Stud Health Technol Inform. 2022 May 25;294:38-42. doi: 10.3233/SHTI220392.

ABSTRACT

The frequency of potential drug-drug interactions (DDI) in published studies on real world data considerably varies due to the methodological framework. Contextualization of DDI has a proven effect in limiting false positives. In this paper, we experimented with the application of various DDIs contexts elements to see their impact on the frequency of potential DDIs measured on the same set of prescription data collected in EDSaN, the clinical data warehouse of Rouen University Hospital. Depending on the context applied, the frequency of daily prescriptions with potential DDI ranged from 0.89% to 3.90%. Substance-level analysis accounted for 48% of false positives because it did not account for some drug-related attributes. Consideration of the patient's context could eliminate up to an additional 29% of false positives.

PMID:35612012 | DOI:10.3233/SHTI220392

Turk J Pediatr. 2022;64(2):210-220. doi: 10.24953/turkjped.2021.4.

ABSTRACT

BACKGROUND: We aimed to investigate the effectiveness of ketogenic diet (KD) in children with various types of refractory epilepsy.

METHODS: A total of 91 children (49 females) aged 3 to 193 months (median, 52 months) with drug resistant epilepsy who received KD treatment for at least 12 months were enrolled in the study. Seizure frequency, adherence to diet, reason for discontinuation of KD, and adverse effects were recorded. Response was defined as ≥50% improvement in seizure frequency compared to baseline. We also searched for influences of different variables on the outcome.

RESULTS: Intent-to-treat analysis revealed an improvement in seizure frequency for ≥50% in 73.6%, 80.2%, 75.8%, 73.6%, and 70.3% of patients at month-1, -3, -6, -9, and month-12, respectively. Overall, 32 (35.2%) patients remained seizure-free at month-12. There was no significant differences between responders and nonresponders in terms of age at onset of epilepsy, age at onset of KD, gender, or etiology. Mild hyperlipidemia was associated with a higher response rate. At the last follow-up (median: 20 months), 38 (41.8%) patients were still maintained on KD. While 15.4% of patients completed the diet with a success in seizure control, remainder discontinued KD due to lack of efficacy (23.1%), non-adharence to diet (11%), intercurrent infection (4.4%), adverse effects (3.3%), and death (1.1%).

CONCLUSION: Ketogenic diet treatment appears to be effective in about two-thirds of children with various types of drug-resistant epilepsy, including one-third remaining seizure free. Mild hyperlipidemia seems to be associated with a higher response rate. Discontinuation of KD is mostly due to lack of efficacy or nonadherence, and rarely side effects.

PMID:35611409 | DOI:10.24953/turkjped.2021.4

PLoS One. 2022 May 25;17(5):e0267183. doi: 10.1371/journal.pone.0267183. eCollection 2022.

ABSTRACT

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is an invariably lethal progressive disease, causing degeneration of neurons and muscle. No current treatment halts or reverses disease advance. This single arm, open label, clinical trial in patients with ALS investigated the safety and tolerability of a novel modified low molecular weight dextran sulphate (LMW-DS, named ILB®) previously proven safe for use in healthy volunteers and shown to exert potent neurotrophic effects in pre-clinical studies. Secondary endpoints relate to efficacy and exploratory biomarkers.

METHODS: Thirteen patients with ALS were treated with 5 weekly subcutaneous injections of ILB®. Safety and efficacy outcome measures were recorded weekly during treatment and at regular intervals for a further 70 days. Functional and laboratory biomarkers were assessed before, during and after treatment.

RESULTS: No deaths, serious adverse events or participant withdrawals occurred during or after ILB® treatment and no significant drug-related changes in blood safety markers were evident, demonstrating safety and tolerability of the drug in this cohort of patients with ALS. The PK of ILB® in patients with ALS was similar to that seen in healthy controls. The ILB® injection elicited a transient elevation of plasma Hepatocyte Growth Factor, a neurotrophic and myogenic growth factor. Following the ILB® injections patients reported increased vitality, decreased spasticity and increased mobility. The ALSFRS-R rating improved from 36.31 ± 6.66 to 38.77 ± 6.44 and the Norris rating also improved from 70.61 ± 13.91 to 77.85 ± 14.24 by Day 36. The improvement of functions was associated with a decrease in muscle atrophy biomarkers. These therapeutic benefits decreased 3-4 weeks after the last dosage.

