Standardizing Specialty Pharmacist Follow-Up Frequency in Patients Prescribed Inflammatory Disease-Modifying Therapies

Submission Category Specialty Pharmacy Purpose Specialty medications for inflammatory conditions have demonstrated decreased effectiveness, safety, and quality of life, largely attributable to inadequate medication adherence. Furthermore, with poorer health outcomes, patients face greater healthcare costs associated with exacerbations, flares, and hospitalizations. Monitoring for non-adherence, side effects, and health status changes is essential for patients diagnosed with inflammatory conditions. The benefit of a standardized pharmacist clinical follow-up assessment is currently lacking in specialty pharmacy literature. This study will implement a standardized pharmacist follow-up frequency guide and determine its clinical value and utility for patient safety and therapeutic goals in newly established patients diagnosed with inflammatory conditions. Methods A standardized follow-up frequency adjustment guide based on patient-specific factors, such as patient adherence, side effects experienced, and therapy efficacy was provided to all pharmacists where clinical consultations should be conducted at month 0, 1, and 4. After the implementation of the pharmacist guide, the electronic health system record was reviewed for all patients who received an inflammatory condition new patient consultation between August 5th, 2019 and October 4th, 2019. Pharmacist consultations are conducted by utilizing pre-designed assessment forms, the “New Patient Inflammatory Assessment” for initial consults and the “Specialty Medication Management Services (SMMS) Inflammatory Assessment” for follow-up assessments. How often pharmacists consistently stay within the standardized follow-up intervals versus how many times they deviate from the guide for patient care or safety reasons will be evaluated as the primary outcome. Secondary outcomes include categorizing and assessing the reasons for pharmacist deviation, assessing quantity and types of pharmacist (RPh) interventions made during deviations from the guide by medication and condition, evaluate patient reported medication adherence, quality-of-life (QoL) metrics, and pharmacist time spent per assessment. Patient-reported QoL was reported on a scale of 0 to 10, with 0 representing the best QoL and 10 representing poor QoL. Results There were a total of 154 patients enrolled into the study. Out of the 185 completed follow-up assessments, 36 were deviations. The reasons for pharmacist deviation from the guide included inability to reach the patient during standardized follow-up frequency (41.7%), RPh clinical decision that sooner follow up was necessary (27.8%), patient initiated consult (25%), and RPh failed to attempt follow-up consultation at month 1 and/or 2 (5.6%). Pharmacist interventions occurred predominantly at month 0 (71.7%), month 1 (15.5%), & month 4 (6.6%). The most frequent pharmacist interventions during consult deviations comprised of medication reconciliation (37%), and side effect management (33%), the remaining interventions were equal to or less than 7%. Following the initial assessment, the medication adalimumab and inflammatory condition psoriatic arthritis required the most pharmacist intervention at 32.2% and 21.5% of all follow-up interventions, respectively. However, it was tofacitinib and ankylosing spondylitis, which required the most pharmacist consultation time. Tofacitinib averaged 13.2 minutes and ankylosing spondylitis averaged 15.2 minutes per consultation. Patients taking adalimumab reported missed or late doses most frequently (33.3% of the 24 reported). Although QoL metrics were not consistently reported, there is a notable improvement from baseline to month 4. At month 0, the average patient-reported QoL was 5.6, while after 4 months of treatment, QoL scores improved to 3.6. Conclusion The standardized pharmacist follow-up frequency guide has provided a clinically meaningful strategy to monitor and follow-up with patients prescribed high-cost, high-risk inflammatory disease-modifying therapies. By establishing that the majority of clinically significant interventions occurred during the standardized frequency intervals, this guide accomplished maintaining patient safety, in addition to aiding patients with their clinical goals and overall quality of life. In addition, this data supports continuing a standard follow-up frequency at month 1 and 4 by demonstrating that no critical interventions were missed and most deviations occurred due to pharmacist’s inability to reach patients during the pre-defined intervals. Although most pharmacist interventions occurred at the recommended intervals, it is important to consider patient-specific factors when determining follow-up frequency. Thus, it is reasonable for specialty pharmacists to utilize a standardized follow-up frequency guide that allows modifications based on clinical judgment to manage patients diagnosed with an inflammatory condition.https://digitalcommons.psjhealth.org/pharmacy_PGY1/1015/thumbnail.jp

Temporal Changes in Cortical and Hippocampal Expression of Genes Important for Brain Glucose Metabolism Following Controlled Cortical Impact Injury in Mice

