Embryonic motor neuron programming factors reactivate immature gene expression and suppress ALS pathologies in postnatal motor neurons.

Aging is a major risk factor in amyotrophic lateral sclerosis (ALS) and other adult-onset neurodegenerative disorders. Whereas young neurons are capable of buffering disease-causing stresses, mature neurons lose this ability and degenerate over time. We hypothesized that the resilience of young motor neurons could be restored by re-expression of the embryonic motor neuron selector transcription factors ISL1 and LHX3. We found that viral re-expression of ISL1 and LHX3 reactivates aspects of the youthful gene expression program in mature motor neurons and alleviates key disease-relevant phenotypes in the SOD1G93A mouse model of ALS. Our results suggest that redeployment of lineage-specific neuronal selector transcription factors can be an effective strategy to attenuate age-dependent phenotypes in neurodegenerative disease.

The Development and Implementation of an Evidence-Based Tumescent Liposuction Protocol, Online Educational Course for Perioperative Staff, and Discharge Instructions: A Quality Improvement Project.

PURPOSE: The purpose of this quality improvement project was to improve perioperative management of patients undergoing tumescent liposuction (TL) through the development and implementation of a perioperative evidence-based protocol, educational course for perioperative staff, and patient discharge instructions. DESIGN: The TL protocol was validated using the modified Delphi process. The educational course and discharge instructions used a pre and postimplementation design. METHODS: An evidence-based protocol, an educational course for perioperative staff, and readable discharge instructions for patients undergoing TL were developed in accordance with best practice guidelines. The protocol was validated by subject matter experts at the facility and submitted for adoption. The evidence-based educational course was implemented, and the effectiveness of the course was evaluated for improving providers' knowledge and self-confidence. The evidence-based discharge instructions were implemented and evaluated for patient satisfaction and readability. FINDINGS: Three items were removed from the protocol, 2 items were modified, and 25 items were accepted with no change from modified Delphi analysis. Provider knowledge scores improved from 85.7% ± 16.18 to 97.1% ± 4.88; however, this was not statistically significant (P = .066). There was a trend toward improved confidence scores (P = .180). Overall patient satisfaction scores slightly improved postimplementation; results were not statistically significant (P > .05). CONCLUSIONS: All three phases of perioperative care in patients receiving TL were evaluated, reflecting best practice guidelines and successful adoption. There was no statistically significant improvement in provider knowledge, provider self-confidence, or patient satisfaction. A small sample size was a significant limiting factor.

First-Person Point-of-View Instructional Video on Lumbar Puncture Procedure.

OBJECTIVES: Tutorial videos filmed from a first-person point of view (FP-POV) are generally well received. Pediatric residents are expected to be competent in performing the lumbar puncture (LP). The educational effectiveness of a FP-POV in lumbar puncture procedure training for resident physicians has yet to be evaluated. We compared a FPPOV LP video with a standard in-person demonstration of the LP. METHODS: We designed an assigned cohort study to compare a FP-POV procedural instructional video of a simulated pediatric LP to the standard in-person procedure demonstration.After the intervention, residents completed an LP observed by one of two blinded reviewers who assessed the procedure using a modified, published assessment tool.Participants completed preintervention and postintervention surveys to rate self-confidence and usefulness of the FP-POV educational method. The data was analyzed using a Wilcoxon Rank sum test. z Scores were calculated on the raw assessment scores. RESULTS: Eighteen first year pediatric residents participated, nine in each group. The median modified assessment tool score was 17 in the FP-POV group (min, 14; max, 17; IQR:, 1.5) and 14 in the standard demonstration group (min, 6; max, 17; IQR, 4.5), with the higher score being more successful. There was a statistical difference between the assessment scores between the 2 groups (z score = 2.18, P = 0.04). Postintervention survey data demonstrated relative satisfaction with the FPPOV educational method. CONCLUSIONS: This study supports the educational effectiveness of a FP-POV procedure tutorial.Future studies with a larger sample size are needed.

Understanding the medication experience of patients with advanced non-small cell lung cancer taking epidermal growth factor receptor-tyrosine kinase inhibitors: A phenomenological study.

