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Frontiers in Oncology 2023To identify modifiable risk factors associated with prolonged clearance of methotrexate in pediatric, adolescent, and young adult (AYA) oncology patients receiving high...
PURPOSE
To identify modifiable risk factors associated with prolonged clearance of methotrexate in pediatric, adolescent, and young adult (AYA) oncology patients receiving high dose methotrexate (HDMTX).
DESIGN/METHOD
A single institution, retrospective chart review of patients receiving HDMTX between 2010-2017. Patients had a diagnosis of either leukemia or osteosarcoma. Data included demographics, concurrent intravenous (IV) medications, IV fluids (IVF) administered, urine output (UO), and rises in serum creatinine (RSC) reflective of renal toxicity (RT). Outcome measures included 1) delayed targeted MTX clearance (DC), 2) actual time to clearance (TTC) and 3) length of stay (LOS).
RESULTS
Data from 447 HDMTX administrations were analyzed. The sample consisted of 241 (54%) osteosarcoma encounters, and 206 (46%) leukemia encounters, with an average patient age of 12.7 years. Multivariate analysis showed that DC was associated with the diagnosis of leukemia (OR 7.64, p <.0001), and less UO on day 1 (OR 0.76, p=0.005). Increased TTC was associated with increasing age (RR 1.02, p<0.0001), higher 24-hour MTX levels (RR 1.001, p=0.012) and 48-hour MTX levels (RR 1.02, p<0.0001), RT (RR 1.004, p<0.0001), use of IV lorazepam (RR 1.08, p=0.001) and IV metoclopramide (RR 1.08, p<0.001) both on day 3. Like TTC, LOS was affected by MTX levels at 24 (RR 1.001, p=0.025) and 48 hours (RR 1.03, p<0.0001), RT (RR 1.006, p<0.0001), total IV medications on day 3 (RR 1.042, p<0.0001), and the use of leucovorin on day 2 (RR 0.93, p=0.002).
CONCLUSION
Multiple modifiable risk factors were identified which can be leveraged to improve HDMTX clearance. Subsequent efforts will assess whether acting on such risk factors can improve MTX clearance and shorten LOS.
PubMed: 37965460
DOI: 10.3389/fonc.2023.1280587 -
Clinical NeuropharmacologyNeuroleptic malignant syndrome (NMS) is a life-threatening condition that occurs as an adverse reaction to antipsychotic and antiemetic agents or sudden withdrawal of...
OBJECTIVES
Neuroleptic malignant syndrome (NMS) is a life-threatening condition that occurs as an adverse reaction to antipsychotic and antiemetic agents or sudden withdrawal of dopaminergic medications. Given the metabolic and functional reserves and the comorbidities in older adults, NMS may show an atypical course.
METHODS
The medical records of patients with neurodegenerative diseases leading to dementia between 2013 and 2020 were reviewed for the diagnosis of NMS. Demographic and clinical characteristics of the patients were obtained from the records of laboratory parameters, management, and length of stay.
RESULTS
Fifteen older adults (19 episodes) diagnosed with NMS were included. The median age was 76 years, and 5 were female. Ten of 15 NMS patients were atypical. Most of them had an infection accompanying NMS. Neuroleptic malignant syndrome was caused by antidopaminergic agents (5 antipsychotics, 1 metoclopramide) in 6 episodes and discontinuation of a dopaminergic agent, l -DOPA, in 12 episodes. In 1 patient, it was associated with simultaneous use of domperidone and amantadine withdrawal. Rigidity in NMS due to l -DOPA discontinuation was higher than in those due to antipsychotic use ( P = 0.027). Two of our patients needed intensive care, and 1 died.
CONCLUSIONS
This study highlights the high frequency of atypical NMS and the importance of early recognition of this potentially fatal syndrome, which can accompany neurodegenerative diseases and infections in older adults.
