scholarly journals P.056 Optimizing IVIg Use for Neuromuscular Conditions in British Columbia, Canada – Targeting High and Chronic User Groups

2021 ◽  
Vol 48 (s3) ◽  
pp. S35-S35
Author(s):  
K Chapman ◽  
A Beauchamp ◽  
M Moisa Popurs ◽  
R Mosewich ◽  
K Beadon
Keyword(s):  
Patient Specific ◽  
High Dose ◽  
Review Panel ◽  
Treatment Algorithms ◽  
Chronic User ◽  
Number Of Patients ◽  
Initial Cohort ◽  
User Groups ◽  
Neuromuscular Conditions ◽  
Chronic Use

Background: Neuromuscular conditions account for 1/3 of IVIg use in BC and costs over $10 million annually. Since 2013, the BC Neuromuscular Review Panel has developed diagnostic and treatment algorithms for the use of IVIg. A framework was created to review high dose and chronic users. Methods: Utilizing Central Transfusion Registry data, all patients treated with IVIg for approved neuromuscular conditions (CIDP, MG, MMN) since April 1, 2013 were identified. Annual cohorts for patients using higher than usual dose and chronic use (>3 years) were established, and evaluated annually. Patient specific recommendations were made. Results: The initial cohort identified 38 high users of 377 patients receiving IVIg. 27 appropriate, 9 “not appropriate”. Subsequent cohorts showed a decrease in number of patients receiving inappropriate IVIg doses. In BC there has been a 36% increase in neuromuscular patients treated with IVIg (377 in 2013/14 to 512 in 2016/17). Despite this, IVIg the program has effectively reduced the annual grams/patient from 516 gm/patient in 2013/14 to 489 gm/patient in 2016/17. Conclusions: The BC Neuromuscular IVIg Review confirms that the majority of IVIg use is appropriate. Following yearly cohorts of chronic and high dose users helps optimize IVIg use, which may lead to improved patient care.

scholarly journals Colchicine Use and Risks of Stroke Recurrence in Acute Non-Cardiogenic Ischemic Stroke Patients: A Population-Based Cohort Study

2021 ◽  
Vol 11 (9) ◽  
pp. 935
Author(s):  
Chi-Hung Liu ◽  
Yu-Sheng Lin ◽  
Pi-Shan Sung ◽  
Yi-Chia Wei ◽  
Ting-Yu Chang ◽  
...  
Keyword(s):  
Lower Risk ◽  
Protective Effects ◽  
User Group ◽  
Number Of Patients ◽  
User Groups ◽  
Chronic Use ◽  
Use Categories ◽  
Use Category

Background: The objective is to study whether the cardiovascular protective effects of colchicines could be applied to non-cardiogenic ischemic stroke (IS) patients. Patients and Methods: Non-cardiogenic IS patients were identified from the National Health Insurance Research Database. Eligible patients were divided into chronic and non-chronic use categories based on their long-term status of colchicine use. The non-chronic use category was subdivided into (1) non-user and (2) new user groups while the chronic use category was divided into (3) former user and (4) long-term user groups according to the patient’s recent status of colchicine use. Inverse probability of treatment weights for propensity scores was used to balance the baseline characteristics. The primary outcome was recurrent IS, which was compared within the non-chronic use and chronic use categories. Results: In the non-chronic use category, the number of patients was 355,498 and 912 in the non-user and new user groups, respectively. In the chronic use category, the number of patients was 4737 and 4354 in the former user and long-term user groups, respectively. In the non-chronic use category, patients in the new user group had a marginally lower risk of recurrent IS at 6-months (subdistribution hazard ratio [SHR], 0.95; 95% confidence interval [CI], 0.94–0.97) and 2-years (SHR, 0.92; 95% CI, 0.91–0.93) follow up. In the chronic use category, patients in the long-term user group also had a marginally lower risk of recurrent IS at 6-months (SHR, 0.87; 95% CI, 0.86–0.88) and 2-years (SHR, 0.87; 95% CI, 0.86–0.88) follow up. The effect of colchicine on the reduced risk of recurrent IS was more favorable in patients who also used statins. Conclusions: Recent colchicine use in acute non-cardiogenic IS patients is associated with marginal fewer incidences of recurrent IS. Patients with concurrent statin use may have more profound protective effects.