CONCLUSIONS: This pilot clinical study demonstrates safety and tolerability of ILB® in patients with ALS. The exploratory biomarker and functional measures must be cautiously interpreted but suggest clinical benefit and have a bearing on the mechanism of action of ILB®. The results support the drug's potential as the first disease modifying treatment for patients with ALS.

TRIAL REGISTRATION: EudraCT 2017-005065-47.

PMID:35613082 | DOI:10.1371/journal.pone.0267183

Stud Health Technol Inform. 2022 May 25;294:880-881. doi: 10.3233/SHTI220616.

ABSTRACT

The objective of our work was to develop deep learning methods for extracting and normalizing patient-reported free-text side effects in a cancer chemotherapy side effect remote monitoring web application. The F-measure was 0.79 for the medical concept extraction model and 0.85 for the negation extraction model (Bi-LSTM-CRF). The next step was the normalization. Of the 1040 unique concepts in the dataset, 62, 3% scored 1 (corresponding to a perfect match with an UMLS CUI). These methods need to be improved to allow their integration into home telemonitoring devices for automatic notification of the hospital oncologists.

PMID:35612235 | DOI:10.3233/SHTI220616

Neuropsychopharmacol Rep. 2022 May 24. doi: 10.1002/npr2.12259. Online ahead of print.

ABSTRACT

INTRODUCTION: Lurasidone has few metabolic adverse effects and is recommended as an alternative when other antipsychotic drugs considerably increase body weight or blood sugar concentrations.

CASE PRESENTATION: An 81-year-old man with bipolar disorder developed hyperosmolar hyperglycemic syndrome as a side effect of lurasidone. Routine monitoring of blood glucose concentrations led to the early detection and treatment of this disease, preventing life-threatening complications.

DISCUSSION AND CONCLUSION: We describe a rare case of lurasidone-induced hyperosmolar hyperglycemic syndrome. The mortality rate of this syndrome is estimated to be up to 20%. This rate is significantly higher than that of diabetic ketoacidosis (currently <2%). Although lurasidone is considered to have a low risk of raising blood glucose concentrations, symptoms of hyperglycemia must be evaluated and blood glucose concentrations should be monitored regularly.

PMID:35609885 | DOI:10.1002/npr2.12259

Toxicol Pathol. 2022 May 24:1926233221100414. doi: 10.1177/01926233221100414. Online ahead of print.

ABSTRACT

Drug-induced kidney injury has historically been associated with renal tubule injury related to small molecule pharmaceuticals such as nonsteroidal anti-inflammatory drugs, antineoplastic agents, or antibiotics, but as a greater number of alternative classes of medicines such as biotherapeutics, molecular-targeted antineoplastic drugs, chimeric antigen receptor T-cell therapies, antibody-drug conjugates, oligonucleotide therapies, or other immunomodulatory drugs come to market, the presentation of drug-induced nephrotoxicity is changing. This review article describes the potential rare clinical events in drug-induced kidney injury that might be noted with these new therapies and their potential impact on patients. Potential pathogenic mechanisms related to immunogenicity, immune complex formation, and stimulation of downstream proinflammatory pathways with some of these alternative medicine classes have resulted in the potential for glomerulonephritis, acute interstitial nephritis, renal vasculitis, and other immune-mediated renal disorders in humans. This contrasts with nonclinical toxicity studies, where biologic therapies more often result in vasculitis and glomerulonephritis associated with antidrug antibodies and immunomodulatory pharmacology, and which are not always predictive of clinical effects. While nonclinical antidrug antibody-related renal disease is generally not clinically relevant, other immune-mediated nephrotoxicities associated with immunomodulatory drugs may be predictive of clinical adverse events. Fortunately, these conditions are still rare and account for a small percentage of serious adverse events in kidneys of patients.

PMID:35608030 | DOI:10.1177/01926233221100414

Math Biosci Eng. 2022 Apr 6;19(6):5754-5771. doi: 10.3934/mbe.2022269.