Traumatic brain injury (TBI) causes transient increases and subsequent decreases in brain glucose utilization. The underlying molecular pathways are orchestrated processes and poorly understood. In the current study, we determined temporal changes in cortical and hippocampal expression of genes important for brain glucose/lactate metabolism and the effect of a known neuroprotective drug telmisartan on the expression of these genes after experimental TBI. Adult male C57BL/6J mice (n = 6/group) underwent sham or unilateral controlled cortical impact (CCI) injury. Their ipsilateral and contralateral cortex and hippocampus were collected 6 h, 1, 3, 7, 14, 21, and 28 days after injury. Expressions of several genes important for brain glucose utilization were determined by qRT-PCR. In results, (1) mRNA levels of three key enzymes in glucose metabolism [hexo kinase (HK) 1, pyruvate kinase, and pyruvate dehydrogenase (PDH)] were all increased 6 h after injury in the contralateral cortex, followed by decreases at subsequent times in the ipsilateral cortex and hippocampus; (2) capillary glucose transporter Glut-1 mRNA increased, while neuronal glucose transporter Glut-3 mRNA decreased, at various times in the ipsilateral cortex and hippocampus; (3) astrocyte lactate transporter MCT-1 mRNA increased, whereas neuronal lactate transporter MCT-2 mRNA decreased in the ipsilateral cortex and hippocampus; (4) HK2 (an isoform of hexokinase) expression increased at all time points in the ipsilateral cortex and hippocampus. GPR81 (lactate receptor) mRNA increased at various time points in the ipsilateral cortex and hippocampus. These temporal alterations in gene expression corresponded closely to the patterns of impaired brain glucose utilization reported in both TBI patients and experimental TBI rodents. The observed changes in hippocampal gene expression were delayed and prolonged, when compared with those in the cortex. The patterns of alterations were specific to different brain regions and exhibited different recovery periods following TBI. Oral administration of telmisartan (1 mg/kg, for 7 days, n = 10 per group) ameliorated cortical or hippocampal mRNA for Glut-1/3, MCT-1/2 and PDH in CCI mice. These data provide molecular evidence for dynamic alteration of multiple critical factors in brain glucose metabolism post-TBI and can inform further research for treating brain metabolic disorders post-TBI

Characterization and functionality of proliferative human sertoli cells

It has long been thought that mammalian Sertoli cells are terminally differentiated and nondividing postpuberty. For most previous in vitro studies immature rodent testes have been the source of Sertoli cells and these have shown little proliferative ability when cultured. We have isolated and characterized Sertoli cells from human cadaveric testes from seven donors ranging from 12 to 36 years of age. The cells proliferated readily in vitro under the optimized conditions used with a doubling time of approximately 4 days. Nuclear 5-ethynyl-2´-deoxyuridine (EdU) incorporation confirmed that dividing cells represented the majority of the population. Classical Sertoli cell ultrastructural features, lipid droplet accumulation, and immunoexpression of GATA-4, Sox9, and the FSH receptor (FSHr) were observed by electron and fluorescence microscopy, respectively. Flow cytometry revealed the expression of GATA-4 and Sox9 by more than 99% of the cells, and abundant expression of a number of markers indicative of multipotent mesenchymal cells. Low detection of endogenous alkaline phosphatase activity after passaging showed that few peritubular myoid cells were present. GATA-4 and SOX9 expression were confirmed by reverse transcription polymerase chain reaction (RT-PCR), along with expression of stem cell factor (SCF), glial cell line-derived neurotrophic factor (GDNF), and bone morphogenic protein 4 (BMP4). Tight junctions were formed by Sertoli cells plated on transwell inserts coated with fibronectin as revealed by increased transepithelial electrical resistance (TER) and polarized secretion of the immunoregulatory protein, galectin-1. These primary Sertoli cell populations could be expanded dramatically in vitro and could be cryopreserved. The results show that functional human Sertoli cells can be propagated in vitro from testicular cells isolated from adult testis. The proliferative human Sertoli cells should have important applications in studying infertility, reproductive toxicology, testicular cancer, and spermatogenesis, and due to their unique biological properties potentially could be useful in cell therapy.Fil: Chui, Kitty. MandalMed Inc. ; Estados UnidosFil: Trivedi, Alpa. MandalMed Inc.; Estados Unidos. University of California; Estados UnidosFil: Cheng, C. Yan. Lonza Walkersville; Estados UnidosFil: Cherbavaz, Diana B.. MandalMed Inc.; Estados UnidosFil: Dazin, Paul F.. MandalMed; Estados UnidosFil: Huynh, Ai Lam Thu. MandalMed Inc.; Estados UnidosFil: Mitchel, James B.. Lonza Walkersville; Estados UnidosFil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); ArgentinaFil: Noble Haeusslein, Linda J.. University of California; Estados UnidosFil: John, Constance M.. MandalMed Inc.; Estados Unido