scholarly journals Cardiomyocyte-Specific Circulating Cell-Free Methylated DNA in Esophageal Cancer Patients Treated with Chemoradiation

2021 ◽  
Vol 3 (3) ◽  
pp. 100-112
Author(s):  
Sarah Martinez Roth ◽  
Eveline E. Vietsch ◽  
Megan E. Barefoot ◽  
Marcel O. Schmidt ◽  
Matthew D. Park ◽  
...  
Keyword(s):  
Esophageal Cancer ◽  
Cardiac Toxicity ◽  
Amplicon Sequencing ◽  
Neoadjuvant Chemoradiation ◽  
Patient Specific ◽  
High Dose ◽  
Specific Cell ◽  
Methylated Dna ◽  
Bisulfite Treatment ◽  
Dose Radiation

Thoracic high-dose radiation therapy (RT) for cancer has been associated with early and late cardiac toxicity. To assess altered rates of cardiomyocyte cell death due to RT we monitored changes in cardiomyocyte-specific, cell-free methylated DNA (cfDNA) shed into the circulation. Eleven patients with distal esophageal cancer treated with neoadjuvant chemoradiation to 50.4 Gy (RT) and concurrent carboplatin and paclitaxel were enrolled. Subjects underwent fasting blood draws prior to the initiation and after completion of RT as well as 4–6 months following RT. An island of six unmethylated CpGs in the FAM101A locus was used to identify cardiomyocyte-specific cfDNA in serum. After bisulfite treatment this specific cfDNA was quantified by amplicon sequencing at a depth of >35,000 reads/molecule. Cardiomyocyte-specific cfDNA was detectable before RT in the majority of patient samples and showed some distinct changes during the course of treatment and recovery. We propose that patient-specific cardiac damages in response to the treatment are indicated by these changes although co-morbidities may obscure treatment-specific events.

scholarly journals Perioperative Management of Chronic Antithrombotic Agents in Elective Hip and Knee Arthroplasty

Medicina ◽  
2021 ◽  
Vol 57 (2) ◽  
pp. 188
Author(s):  
Daniel C. Santana ◽  
Matthew J. Hadad ◽  
Ahmed Emara ◽  
Alison K. Klika ◽  
Wael Barsoum ◽  
...  
Keyword(s):  
Knee Arthroplasty ◽  
Perioperative Management ◽  
Recent Literature ◽  
Patient Specific ◽  
Antithrombotic Agents ◽  
Coronary Syndrome ◽  
Risk Of Bleeding ◽  
Post Operative Period ◽  
Number Of Patients ◽  
Hip And Knee Arthroplasty

Total hip and knee arthroplasty are common major orthopedic operations being performed on an increasing number of patients. Many patients undergoing total joint arthroplasty (TJA) are on chronic antithrombotic agents due to other medical conditions, such as atrial fibrillation or acute coronary syndrome. Given the risk of bleeding associated with TJAs, as well as the risk of thromboembolic events in the post-operative period, the management of chronic antithrombotic agents perioperatively is critical to achieving successful outcomes in arthroplasty. In this review, we provide a concise overview of society guidelines regarding the perioperative management of chronic antithrombotic agents in the setting of elective TJAs and summarize the recent literature that may inform future guidelines. Ultimately, antithrombotic regimen management should be patient-specific, in consultation with cardiology, internal medicine, hematology, and other physicians who play an essential role in perioperative care.

scholarly journals Combination of subtherapeutic anti-TNF dose with dasatinib restores clinical and molecular arthritogenic profiles better than standard anti-TNF treatment

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Lydia Ntari ◽  
Christoforos Nikolaou ◽  
Ksanthi Kranidioti ◽  
Dimitra Papadopoulou ◽  
Eleni Christodoulou-Vafeiadou ◽  
...  
Keyword(s):  
Gene Expression ◽  
Therapeutic Effect ◽  
Expression Analysis ◽  
Mode Of Action ◽  
Gene Expression Analysis ◽  
Kinase Inhibitors ◽  
High Dose ◽  
Dependent Manner ◽  
Combination Therapies ◽  
Number Of Patients