Topics: Humans; Female; Aged; Male; Neuroleptic Malignant Syndrome; Antipsychotic Agents; Neurodegenerative Diseases; Dementia; Dihydroxyphenylalanine
PubMed: 37962307
DOI: 10.1097/WNF.0000000000000570 -
Clinical Gastroenterology and... Nov 2023Metoclopramide nasal spray (MNS) was developed as an alternative to oral metoclopramide. Prior phase 2 studies demonstrated efficacy in reducing symptoms in women, but...
BACKGROUND & AIMS
Metoclopramide nasal spray (MNS) was developed as an alternative to oral metoclopramide. Prior phase 2 studies demonstrated efficacy in reducing symptoms in women, but not men with diabetic gastroparesis. The aim of this phase 3 study was to further determine the safety and efficacy of MNS compared with placebo in reducing symptoms of diabetic gastroparesis in women.
METHODS
This US multicenter, randomized, double-blind, parallel group study enrolled women aged 18-75 years with diabetic gastroparesis and delayed gastric emptying. Subjects were randomized 1:1 to receive placebo or MNS 10 mg. The primary efficacy end point was change in mean daily Gastroparesis Symptom Assessment total score from baseline to Week 4. The Gastroparesis Symptom Assessment daily diary is a validated patient-reported outcome instrument that averages scores of nausea, early satiety, prolonged fullness, bloating, and upper abdominal pain on a 5-point ordinal scale.
RESULTS
Two hundred and five subjects were randomized to receive placebo (n = 103) or MNS (n = 102). Overall, the MNS group did not experience a significant reduction in symptoms compared with the placebo group from baseline to Week 4 (P = .881). However, subjects with moderate-to-severe symptoms at baseline had a significant treatment effect from Weeks 1 to 3 (P < .05) and experienced a significant reduction in nausea and upper abdominal pain for all 4 weeks versus placebo (P < .05). Treatment-emergent adverse events were primarily mild to moderate with headache and abdominal pain reported most frequently.
CONCLUSIONS
Although the primary end point was not met using all enrolled patients, treatment with MNS provided significant relief for women with moderate-to-severe diabetic gastroparesis symptoms. MNS was well tolerated and demonstrated a similar safety profile to placebo. (ClinicalTrials.gov identifier: NCT02025725.).
PubMed: 37924856
DOI: 10.1016/j.cgh.2023.10.022 -
BMC Gastroenterology Oct 2023Since the previous network meta-analysis assessing the efficacy of prokinetics for functional dyspepsia (FD), there have been a number of new studies and cinitapride is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Since the previous network meta-analysis assessing the efficacy of prokinetics for functional dyspepsia (FD), there have been a number of new studies and cinitapride is a new prokinetic agent for FD. This updated meta-analysis aimed to explore the efficacy and safety of prokinetics for FD.
METHODS
An updated study search in Pubmed, EMBASE, Cochrane Library and Web of Science was conducted in literatures published from July 2015 to March 2023. Randomized controlled trials investigating the use of prokinetics in adult FD patients were included. The primary outcome was the total efficacy rate and the secondary outcome was adverse events. A Bayesian network meta-analysis was performed using R software.
RESULTS
A total of 28 studies were included. Network meta-analysis showed that metoclopramide had a higher total efficacy rate than mosapride (OR: 3.53, 95%CI: 1.70-7.47), domperidone (OR: 2.29, 95%CI: 1.16-4.63), itopride(OR: 2.77, 95%CI: 1.41-5.59), acotiamide(OR: 2.63, OR: 1.33-5.36), and placebo(OR: 5.68, 95%CI: 2.98-11.10), however similar to cinitapride (OR: 1.62, 95%CI: 0.75-3.53). Cinitapride had a higher total efficacy rate than mosapride (OR: 2.18, 95%CI: 1.16-4.14) and placebo (OR: 3.52, 95%CI: 2.01-6.24). Cinitapride had lower risk of total adverse events than domperidone. There was no difference in the risk of drug-related adverse events between the prokinetics.