ABSTRACT

The study of drug side effects is a significant task in drug discovery. Candidate drugs with unaccepted side effects must be eliminated to prevent risks for both patients and pharmaceutical companies. Thus, all side effects for any candidate drug should be determined. However, this task, which is carried out through traditional experiments, is time-consuming and expensive. Building computational methods has been increasingly used for the identification of drug side effects. In the present study, a new path-based method was proposed to determine drug side effects. A heterogeneous network was built to perform such method, which defined drugs and side effects as nodes. For any drug and side effect, the proposed path-based method determined all paths with limited length that connects them and further evaluated the association between them based on these paths. The strong association indicates that the drug has a side effect with a high probability. By using two types of jackknife test, the method yielded good performance and was superior to some other network-based methods. Furthermore, the effects of one parameter in the method and heterogeneous network was analyzed.

PMID:35603377 | DOI:10.3934/mbe.2022269

Drug Ther Bull. 2022 May 23:dtb-2022-000029. doi: 10.1136/dtb.2022.000029. Online ahead of print.

NO ABSTRACT

PMID:35606103 | DOI:10.1136/dtb.2022.000029

Asia Pac J Clin Oncol. 2022 May 22. doi: 10.1111/ajco.13772. Online ahead of print.

ABSTRACT

AIM: Buprenorphine is one of the strongest opioids used for the relief of cancer pain. This study aims to evaluate the real-world clinical experiences of transdermal buprenorphine used in moderate to severe cancer pain in the Asian population.

METHODS: This is an open-labeled, multicenter, 4-week observational study. Stable cancer pain patients who decided to switch the previous opioid to transdermal buprenorphine will be enrolled in this study. The safety and effectiveness were observed and collected. Pain assessment was performed using a numerical rating scale by the investigators and the Brief Pain Inventory Short Form (BPI-SF) by the patient. The safety profiles included concomitant medications and adverse events (AEs).

RESULTS: A total of 83 patients were enrolled in this study. The global pain scores in the BPI, as well as the four individual pain parameters (worst, least, average, and right now), showed a continued decrease (p < .05) from week 2 to week 4. Significant improvements were observed in normal work activities, relations with other people, sleep, enjoyment of life, and global BPI pain interference score on week 4. Pain assessments conducted by investigators demonstrated significant, continuous improvements during the study periods. In addition, transdermal buprenorphine demonstrated good safety/tolerability with limited drug-related AEs in the Asian population with cancer pain.

CONCLUSION: This study demonstrated that transdermal buprenorphine in the Asian population has good safety profiles and continued improvements in pain relief, sleep, and pain interferences. Transdermal buprenorphine can be an effective and convenient option as a transdermal opioid for patients with moderate to severe cancer pain in Taiwan. (NCT Number: NCT04315831).

PMID:35604203 | DOI:10.1111/ajco.13772

Intern Med J. 2022 May 23. doi: 10.1111/imj.15822. Online ahead of print.

ABSTRACT

BACKGROUND: Thiopurines are effective therapies for inflammatory bowel disease (IBD), however treatment comes with safety concerns and adverse effects. Knowledge of the impact of pharmacists performing thiopurine monitoring is limited.

AIMS: To determine the impact of a pharmacist led monitoring service in patients with IBD commencing thiopurine therapy managed in the ambulatory care setting.

METHODS: Patients commencing thiopurine therapy for IBD pre and post introduction of a pharmacist led monitoring intervention were assessed. Pre-intervention patients received standard of care, while the post-intervention cohort were managed by the pharmacist. Data was acquired via retrospective audit of hospital medical records. The primary endpoint was the proportion of patients with documented review for thiopurine adverse effects within the initial three weeks. Secondary endpoints included achievement of therapeutic drug levels, persistence with thiopurine therapy, IBD related episodes of care and number of outpatient medical reviews.

