Training to Increase Minority Enrollment in Lupus Clinical Trials With Community Engagement: Enhancing Lupus Clinical Trial Recruitment Through Provider and Community Health Worker Engagement.

OBJECTIVE: This study evaluates the effectiveness of the Training to Increase Minority Enrollment in Lupus Clinical Trials with Community Engagement (TIMELY) program on enhancing referrals of underrepresented patients to lupus clinical trials. TIMELY leverages two existing American College of Rheumatology online educational initiatives: Materials to Increase Minority Involvement in Clinical Trials (MIMICT), a continuing medical education activity for health care providers, and the community health worker (CHW) Lupus Clinical Trials Training (LuCTT). TIMELY introduced a unique roundtable meeting format to build on the existing online educational programs and facilitate discussions between local clinical trial sites and provider and CHW participants. METHODS: This study used an online pretest and posttest design to assess changes in theory-based behavioral predictors of lupus clinical trial referrals and engagement (ie, knowledge, attitudes, self-efficacy, and intentions) among providers and CHWs. Participants completed MIMICT or LuCTT and then were eligible to participate in roundtable meetings. Paired t-tests were used to assess changes in composite scores before and after the intervention for each of the outcomes. RESULTS: The final sample included 40 providers and 18 CHWs. Knowledge scores increased significantly for both providers (P < 0.01) and CHWs (P < 0.001) on completion of MIMICT and LuCTT, respectively. After participating in the TIMELY roundtable, providers' composite scores for self-efficacy and intentions significantly increased (P < 0.001). Provider self-efficacy gains were sustained at three months' follow-up (P < 0.001). CONCLUSION: These promising findings highlight the potential and opportunities for the TIMELY program to improve behavioral predictors of trial referrals, including CHW knowledge and providers' knowledge, self-efficacy, and intentions to refer underrepresented patients to lupus clinical trials.

Seizure control via pH manipulation: a phase II double-blind randomised controlled trial of inhaled carbogen as adjunctive treatment of paediatric convulsive status epilepticus (Carbogen for Status Epilepticus in Children Trial (CRESCENT)).

BACKGROUND: Paediatric convulsive status epilepticus is the most common neurological emergency presenting to emergency departments. Risks of resultant neurological morbidity and mortality increase with seizure duration. If the seizure fails to stop within defined time-windows, standard care follows an algorithm of stepwise escalation to more intensive treatments, ultimately resorting to induction of general anaesthesia and ventilation. Additionally, ventilatory support may also be required to treat respiratory depression, a common unwanted effect of treatment. There is strong pre-clinical evidence that pH (acid-base balance) is an important determinant of seizure commencement and cessation, with seizures tending to start under alkaline conditions and terminate under acidic conditions. These mechanisms may be particularly important in febrile status epilepticus: prolonged fever-related seizures which predominantly affect very young children. This trial will assess whether imposition of mild respiratory acidosis by manipulation of inhaled medical gas improves response rates to first-line medical treatment. METHODS: A double-blind, placebo-controlled trial of pH manipulation as an adjunct to standard medical treatment of convulsive status epilepticus in children. The control arm receives standard medical management whilst inhaling 100% oxygen; the active arm receives standard medical management whilst inhaling a commercially available mixture of 95% oxygen, 5% carbon dioxide known as 'carbogen'. Due to the urgent need to treat the seizure, deferred consent is used. The primary outcome is success of first-line treatment in seizure cessation. Planned subgroup analyses will be undertaken for febrile and non-febrile seizures. Secondary outcomes include rates of induction of general anaesthesia, admission to intensive care, adverse events, and 30-day mortality. DISCUSSION: If safe and effective 95% oxygen, 5% carbon dioxide may be an important adjunct in the management of convulsive status epilepticus with potential for pre-hospital use by paramedics, families, and school staff. TRIAL REGISTRATION: EudraCT: 2021-005367-49. CTA: 17136/0300/001. ISRCTN: 52731862. Registered on July 2022.

Dual bronchodilators in Bronchiectasis study (DIBS): protocol for a pragmatic, multicentre, placebo-controlled, three-arm, double-blinded, randomised controlled trial studying bronchodilators in preventing exacerbations of bronchiectasis.