Abstract Background New medications for Rheumatoid Arthritis (RA) have emerged in the last decades, including Disease Modifying Antirheumatic Drugs (DMARDs) and biologics. However, there is no known cure, since a significant proportion of patients remain or become non-responders to current therapies. The development of new mode-of-action treatment schemes involving combination therapies could prove successful for the treatment of a greater number of RA patients. Methods We investigated the effect of the Tyrosine Kinase inhibitors (TKIs) dasatinib and bosutinib, on the human TNF-dependent Tg197 arthritis mouse model. The inhibitors were administered either as a monotherapy or in combination with a subtherapeutic dose of anti-hTNF biologics and their therapeutic effect was assessed clinically, histopathologically as well as via gene expression analysis and was compared to that of an efficient TNF monotherapy. Results Dasatinib and, to a lesser extent, bosutinib inhibited the production of TNF and proinflammatory chemokines from arthritogenic synovial fibroblasts. Dasatinib, but not bosutinib, also ameliorated significantly and in a dose-dependent manner both the clinical and histopathological signs of Tg197 arthritis. Combination of dasatinib with a subtherapeutic dose of anti-hTNF biologic agents, resulted in a synergistic inhibitory effect abolishing all arthritis symptoms. Gene expression analysis of whole joint tissue of Tg197 mice revealed that the combination of dasatinib with a low subtherapeutic dose of Infliximab most efficiently restores the pathogenic gene expression profile to that of the healthy state compared to either treatment administered as a monotherapy. Conclusion Our findings show that dasatinib exhibits a therapeutic effect in TNF-driven arthritis and can act in synergy with a subtherapeutic anti-hTNF dose to effectively treat the clinical and histopathological signs of the pathology. The combination of dasatinib and anti-hTNF exhibits a distinct mode of action in restoring the arthritogenic gene signature to that of a healthy profile. Potential clinical applications of combination therapies with kinase inhibitors and anti-TNF agents may provide an interesting alternative to high-dose anti-hTNF monotherapy and increase the number of patients responding to treatment.

scholarly journals Bayesian adaptive design of early-phase clinical trials for precision medicine based on cancer biomarkers

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
Shinjo Yada
Keyword(s):  
Neural Network ◽  
Clinical Trials ◽  
Precision Medicine ◽  
Early Phase ◽  
Patient Specific ◽  
Specific Gene ◽  
Cancer Type ◽  
Background Characteristics ◽  
Number Of Patients ◽  
Early Phase Clinical Trials

Abstract Cancer tissue samples obtained via biopsy or surgery were examined for specific gene mutations by genetic testing to inform treatment. Precision medicine, which considers not only the cancer type and location, but also the genetic information, environment, and lifestyle of each patient, can be applied for disease prevention and treatment in individual patients. The number of patient-specific characteristics, including biomarkers, has been increasing with time; these characteristics are highly correlated with outcomes. The number of patients at the beginning of early-phase clinical trials is often limited. Moreover, it is challenging to estimate parameters of models that include baseline characteristics as covariates such as biomarkers. To overcome these issues and promote personalized medicine, we propose a dose-finding method that considers patient background characteristics, including biomarkers, using a model for phase I/II oncology trials. We built a Bayesian neural network with input variables of dose, biomarkers, and interactions between dose and biomarkers and output variables of efficacy outcomes for each patient. We trained the neural network to select the optimal dose based on all background characteristics of a patient. Simulation analysis showed that the probability of selecting the desirable dose was higher using the proposed method than that using the naïve method.

scholarly journals 577. Incidence and Outcomes of Positive Outpatient Surveillance Blood Cultures in Hematopoietic Stem Cell Transplant (HSCT) Patients with Graft Versus Host Disease (GvHD) On High Dose ≥ 0.5 mg/kg/day (HD) and Low Dose < 0.5mg/kg/day (LD) Steroid Therapy

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S353-S354
Author(s):  
Sarah Perreault ◽  
Molly Schiffer ◽  
Jennifer Zhao ◽  
Dayna McManus ◽  
Francine Foss ◽  
...  
Keyword(s):  
Steroid Therapy ◽  
Central Line ◽  
Blood Cultures ◽  
High Dose ◽  
Cell Transplant ◽  
Coagulase Negative Staphylococci ◽  
Hematopoietic Stem ◽  
Surveillance Cultures ◽  
Number Of Patients ◽  
Clinically Significant

