Targeted Combined Endpoint Improvement in Patient and Disease Domains in Atopic Dermatitis: A Treat-to-Target Analysis of Adults with Moderate-to-Severe Atopic Dermatitis Treated with Upadacitinib.

A treat-to-target approach was recently developed to guide systemic treatment for adults with atopic dermatitis (AD). Recommendations outlined criteria for a 3-month initial acceptable treatment target and a 6-month optimal target, evaluated using global assessment of patient-reported disease severity, as well as Eczema Area and Severity Index, itch assessed on an 11-point numerical rating scale, Dermatology Life Quality Index, or Patient-Oriented Eczema Measure. Achievement of these targets with once-daily upadacitinib (15 mg and 30 mg) monotherapy was evaluated using integrated adult data from the Measure Up 1 and 2 phase 3 studies. Among the 852 patients treated with upadacitinib 15 mg or 30 mg, the 3-month initial acceptable target was achieved by >80%, >78%, and ≥87% of patients, and the 6-month optimal target was achieved by ≥53%, >61%, and >73% of patients at weeks 2, 16, and 52, respectively. Achievement of all 6 individual criteria for each of the target goals also increased over time. These findings suggest that upadacitinib 15 mg and 30 mg may help improve standards of care in patients with moderate-to-severe AD by achieving 6-month target goals at 16 weeks and as early as 2 weeks for most patients.

Safety and Quality Within the Healthcare Supply Chain: A Great Unknown.

Quality and safety in healthcare have emerged as key factors impacting on both clinical effectiveness and clinical outcomes. While improving the healthcare supply chain has been extensively researched, the impact of the healthcare supply chain on clinical safety has received little attention in the literature, largely due to the complexity of such studies and the involvement of multiple stakeholders. This research proposes an evaluation model using key performance measurements for an electronic procurement system that enables digital transformation of the healthcare supply chain. The model will be tested before and after the introduction of an electronic procurement system in the healthcare supply chain for small and medium sized healthcare providers to provide evidence of both the usefulness of the model itself within industry and to further contribute to the knowledge base. Future use of the model may provide benchmarking and important data and insights to enable enhanced clinical safety in the healthcare supply chain.

Challenges and Efficacy of Astrocyte-to-Neuron Reprogramming in Spinal Cord Injury: In Vitro Insights and In Vivo Outcomes.

Traumatic spinal cord injury (SCI) leads to the disruption of neural pathways, causing loss of neural cells, with subsequent reactive gliosis and tissue scarring that limit endogenous repair. One potential therapeutic strategy to address this is to target reactive scar-forming astrocytes with direct cellular reprogramming to convert them into neurons, by overexpression of neurogenic transcription factors. Here we used lentiviral constructs to overexpress Ascl1 or a combination of microRNAs (miRs) miR124, miR9/9*and NeuroD1 transfected into cultured and in vivo astrocytes. In vitro experiments revealed cortically-derived astrocytes display a higher efficiency (70%) of reprogramming to neurons than spinal cord-derived astrocytes. In a rat cervical SCI model, the same strategy induced only limited reprogramming of astrocytes. Delivery of reprogramming factors did not significantly affect patterns of breathing under baseline and hypoxic conditions, but significant differences in average diaphragm amplitude were seen in the reprogrammed groups during eupneic breathing, hypoxic, and hypercapnic challenges. These results show that while cellular reprogramming can be readily achieved in carefully controlled in vitro conditions, achieving a similar degree of successful reprogramming in vivo is challenging and may require additional steps.

Understanding the Impact of Different Doses of Reducose® Mulberry Leaf Extract on Blood Glucose and Insulin Responses after Eating a Complex Meal: Results from a Double-Blind, Randomised, Crossover Trial.