INTRODUCTION: Bronchiectasis is a long-term lung condition, with dilated bronchi, chronic inflammation, chronic infection and acute exacerbations. Recurrent exacerbations are associated with poorer clinical outcomes such as increased severity of lung disease, further exacerbations, hospitalisations, reduced quality of life and increased risk of death. Despite an increasing prevalence of bronchiectasis, there is a critical lack of high-quality studies into the disease and no treatments specifically approved for its treatment. This trial aims to establish whether inhaled dual bronchodilators (long acting beta agonist (LABA) and long acting muscarinic antagonist (LAMA)) taken as either a stand-alone therapy or in combination with inhaled corticosteroid (ICS) reduce the number of exacerbations of bronchiectasis requiring treatment with antibiotics during a 12 month treatment period. METHODS: This is a multicentre, pragmatic, double-blind, randomised controlled trial, incorporating an internal pilot and embedded economic evaluation. 600 adult patients (≥18 years) with CT confirmed bronchiectasis will be recruited and randomised to either inhaled dual therapy (LABA+LAMA), triple therapy (LABA+LAMA+ICS) or matched placebo, in a 2:2:1 ratio (respectively). The primary outcome is the number of protocol defined exacerbations requiring treatment with antibiotics during the 12 month treatment period. ETHICS AND DISSEMINATION: Favourable ethical opinion was received from the North East-Newcastle and North Tyneside 2 Research Ethics Committee (reference: 21/NE/0020). Results will be disseminated in peer-reviewed publications, at national and international conferences, in the NIHR Health Technology Assessments journal and to participants and the public (using lay language). TRIAL REGISTRATION NUMBER: ISRCTN15988757.

Immunological differences between heart- and kidney-transplanted children: a cross-sectional study.

Post-transplantation lymphoproliferative disorder is a potentially mortal complication after heart transplantation in children. As the immune system plays a crucial role in the development of lymphoma, we explored the influence of thymus function in relation to immunosuppressive treatment in organ-transplanted children and healthy control subjects. A prospective case-control study was performed at a single centre, in which 36 children who had undergone heart transplantation were compared to two control groups: 34 kidney-transplanted children and 33 healthy age- and sex-matched children. T- and B-lymphocyte subtypes and monocytes were analysed by flow cytometry, and T-cell receptor excision circles were assessed using quantitative polymerase chain reaction. Heart-transplanted children had a lymphocyte profile characterised by reduced or absent thymic function with low numbers of T-cell receptor excision circles and total and naïve T cells, together with immune activation against the allograft. Despite similar immunosuppressive treatment, the kidney-transplanted group showed an activated T-lymphocyte compartment.

Perspectivas actuales del rol de la anestesia en los trastornos del sueño postoperatorio / Sleep disorders and anesthesia: An actual perspective

Current perspectives on the role of anesthesia in postoperative sleep disorders. Postoperative sleep disorders are attributed to different causes, such as surgical stress, pain, drugs, environmental factors typical of critical patient units and they can cause serious effects that will affect surgical results. Mainly, a decrease in the deep and REM sleep stages is observed in the first two postoperative days with a significant rebound of REM sleep between days two and five, a period in which most of the postoperative complications are also observed. Anesthesia has a minor role in the appearance of sleep disorders, and this depends on the type of anesthesia. General anesthesia induces a desynchronization of the circadian rhythm and is related to a higher incidence of postoperative sleep disorders than regional anesthesia. The magnitude and type of disorders depends on the different types of anesthetics, the mechanism of action on the central nervous system level, the dose used and the time of day in which it is administered, as well as the patient's own conditions such as age or comorbidities. A better understanding of the relationship between anesthesia and the circadian rhythm can have a significant impact on the postoperative recovery of patients.

Los trastornos del sueño posoperatorio pueden causar efectos graves, que afectan los resultados quirúrgicos y se atribuyen al estrés quirúrgico, al dolor, a los fármacos y a factores ambientales propios de las unidades de paciente crítico. Principalmente se observa disminución de las etapas de sueño profundo y REM en los primeros dos días postoperatorios con importante rebote del REM entre el día dos y cinco, período en el cual también se observan la mayoría de las complicaciones posquirúrgicas. El rol de la anestesia en la aparición de los trastornos del sueño es menor y depende del tipo de anestesia empleado. La anestesia general induce desincronización del ritmo circadiano y se relaciona a mayor incidencia de trastornos del sueño posoperatorio que la anestesia regional. La magnitud y el tipo de alteraciones depende de los diferentes tipos de anestésicos, del mecanismo de acción a nivel de sistema nervioso central, de la dosis empleada y del momento del día en el cual se administra, además de condiciones propias del paciente como edad o comorbilidad. Existe gran interés en comprender mejor la relación entre la anestesia y el ritmo circadiano ya que eso puede tener importante impacto en la recuperación postoperatoria de los pacientes.