BACKGROUND AND OBJECTIVE: Patients with cancer taking oral antineoplastic medications may encounter problems including suboptimal adherence as well as physical and psychological disease burden. Despite increase in the use of oncology pharmacy services, there are wide variations between healthcare professionals and patient perceptions of patients' medication experiences. The objective of the study was to explore the medication experience of taking oral targeted therapy in patients with advanced non-small cell lung cancer (NSCLC). METHOD: We purposively sampled advanced stage (stage III or IV) NSCLC patients taking epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in a medical center in Taiwan. Face-to-face interviews using semi-structured interview guides were conducted. Interviews were transcribed verbatim and thematic analysis was applied. A phenomenological methodology was adopted to explore the underlying meaning of patients' lived experience. RESULTS: A total of 19 participants with a mean age of 68.2 years were interviewed. The duration of EGFR-TKIs use ranged from 2 weeks to 5 years. When first learned about the unexpected yet 'treatable' cancer, participants expressed strong emotional responses based on their intrinsic beliefs of the terminal disease and therapy. They walked along an unfamiliar trail while confronting physical and psychological challenges and made compromises to treatment. Gaining experiences from cancer journey, patients with cancer continuously seek the ultimate goals-'return to normal'. CONCLUSIONS: This study also revealed medication experiences of participants' journey from seeking information in the initial phase and living with cancer, to taking back control of their own lives. Healthcare professionals could better empathize with patients' loss of control and understand their perspectives when making clinical decisions. These findings can guide interdisciplinary teams to integrate patients' beliefs and conduct pre-screening assessments of health literacy levels to tailor communication. Subsequent interventions should be developed to identify barriers to medication self-management and empower patients by building social networks.

An Energy-Efficient T-Based Routing Topology for Target Tracking in Battery Operated Mobile Wireless Sensor Networks.

Real-time smart applications are now possible because to developments in communication and sensor technology. Wireless sensor networks (WSNs) are used to collect data from specific disaster sites, such as fire events, gas leaks, land mines, earthquake, landslides, etc., where it is necessary to know the exact location of the detected information to safely rescue the people. For instance, the detection and disposal of explosive materials is a difficult task because land mines consistently threaten human life. Here, the T-based Routing Topology (TRT) is suggested to gather data from sensors (metal detectors, Ground Penetrating Radars (GPR), Infra-Red sensors, etc.), Global Positioning System (GPS), and cameras in land mine-affected areas. Buried explosive materials can be found and located with high accuracy. Additionally, it will be simpler to eliminate bombs and reduce threats to humans. The efficiency of the suggested data collection method is evaluated using Network Simulator-2 (NS-2). Also, the proposed T-based routing topology requires a minimal number of nodes to cover the entire searching area and establish effective communication. In contrast, the number of nodes participating in the sensing area grows, as the depth of the tree increases in the existing tree topology-based data gathering. And for cluster topology, the number of nodes deployment depends on the transmission range of the sensor nodes.

Large-gap peripheral nerve repair using xenogeneic transplants in rhesus macaques.

Surgical intervention is required to successfully treat severe, large-gap (≥4 cm) peripheral nerve injuries. However, all existing treatments have shortcomings and an alternative to the use of autologous nerves is needed. Human and porcine nerves are physiologically similar, with comparable dimensions and architecture, presence and distribution of Schwann cells, and conserved features of the extracellular matrix (ECM). We report the repair of fully transected radial nerves in 10 Rhesus Macaques using viable, whole sciatic nerve from genetically engineered (GalT-KO), designated pathogen free (DPF) porcine donors. This resulted in the regeneration of the transected nerve, and importantly, recovery of wrist extension function, distal muscle reinnervation, and recovery of nerve conduction velocities and compound muscle action potentials similar to autologous controls. We also demonstrate the absence of immune rejection, systemic porcine cell migration, and detectable residual porcine material. Our preliminary findings support the safety and efficacy of viable porcine nerve transplants, suggest the interchangeable therapeutic use of cross-species cells, and highlight the broader clinical potential of xenotransplantation.

Adolescent Experiences With Social Media and Suicidality.

