Agreement between self-report and urine drug test results in a sample patients treated with buprenorphine for opioid use disorder

BACKGROUND: Urine drug testing (UDT) is recommended to monitor primary care patients treated for opioid use disorder with buprenorphine. Whether UDT data contributes clinically useful information beyond patient self-report of drug use has received minimal attention. It is unclear whether differences between patient self-report and UDT results varies with time in treatment. OBJECTIVES: To estimate concordance between self-report and UDT results and evaluate if discordant results are associated with time in treatment. METHODS: Retrospective review of electronic medical records of patients enrolled in the Office Based Opioid Treatment program at Boston Medical Center between January 2011–April 2013. Typically, patients submit a urine sample for UDT at the beginning of a clinical visit and are subsequently asked about recent cocaine and opioid use which is documented in the electronic medical record. We compared UDT results to patient self-report of cocaine and opioid use. RESULTS: Of 1,755 UDT from 130 patients, 4% (78/1755) were positive for cocaine and 10% (157/1563) for opioids other than buprenorphine. At visits with a cocaine positive UDT, 76% of patients (59/78) did not disclose cocaine use. At visits with an opioid positive UDT, 57% of patients (89/157) did not disclose opioid use. The odds of having a positive UDT for either cocaine or opioids with no disclosure of use decreased over a year of treatment. CONCLUSION: In a sample of primary care patients with opioid use disorder treated with buprenorphine, fewer than 10% of UDTs were positive for cocaine or opioids, and in these instances patient self-reported use of cocaine or opioids less than half the time. As duration of treatment increased, patients were more likely to disclose use. Urine drug testing contributes new and useful information for clinical consideration of the optimal care of patients with drug use disorders; how best to collect and utilize this information merits further study

Receipt of medications for opioid use disorder among youth engaged in primary care: data from 6 health systems

PURPOSE: Little is known about prevalence and treatment of OUD among youth engaged in primary care (PC). Medications are the recommended treatment of opioid use disorder (OUD) for adolescents and young adults (youth). This study describes the prevalence of OUD, the prevalence of medication treatment for OUD, and patient characteristics associated with OUD treatment among youth engaged in PC. METHODS: This cross-sectional study includes youth aged 16-25 years engaged in PC. Eligible patients had ≥ 1 PC visit during fiscal years (FY) 2014-2016 in one of 6 health systems across 6 states. Data from electronic health records and insurance claims were used to identify OUD diagnoses, office-based OUD medication treatment, and patient demographic and clinical characteristics in the FY of the first PC visit during the study period. Descriptive analyses were conducted in all youth, and stratified by age (16-17, 18-21, 22-25 years). RESULTS: Among 303,262 eligible youth, 2131 (0.7%) had a documented OUD diagnosis. The prevalence of OUD increased by ascending age groups. About half of youth with OUD had documented depression or anxiety and one third had co-occurring substance use disorders. Receipt of medication for OUD was lowest among youth 16-17 years old (14%) and highest among those aged 22-25 (39%). CONCLUSIONS: In this study of youth engaged in 6 health systems across 6 states, there was low receipt of medication treatment, and high prevalence of other substance use disorders and mental health disorders. These findings indicate an urgent need to increase medication treatment for OUD and to integrate treatment for other substance use and mental health disorders

The Human Phenotype Ontology in 2024: phenotypes around the world.

The Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

P858 An open-label, multi-center trial of INO-5401 and INO-9012 delivered by electroporation (EP) in combination with cemiplimab in subjects with newly-diagnosed glioblastoma (GBM)

BackgroundGBM is one of the most deadly cancers and treatment is surgery, followed by radiation (RT) and temozolomide (TMZ) daily during RT followed by cycles of TMZ for select patients.1 New immunotherapies, such as checkpoint inhibition, may benefit patients with GBM. T cell-enabling therapies, in combination with checkpoint inhibition, may improve overall survival (OS). In this study, a novel antigen-specific T cell-generating therapy, INO-5401 (synthetic DNA plasmids encoding for human telomerase [hTERT], Wilms Tumor-1 [WT-1] and prostate specific membrane antigen [PSMA]), plus INO-9012 (synthetic DNA plasmid encoding for IL-12), with the PD-1 checkpoint inhibitor, cemiplimab, was given to patients with newly-diagnosed GBM to evaluate tolerability, immunogenicity and clinical efficacy of the combination.MethodsPhase I/II, single arm, two cohort study (A: MGMT Promoter Unmethylated, B: MGMT Promoter Methylated). The primary objective is to evaluate the safety of INO-5401 and INO-9012 followed by EP with CELLECTRA® 2000 in combination with cemiplimab. Secondary objectives include the evaluation of preliminary clinical efficacy and immunogenicity. Treatment is with 9 mg INO-5401 with 1 mg INO-9012 every three weeks (Q3W) for four doses, then Q9W; and cemiplimab (350 mg IV Q3W). RT is given as 40 Gy over three weeks; TMZ is given concurrent with radiation (Cohorts A and B), followed by maintenance TMZ (Cohort B).Results52 patients were enrolled onto this study; 32 in Cohort A and 20 in Cohort B. 18 were women (35%) and 47 were white (90%). The median age was 60 years (range 19-78 years). The most common Grade ≥3 adverse events were elevations in alanine or aspartate aminotransferase (ALT/AST; 5 patients), and tumor inflammation/edema (5 patients); there was one Grade 5 unrelated event of urosepsis. The only related SAE reported in more than one patient was pyrexia. 22 patients (42%) reported immune-related AEs, with the most common being elevations in ALT or AST (8 patients), and were reported most commonly within the first nine weeks of treatment. The safety profile was consistent with that of patients with GBM and of checkpoint inhibitors. ELISpot assessments performed to date demonstrated the majority of patients have T cell responses to INO-5401. PFS6 was 75% (95% CI 56.6, 88.5) in Cohort A (preliminary; Cohort B pending).ConclusionsINO-5401 + INO-9012 with cemiplimab has an acceptable safety profile, is immunogenic and is potentially efficacious in patients with newly-diagnosed GBM. This combination is promising; survival results will be updated next year.Trial RegistrationNCT03491683.Ethics ApprovalThis study was approved by New York University institution’s Ethics Board; approval number i17-00764.ReferencesStupp R, et al. (2009). Lancet Oncology 10(5): 459–466