Traditional Farming Lifestyle in Old Older Mennonites Modulates Human Milk Composition.

Background: In addition to farming exposures in childhood, maternal farming exposures provide strong protection against allergic disease in their children; however, the effect of farming lifestyle on human milk (HM) composition is unknown. Objective: This study aims to characterize the maternal immune effects of Old Order Mennonite (OOM) traditional farming lifestyle when compared with Rochester (ROC) families at higher risk for asthma and allergic diseases using HM as a proxy. Methods: HM samples collected at median 2 months of lactation from 52 OOM and 29 ROC mothers were assayed for IgA1 and IgA2 antibodies, cytokines, endotoxin, HM oligosaccharides (HMOs), and targeted fatty acid (FA) metabolites. Development of early childhood atopic diseases in children by 3 years of age was assessed. In addition to group comparisons, systems level network analysis was performed to identify communities of multiple HM factors in ROC and OOM lifestyle. Results: HM contains IgA1 and IgA2 antibodies broadly recognizing food, inhalant, and bacterial antigens. OOM HM has significantly higher levels of IgA to peanut, ovalbumin, dust mites, and Streptococcus equii as well TGF-ß2, and IFN-λ3. A strong correlation occurred between maternal antibiotic use and levels of several HMOs. Path-based analysis of HMOs shows lower activity in the path involving lactoneohexaose (LNH) in the OOM as well as higher levels of lacto-N-neotetraose (LNnT) and two long-chain FAs C-18OH (stearic acid) and C-23OH (tricosanoic acid) compared with Rochester HM. OOM and Rochester milk formed five different clusters, e.g., butyrate production was associated with Prevotellaceae, Veillonellaceae, and Micrococcaceae cluster. Development of atopic disease in early childhood was more common in Rochester and associated with lower levels of total IgA, IgA2 to dust mite, as well as of TSLP. Conclusion: Traditional, agrarian lifestyle, and antibiotic use are strong regulators of maternally derived immune and metabolic factors, which may have downstream implications for postnatal developmental programming of infant's gut microbiome and immune system.

Infant gut microbiome is enriched with Bifidobacterium longum ssp. infantis in Old Order Mennonites with traditional farming lifestyle.

BACKGROUND: Growing up on traditional, single-family farms is associated with protection against asthma in school age, but the mechanisms against early manifestations of atopic disease are largely unknown. We sought determine the gut microbiome and metabolome composition in rural Old Order Mennonite (OOM) infants at low risk and Rochester, NY urban/suburban infants at high risk for atopic diseases. METHODS: In a cohort of 65 OOM and 39 Rochester mother-infant pairs, 101 infant stool and 61 human milk samples were assessed by 16S rRNA gene sequencing for microbiome composition and qPCR to quantify Bifidobacterium spp. and B. longum ssp. infantis (B. infantis), a consumer of human milk oligosaccharides (HMOs). Fatty acids (FAs) were analyzed in 34 stool and human 24 milk samples. Diagnoses and symptoms of atopic diseases by 3 years of age were assessed by telephone. RESULTS: At a median age of 2 months, stool was enriched with Bifidobacteriaceae, Clostridiaceae, and Aerococcaceae in the OOM compared with Rochester infants. B. infantis was more abundant (p < .001) and prevalent, detected in 70% of OOM compared with 21% of Rochester infants (p < .001). Stool colonized with B. infantis had higher levels of lactate and several medium- to long/odd-chain FAs. In contrast, paired human milk was enriched with a distinct set of FAs including butyrate. Atopic diseases were reported in 6.5% of OOM and 35% of Rochester children (p < .001). CONCLUSION: A high rate of B. infantis colonization, similar to that seen in developing countries, is found in the OOM at low risk for atopic diseases.

Bone marrow mesenchymal stem cells from patients with SLE maintain an interferon signature during in vitro culture.