OBJECTIVE: Examine social media experiences of the suicidal adolescent presenting to the emergency department with an acute mental health crisis. METHODS: We used qualitative interviews to obtain in-depth understanding of both negative and positive impacts of social media use on acute adolescent suicidal behavior. A bilingual transcriptionist transcribed audio recordings. Three investigators independently reviewed transcripts to identify themes and develop initial coding scheme through "open coding." Using grounded theory, data collection proceeded along with cultivation of themes until thematic saturation was achieved. Thematic saturation was determined when no new themes were generated from the data. Data were coded in Dedoose software to facilitate reporting of themes and quotes. Techniques to ensure trustworthiness included iterative data collection, use of a coding framework, and multiple coders. RESULTS: Seventeen interviews were conducted from May to October 2020. Median participant age was 15 years. Twenty-four percent were of Hispanic ethnicity and 82% identified as cisgender. Major themes include distraction from negative emotions; facilitated communication resulting in improved social connectedness; metric of connectedness; comparison of self to others; and desensitization and normalization to suicidal acts. Minor theme of increased time on social media is also discussed. These themes echoed components of current suicide theory. CONCLUSIONS: Acutely suicidal adolescents report social media experiences that reflect themes of social alienation and learned capacity for suicidal acts. Themes echo components of current suicide theory. Our participants also reported positive uses of social media. These protective experiences should be leveraged to inform strategies to interrupt behaviors leading to acute suicidality.

Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio as Biomarkers in Axial Spondyloarthritis: Observational Studies From the Program to Understand the Longterm Outcomes in Spondyloarthritis Registry.

OBJECTIVES: This study was conducted to assess the utility of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in predicting radiographic sacroiliitis and active disease in axial spondyloarthritis (SpA) and to explore the association between use of a tumor necrosis factor inhibitor (TNFi) and these laboratory values compared with traditional inflammatory markers. METHODS: Observational data from the Program to Understand the Longterm Outcomes in Spondyloarthritis (PULSAR) registry were analyzed. We generated receiver operating characteristic curves to calculate laboratory cutoff values; we used these values in multivariable logistic regression models to identify associations with radiographically confirmed sacroiliitis and active disease. We also used logistic regression to determine the likelihood of elevated laboratory values after initiation of TNFi. RESULTS: Most study participants (n = 354) were White, male, and HLA-B27 positive. NLR (odds ratio [OR] 1.459, P = 0.034), PLR (OR 4.842, P < 0.001), erythrocyte sedimentation rate (OR 4.397, P < 0.001), and C-reactive protein (CRP) level (OR 2.911, P = 0.001) were independent predictors of radiographic sacroiliitis. Models that included PLR with traditional biomarkers performed better than those with traditional biomarkers alone. NLR (OR 6.931, P = 0.002) and CRP (OR 2.678, P = 0.004) were predictors of active disease, but the model that included both NLR and CRP performed better than CRP alone. TNFi use reduced the odds of elevated NLR (OR 0.172, P < 0.001), PLR (OR 0.073, P < 0.001), erythrocyte sedimentation rate (OR 0.319, P < 0.001), and CRP (OR 0.407, P < 0.001), but models that included NLR or PLR and traditional biomarkers performed best. CONCLUSIONS: These findings demonstrate an association between NLR and PLR and sacroiliitis and disease activity, with NLR and PLR showing response after TNFi treatment and adding useful clinical information to established biomarkers, thus perhaps assisting in management of axial SpA.

Effects of caregiver counselling on medication persistence and adherence in patients with dementia at a pharmacist-managed clinic: A pilot study.

WHAT IS KNOWN AND OBJECTIVE: Low treatment persistence and adherence in patients with dementia results in a rapid loss of disease control. This pilot study evaluated the impact of pharmacist-provided caregiver counselling on treatment persistence, adherence, quality of life (QoL) in patients with dementia, as well as caregiver's knowledge of dementia, and caregiver burden. METHODS: This prospective, randomized controlled study was performed at a hospital-based pharmacist-managed clinic from December 2017 to December 2019. Patients with mild-to-moderate Alzheimer's disease (AD), initiating cholinesterase inhibitors within 3 months, and coming with their caregivers were included and randomized 1:1 to intervention or control group. The intervention group received pharmacist counselling and education sheets about AD, whereas the control group only received standard of care. Patients' treatment persistence and adherence were assessed at months 3, 6, 9, and 12; QoL, and caregiver burden were assessed at baseline and month 12. Caregiver's knowledge of dementia was assessed at baseline and 2 weeks after counselling in the intervention group. Nonparametric statistics and generalized estimating equation models were used for statistical analysis. RESULTS AND DISCUSSION: A total of 40 patients and 40 caregivers were included, with 20 pairs for each group. One-year medication persistence (16/20 vs. 16/20) and adherence rates (87%-99%) were high in both groups without significant differences. Dementia knowledge scores improved significantly after counselling in the intervention group (77.5 vs. 95.8, p < 0.01). Although the change of caregiver burden was non-significant between groups, the score decreased in the intervention group (-0.89; p = 0.78) but increased in the control group (+6.01; p = 0.07). WHAT IS NEW AND CONCLUSION: In this pilot study, pharmacist's counselling for patients with dementia and their caregivers is feasible and can enhance caregiver knowledge of dementia. Further study with larger scale is needed to confirm the impact on these outcomes.