RESULTS: Pre and post intervention cohorts comprised of 37 and 33 patients respectively. Pharmacist intervention increased the proportion of patients with documented monitoring within three weeks from 8.1% to 84.8% (p <0.01). No difference in thiopurine dose optimisation was seen (27% vs 27.3%). Persistence with thiopurine therapy increased from 65.7 to 87.9% (p <0.03) at six months. IBD related emergency department presentations were not significantly decreased (8.1% vs 3%, p=0.62). No significant change was observed in hospital admissions (16.2% vs 12.1%, p=0.74) or outpatient medical reviews.

CONCLUSIONS: Pharmacist monitoring of thiopurine therapy initiation in IBD outpatients improves adverse effect monitoring and increases medication persistence. This article is protected by copyright. All rights reserved.

PMID:35603759 | DOI:10.1111/imj.15822

Commun Med (Lond). 2021 Aug 2;1:21. doi: 10.1038/s43856-021-00021-3. eCollection 2021.

ABSTRACT

BACKGROUND: Therapeutic management of epilepsy remains a challenge, since optimal systemic antiseizure medication (ASM) concentrations do not always correlate with improved clinical outcome and minimal side effects. We tested the feasibility of noninvasive real-time breath metabolomics as an extension of traditional therapeutic drug monitoring for patient stratification by simultaneously monitoring drug-related and drug-modulated metabolites.

METHODS: This proof-of-principle observational study involved 93 breath measurements of 54 paediatric patients monitored over a period of 2.5 years, along with an adult's cohort of 37 patients measured in two different hospitals. Exhaled breath metabolome of epileptic patients was measured in real time using secondary electrospray ionisation-high-resolution mass spectrometry (SESI-HRMS).

RESULTS: We show that systemic ASM concentrations could be predicted by the breath test. Total and free valproic acid (VPA, an ASM) is predicted with concordance correlation coefficient (CCC) of 0.63 and 0.66, respectively. We also find (i) high between- and within-subject heterogeneity in VPA metabolism; (ii) several amino acid metabolic pathways are significantly enriched (p < 0.01) in patients suffering from side effects; (iii) tyrosine metabolism is significantly enriched (p < 0.001), with downregulated pathway compounds in non-responders.

CONCLUSIONS: These results show that real-time breath analysis of epileptic patients provides reliable estimations of systemic drug concentrations along with risk estimates for drug response and side effects.

PMID:35602217 | PMC:PMC9053280 | DOI:10.1038/s43856-021-00021-3

BMC Cancer. 2022 May 21;22(1):569. doi: 10.1186/s12885-022-09622-0.

ABSTRACT

BACKGROUND: This report summarizes three phase I studies evaluating volasertib, a polo-like kinase inhibitor, plus azacitidine in adults with myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia, or acute myeloid leukemia.

METHODS: Patients received intravenous volasertib in 28-day cycles (dose-escalation schedules). In Part 1 of 1230.33 (Study 1; NCT01957644), patients received 250-350 mg volasertib on day (D)1 and D15; in Part 2, patients received different schedules [A, D1: 170 mg/m2; B, D7: 170 mg/m2; C, D1 and D7: 110 mg/m2]. In 1230.35 (Study 2; NCT02201329), patients received 200-300 mg volasertib on D1 and D15. In 1230.43 (Study 3; NCT02721875), patients received 110 mg/m2 volasertib on D1 and D8. All patients in Studies 1 and 2, and approximately half of the patients in Study 3, were scheduled to receive subcutaneous azacitidine 75 mg/m2 on D1-7.

RESULTS: Overall, 22 patients were treated (17 with MDS; 12 previously untreated). Across Studies 1 and 2 (n = 21), the most common drug-related adverse events were hematological (thrombocytopenia [n = 11]; neutropenia [n = 8]). All dose-limiting toxicities were grade 4 thrombocytopenia. The only treated patient in Study 3 experienced 18 adverse events following volasertib monotherapy. Studies 1 and 2 showed preliminary activity (objective response rates: 25 and 40%).

CONCLUSIONS: The safety of volasertib with azacitidine in patients with MDS was consistent with other volasertib studies. All studies were terminated prematurely following the discontinuation of volasertib for non-clinical reasons by Boehringer Ingelheim; however, safety information on volasertib plus azacitidine are of interest for future studies in other diseases.