Влияние механической активации гидрида титана на его взаимодействие с азотом и кислородом

Показано, что размол гидрида титана в планетарной мельнице приводит к повышению удельной поверхности порошка, росту микроискажений кристаллической решетки, уменьшению содержания в нем водорода и повышению химической активности, что позволяет получать нитрид титана из него в среде азота уже при температуре 500 °С. За счет кислорода, адсорбирован ного механически активированным порошком при нагревании в атмосфере азота, происходят реакции окисления атомов титана, в результате чего образуется низший оксид Tі2О.Показано, що подрібнення гідриду титану в планетарному млині приводить до підвищення питомої поверхні порошку, зростанню дефектів кристалічної ґратки, зменшенню вмісту в ній водню і підвищенню хімічної активності. Це дає змогу досягти повного перетворення механічно активованого гідриду в нітрид титану вже за температури 500 °С і витримці упродовж однієї години в середовищі азоту. За рахунок кисню, адсорбованого механічно активованим порошком при нагрівання в атмосфері азоту, проходять реакції окиснення, в результаті чого утворюється нижчий оксид Ti2O.Milling of titanium hydride in planetary mill is shoun to increase the speci surface area of powder, to decrease the hydrogen content in it and to intensity chemical activity. This makesit possible to obtain titanium nitride from the titanium hydride in a nitrogen atmosphere at as low temperature as 500 °C . Thanks to the presence of oxygen adsorbed by mechanically activated powder under heating in a nitrogen atmosphere? Reaction of intramolecular oxidation -reduction, of titanium takes place, which results in forming the lower oxide Ti2O

MAMBO 1.2mm observations of luminous starbursts at z~2 in the SWIRE fields

We report on--off pointed MAMBO observations at 1.2 mm of 61 Spitzer-selected star-forming galaxies from the SWIRE survey. The sources are selected on the basis of bright 24um fluxes (f_24um>0.4mJy) and of stellar dominated near-infrared spectral energy distributions in order to favor z~2 starburst galaxies. The average 1.2mm flux for the whole sample is 1.5+/-0.2 mJy. Our analysis focuses on 29 sources in the Lockman Hole field where the average 1.2mm flux (1.9+/-0.3 mJy) is higher than in other fields (1.1+/-0.2 mJy). The analysis of the sources multi-wavelength spectral energy distributions indicates that they are starburst galaxies with far-infrared luminosities ~10^12-10^13.3 Lsun, and stellar masses of ~0.2-6 x10^11 M_sun. Compared to sub-millimeter selected galaxies (SMGs), the SWIRE-MAMBO sources are among those with the largest 24um/millimeter flux ratios. The origin of such large ratios is investigated by comparing the average mid-infrared spectra and the stacked far-infrared spectral energy distributions of the SWIRE-MAMBO sources and of SMGs. The mid-infrared spectra exhibit strong PAH features, and a warm dust continuum. The warm dust continuum contributes to ~34% of the mid-infrared emission, and is likely associated with an AGN component. This constribution is consistent with what is found in SMGs. The large 24um/1.2mm flux ratios are thus not due to AGN emission, but rather to enhanced PAH emission compared to SMGs. The analysis of the stacked far-infrared fluxes yields warmer dust temperatures than typically observed in SMGs. Our selection favors warm ultra-luminous infrared sources at high-z, a class of objects that is rarely found in SMG samples. Our sample is the largest Spitzer-selected sample detected at millimeter wavelengths currently available.Comment: Accepted for publication in ApJ (51 pages; 16 figures). The quality of some figures has been degraded for arXiv purposes. Full resolution version available at this http://www.iasf-milano.inaf.it/~polletta/mambo_swire/lonsdale08_ApJ_accepted.pd

Genetic Variation in OAS1 Is a Risk Factor for Initial Infection with West Nile Virus in Man