Medications Without Borders: Themes in Caregiver Administration of Imported Medications in Pediatrics.

OBJECTIVE: This study aimed to identify motivating factors in why parents administer imported medications to their children. METHODS: In this qualitative study, we enrolled caregivers of patients younger than 18 years who presented for care at a pediatric emergency department. The study team conducted face-to-face interviews with caregivers in the emergency department and used a semistructured question guide to probe for themes regarding the use of imported medications in children. Interviews were recorded, transcribed, translated if necessary, and coded. We applied grounded theory methodology to assess for themes and adapted the Andersen model of health care utilization to provide a framework for the identified themes. RESULTS: We completed 30 interviews, 9 of which were conducted in Spanish. Themes surrounding imported medication usage were categorized into predisposing, enabling, and need factors. Predisposing factors included perception that an ill child needs medication to get better, perception of medication quality, and past experiences with medications. Enabling factors included proximity to foreign countries, cost, limited access to primary care, and convenience of obtaining medications. Need factors included utilization of foreign medications for a "simple illness" and utilization of foreign care for a "second opinion." CONCLUSIONS: Our study used qualitative methodology to gain important insights into the caregiver experience of a diverse patient population. We identify themes not previously published in the medication importation literature. These concepts can provide insights in educational strategies aimed at mitigating the potential dangers of imported medication use in pediatrics.

Telemedicine Use During the COVID-19 Pandemic by Resilient Rheumatology Providers: A National Veterans Affairs Follow-up Survey.

OBJECTIVE: To assess rheumatology provider experience and practices at Veterans Affairs (VA) facilities during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: We performed an anonymized follow-up national cross-sectional survey (November 5, 2020 to January 1, 2021) to assess provider resilience, experience, practices, views, and opinions about changes to medications and laboratory monitoring of veterans with rheumatic diseases. RESULTS: Of the 143 eligible VA rheumatology providers, 114 (80%) responded. Compared to the original survey, fewer providers reported using telephone visits (78% vs 91%, P = 0.009), and more used clinical video telehealth (CVT; 16% vs 7%, P = 0.04) or in-person visits (76% vs 59%, P = 0.007). Most providers were somewhat or very comfortable with the quality of clinical encounters for established but not new patients for telephone, video-based VA Video Connect (VVC), and CVT. The mean 2-item Connor-Davidson Resilience Scale score was 6.85 (SD 1.06, range 0-8), significantly higher than the original April-May 2020 survey score of 6.35 (SD 1.26; P = 0.004). When adjusted for age, sex, and ethnicity, high provider resilience was associated with significantly higher odds of comfort with technology and the quality of the VVC visit for the following: (1) established patients (odds ratio [OR] 1.72, 95% CI, 0.67-4.40 and OR 4.13, 95% CI 1.49-11.44, respectively) and (2) new patients (OR 2.79, 95% CI 1.11-7.05, and OR 2.69, 95% CI 1.06-6.82, respectively). CONCLUSION: Reassuringly, VA rheumatology providers became increasingly comfortable with video visits during the first 10 months of the COVID-19 pandemic. High provider resilience, and its association with better quality CVTs, raise the possibility that video visits might be an acceptable substitute for in-person visits under appropriate circumstances.

Living with Parkinson's disease: disease and medication experiences of patients and caregivers.

PURPOSE: Symptoms and medication use in patients with Parkinson's disease (PD) affect the quality of life of patients and caregivers, yet prior research seldom focused on their experiences with medications. This study explored comprehensive living and medication experience from patients with PD and their caregivers. METHODS: Patients diagnosed with PD for ≥2 years, with or without their caregivers, were recruited from an outpatient clinic in Taiwan. Semi-structured in-depth interviews were conducted based on the Common Sense Model. A qualitative content analysis was used to identify salient themes from verbatim transcripts. RESULTS: In total, 15 patients and eight caregivers were interviewed. Five themes were derived: (1) symptoms and help-seeking behaviours before a diagnosis, (2) emotional impacts and life adaptations after a PD diagnosis, (3) life affected by medications, (4) experiences of caregivers in taking care of PD patients, and (5) communication between doctors and patients. CONCLUSIONS: Patients frequently adjusted their daily schedules to live with PD and the medication side effects. Caregivers struggle to overcome caring burdens and to stay positive to support patients. More attention on providing medication information, mental support, and communication between stakeholders is needed to improve the quality of life of patients and caregivers.