PMID:35597904 | DOI:10.1186/s12885-022-09622-0

Harm Reduct J. 2022 May 19;19(1):46. doi: 10.1186/s12954-022-00630-8.

ABSTRACT

BACKGROUND: British Columbia (BC) has been in a state of public health emergency since 2016, due to the unprecedented numbers of fatal and non-fatal drug toxicity (i.e. overdose) events. Methamphetamine detection in illicit drug toxicity deaths increased from 14% in 2012 to 43% in 2020 suggesting a concerning trend of concurrent methamphetamine and opioid use in BC, consistent with rising patterns identified across North America. People who use methamphetamine concurrently with opioids face an elevated risk of harm. This study aimed to identify behaviours for survival and wellness practiced by people who concurrently use methamphetamine and opioids.

METHODS: One-on-one semi-structured interviews were conducted by peer research assistants in person and by telephone. Thematic analysis was carried out to identify patterns in behaviours participants described as important to their safety in the context of concurrent use of methamphetamine and opioids.

RESULTS: Participants (n = 22) were distributed across the province with at least four participants from each of the five geographic health regions: 64% self-identified as men, and 50% self-identified as Indigenous. Daily methamphetamine use was reported by 72.7% of participants, and 67.3% reported using alone either often or always. Participants made several considerations and adaptations in order to balance the perceived benefits and risks of their use of methamphetamine with opioids. Two overarching themes were identified to describe how participants adapted their use for survival and wellness. The first was personal safety behaviours which included self-regulation and self-care behaviours. The second was interpersonal safety behaviours which included using alongside peers, and engaging with peer-led services (e.g. community outreach organizations) and public health-led services (e.g. overdose prevention sites) to reduce the risk of harm. Participants identified many gaps in available services to meet their diverse needs.

CONCLUSIONS: This manuscript identified diversity in participants' methamphetamine and opioid use (i.e. frequency, route of administration), and a range of behaviours that were performed to improve wellness and survival while using methamphetamine and opioids. Harm reduction and treatment responses must be robust and adaptable to respond to the diversity of patterns of substance use among people who use methamphetamine and opioids concurrently, so as to not perpetuate harm and leave people behind.

PMID:35590375 | PMC:PMC9118627 | DOI:10.1186/s12954-022-00630-8

J Stud Alcohol Drugs. 2022 May;83(3):309-311.

ABSTRACT

Safer opioid supply programs are being expanded in select Canadian cities as interventions to provide alternatives to the toxic drug supply. Programs primarily provide tablet hydromorphone for patients to consume orally, intranasally, or intravenously. However, in the Canadian province of British Columbia, smoking is the most common mode of consumption among those who have died from illicit drug overdoses. There is a need for these programs to provide smokable opioid alternatives in order to attract and retain those most at risk of overdose mortality.

PMID:35590170

BMJ Open. 2022 May 19;12(5):e056039. doi: 10.1136/bmjopen-2021-056039.

ABSTRACT

INTRODUCTION: Patients have contributed <1% of spontaneous adverse drug reaction (ADR) reports in Uganda's pharmacovigilance database. Peer support combined with mobile technologies could empower people living with HIV (PLHIV) to report ADRs and improve ADR management through linkage to care. We seek to test the feasibility and effect of a peer support intervention on ADR reporting by PLHIV receiving combination antiretroviral therapy (cART) in Uganda; identify barriers and facilitators to the intervention; and characterise ADR reporting and management.

METHODS AND ANALYSIS: This is a quasi-experimental study to be implemented over 4 months at 12 intervention and 12 comparison cART sites from four geographical regions of Uganda. Per region, two blocks each with a tertiary, secondary and primary care cART site will be selected by simple random sampling. Blocks per region will be randomly assigned to intervention and comparison arms.Study units will include cART sites and PLHIV receiving cART. PLHIV at intervention sites will be assigned to peer supporters to empower them to report ADRs directly to the National Pharmacovigilance Centre (NPC). Peer supporters will be expert clients from among PLHIV and/or recognised community health workers.Direct patient reporting of ADRs to NPC will leverage the Med Safety App and toll-free unstructured supplementary service data interface to augment traditional pharmacovigilance methods.The primary outcomes are attrition rate measured by number of study participants who remain in the study until the end of follow-up at 4 months; and number of ADR reports submitted to NPC by PLHIV as measured by questionnaire and data abstraction from the national pharmacovigilance database at baseline and 4 months.