INO-5401 and INO-9012 delivered intramuscularly (IM) with electroporation (EP) in combination with cemiplimab (REGN2810) in newly diagnosed glioblastoma (GBM): Interim results

2514 Background: Novel T cell-enabling therapies, in combination with checkpoint inhibition, may improve OS in GBM. INO-5401 (synthetic DNA plasmids encoding for hTERT, WT-1 and PSMA), plus INO-9012 (synthetic DNA plasmid encoding IL-12), with the PD-1 checkpoint inhibitor cemiplimab, is given to patients with newly-diagnosed GBM to evaluate tolerability, efficacy and immunogenicity of the combination. Methods: Phase I/II, single arm, 2 cohort study (A: MGMT unmethylated, B: MGMT methylated). The primary endpoint is safety; efficacy and immunogenicity are secondary. Nine mg INO-5401 plus 1 mg INO-9012 (every 3 weeks for 4 doses, then Q9W) is given with EP by CELLECTRA 2000 with cemiplimab (350 mg IV Q3W). RT is given as 40 Gy over 3 weeks. TMZ is given with radiation (all patients), followed by maintenance (Cohort B only). Results: Fifty two subjects were enrolled: 32 in Cohort A; 20 in Cohort B. 35% women and 90% white. Median age 60 years (range 19-78 years). Common Grade ≥3 AEs reported were: platelet count decreased (11.5%), tumor inflammation (7.7%), seizure (7.7%), ALT increased (7.7%), lymphocyte count decreased (7.7.%). One Grade 5 unrelated event of urosepsis was reported. Of 69 SAEs reported there was only 1 related to the combination therapy, Grade 1 pyrexia. 48% of subjects reported irAEs, most frequently ALT increased (9.6%), AST increased (7.7%), diarrhea (7.7%), pyrexia (7.7%) and tumor inflammation (7.7%). 71% of the reported SAEs and irAEs occurred within the first 12 weeks of treatment. OS at 12 months was 84.4% (95% CI 67.2, 94.7) in Cohort A; Cohort B will be presented at ASCO. ELISpot assessments demonstrated T cell responses to INO-5401. Flow cytometry demonstrated evidence of activated INO-5401-specific CD8+T cells with lytic potential (CD38+Prf+GrzA+) when compared with baseline, post-treatment in the majority of patients assayed. Conclusions: INO-5401 + INO-9012 in combination with cemiplimab and RT/TMZ has an acceptable safety profile, is immunogenic and may show a survival advantage in patients with newly-diagnosed GBM. OS18 data will be presented later this year. Clinical trial information: NCT03491683

The Human Phenotype Ontology in 2024: phenotypes around the world

Funder: French Ministry of HealthFunder: Angela Wright Bennett Foundation; DOI: https://doi.org/10.13039/501100020544Funder: McCusker Charitable Foundation; DOI: https://doi.org/10.13039/100014834Funder: Channel 7 Telethon TrustsFunder: the Stan Perron Charitable Foundation and Mineral ResourcesFunder: Prechter Bipolar Research ProgramThe Human Phenotype Ontology (HPO) is a widely used resource that comprehensively organizes and defines the phenotypic features of human disease, enabling computational inference and supporting genomic and phenotypic analyses through semantic similarity and machine learning algorithms. The HPO has widespread applications in clinical diagnostics and translational research, including genomic diagnostics, gene-disease discovery, and cohort analytics. In recent years, groups around the world have developed translations of the HPO from English to other languages, and the HPO browser has been internationalized, allowing users to view HPO term labels and in many cases synonyms and definitions in ten languages in addition to English. Since our last report, a total of 2239 new HPO terms and 49235 new HPO annotations were developed, many in collaboration with external groups in the fields of psychiatry, arthrogryposis, immunology and cardiology. The Medical Action Ontology (MAxO) is a new effort to model treatments and other measures taken for clinical management. Finally, the HPO consortium is contributing to efforts to integrate the HPO and the GA4GH Phenopacket Schema into electronic health records (EHRs) with the goal of more standardized and computable integration of rare disease data in EHRs