CONCLUSIONS
Metoclopramide and cinitapride may have a better efficacy than other prokinetics in the treatment of FD, and cinitapride may have a lower risk of total adverse events. Further studies using uniform definitions or validated tools to measure the total efficacy rate are needed.
Topics: Adult; Humans; Dyspepsia; Domperidone; Metoclopramide; Network Meta-Analysis; Bayes Theorem; Randomized Controlled Trials as Topic
PubMed: 37907846
DOI: 10.1186/s12876-023-03014-9 -
Mikrobiyoloji Bulteni Oct 2023Malaria is a parasitic disease transmitted by infected female Anopheles mosquitoes. There are five species of Plasmodium species that can infect humans. Of these...
Malaria is a parasitic disease transmitted by infected female Anopheles mosquitoes. There are five species of Plasmodium species that can infect humans. Of these species, especially P.falciparum and P.vivax pose the greatest threat to human health. In the 2014 report of the World Health Organization, it was reported that there were no locally acquired cases of malaria in 16 countries including Türkiye. Malaria cases originating from outside the country and imported due to migration, travel and working abroad are reported as import cases. In this report, a case of non-imported malaria followed with a preliminary diagnosis of leukemia was presented. A 14-year-old female patient who was admitted to a health institution with complaints of high fever, headache, chills, nausea-vomiting, and diarrhea that had been going on for two weeks, was pre-diagnosed as leukemia and was referred to Manisa Celal Bayar University Faculty of Medicine, Hafsa Sultan Hospital, Department of Pediatric Hematology and after pancytopenia was detected in the complete blood count. The anamnesis of the patient revealed that she had no history of international travel and that she had been prescribed medications such as paracetamol, amoxicillin, and metoclopramide for flu-like complaints while working in the Southeastern Anatolia, Aegean, and Mediterranean Regions of Türkiye. Bone marrow aspiration was performed for the etiological examination of pancytopenia. Giemsa-stained blood smears, rapid diagnostics, and real-time quantative polymerase chain reaction (qRt-PCR) analyses were performed in the medical parasitology laboratory and malaria was suspected in both bone marrow and peripheral blood smears. P.vivax erythrocytic forms and gametocytes were present in abundance in smear preparations stained with Giemsa, and rapid diagnosis kit was positive for P.vivax. The strain was genotyped as P.vivax by qRt-PCR analysis. For the treatment of the patient, airalam (artemether + lumefantrine) tablets were provided with 2 x 4 daily posology for three days after the diagnosis, and primaquine was provided after one week of the diagnosis as 1 x 2 tablets (1 x 15 mg) for 14 days, and the patient was discharged without complications following the treatment regimen. The fight against malaria continues uninterruptedly since the establishment of the Republic of Türkiye. Tropical diseases, especially malaria, is of great importance for Türkiye due to numerous reasons such as its location in the subtropical region where Anopheles mosquitoes are capable of malaria transmission, it is situated at the crossroads on the migration routes between continents where human traffic is busy, there are many people who go abroad for work and most importantly rising temperatures due to climate change. For this reason, this case report is important to emphasize the importance of malaria for the country and to increase the awareness of clinicians and laboratories about malaria and the possibility of autochthonous malaria transmission in Türkiye.
Topics: Adolescent; Animals; Female; Humans; Leukemia; Malaria; Malaria, Vivax; Pancytopenia; Plasmodium; Travel
PubMed: 37885398
DOI: 10.5578/mb.20239958 -
Drugs & Aging Dec 2023To reduce prescribing cascades occurring in clinical practice, healthcare providers require information on the prescribing cascades they can recognize and prevent. (Review)
Review
BACKGROUND
To reduce prescribing cascades occurring in clinical practice, healthcare providers require information on the prescribing cascades they can recognize and prevent.
OBJECTIVE
This systematic review aims to provide an overview of prescribing cascades, including dose-dependency information and recommendations that healthcare providers can use to prevent or reverse them.
