante el embarazo es necesario consultar al odontólogo, el 60% cree que el embarazo produce caries y el 70% cree que el embarazo puede producir pérdida de piezas dentarias. Se requieren más esfuerzos en educación durante el control prenatal para entregar conocimientos adecuados a las embarazadas en relación a salud oral y embarazo, incluyendo el factor cultural, que les permita mejorarlas medidas de auto cuidado durante este período (AU)

Vital processes have created questions to humankind. People’s culture gives non-scientific response to some of it, changing beliefs into myths. Related to oral health, several cultures believe that pregnant women could suffer more frequently dental caries than general population, is considered normal that "by each one baby, mother lost a teeth", and some pregnant patients are not able to receive dental treatment, because this procedures could produce damages to fetus in develop; important situation considering absence of information that dental procedures expose to such a low risk to patients in some physicians, whom refuse authorize to pregnant women to receive dental treatment. Culture has a deep relationship to life styles, social relations and self-help; in these intervention mechanisms are based health promotion. The research seeks to know the ideas have a group of pregnant women in prenatal control related to oral health and pregnant. Was made a survey with 5 closed questions, applied to 65 pregnant woman randomly selected. 98% of women think that through pregnant period is necessary to visit a dentist, 60% believe that pregnant cause dental caries and 70% thinks that pregnant could cause lost of tooth. Mayor efforts in education, considering cultural factors, are required through prenatal control to improve knowledge as well as self care in oral health in these patients group (AU)

Tetanus in Barbados

This paper gives a report on the management of 29 cases of tetanus admitted to one hospital during a period of twelve months. The incidence of the disease was roughly the same as in previous years. The number of deaths, however, were markedly reduced. The poor prognosis of respiratory complication is confirmed. Three principles of therapy, high doses of A.T.S., heavy sedation and the use of barbiturates and chlorpromazine are stressed (AU)

The results and treatment of tetanus

This paper gives a report on the management of twenty-nine (29) cases of tetanus admitted to one hospital during a period of twelve months. The incidence of the disease was roughly the same as previous years. The number of deaths, however were markedly reduced. The poor prognosis of respiratory complication is confirmed. Three principles of therapy, high doses ATS, heavy sedation and the use of barbiturates and chlorpromazine are stressed (AU)