Tumor necrosis factor inhibitor (TNFi) persistence and reasons for discontinuation in a predominantly male cohort with axial spondyloarthritis.

Although tumor necrosis factor inhibitors (TNFi) have favorably altered the treatment landscape for patients with axial spondyloarthritis (axSpA), there is limited data regarding TNFi persistence and reasons for discontinuation. This is an observational time-to-event study utilizing data collected for a prospective multiple-disease registry of US Veterans with axSpA treated with TNFi therapies and recruited over a 10 year period. Clinical, serological, and comorbid parameters were collected. Corporate Data Warehouse Pharmacy files provided courses of the 5 TNFi agents, and response to treatment was documented. Individual TNFi persistence was established utilizing univariate and multivariate Cox proportional models, and reasons for discontinuation were obtained by physician chart review. Two-hundred and fifty-five axSpA patients received 731 TNFi courses. A majority of patients (84.3%) had TNFi persistence at 12 months; 63.5% and 47.1% at 24 and 36 months, respectively. Compared to adalimumab, infliximab demonstrated greater persistence, certolizumab the least. Age, smoking status, BMI, comorbidity burden, inflammatory markers and HLA-B27 did not predict TNFi persistence or discontinuation. Stroke and peripheral arterial disease increased the probability of TNFi discontinuation. Secondary non-response (SNR) was the most common reason for discontinuation (46% of all courses); non-adherence (6%) and clinical remission (2%) were uncommon. Pain score at enrollment, myocardial infarction, African American race and inflammatory bowel disease (IBD) predicted TNFi response. While initial persistence of TNFi treatment was high, a large proportion of the patients discontinued initial TNFi therapy by 3 years, primarily due to loss of efficacy. While further research identifying potential predictors of TNFi discontinuation in axSpA is warranted, access to alternate disease-modifying therapies is needed.

Pre-Clinical Activity of Amino-Alcohol Dimeric Naphthoquinones as Potential Therapeutics for Acute Myeloid Leukemia.

BACKGROUND: The clinical outcomes of patients with Acute Myeloid Leukemia (AML) remain unsatisfactory. Therefore the development of more efficacious and better-tolerated therapy for AML is critical. We have previously reported anti-leukemic activity of synthetic halohydroxyl dimeric naphthoquinones (BiQ) and aziridinyl BiQ. OBJECTIVE: This study aimed to improve the potency and bioavailability of BiQ compounds and investigate antileukemic activity of the lead compound in vitro and a human AML xenograft mouse model. METHODS: We designed, synthesized, and performed structure-activity relationships of several rationally designed BiQ analogues with amino alcohol functional groups on the naphthoquinone core rings. The compounds were screened for anti-leukemic activity and the mechanism as well as in vivo tolerability and efficacy of our lead compound was investigated. RESULTS: We report that a dimeric naphthoquinone (designated BaltBiQ) demonstrated potent nanomolar anti-leukemic activity in AML cell lines. BaltBiQ treatment resulted in the generation of reactive oxygen species, induction of DNA damage, and inhibition of indoleamine dioxygenase 1. Although BaltBiQ was tolerated well in vivo, it did not significantly improve survival as a single agent, but in combination with the specific Bcl-2 inhibitor, Venetoclax, tumor growth was significantly inhibited compared to untreated mice. CONCLUSION: We synthesized a novel amino alcohol dimeric naphthoquinone, investigated its main mechanisms of action, reported its in vitro anti-AML cytotoxic activity, and showed its in vivo promising activity combined with a clinically available Bcl-2 inhibitor in a patient-derived xenograft model of AML.

Effectiveness of collaboration between oncology pharmacists and anaesthesiologists for inpatient cancer pain management: A pilot study in Taiwan.

