Dalrymplesehested4772

Introduction Delayed methotrexate clearance in several patients admitted to the oncology unit at a regional medical center necessitated the development of a pharmacist-driven protocol for supportive therapy with high-dose methotrexate. This performance improvement project evaluated the impact of the protocol on inpatient length of stay, patient safety, and clinical outcomes. Methods Retrospective data were collected over 14 months pre-implementation and prospective data were collected over 19 months post-implementation. Primary outcomes included mean length of stay and incidence of kidney injury. Secondary outcomes included myelosuppression, treatment delays, mucositis, protocol adherence, and pharmacist interventions. Chi-squared and unpaired two sample t-test were used for data analysis. Intervention A literature review of consensus recommendations for supportive care post high-dose methotrexate administration was conducted to develop the protocol. Education on implementation was provided to involved disciplines. Results One-hundred ten high-dose methotrexate admissions for 23 patients were analyzed 24 pre-protocol and 86 post-protocol. Mean length of stay was 5.17 nights pre-protocol and 3.91 nights post-protocol (p = 0.026). Incidence of kidney injury significantly decreased (16.7% pre-protocol versus 3.5% post-protocol; p = 0.0394). Lower incidences of all-grade anemia (83.3% versus 58.1%), neutropenia (62.5% versus 29.1%), and thrombocytopenia (58.3% versus 33.7%) as well as treatment delays (29.2% versus 11.6%; p = 0.036) were reported post protocol. No statistically significant difference in mucositis was detected. Pharmacist adherence to protocol was ≥80% resulting in 348 interventions with 99.4% provider acceptance. Conclusion The implementation of a pharmacist-driven high-dose methotrexate management protocol resulted in a statistically significant decrease in inpatient length of stay and kidney injury. Further studies are needed to assess the impact on additional outcomes.Background A period of diagnostic uncertainty often characterizes the clinical transition from relapsing to secondary progressive multiple sclerosis (SPMS). Objective The aim of this study was to describe the length of time required to reclassify relapsing-remitting MS (RRMS) patients who have clinically transitioned to SPMS (diagnosis uncertainty). Methods This is a retrospective multicenter cohort study conducted in Argentina, identifying in every center all patients with diagnosis of MS who transitioned from RRMS to SPMS during the follow-up. We identified the dates of the last definitive RRMS and first definitive SPMS diagnoses for diagnostic uncertainty. Opevesostat mw The time required to reclassify RRMS who transitioned to SPMS and the time from disease onset to reclassify SPMS were calculated using the Kaplan-Meier method. Results A total of 170 patients were included, where the mean age at disease onset (first symptom) was 36 ± 6 years; the length of time required to reclassify RRMS patients who transitioned to SPMS was 3.3 ± 1.1 years (range = 1-7 years); and the time from disease onset to classify SPMS was 19.4 ± 8.5 years (range = 16-35 years). Conclusion A period of diagnostic uncertainty regarding the transition from RRMS to SPMS was present in many of our patients, with a mean time of 3.3 years.Objective The coronavirus disease 2019 (COVID-19) pandemic has caused physicians and surgeons to consider restructuring traditional cancer management paradigms. We aim to review the current evidence regarding the diagnosis and management of head and neck cancer, with an emphasis on the role of the multidisciplinary team (MDT) during a pandemic. Data sources COVID-19 resources from PubMed, Google Scholar, the American Academy of Otolaryngology-Head and Neck Surgery, and the American Head and Neck Society were examined. Review methods Studies and guidelines related to the multidisciplinary management of head and neck cancer in the COVID-19 setting were reviewed. A total of 54 studies were included. Given the continuously evolving body of literature, the sources cited include the latest statements from medical and dental societies. Results The unpredictable fluctuation of hospital resources and the risk of the nosocomial spread of SARS-CoV-2 have direct effects on head and neck cancer management. Using an MDT approach to help define "essential surgery" for immediately life- or function-threatening disease processes in the context of available hospital resources will help to maximize outcomes. Early enrollment in an MDT is often critical for considering nonsurgical options to protect patients and health care workers. The role of the MDT continues after cancer treatment, if delivered, and the MDT plays an essential role in surveillance and survivorship programs in these challenging times. Conclusion Head and neck cancer management during the COVID-19 pandemic poses a unique challenge for all specialists involved. Early MDT involvement is important to maximize patient outcomes and satisfaction in the context of public and community safety.Interleukin-23 (IL-23) is a key cytokine implicated in the pathogenesis of autoimmune disorders, including psoriasis and ulcerative colitis. Although targeted IL-23 antibody therapeutics are used clinically, there are no small-molecule therapeutics that selectively inhibit IL-23 signaling. To address this gap, we developed a high-throughput screening strategy employing an IL-23-responsive cell-based luciferase reporter gene assay as the primary screen, with cellular cytotoxicity and off-target counter screening assays to identify IL-23 pathway-specific inhibitors. The primary screening assay utilized avian DT40 cells, genetically engineered to overexpress IL-23R, IL-12Rβ1, STAT5, and firefly luciferase, in a 1536-well format. Treatment of these cells with IL-23 resulted in the phosphorylation and activation