Abstract Background Treatment of GvHD with steroids increases the risk of infection in HSCT patients due to additive immunosuppression and may delay the diagnosis of infection due to lack of symptoms. Outpatient surveillance blood cultures in HSCT with GvHD being treated with HD steroids has demonstrated a blood culture positivity rate of 3.5%. Currently, the utility of surveillance cultures in patients receiving LD steroid therapy is unknown. Our practice includes weekly outpatient surveillance cultures for all GvHD patients treated with steroids regardless of the dose. The primary endpoint of this study was to assess the incidence of positive surveillance blood cultures in GvHD patients receiving HD or LD steroids. Secondary endpoints included number of patients treated, hospitalization, 30 day mortality due to infection, and organisms isolated. Methods This was a single-center, retrospective review of GvHD patients at Yale New Haven Hospital between January 2013 and May 2019. Patients were excluded if: lack of signs or symptoms of GvHD, treatment with steroids for any indication other than GvHD, and active GvHD without central line. Cultures from patients receiving antibiotics for concurrent infection were also excluded. Results A total of 71 patients met criteria with 901 blood cultures. On HD, eight patients (14%) had 12 positive cultures (4%), and on LD, 16 patients (25%) had 22 positive cultures (4%) (p=0.15). Treatment occurred in six patients (75%) with four (24%) requiring hospitalization on HD, and 12 patients (75%) with 10 (83%) requiring hospitalization on LD (p=0.45). The median duration of steroid therapy was 93 and 236 days with a median dose of steroids of 1mg/kg/day and 0.15mg/kg/day, respectively. The number of positive cultures/1000 steroid days was 1.2 on HD and 0.5 on LD (RR 2.2). 30 day mortality was only noted in one patient (8%) on LD. The most common organism in both groups was Coagulase-negative staphylococci with all six cultures on HD classified as contaminants and 6/10 cultures requiring treatment on LD. Conclusion Although the relative risk of positive surveillance blood cultures in HD patients compared to LD was twofold higher, there were clinically significant infections identified in the LD group. Disclosures All Authors: No reported disclosures

Outcomes of Management of Proximal Humeral Fractures with Patient-Specific, Evidence-Based Treatment Algorithms

2021 ◽  
Vol Publish Ahead of Print ◽  
Author(s):  
Christian Spross ◽  
Vilijam Zdravkovic ◽  
Melanie Manser ◽  
Jan Marino Farei-Campagna ◽  
Matthijs Jacxsens ◽  
...  
Keyword(s):  
Proximal Humeral Fractures ◽  
Humeral Fractures ◽  
Patient Specific ◽  
Evidence Based ◽  
Treatment Algorithms ◽  
Evidence Based Treatment

Potential for Single High-Dose Influenza Immunization in Unprimed Children

PEDIATRICS ◽  
1982 ◽  
Vol 70 (6) ◽  
pp. 982-986 ◽  
Author(s):  
Peter A. Gross ◽  
Gerald V. Quinnan ◽  
Pureza F. Gaerlan ◽  
Carolyn R. Denning ◽  
Anne Davis ◽  
...  
Keyword(s):  
New York ◽  
Influenza A ◽  
Standard Dose ◽  
Geometric Mean ◽  
High Dose ◽  
York Metropolitan Area ◽  
Reaction Index ◽  
Number Of Patients ◽  
Sibling Control ◽  
High Concentrations

High concentrations of split-product vaccine (SPV) are more immunogenic than lower concentrations. These studies were verified with another influenza strain, B/Singapore/22/79. Two ether-treated SPVs were compared in 80 children and young adults. The vaccine strains were influenza A/Bangkok/79, A/Brazil/78, and B/Singapore /79; 44 patients received a high-dose SPV containing 7, 7, and 60 µg each of the respective hemagglutinins (HA) and 36 received a standard dose SPV containing 7, 7, and 7 µg of HA, respectively. Among persons initially seronegative by hemagglutination inhibition (HAI) tests, the geometric mean titer (GMT) in 15 recipients of one high dose was 97 vs GMT of 37 in 18 recipients of one standard dose (P &lt; .05). Furthermore, 87% of high-dose recipients had HAI titer ≥ 40 vs 44% of standard dose recipients. In initially seropositive persons, GMT in 29 recipients of one high dose was 170 vs GMT of 84 in 18 recipients of one standard dose (P &lt; .05). Immune response to the other two virus strains was comparable for the two vaccines. The reaction index for the high dose vaccine was 0.70 vs 0.45 for the standard dose (P = NS). An A/Bangkok epidemic struck the New York metropolitan area. The attack rate in unvaccinated matched sibling control subjects was 35% (15/43). There were no vaccine failures. In conclusion, in the small number of patients studied, a 60-µg HA dose of B/Singapore/79 was significantly more immunogenic than a standard 7-µg HA dose without an increase in reactogenicity.