METHODS
The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was followed. Relevant literature was identified through searches in OVID MEDLINE, OVID Embase, OVID CINAHL, and Cochrane. Additionally, Web of Science and Scopus were consulted to analyze reference lists and citations. Publications in English were included if they analyzed the occurrence of prescribing cascades. Prescribing cascades were included if at least one study demonstrated a significant association and were excluded when the adverse drug reaction could not be confirmed in the Summary of Product Characteristics. Two reviewers independently extracted and grouped similar prescribing cascades. Descriptive summaries were provided regarding dose-dependency analyses and recommendations to prevent or reverse these prescribing cascades.
RESULTS
A total of 95 publications were included, resulting in 115 prescribing cascades with confirmed adverse drug reactions for which at least one significant association was found. For 52 of these prescribing cascades, information regarding dose dependency or recommendations to prevent or reverse prescribing cascades was found. Dose dependency was analyzed and confirmed for 12 prescribing cascades. For example, antipsychotics that may cause extrapyramidal syndrome followed by anti-parkinson drugs. Recommendations focused on dosage lowering, discontinuing medication, and medication switching. Explicit recommendations regarding alternative options were given for three prescribing cascades. One example was switching to ondansetron or granisetron when extrapyramidal syndrome is experienced using metoclopramide.
CONCLUSIONS
In total, 115 prescribing cascades were identified and an overview of 52 of them was generated for which recommendations to prevent or reverse them were provided. Nonetheless, information regarding alternative options for managing prescribing cascades was scarce.
Topics: Humans; Health Personnel; Drug-Related Side Effects and Adverse Reactions
PubMed: 37863868
DOI: 10.1007/s40266-023-01072-y -
BMJ Supportive & Palliative Care Oct 2023Our work aims to critically review the use of anticipatory medicines in our inner-city hospice community population and whether our current practices are fit for purpose.
OBJECTIVES
Our work aims to critically review the use of anticipatory medicines in our inner-city hospice community population and whether our current practices are fit for purpose.
METHODS
Retrospective audit of community palliative care patients at the end-of-life prescribed anticipatory medicines within a 3-month period. Anticipatory charts and case notes reviewed. Intervention included updating local guidelines, local teaching for medical and non-medical prescribers and sharing results nationally. Eighteen months later, reaudit was performed assessing impact.
RESULTS
In total, 76 patients included. 75/76 (99%) were prescribed an analgesic, antiemetic, antisecretory and anxiolytic. 49/76 (64%) were administered 'as required' medications at home. Haloperidol was the favoured antiemetic (88%), costing our hospice ~£2000/month. Case note review highlighted prescribing and administration issues. Reaudit showed a reduction in prescriptions of antisecretory (by 57%) and antiemetic (by 50%), with a wider range of antiemetics (levomepromazine 47%, haloperidol 35%, cyclizine 14%, metoclopramide 3%) indicating individualised prescribing. Those without an antiemetic prescribed did not later require one dispensing.
CONCLUSION
Our work challenges the orthodoxy that an analgesic, antiemetic, antisecretory and anxiolytic medication must always be included for effective anticipatory prescribing. Antiemetics may not be universally required and individualised prescribing was cost-effective and safe at a local level. Further work evaluating the impacts of altered practice on patients, caregivers, professionals and in other community settings is required.
PubMed: 37852662
DOI: 10.1136/spcare-2023-004270 -
Advances in Clinical and Experimental... Oct 2023Intravenous ketorolac and metoclopramide are common emergency treatments for adult patients with migraine headaches. The comparison between ketorolac and metoclopramide...
BACKGROUND
Intravenous ketorolac and metoclopramide are common emergency treatments for adult patients with migraine headaches. The comparison between ketorolac and metoclopramide for migraine treatment is an intriguing issue for research and clinical practice.
OBJECTIVES
To provide an updated systematic review and meta-analysis of randomized clinical trials (RCTs) to help determine which treatment has better effects for migraine patients.
MATERIAL AND METHODS
Intravenous ketorolac and metoclopramide were compared to evaluate whether intravenous ketorolac is associated with significant benefits for pain intensity, short-term headache relief and sustained headache relief among adult patients with migraines. Adverse effects were also analyzed. Five studies with a total of 674 adult patients were included in the analysis, which focused on the outcomes of pain intensity, short-term headache relief, sustained headache relief, and adverse effects.