of STAT5, which was completely inhibited by the pan-JAK inhibitor tofacitinib. Assay performance was robust, with signal-to-background >7-fold and Z' > 0.5 over 40 screening plates (approximately 24,000 compounds), with a hit rate of 5% (>66.9% activity cutoff). Of these 1288 hits, 66% were identified as cytotoxic by incubating the IL-23 reporter cells with compound overnight and measuring cell viability. Further assessment of specificity via examination of impact on off-target IFN-γ signaling eliminated an additional 230 compounds, leaving 209 that were evaluated for dose-response activity. Of these compounds, 24 exhibited IC50 values of 3-fold selectivity over IFN-γ inhibition, thus representing promising starting points for prospective IL-23 pathway small-molecule inhibitors.Objective Cisplatin is a platinum-based chemotherapeutic drug that secondarily induces toxicity in inner ear sensory epithelia, contributing to auditory and vestibular dysfunction. We describe the creation of a drug reservoir device (DRD) to combat this ototoxicity for the duration of chemotherapy. As ototoxic side effects of chemotherapy may limit an oncologist's ability to prescribe first-line agents such as cisplatin, mitigating such devastating effects through prolonged topical therapy would be tremendously valuable. Study design We investigated (1) the ability of an electrospun polylactic acid DRD to provide prolonged delivery of the posited otoprotectant metformin and (2) the development of an in vitro model utilizing Sh-Sy5y human neuroblastoma cells to assess the efficacy of metformin in reducing cisplatin-induced toxicity. Setting Neurophysiology laboratory. Methods Basic science experiments were performed to assess DRD properties and metformin's effects on cisplatin toxicity in culture. Results We found that DRDs with increasing polylactic acid concentrations exhibited metformin release for up to 8 weeks. In modeling elution across the round window in vitro, continued elution of metformin was observed for at least 6 weeks, as quantified by spectrophotometry. Unfortunately, metformin did not exhibit protective efficacy in this model using Sh-Sy5y cells. Conclusion While metformin was not found to be protective in Sh-Sy5y cells, these results suggest that an electrospun DRD can provide a tailorable drug delivery system providing medication for the duration of chemotherapy treatment. This represents a novel drug delivery system and efficacy screening assay with broad clinical applications in personalized delivery of inner ear therapies.Observed genetic associations with educational attainment may be due to direct or indirect genetic influences. Recent work highlights genetic nurture, the potential effect of parents' genetics on their child's educational outcomes via rearing environments. To date, few mediating childhood environments have been tested. We used a large sample of genotyped mother-child dyads (N = 2,077) to investigate whether genetic nurture occurs via the prenatal environment. We found that mothers with more education-related genes are generally healthier and more financially stable during pregnancy. Further, measured prenatal conditions explain up to one third of the associations between maternal genetics and children's academic and developmental outcomes at the ages of 4 to 7 years. By providing the first evidence of prenatal genetic nurture and showing that genetic nurture is detectable in early childhood, this study broadens our understanding of how parental genetics may influence children and illustrates the challenges of within-person interpretation of existing genetic associations.Objective Radiographic joint erosions are a hallmark of rheumatoid arthritis (RA). Magnetic resonance imaging (MRI) is more sensitive than radiographs in detecting erosions. It is unknown whether MRI-detected erosions are predictive for RA development in patients with clinically suspect arthralgia (CSA). Therefore, we investigated the prognostic value of MRI-detected erosions, defined as any MRI erosion, or MRI erosion characteristics that were recently identified as specific for RA in patients with evident arthritis. Method Patients presenting with CSA (n = 490) underwent contrast-enhanced 1.5 T MRI of the wrist, metacarpophalangeal (MCP) and metatarsophalangeal (MTP) joints. MRIs were scored according to the Rheumatoid Arthritis Magnetic Resonance Imaging Scoring system (RAMRIS). Presence of any MRI erosion (present in less then 5% of symptom-free controls) and RA-specific erosion characteristics as identified previously (grade ≥ 2 erosions, erosions in MTP5, erosions in MTP1 if aged less then 40 years)ical value in CSA.A number of studies have examined the association between male involvement in sports and sexual violence (SV) perpetration, especially among college-age males. Less is known about the association between sports involvement and SV perpetration for adolescent males and females. To address this gap, the current study examined sports involvement in middle school (no sports, no/low contact, and high contact) among 1,561 students, who were then followed into high school and asked about the frequency of SV perpetration. Results from logistic regression models indicated that, even after controlling for mother's education, race/ethnicity, SV perpetration in middle school, and traditional beliefs about masculinity and substance use, middle school sports participation was significantly associated with risk of SV perpetration in high school. Compared with youth who reported no sports involvement in middle school, youth categorized as no/low contact sports involvement had greater odds of SV perpetration in high school. Sex differences emerged, revealing that no/low contact sports involvement was associated with SV perpetration for females and high contact sports involvement was associated with SV perpetration for males, compared with no sports involvement.