Non-communicable diseases (NCDs) are becoming an increasingly important health concern due to a rapidly ageing global population. The fastest growing NCD, type 2 diabetes mellitus (T2DM), is responsible for over 2 million deaths annually. Lifestyle changes, including dietary changes to low glycemic response (GR) foods, have been shown to reduce the risk of developing T2DM. The aim of this study was to investigate whether three different doses of Reducose®, a mulberry leaf extract, could lower the GR and insulinemic responses (IR) to a full meal challenge in healthy individuals. A double-blind, randomised, placebo-controlled, repeat-measure, crossover design trial was conducted by the Oxford Brookes Centre for Nutrition and Health; 37 healthy individuals completed the study. Participants consumed capsules containing either 200 mg, 225 mg, 250 mg Reducose® or placebo before a test meal consisting of 150 g white bread and egg mayo filler. Capillary blood samples were collected at 15-min intervals in the first hour and at 30-min intervals over the second and third hours to determine glucose and plasma insulin levels. The consumption of all three doses of Reducose® resulted in significantly lower blood glucose and plasma insulin levels compared to placebo. All three doses of Reducose® (200 mg, 225 mg, 250 mg) significantly lowered glucose iAUC 120 by 30% (p = 0.003), 33% (p = 0.001) and 32% (p = 0.002), respectively, compared with placebo. All three doses of Reducose® (200 mg, 225 mg, 250 mg) significantly lowered the plasma insulin iAUC 120 by 31% (p = 0.024), 34% (p = 0.004) and 38% (p < 0.001), respectively. The study demonstrates that the recommended dose (250 mg) and two lower doses (200 mg, 225 mg) of Reducose® can be used to help lower the GR and IR of a full meal containing carbohydrates, fats and proteins.

Human spinal interneurons repair the injured spinal cord through synaptic integration.

Advances in cell therapy offer promise for some of the most devastating neural injuries, including spinal cord injury (SCI). Endogenous VSX2-expressing spinal V2a interneurons have been implicated as a key component in plasticity and therapeutically driven recovery post-SCI. While transplantation of generic V2a neurons may have therapeutic value, generation of human spinal V2a neurons with rostro-caudal specificity and assessment of their functional synaptic integration with the injured spinal cord has been elusive. Here, we efficiently differentiated optogenetically engineered cervical V2a spinal interneurons (SpINs) from human induced pluripotent stem cells and tested their capacity to form functional synapses with injured diaphragm motor networks in a clinically-relevant sub-acute model of cervical contusion injury. Neuroanatomical tracing and immunohistochemistry demonstrated transplant integration and synaptic connectivity with injured host tissue. Optogenetic activation of transplanted human V2a SpINs revealed functional synaptic connectivity to injured host circuits, culminating in improved diaphragm activity assessed by electromyography. Furthermore, optogenetic activation of host supraspinal pathways revealed functional innervation of transplanted cells by host neurons, which also led to enhanced diaphragm contraction indicative of a functional neuronal relay. Single cell analyses pre- and post-transplantation suggested the in vivo environment resulted in maturation of cervical SpINs that mediate the formation of neuronal relays, as well as differentiation of glial progenitors involved in repair of the damaged spinal cord. This study rigorously demonstrates feasibility of generating human cervical spinal V2a interneurons that develop functional host-transplant and transplant-host connectivity resulting in improved muscle activity post-SCI.

Outpatient Parenteral Antimicrobial Therapy in a Safety Net Hospital: Opportunities for Improvement.

