Vaccine immunotherapy may improve survival in Glioblastoma (GBM). A multicenter phase II trial was designed to determine: (1) the success rate of manufacturing the Aivita GBM vaccine (AV-GBM-1), (2) ...Adverse Events (AE) associated with AV-GBM-1 administration, and (3) survival.
Fresh suspected glioblastoma tissue was collected during surgery, and patients with pathology-confirmed GBM enrolled before starting concurrent Radiation Therapy and Temozolomide (RT/TMZ) with Intent to Treat (ITT) after recovery from RT/TMZ. AV-GBM-1 was made by incubating autologous dendritic cells with a lysate of irradiated autologous Tumor-Initiating Cells (TICs). Eligible patients were adults (18 to 70 years old) with a Karnofsky Performance Score (KPS) of 70 or greater, a successful TIC culture, and sufficient monocytes collected. A cryopreserved AV-GBM-1 dose was thawed and admixed with 500 μg of Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) before every subcutaneous (s.c.) administration.
Success rates were 97% for both TIC production and monocyte collection. AV-GBM-1 was manufactured for 63/63 patients; 60 enrolled per ITT; 57 started AV-GBM-1. The most common AEs attributed to AV-GBM-1 were local injection site reactions (16%) and flu-like symptoms (10%). Treatment-emergent AEs included seizures (33%), headache (37%), and focal neurologic symptoms (28%). One patient discontinued AV-GBM-1 because of seizures. Median Progression-Free Survival (mPFS) and median Overall Survival (mOS) from ITT enrollment were 10.4 and 16.0 months, respectively. 2-year Overall Survival (OS) is 27%.
AV-GBM-1 was reliably manufactured. Treatment was well-tolerated, but there were numerous treatment-emergent central nervous system AEs. mPFS was longer than historical benchmarks, though no mOS improvement was noted.
NCT, NCT03400917 , Registered 10 January 2018.
Forensic hospitals throughout the country house individuals with severe mental illness and history of criminal violations. Insomnia affects 67.4% of hospitalized patients with chronic ...neuropsychiatric disorders, indicating that these conditions may hijack human somnogenic pathways. Conversely, somnolence is a common adverse effect of many antipsychotic drugs, further highlighting a common etiopathogenesis. Since the brain salience network is likely the common denominator for insomnia, neuropsychiatric and neurodegenerative disorders, here, we focus on the pathology of this neuronal assembly and its likely driver, the dysfunctional neuronal and mitochondrial membrane. We also discuss potential treatment strategies ranging from membrane lipid replacement to mitochondrial transplantation. The aims of this review are threefold: 1. Examining the causes of insomnia in forensic detainees with severe mental illness, as well as its role in predisposing them to neurodegenerative disorders. 2. Educating State hospital and prison clinicians on frontotemporal dementia behavioral variant, a condition increasingly diagnosed in older first offenders which is often missed due to the absence of memory impairment. 3. Introducing clinicians to natural compounds that are potentially beneficial for insomnia and severe mental illness.
Background:
Eligible patients with kidney failure should have equal access to kidney transplantation. Transplant referral is the first crucial step toward receiving a kidney transplant; however, ...studies suggest substantial variation in the rate of kidney transplant referral across regions. The province of Ontario, Canada, has a public, single-payer health care system with 27 regional chronic kidney disease (CKD) programs. The probability of being referred for kidney transplant may not be equal across CKD programs.
Objective:
To determine whether there is variability in kidney transplant referral rates across Ontario’s CKD programs.
Design:
Population-based cohort study using linked administrative health care databases from January 1, 2013, to November 1, 2016.
Setting:
Twenty-seven regional CKD programs in the province of Ontario, Canada.
Patients:
Patients approaching the need for dialysis (advanced CKD) and patients receiving maintenance dialysis (maximum follow-up: November 1, 2017).
Measurements:
Kidney transplant referral.
Methods:
We calculated the 1-year unadjusted cumulative probability of kidney transplant referral for Ontario’s 27 CKD programs using the complement of Kaplan-Meier estimator. We calculated standardized referral ratios (SRRs) for each CKD program, using expected referrals from a 2-staged Cox proportional hazards model, adjusting for patient characteristics in the first stage. Standardized referral ratios with a value less than 1 were below the provincial average (maximum possible follow-up of 4 years 10 months). In an additional analysis, we grouped CKD programs according to 5 geographic regions.