RESULTS
The meta-analysis showed that the only modest but statistically significant difference was present in short-term headache relief when comparing intravenous ketorolac with intravenous metoclopramide. There were no significant differences between intravenous ketorolac and metoclopramide in terms of pain intensity, sustained headache relief or adverse effects.
CONCLUSION
The results suggest that there are no significant differences in most treatment effects (aside from short-term headache relief) and adverse effects when comparing intravenous ketorolac with intravenous metoclopramide. However, the paucity of literature on this topic might have limited the interpretation of the current results. Thus, more relevant studies are warranted.
PubMed: 37849443
DOI: 10.17219/acem/171697 -
Journal of Pain & Palliative Care... Mar 2024Symptoms of nausea and vomiting are common in palliative care and hospice patients. One of the many classes of medications used for the treatment of nausea and vomiting... (Review)
Review
Symptoms of nausea and vomiting are common in palliative care and hospice patients. One of the many classes of medications used for the treatment of nausea and vomiting is dopamine receptor antagonists which are particularly helpful for treating nausea mediated by the chemoreceptor trigger zone (CTZ) and impaired gastrointestinal function. While dopamine antagonists can be very effective treatments for nausea they should be used with caution as they carry the risk of QTc prolongation, have a FDA black box warning for tardive dyskinesia (TD), and increased risk of precipitating psychosis and death in patients with dementia. This review will cover haloperidol, olanzapine, prochlorperazine, and metoclopramide for treatment of nausea and vomiting including evidence of efficacy, pharmacokinetics, and pharmacodynamics to improve safe and effective utilization in clinical practice. This includes medication receptor site affinities at histaminic, muscarinic, serotonergic, and alpha-adrenergic receptors which can help providers anticipate potential adverse effects and risk of extrapyramidal symptoms (EPS), TD, and QTc prolongation. This review also includes considerations for dose adjustments based on renal function, hepatic function, and age. Understanding the pharmacology of dopamine antagonists can help providers choose the best treatment for control of nausea and vomiting and subsequently improve patients' quality of life.
Topics: Humans; Dopamine Antagonists; Palliative Care; Quality of Life; Vomiting; Nausea; Long QT Syndrome
PubMed: 37843383
DOI: 10.1080/15360288.2023.2268065 -
European Review For Medical and... Oct 2023Linezolid is commonly used in intensive care units (ICU) but has the potential to interact with other drugs. This study aimed to evaluate the prevalence of potential...
OBJECTIVE
Linezolid is commonly used in intensive care units (ICU) but has the potential to interact with other drugs. This study aimed to evaluate the prevalence of potential drug-drug interactions in ICU patients receiving linezolid.
PATIENTS AND METHODS
Data of ICU patients receiving linezolid were extracted and included in the Hospital Prescription Analysis Program of China, and the risk of potential drug-drug interactions between concomitant drugs and linezolid was evaluated using the Lexicomp database.
RESULTS
A total of 3,712 ICU patients from 59 hospitals were included in the analysis, and patients received an average of 17 concomitant drugs. A total of 67.9% of patients had potential drug-drug interactions. Patients receiving concomitant drugs with risk ratings of "X", "D", and "C" categories were 20.8%, 30.4%, and 35.1%, respectively. Opioids were the most frequently prescribed drug class with drug-drug interactions (DDIs) in the "X" category, whereas butorphanol, metoclopramide, and sufentanil were the most contraindicated concomitant drugs.
CONCLUSIONS
ICU patients receiving linezolid have a high prevalence of potential drug-drug interactions, and efforts should be made to better recognize and manage this risk.
Topics: Humans; Linezolid; Cross-Sectional Studies; Prevalence; Drug Interactions; Intensive Care Units
PubMed: 37843351
DOI: 10.26355/eurrev_202310_33967