ETHICS AND DISSEMINATION: The study received ethical approval from: School of Health Sciences Research and Ethics Committee at Makerere University (MAKSHSREC-2020-64) and Uganda National Council for Science and Technology (HS1206ES). Results will be shared with PLHIV, policy-makers, the public and academia.

TRIAL REGISTRATION NUMBER: ISRCTN75989485.

PMID:35589351 | DOI:10.1136/bmjopen-2021-056039

Brain Nerve. 2022 May;74(5):600-607. doi: 10.11477/mf.1416202086.

ABSTRACT

The treatment of cryptococcal encephalomyelitis is often complicated by an inadequate response to antifungal therapy and the reduction or withdrawal of antifungal agents due to adverse effects. To achieve a favorable prognosis, patients should be treated with appropriate drugs according to the latest guidelines. In addition to systemic antifungal drug administration in refractory cases, intracerebroventricular administration of amphotericin B may be considered.

PMID:35589653 | DOI:10.11477/mf.1416202086

Brain Nerve. 2022 May;74(5):588-599. doi: 10.11477/mf.1416202085.

ABSTRACT

Cryptococcal meningoencephalitis is mainly caused by Cryptococcus neoformans and accounts for 90% of fungal meningitis cases in Japan. Cryptococcal meningoencephalitis is a rare disease, and similar to tuberculosis meningitis. It often exhibits subacute or chronic progression symptoms such as headache, fever, coma, personality changes, and memory disturbance. Cryptococcal meningoencephalitis often develops in immunosuppressed hosts, but can sometimes occur in healthy individuals, and the mortality rate is 10-25%, indicating a poor prognosis. For the treatment of cryptococcal meningoencephalitis, introduction therapy using a combination of liposomal amphotericin B and flucytosine is recommended. However, in practice, cryptococcal meningoencephalitis is refractory and often requires prolonged treatment; therefore, it is the most difficult to treat among the central nervous system infections. We discuss the following 11 issues: I. Sustainability of first-line treatments, II. Treatment options in case of decreased renal function, III. Association with increased intracranial pressure IV. Causes of visual impairment, V. Necessary steps when symptoms/laboratory findings worsen during antifungal treatment, VI. Cerebral infarction, VII. Difficulty in controlling underlying and comorbid diseases, VIII. Indications for lumbar and ventricular drainage (Ommaya reservoir placement), IX. Pros and cons of concomitant use of corticosteroids, X. Treatment evaluation index: usefulness of head MRI, and XI. Determining the end of treatment and the need for preventive medication.

PMID:35589652 | DOI:10.11477/mf.1416202085

J Geriatr Oncol. 2022 May 16:S1879-4068(22)00110-2. doi: 10.1016/j.jgo.2022.05.002. Online ahead of print.

ABSTRACT

PURPOSE: The COVID-19 vaccination campaign began in December 2020, in France, and primarily targeted the oldest people. Our study aimed to determine the level of acceptance of vaccination in a population of older patients with cancer.

METHODS: From January 2021, we offered vaccination with the BNT162b2 COVID-19 vaccine to all patients 70 years and older referred to our geriatric oncology center in Marseille University Hospital (AP-HM) for geriatric assessment before initiation of an oncological treatment. Objectives were to evaluate acceptance rate of COVID-19 vaccination and to assess vaccine safety, reactogenicity, and efficacy two months after the first dose.

RESULTS: Between January 18, 2021 and May 7, 2021, 150 older patients with cancer were offered vaccination after a geriatric assessment. The majority were men (61.3%), with a mean age of 81 years. The two most frequent primary tumors were digestive (29.4%) and thoracic (18%). The vaccine acceptance rate was 82.6% and the complete vaccination rate (2 doses) reached 75.3%. Among the vaccinated patients, 15.9% reported mild side effects after the first dose and 23.4% after the second dose, mostly arm pain and fatigue. COVID-19 cases were observed in 5.1% of vaccinated patients compared with 16.7% in unvaccinated patients. Of the 22 vaccinated patients who agreed to have their serum tested, 15 had antibodies against the spike protein at day 21 after the first dose.