Results:
Among 8641 patients with advanced CKD, the 1-year cumulative probability of kidney transplant referral ranged from 0.9% (95% confidence interval CI: 0.2%-3.7%) to 21.0% (95% CI: 17.5%-25.2%) across the 27 CKD programs. The adjusted SRR ranged from 0.2 (95% CI: 0.1-0.4) to 4.2 (95% CI: 2.1-7.5). Among 6852 patients receiving maintenance dialysis, the 1-year cumulative probability of transplant referral ranged from 6.4% (95% CI: 4.0%-10.2%) to 34.5% (95% CI: 29.5%-40.1%) across CKD programs. The adjusted SRR ranged from 0.2 (95% CI: 0.1-0.3) to 1.8 (95% CI: 1.6-2.1). When we grouped CKD programs according to geographic region, we found that patients residing in Northern regions had a substantially lower 1-year cumulative probability of transplant referral.
Limitations:
Our cumulative probability estimates only captured referrals within the first year of advanced CKD or maintenance dialysis initiation.
Conclusions:
There is marked variability in the probability of kidney transplant referral across CKD programs operating in a publicly funded health care system.
Patients receiving maintenance hemodialysis have multiple comorbidities and are at high risk of presenting to the hospital. However, the incidence and cost of acute health care utilization in the ...in-center hemodialysis population and how this compares with other populations is poorly understood.
To determine the rate, pattern, and cost of emergency department visits and hospitalizations in patients receiving in-center hemodialysis compared with a matched general population.
Population-based matched cohort study.
We used linked administrative health care databases from Ontario, Canada.
We included 25 379 patients (incident and prevalent) receiving in-center hemodialysis between January 1, 2010, and December 31, 2018. Patients were matched on birth date (±2 years), sex, and cohort entry date using a 1:4 ratio to 101 516 individuals from the general population.
Our primary outcomes were emergency department visits (allowing for multiple visits per individual) and hospital admissions from the emergency department. We also assessed all-cause hospitalizations, all-cause readmissions within 30 days of discharge from the original hospitalization, length of stay for hospital admissions (including multiple visits per individual), and the financial cost of these admissions.
We presented the rate, percentage, median (25th, 75th percentiles), and incidence rate per 1000 person-years for emergency department visits and hospitalizations. Individual-level health care costs for emergency department visits and all-cause hospitalization were estimated using resource intensity weights multiplied by the cost per weighted case.
Patients receiving in-center hemodialysis had substantially more comorbidities (eg, diabetes) than the matched general population. Eighty percent (n = 20 309) of patients receiving in-center hemodialysis had at least 1 emergency department visit compared with 56% (n = 56 452) of individuals in the matched general population, over a median follow-up of 1.8 years (25th, 75th percentiles: 0.7, 3.6) and 5.2 (2.5, 8.4) years, respectively. The incidence rate of emergency department visits, allowing for multiple visits per individual, was 2274 per 1000 person-years (95% confidence interval CI: 2263, 2286) for patients receiving in-center hemodialysis, which was almost 5 times as high as the matched general population (471 per 1000 person-years; 95% CI: 469, 473). The rate of hospital admissions from the emergency department and the rate of all-cause hospital admissions in the in-center hemodialysis population was more than 7 times as high as the matched general population (hospital admissions from the emergency department: 786 vs 101 per 1000 person-years; all-cause hospital admissions: 1056 vs 139 per 1000 person-years). The median number of all-cause hospitalization days per patient year was 4.0 (0, 16.5) in the in-center hemodialysis population compared with 0 (0, 0.5) in the matched general population. The cost per patient-year for emergency department visits in the in-center hemodialysis population was approximately 5.5 times as high as the matched general population while the cost of hospitalizations in the in-center hemodialysis population was approximately 11 times as high as the matched general population (emergency department visits: CAN$ 1153 vs CAN$ 209; hospitalizations: CAN$ 21 151 vs CAN$ 1873 all costs in 2023 CAN$).
External generalizability and we could not determine whether emergency department visits and hospitalizations were preventable.
Patients receiving in-center hemodialysis have high acute health care utilization. These results improve our understanding of the burden of disease and the associated costs in the in-center hemodialysis population, highlight the need to improve acute outcomes, and can aid health care capacity planning. Additional research is needed to address the risk of hospitalization after controlling for patient comorbidities.
This is not applicable as this is a population-based matched cohort study and not a clinical trial.