Abstract WP374: Implementation of the Stroke Transition Discharge Center Improves 30-day Readmission Rate

Stroke ◽  
2017 ◽  
Vol 48 (suppl_1) ◽  
Author(s):  
Susan Quimby ◽  
Javicia Peterson-Cole
Keyword(s):  
Readmission Rate ◽  
Inverse Correlation ◽  
Signs And Symptoms ◽  
Patient Specific ◽  
Readmission Rates ◽  
Hospital System ◽  
Practice Nurses ◽  
Time Period ◽  
Number Of Patients ◽  
Discharge Center

Background: Stroke patients and their caregivers require formalized education, medications, testing and rehabilitation to assist in prevention of recurrence and of post-stroke complications for optimal outcomes. Objective: The purpose of this program was to evaluate the effect of the Stroke Transition Discharge Center (STDC) on stroke readmission. Methods: The Advanced Practice Nurses (APN) see all stroke and TIA patients one week after discharge from hospital to home or one week after discharge from rehab to home. During the hour encounter, the APN reviews medications, test results, signs and symptoms of stroke, complete education including patient specific risk factors and ensure appropriate follow up. The APN coordinates and facilitates multiple services and disciplines impacting the patient, assuring the most efficient and effective goal-directed activities are provided at the right time and in partnership with all other disciplines providing care. Results: Implementation of the STDC enhances patient outcomes and improves 30-day readmission rates. Prior to our intervention, the readmission rate was 15.3%. After the implementation of the STDC, there was a 61% reduction in 30-day readmission rates to 6%, which is significantly below the hospital system benchmark of 11%. There was an increase in the readmission rate in the first two quarters of 2016 noted. There is an inverse correlation with the number of patients seen in the STDC during the same time period. Further analysis demonstrates that only one readmission in this time period had been seen prior in the STDC. Conclusion: Implementing the Stroke Transition Discharge Center demonstrated a dramatic reduction in 30-day readmission rates. Our data suggests that utilization of the clinic and participation by the patients has a direct and inverse effect on readmissions. Further data will need to be collected to determine if this is a sustained response.

scholarly journals Two-cycle timed-sequential chemotherapy for adult acute nonlymphocytic leukemia

Blood ◽  
1984 ◽  
Vol 64 (5) ◽  
pp. 975-980
Author(s):  
WP Vaughan ◽  
JE Karp ◽  
PJ Burke
Keyword(s):  
Complete Remission ◽  
Leukemia Cell ◽  
High Dose ◽  
Acute Nonlymphocytic Leukemia ◽  
Single Cycle ◽  
Number Of Patients ◽  
Dose Infusion ◽  
First Remission ◽  
Sequential Regimen

Based on a series of clinical and laboratory studies of leukemia cell kinetics and responses to chemotherapy, we have developed an intensive timed-sequential regimen of daunorubicin and high-dose infusion 1-beta- D-arabinofuranosyl cytosine for the treatment of adult acute nonlymphocytic leukemia. Of the first 34 patients achieving complete remission (CR) with a single cycle of this therapy, four (12%) remain in complete remission without further therapy after a minimum of five years of follow-up. Treatment of relapsed patients with a second course of the same regimen at relapse and no chemotherapy in second remission increased to seven (21%) the number of patients expected to remain in remission for four years or more from their last chemotherapy. Beginning in 1980, however, we gave all consenting adults a second cycle of this chemotherapy in early first remission. Of the first 25 patients treated with a second cycle of this chemotherapy in early first remission, there was one toxic death, but 11 patients (44%) remain in CR with a median follow-up of almost three years.

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