CONCLUSION: Our study showed a high acceptance rate of COVID-19 vaccination, with good tolerance in this frail population. These results highlight the benefits of organizing vaccination campaigns at the very beginning of oncological management in older patients.

CLINICAL TRIAL REGISTRATION: This study was registered May 23, 2019 in ClinicalTrials.gov (NCT03960593).

PMID:35589542 | DOI:10.1016/j.jgo.2022.05.002

J Patient Saf. 2022 May 18. doi: 10.1097/PTS.0000000000001030. Online ahead of print.

ABSTRACT

OBJECTIVES: Korea's national health insurance authority introduced a drug utilization review modernization pilot project in which health professionals provided follow-up services to monitor adverse drug events. We aimed to evaluate the effects of the project on clinical and economic outcomes.

METHODS: We conducted difference-in-differences analysis using National Health Insurance claims data from the Health Insurance Review and Assessment Service. We calculated the number of adverse drug events and allergic reactions as a clinical indicator and medical costs incurred to manage these events as an economic indicator. Absolute difference in each outcome measure was defined as the value after the project minus the value before the project. Difference-in-differences was defined as a difference in absolute differences between the intervention group and the control group.

RESULTS: Overall, difference-in-differences were -43 and -826 for the number of drug-related adverse events and allergic reactions and -$198,700 and $53,318 for medical costs in the inpatient and outpatient settings, respectively. For outpatients, the monthly number of adverse drug events and allergic reactions has grown higher for the control group than for the intervention group after implementation of the pilot project.

CONCLUSIONS: Implementation of the pilot project lowered the number of adverse drug events and allergic reactions in the inpatient and outpatient setting. The project also lowered medical costs incurred to manage these events in the inpatient setting only. Based on our findings, we recommend that the pilot project be expanded on a nationwide level at least in the inpatient setting.

PMID:35587895 | DOI:10.1097/PTS.0000000000001030

Drug Des Devel Ther. 2022 May 9;16:1365-1381. doi: 10.2147/DDDT.S359501. eCollection 2022.

ABSTRACT

OBJECTIVE: To investigate the pharmacokinetics and safety of peficitinib (Janus kinase inhibitor for the treatment of rheumatoid arthritis) in healthy Chinese subjects following single and multiple doses.

METHODS: This open-label, randomized study was conducted at one site in China. Subjects received peficitinib 50, 100 or 150 mg as a single dose on Day 1 (fasted) and once daily from Days 8 to 13 in the multiple-dose period (fed). Blood samples were collected before administration each day, and up to 72h post administration. Pharmacokinetic assessments included area under the concentration curve (AUC), half-life (t1/2), maximum concentration (Cmax), and time to maximum concentration (tmax) of peficitinib and its metabolites (H1, H2 and H4). Treatment-emergent adverse events (TEAEs) were evaluated.

RESULTS: Thirty-six subjects were enrolled (12 per dose group). After a single dose of peficitinib, median tmax was 1.0-1.5h and mean t1/2 was 7.4-13.0h for all doses. In the multiple-dose period, median tmax was 1.5-2.0h. Dose-proportional increases in Cmax and AUC24h were observed for peficitinib and its metabolites following single and multiple doses, with minimal drug accumulation. The major metabolite was H2, with a systemic exposure of >150% of the parent AUC. Drug-related TEAEs were experienced by 5 (13.9%) and 12 (33.3%) subjects in the single- and multiple-dose periods, respectively. Following multiple doses of peficitinib, TEAEs were more frequent in higher than lower dose groups but were mild in severity with no related discontinuation or death.

CONCLUSION: Following single and multiple doses of peficitinib in healthy Chinese subjects, peficitinib demonstrated rapid absorption and was well tolerated at all doses.

CLINICALTRIALSGOV IDENTIFIER: NCT04143477.

PMID:35586186 | PMC:PMC9109889 | DOI:10.2147/DDDT.S359501