Background:
Guidelines in Ontario, Canada, recommend timely referral for multidisciplinary kidney care to facilitate planned dialysis initiation. Many patients do not receive recommended ...multidisciplinary kidney care prior to dialysis.
Objective:
To better understand why this gap in pre-dialysis care exists, we conducted a study to describe the pathways by which patients initiate maintenance dialysis.
Design:
A retrospective cohort study.
Setting:
Population-based, using health care administrative databases from Ontario, Canada.
Patients:
Adults initiating maintenance dialysis from April 2016 to March 2019.
Measurements and methods:
Patients were grouped based on whether they received recommended multidisciplinary kidney care prior to dialysis initiation (at least 1 year of care with at least 2 visits). For those who did not receive recommended care, we grouped patients as having no identified care gap or into the following groups: (1) lack of timely chronic kidney disease (CKD) screening, (2) late nephrology referral (<1 year), or (3) late or no referral for multidisciplinary kidney care among patients followed by a nephrologist for at least 1 year.
Results:
A total of 9216 patients were included with a mean (standard deviation) age of 66 (15) years, and 61.5% were male. Of the total, 896 (9.7%) patients died, 7671 (83.2%) remained on dialysis at 90 days, and 649 (7.0%) had stopped dialysis due to kidney function recovery within 90 days. Of the 9216 patients, 5434 (59%) had not received recommended multidisciplinary kidney care. Among those without recommended care, there were 2251 (41.4%) patients with no identified care gaps, 1351 (24.9%) patients with a lack of timely CKD screening, 359 (6.6%) patients with late nephrology referral, and 1473 (27.1%) patients with late or no referral for multidisciplinary kidney care.
Limitations:
We could not determine if patients were referred but declined multidisciplinary kidney care.
Conclusions:
More than half of patients had not received recommended multidisciplinary kidney care. Many patients experienced an acute decline in kidney function, which may not be preventable, but in others, there were missed opportunities for CKD screening or early referral to nephrology, or at the level of nephrology practice for early referral for multidisciplinary care. This work could be used to inform policies aimed at improving increased uptake of multidisciplinary kidney care prior to dialysis.
It is unclear whether the use of higher dialysate bicarbonate concentrations is associated with clinically relevant changes in the pre-dialysis serum bicarbonate concentration.
The objective is to ...examine the association between the dialysate bicarbonate prescription and the pre-dialysis serum bicarbonate concentration.
This is a retrospective cohort study.
The study was performed using linked administrative health care databases in Ontario, Canada.
Prevalent adults receiving maintenance in-center hemodialysis as of April 1, 2020 (n = 5414) were included.
Patients were grouped into the following dialysate bicarbonate categories at the dialysis center-level: individualized (adjustment based on pre-dialysis serum bicarbonate concentration) or standardized (>90% of patients received the same dialysate bicarbonate concentration). The standardized category was stratified by concentration: 35, 36 to 37, and ≥38 mmol/L. The primary outcome was the mean outpatient pre-dialysis serum bicarbonate concentration at the patient level.
We examined the association between dialysate bicarbonate category and pre-dialysis serum bicarbonate using an adjusted linear mixed model.
All dialysate bicarbonate categories had a mean pre-dialysis serum bicarbonate concentration within the normal range. In the individualized category, 91% achieved a pre-dialysis serum bicarbonate ≥22 mmol/L, compared to 87% in the standardized category. Patients in the standardized category tended to have a serum bicarbonate that was 0.25 (95% confidence interval CI = -0.93, 0.43) mmol/L lower than patients in the individualized category. Relative to patients in the 35 mmol/L category, patients in the 36 to 37 and ≥38 mmol/L categories tended to have a serum bicarbonate that was 0.70 (95% CI = -0.30, 1.70) mmol/L and 0.87 (95% CI = 0.14, 1.60) mmol/L higher, respectively. There was no effect modification by age, sex, or history of chronic lung disease.
We could not directly confirm that all laboratory measurements were pre-dialysis. Data on prescribed dialysate bicarbonate concentrations for individual dialysis sessions were not available, which may have led to some misclassification, and adherence to a practice of individualization could not be measured. Residual confounding is possible.
We found no significant difference in the pre-dialysis serum bicarbonate concentration irrespective of whether an individualized or standardized dialysate bicarbonate was used. Dialysate bicarbonate concentrations ≥38 mmol/L (vs 35 mmol/L) may increase the pre-dialysis serum bicarbonate concentration by 0.9 mmol/L.
PDF