BACKGROUND: We have previously shown that SLE BMSC have decreased proliferation, increased ROS, increased DNA damage and repair (DDR), a senescence associated secretory phenotype, and increased senescence-associated ß-galactosidase. We have also shown SLE BMSC produce increased amounts of interferon beta (IFNß), have increased mRNA for several genes induced by IFNß, and have a pro-inflammatory feedback loop mediated by a MAVS. To better understand the phenotype of SLE BMSC we conducted mRNA sequencing. METHODS: Patients fulfilling SLE classification criteria and age and sex matched healthy controls were recruited under an Institutional Review Board approved protocol. Bone marrow aspirates and peripheral blood samples were obtained. BMSC were isolated and grown in tissue culture. Early passage BMSC were harvested and mRNA samples were sent for RNAseq. Serum samples were assayed for IFNß by ELISA. RESULTS: On the basis of top differentially expressed genes between SLE and healthy controls, SLE patients with high levels of serum IFNß clustered together while SLE patients with low levels of IFNß clustered with healthy controls. Those genes differentially expressed in SLE patients generally belonged to known IFN pathways, and showed a strong overlap with the set of genes differentially expressed in IFNß high subjects, per se. Moreover, gene expression changes induced by treating healthy BMSC with exogenous IFNß were remarkably similar to gene expression differences in SLE IFNß high vs low BMSC. CONCLUSIONS: BMSCs from SLE patients are heterogeneous. A subgroup of SLE BMSC is distinguished from other SLE BMSC and from controls by increased levels of mRNAs induced by type I interferons. This subgroup of SLE patients had increased levels of IFNß in vivo.

Diagnostico bacteriológico de sepsis neonatal / Bacteriological diagnosis of sepsis neonatal

Con la finalidad de investigar la flora bacteriana más común y la forma de realización del diagnóstico bacteriológico se plantea este estudio, por considerarse la sepsis una patología relevante del período neonatal, la cual debida a la inmadurez del sitema inmunológico del recién nacido, puede desencadenar la muerte del mismo y/o producir secuelas irreversibles. Se realizó un estudio retrospectivo, descriptivo y transversal con 78 historias de recién nacidos con diagnóstico de egreso de sepsis neonatal, evaluados en el Servicio de Peditría del Hospital Dr Domingo Guzmán Lander, en la ciudad de Barcelona, durante 1992-1997. Se evaluaron los siguientes parámetros: sexo, sepsis temprana o tardía, alteraciones de laboratorio, resultados de cultivos, signología clínica. La sepsis de aparición, temprana estuvo presente en un 63 por ciento de los casos estudiados y en forma tardía en un 37 por ciento. Los 5 signos encontrados con más frecuencia fueron: ictericia, dificultad respiratoria (tirajes), fiebre, hipoactividad y cianosis. Se tomó muaestra para cultivo en sólo 26 casos (33 por ciento). Se cultivaron muestras de : heces, sangre, orina, oído, ombligo, exudado faríngeo, contenido gástrico y cavidad abdominal. El germen frecuente aislado fue klebsiella pneumoniae, presente un 31 por ciento de los cultivos. El aislamiento del germen causal de bacteriemia constituye la prueba diagnóstica de certeza para sepsis neonatal. Sólo la práctica rutinaria de hemocultivos en estos pacientes, permitirá conocer las bacterianas más frecuentes implicadas en esta patología y su respectro de sensibilidad a los agentes antimicrobianos.

Relacíon del bajo peso al nacer con el desarrollo psicomotor del niño de Puriscal / Low birth weight and psychomotor development in children in Puriscal, Costa Rica

Se realizó un estudio del desarrollo psicomotor en 84 niños de los distritos de Barbacoas, Grifo Alto y Candelarita de Puriscal, a los 18 meses de edad. El estudio comprendió las áreas de motricidad, adaptación, lenguaje, personal-social, utilización de recursos, búsqueda del objeto y exploración, evaluadas por medio de pruebas de desarrollo psicomotor de Gesell y Casati-Lezine. Luego de evaluar las áreas se obtuvo un índice de desarrollo (I.D.) global que fue relacionado con la edad gestacional y el peso al nacer de los niños. Los niños de pretérmino mostraron I.D. inferiores en relación con los nacidos a término (p=0,003). Además, se encontró una relación directa entre el peso al nacer y el índice de desarrollo, pues cuanto más bajo era el peso, más bajo fue el índice (r=0,39, p=0,001). Al combinarse el bajo peso al nacer con la prematuridad, el I.D. fue aún más bajo