West Nile virus (WNV) is a re-emerging pathogen that can cause fatal encephalitis. In mice, susceptibility to WNV has been reported to result from a single point mutation in oas1b, which encodes 2′–5′ oligoadenylate synthetase 1b, a member of the type I interferon-regulated OAS gene family involved in viral RNA degradation. In man, the human ortholog of oas1b appears to be OAS1. The ‘A’ allele at SNP rs10774671 of OAS1 has previously been shown to alter splicing of OAS1 and to be associated with reduced OAS activity in PBMCs. Here we show that the frequency of this hypofunctional allele is increased in both symptomatic and asymptomatic WNV seroconverters (Caucasians from five US centers; total n = 501; OR = 1.6 [95% CI 1.2–2.0], P = 0.0002 in a recessive genetic model). We then directly tested the effect of this SNP on viral replication in a novel ex vivo model of WNV infection in primary human lymphoid tissue. Virus accumulation varied markedly among donors, and was highest for individuals homozygous for the ‘A’ allele (P<0.0001). Together, these data identify OAS1 SNP rs10774671 as a host genetic risk factor for initial infection with WNV in humans

Novel point-of-care cytokine biomarker lateral flow test for the screening for sexually transmitted infections and bacterial vaginosis: study protocol of a multicentre multidisciplinary prospective observational clinical study to evaluate the performance and feasibility of the Genital InFlammation Test (GIFT).

INTRODUCTION: A prototype lateral flow device detecting cytokine biomarkers interleukin (IL)-1α and IL-1β has been developed as a point-of-care test-called the Genital InFlammation Test (GIFT)-for detecting genital inflammation associated with sexually transmitted infections (STIs) and/or bacterial vaginosis (BV) in women. In this paper, we describe the rationale and design for studies that will be conducted in South Africa, Zimbabwe and Madagascar to evaluate the performance of GIFT and how it could be integrated into routine care. METHODS AND ANALYSIS: We will conduct a prospective, multidisciplinary, multicentre, cross-sectional and observational clinical study comprising two distinct components: a biomedical ('diagnostic study') and a qualitative, modelling and economic ('an integration into care study') part. The diagnostic study aims to evaluate GIFT's performance in identifying asymptomatic women with discharge-causing STIs (Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), Trichomonas vaginalis (TV) and Mycoplasma genitalium (MG)) and BV. Study participants will be recruited from women attending research sites and family planning services. Several vaginal swabs will be collected for the evaluation of cytokine concentrations (ELISA), STIs (nucleic acid amplification tests), BV (Nugent score) and vaginal microbiome characteristics (16S rRNA gene sequencing). The first collected vaginal swab will be used for the GIFT assay which will be performed in parallel by a healthcare worker in the clinic near the participant, and by a technician in the laboratory. The integration into care study aims to explore how GIFT could be integrated into routine care. Four activities will be conducted: user experiences and/or perceptions of the GIFT device involving qualitative focus group discussions and in-depth interviews with key stakeholders; discrete choice experiments; development of a decision tree classification algorithm; and economic evaluation of defined management algorithms. ETHICS AND DISSEMINATION: Findings will be reported to participants, collaborators and local government for the three sites, presented at national and international conferences, and disseminated in peer-reviewed publications.The protocol and all study documents such as informed consent forms were reviewed and approved by the University of Cape Town Human Research Ethics Committee (HREC reference 366/2022), Medical Research Council of Zimbabwe (MRCZ/A/2966), Comité d'Ethique pour la Recherche Biomédicale de Madagascar (N° 143 MNSAP/SG/AMM/CERBM) and the London School of Hygiene and Tropical Medicine ethics committee (LSHTM reference 28046).Before the start, this study was submitted to the Clinicaltrials.gov public registry (NCT05723484). TRIAL REGISTRATION NUMBER: NCT05723484

Genome-wide analysis identifies 12 loci influencing human reproductive behavior.

The genetic architecture of human reproductive behavior-age at first birth (AFB) and number of children ever born (NEB)-has a strong relationship with fitness, human development, infertility and risk of neuropsychiatric disorders. However, very few genetic loci have been identified, and the underlying mechanisms of AFB and NEB are poorly understood. We report a large genome-wide association study of both sexes including 251,151 individuals for AFB and 343,072 individuals for NEB. We identified 12 independent loci that are significantly associated with AFB and/or NEB in a SNP-based genome-wide association study and 4 additional loci associated in a gene-based effort. These loci harbor genes that are likely to have a role, either directly or by affecting non-local gene expression, in human reproduction and infertility, thereby increasing understanding of these complex traits