Background: Outpatient parenteral antimicrobial therapy (OPAT) is a safe and cost-effective transitional care approach administered via different delivery models. No standards exist for appropriate OPAT program staffing. We examined outcomes of patients receiving OPAT via different care models to identify strategies to improve safety while reducing health care overuse. Methods: Retrospective demographic, clinical, and outcome data of patients discharged with OPAT were reviewed in 2 periods (April-June 2021 and January-March 2022; ie, when staffing changed) and stratified by care model: self-administered OPAT, health care OPAT, and skilled nursing facility OPAT. Results: Of 342 patients, 186 (54%) received OPAT in 2021 and 156 (46%) in 2022. Hospital length of stay rose from 12.4 days to 14.3 in 2022. In a Cox proportional hazards regression model, visits to the emergency department (ED) within 30 days of OPAT initiation (hazard ratio, 1.76; 95% CI, 1.13-2.73; P = .01) and readmissions (hazard ratio, 2.34; 95% CI, 1.22-4.49; P = .01) increased in 2022 vs 2021, corresponding to decreases in OPAT team staffing. Higher readmissions in the 2022 cohort were for reasons unrelated to OPAT (P = .01) while readmissions related to OPAT did not increase (P = .08). Conclusions: In a well-established OPAT program, greater health care utilization-length of stay, ED visits, and readmissions-were seen during periods of higher staff turnover and attrition. Rather than blunt metrics such as ED visits and readmissions, which are influenced by multiple factors besides OPAT, our findings suggest the need to develop OPAT-specific outcome measures as a quality assessment tool and to establish optimal OPAT program staffing ratios.

The effects of hyperbaric oxygen therapy on snake-bite-associated wounds in dogs.

OBJECTIVE: To assess the effect of hyperbaric oxygen therapy (HBOT) on Crotalinae envenomation-induced wound swelling and severity and pain in dogs, and to describe the safety and complications of HBOT. DESIGN: Prospective, randomized, controlled, blinded study (2017-2021). SETTING: University teaching hospital, private veterinary practice. ANIMALS: Thirty-six client-owned dogs presenting within 24 hours of a confirmed or suspected naturally occurring Crotalinae snake bite injury were enrolled between 2017 and 2021. INTERVENTIONS: In addition to the standard of care treatment, dogs received 2 interventions with either HBOT (n = 19) or control (n = 16) within 24 hours of hospital admission. Dogs receiving HBOT were pressurized over 15 minutes (1 psi/min), maintained at a target pressure of 2 atmosphere absolute (ATA) for 30 minutes, and decompressed over 15 minutes. Control dogs received 1 ATA for 1 hour. Local wound swelling, wound severity score, and pain score were assessed at admission, before and after each intervention, and at hospital discharge. MEASUREMENTS AND MAIN RESULTS: There was no significant difference in wound swelling (P = 0.414), severity score (P = 1.000), or pain score (P = 0.689) between HBOT and control groups. Pain decreased significantly over time regardless of the study intervention (P < 0.001). There were no major adverse effects associated with either study intervention. CONCLUSIONS: HBOT did not significantly alter the short-term recovery from Crotalinae envenomation in this study population. However, the study might be underpowered to detect a significant treatment effect.

Association Between Achievement of Clinical Disease Control and Improvement in Patient-Reported Outcomes and Quality of Life in Patients With Psoriatic Arthritis in the Phase 3 SELECT-PsA 1 and 2 Randomized Controlled Trials.

OBJECTIVE: We explored the relationship between achievement of clinical disease control and improvements in and normative values for patient-reported outcomes (PROs), including quality of life (QoL) measures, in patients with psoriatic arthritis (PsA). METHODS: This was a post hoc analysis of 104-week data from the SELECT-PsA 1 and 2 trials in adults with PsA and inadequate response to one or more conventional synthetic (SELECT-PsA 1) or biologic (SELECT-PsA 2) disease-modifying antirheumatic drug. Patients were initially randomized to upadacitinib 15 mg once daily (QD) to placebo switched to upadacitinib 15 mg QD at week 24 or to adalimumab 40 mg every other week (SELECT-PsA 1 only), and data were pooled across treatments and analyzed. We evaluated several clinical disease control measures (minimal disease activity [MDA]; very low disease activity [VLDA]; and low disease activity [LDA] and/or remission by Disease Activity in Psoriatic Arthritis [DAPSA], Psoriatic Arthritis Disease Activity Score [PASDAS], and Routine Assessment of Patient Index Data 3 [RAPID3]) and examined their associations with improvements and normative values for various PROs. RESULTS: A total of 1,069 and 317 patients were analyzed for SELECT-PsA 1 and 2, respectively. In both studies, responders (patients who achieved MDA or VLDA, and DAPSA, PASDAS, and RAPID3 LDA or remission) at week 104 achieved more marked changes from baseline, and more responders achieved normative values in PROs compared with nonresponders (most nominal P < 0.0001). Furthermore, numerically larger proportions of responders achieved minimal clinically important differences across PROs compared with nonresponders in both studies. In addition, patients who achieved MDA or VLDA were more likely to achieve DAPSA, PASDAS, and RAPID3 LDA or remission (all nominal P < 0.0001) for upadacitinib 15 mg QD and when treatment arms were pooled. CONCLUSION: Patients with PsA who achieve clinical disease control are more likely to achieve improvements and normative values in PROs and QoL measures, which reinforces disease control as a treatment target.