OBJECTIVE: To evaluate the effectiveness of the collaboration between oncology pharmacists and anaesthesiologists for improving pain control management in cancer patients. METHODS: This retrospective case-control pilot study enrolled inpatients with active cancer and a pain score of >3 at least once per day for 3 consecutive days. The study group was selected from June 2018 to January 2019. Patients with the same inclusion criteria were selected between November 2017 and May 2018 to serve as the comparison group. The primary outcome was the percentage of patients that experienced pain relief within 7 days from initial pain attack. RESULTS: A total of 71 and 77 patients were enrolled in the study and comparison groups. More patients in the study group experienced pain relief within 7 days from the index date (78.9% [56 of 71 patients] versus 72.7% [56 of 77 patients], respectively). The service increased the rate of intervention from attending physicians within 4 days from index date and quality of opioid management. CONCLUSION: The collaboration between oncology pharmacists and anaesthesiologists for cancer pain management may be associated with an increase in the rate of pain relief in cancer patients with poor pain control.

Efficacy of AST-120 for Patients With Chronic Kidney Disease: A Network Meta-Analysis of Randomized Controlled Trials.

AST-120, an oral spherical activated carbon, may delay the need for kidney dialysis and improve uremia symptoms because it can adsorb acidic and basic organic compounds, especially small-molecule uremic toxins. However, previous studies produced no conclusive evidence regarding the benefits of AST-120 in delaying the progression of chronic kidney disease (CKD). Therefore, this systematic review and network meta-analysis evaluated the effects of AST-120 in patients with CKD. Related keywords of CKD and AST-120 were used to search four databases to obtain potential evidence on this topic, and two authors individually completed evidence selection, data extraction, and quality assessment. Network meta-analysis was performed for mortality, end-stage renal disease, composite renal outcomes, and laboratory outcomes based on a frequentist approach. In total, 15 randomized controlled trials (n = 3,763) were included in the present synthesis, and the pooled results revealed non-significant differences in mortality among the treatment strategies. Low- and high-dose AST-120 were not superior to no AST-120 treatment regarding renal outcomes. However, the event rates of end-stage renal disease (risk ratio [RR] = 0.78, 95% confidence interval [CI] = 0.62-0.99) and composite renal outcomes (RR = 0.78, 95% CI: 0.63-0.97) were significantly lower in the tailored-dose AST-120 group than in no AST-120 group. The results did not reveal a small-study effect on the outcomes. Tailored dosing of AST-120 appeared to represent an optimal treatment strategy because it resulted in lower rates of composite renal outcomes and end-stage renal disease.

A qualitative study on the development of pharmacist-managed clinics in Taiwan.

WHAT IS KNOWN AND OBJECTIVE: Pharmacist-managed clinics (PMCs) are established to solve drug-related problems and enhance the quality of care of ambulatory patients. Although the benefits of such services have been demonstrated, little is known about PMC operations, especially outside the United States. The aim of this study was to explore how PMCs were established and to discuss implementation issues of PMCs in Taiwan. METHODS: A purposive sample of pharmacists, pharmacy administrators and physicians involved with PMCs was recruited from hospitals of varying scales across Taiwan. Semi-structured, individual interviews were conducted to understand the perceptions of the clinical service of PMCs. Interviews were transcribed verbatim and analysed by thematic analysis to find underlying themes. RESULTS: A total of 12 pharmacists, 5 pharmacy administrators and 3 physicians from 8 institutions were interviewed. Pharmacists spent 4 to 20 h per week at PMCs, and the practice experiences of PMC ranged from 1 to 6 years. PMCs have been provided in these institutions for 4 to 11 years with an average volume of 28 h and 25 patient visits weekly. Study participants described influential factors in establishing PMCs, including clinical expertise, attitude towards patient care and trust building with collaborating physicians. Operational concerns in implementing PMCs included role clarifications, manpower shortage, inadequate advanced training or certification, regulatory issues and a lack of service promotion. WHAT IS NEW AND CONCLUSION: This research broadens the understanding of operating PMC services and reveals key requirements and concerns regarding the care model, which can be useful for other countries. Resolving perceived barriers and collecting other stakeholders' perspectives may reinforce the integration of PMCs into patient care in the future.

Small molecules inhibitors of the heterogeneous ribonuclear protein A18 (hnRNP A18): a regulator of protein translation and an immune checkpoint.