Influence of mental disorders on school dropout in Mexico / Influencia de los trastornos mentales en el abandono escolar en México

OBJECTIVE: To study the impact of mental disorders on failure in educational attainment in Mexico. METHODS: Diagnoses and age of onset for each of 16 DSM-IV disorders were assessed through retrospective self-reports with the Composite International Diagnostic Instrument (CIDI) during fieldwork in 2001-2002. Survival analysis was used to examine associations between early onset DSM-IV/CIDI disorders and subsequent school dropout or failure to reach educational milestones. RESULTS: More than one of two Mexicans did not complete secondary education. More than one-third of those who finished secondary education did not enter college, and one of four students who entered college did not graduate. Impulse control disorders and substance use disorders were associated with higher risk for school dropout, secondary school dropout and to a lesser degree failure to enter college. Anxiety disorders were associated with lower risk for school dropout, especially secondary school dropout and, to a lesser degree, primary school dropout. CONCLUSIONS: The heterogeneity of results found in Mexico may be due to the effect of mental disorders being diminished or masked by the much greater effect of economic hardship and low cultural expectations for educational achievement. Future research should inquire deeper into possible reasons for the better performance of students with anxiety disorders in developing countries.

OBJETIVO: Estudiar la repercusión de los trastornos mentales en el fracaso escolar en México. MÉTODOS: De septiembre del 2001 a mayo del 2002, se evaluaron los diagnósticos y la edad de aparición para cada uno de los 16 trastornos del DSM-IV mediante autoinformes retrospectivos recogidos por medio de la Entrevista Diagnóstica Internacional Compuesta (CIDI). Se empleó el anßlisis de supervivencia para analizar las asociaciones entre los trastornos del DSM-IV/CIDI de aparición temprana y el subsiguiente abandono escolar o fracaso en el logro de los hitos educativos. RESULTADOS: Mßs de uno de cada dos mexicanos no completó la educación secundaria. Mßs de una tercera parte de los que terminaron la educación secundaria no entraron en la universidad y uno de cada cuatro estudiantes que entraron el la universidad no llegó a graduarse. Los trastornos de control de los impulsos y los trastornos relacionados con el consumo de sustancias se asociaron con un mayor riesgo de abandono escolar, principalmente de abandono de la escuela secundaria y, en menor grado, de fracaso en entrar en la universidad. Los trastornos de ansiedad se asociaron con un menor riesgo de abandono escolar, especialmente de abandono de la escuela secundaria y, en menor grado, de la escuela primaria. CONCLUSIONES: La heterogeneidad de los resultados observados en México puede deberse a que el efecto de los trastornos mentales queda disminuido u oculto ante el efecto mucho mayor de las dificultades económicas y las reducidas expectativas culturales en cuanto al rendimiento escolar. En el futuro, la investigación debe inquirir mßs a fondo las posibles razones con objeto de mejorar el desempe±o de los estudiantes aquejados de trastornos de ansiedad en los países en desarrollo.