We have identified chemical probes that simultaneously inhibit cancer cell progression and an immune checkpoint. Using the computational Site Identification by Ligand Competitive Saturation (SILCS) technology, structural biology and cell-based assays, we identify small molecules that directly and selectively bind to the RNA Recognition Motif (RRM) of hnRNP A18, a regulator of protein translation in cancer cells. hnRNP A18 recognizes a specific RNA signature motif in the 3'UTR of transcripts associated with cancer cell progression (Trx, VEGF, RPA) and, as shown here, a tumor immune checkpoint (CTLA-4). Post-transcriptional regulation of immune checkpoints is a potential therapeutic strategy that remains to be exploited. The probes target hnRNP A18 RRM in vitro and in cells as evaluated by cellular target engagement. As single agents, the probes specifically disrupt hnRNP A18-RNA interactions, downregulate Trx and CTLA-4 protein levels and inhibit proliferation of several cancer cell lines without affecting the viability of normal epithelial cells. These first-in-class chemical probes will greatly facilitate the elucidation of the underexplored biological function of RNA Binding Proteins (RBPs) in cancer cells, including their effects on proliferation and immune checkpoint activation.

Management of Rheumatic Diseases During the COVID-19 Pandemic: A National Veterans Affairs Survey of Rheumatologists.

OBJECTIVE: To assess the experience, views, and opinions of rheumatology providers at Veterans Affairs (VA) facilities about rheumatic disease health care issues during the COVID-19 pandemic. METHODS: We performed an anonymized cross-sectional survey, conducted from April 16 to May 18, 2020, of VA rheumatology providers. We assessed provider perspectives on COVID-19 issues and resilience. RESULTS: Of the 153 eligible VA rheumatologists, 103 (67%) completed the survey. A significant proportion of providers reported a ≥50% increase related to COVID-19 in visits by telephone (53%), video-based VA video connect (VVC; 44%), and clinical video telehealth with a facilitator (29%). A majority of the responders were somewhat or very comfortable with technology for providing health care to established patients during the COVID-19 pandemic using telephone (87%), VVC (64%), and in-person visits (54%). A smaller proportion were comfortable with technology providing health care to new patients. At least 65% of rheumatologists considered telephone visits appropriate for established patients with gout, osteoporosis, polymyalgia rheumatica, stable rheumatoid arthritis, stable spondyloarthritis, or osteoarthritis; 32% reported a rheumatology medication shortage. Adjusted for age, sex, and ethnicity, high provider resilience was associated with significantly higher odds ratios (ORs) of comfort with technology for telephone (OR 3.1 [95% confidence interval (95% CI) 1.1-9.7]) and VVC visits for new patients (OR 4.7 [95% CI 1.4-15.7]). CONCLUSION: A better understanding of COVID-19 rheumatic disease health care issues using a health-system approach can better inform providers, improve provider satisfaction, and have positive effects on the care of veterans with rheumatic disease.

Shared decision-making in gout treatment: a national study of rheumatology provider opinion and practice.

To assess rheumatologists' views and practices related to shared decision-making (SDM) in gout treatment. We performed a cross-sectional electronic survey of rheumatologists at U.S. Veterans Affairs (VA) medical centers, assessing views and practices related to SDM in gout. Of the 154 VA rheumatology providers eligible, 90 responded (response rate, 58%). Fifty-eight percent were female, the mean age was 51 years (standard deviation, 9.6), 42% had > 20 years of experience in medical practice. Rheumatologists reported routinely offering a choice to their patients for (1) starting urate-lowering therapy (ULT) for gout vs. doing nothing (70%); (2) choosing NSAIDs, corticosteroids, or colchicine for the treatment of acute flares (67%); and (3) choosing NSAIDs, corticosteroids, or colchicine for anti-inflammatory prophylaxis when starting ULT (51%). Very few rheumatologists offered choice regarding (4) choosing allopurinol vs. febuxostat as the first ULT (16%) and (5) taking daily ULT long-term vs. intermittently (15%). Rheumatologists perceived that a large proportion of patients were often or sometimes unsure of the best choice for these five decisions, 34%, 76%, 76%, 52%, and 54%, respectively. Similar proportions of rheumatologists felt that patients were uninformed about both medication benefits and risks, unclear about the personal importance of the benefits and risks, and unsupported in decision-making. For the five decisions respectively, rheumatologists supported SDM with patients in 76%, 56%, 58%, 27%, and 25%. The majority of VA rheumatologists incorporated SDM in several gout treatment decisions. Rheumatologists also recognized that patients need better support to participate in SDM in gout. Key Points: • Rheumatologists offered shared decision-making to gout patients for 3 key treatment decisions. • Rheumatologists perceived that many patients were unsure of the best choice for these decisions. • Rheumatologists felt that patients were uninformed about medication benefits/risks and unsupported in decision-making.