Expert Opin Drug Saf. 2022 Dec;21(12):1483-1494. doi: 10.1080/14740338.2022.2160446.

ABSTRACT

INTRODUCTION: Liver involvement in COVID-19 is multifactorial, and the three potential mechanisms are direct hepatocyte viral damage, vascular or cellular damage during the cytokine storm of severe COVID-19 and drug-induced liver injury. To date, three antivirals are licensed for the treatment of COVID-19 by most guidelines: remdesivir, molnupiravir, and ritonavir-boosted nirmatrelvir.

AREAS COVERED: We performed a narrative review about the hepatic safety profile of the three antivirals licensed for COVID-19 treatment. We used data about hepatobiliary adverse events from English-language randomized clinical trials (RCTs).

EXPERT OPINION: Remdesivir was found to be potentially hepatotoxic, and liver biochemistry abnormalities were common (2-34%) but mild and reversible. Molnupiravir exhibits a favorable safety profile and the increase in aminotransferases was usually mild and reversible (up to 11% of patients in one study). Ritonavir-boosted nirmatrelvir is potentially hepatotoxic, but in the only phase 3 RCT there were no safety issues and aspartate aminotransferase/alanine aminotransferase levels increase did not exceed 2.4% of patients. All antivirals have a favorable safety profile, but they are not sufficiently studied in patients with underlying chronic kidney or liver disease. In this special populations, antivirals should be used with caution and careful monitoring during treatment should be pursued on a case-by-case basis.

PMID:36597859 | DOI:10.1080/14740338.2022.2160446

Cleve Clin J Med. 2023 Jan 3;90(1):53-62. doi: 10.3949/ccjm.90a.22069.

ABSTRACT

Data have been accumulating on the risk of developing type 2 diabetes in patients receiving statins and on the potential adverse effects of these drugs on glycemic control in patients who already have type 2 diabetes. This article reviews data linking statin use and new-onset diabetes mellitus, the effects of statins on glycemic control in type 2 diabetes, the benefit-risk considerations of statin use and type 2 diabetes, and how these factors affect patient management.

PMID:36596598 | DOI:10.3949/ccjm.90a.22069

PLoS One. 2023 Jan 3;18(1):e0279842. doi: 10.1371/journal.pone.0279842. eCollection 2023.

ABSTRACT

To reduce adverse drug events (ADEs), hospitals need a system to support them in monitoring ADE occurrence routinely, rapidly, and at scale. Natural language processing (NLP), a computerized approach to analyze text data, has shown promising results for the purpose of ADE detection in the context of pharmacovigilance. However, a detailed qualitative assessment and critical appraisal of NLP methods for ADE detection in the context of ADE monitoring in hospitals is lacking. Therefore, we have conducted a scoping review to close this knowledge gap, and to provide directions for future research and practice. We included articles where NLP was applied to detect ADEs in clinical narratives within electronic health records of inpatients. Quantitative and qualitative data items relating to NLP methods were extracted and critically appraised. Out of 1,065 articles screened for eligibility, 29 articles met the inclusion criteria. Most frequent tasks included named entity recognition (n = 17; 58.6%) and relation extraction/classification (n = 15; 51.7%). Clinical involvement was reported in nine studies (31%). Multiple NLP modelling approaches seem suitable, with Long Short Term Memory and Conditional Random Field methods most commonly used. Although reported overall performance of the systems was high, it provides an inflated impression given a steep drop in performance when predicting the ADE entity or ADE relation class. When annotating corpora, treating an ADE as a relation between a drug and non-drug entity seems the best practice. Future research should focus on semi-automated methods to reduce the manual annotation effort, and examine implementation of the NLP methods in practice.

PMID:36595517 | PMC:PMC9810201 | DOI:10.1371/journal.pone.0279842

BMJ Case Rep. 2022 Dec 8;15(12):e251966. doi: 10.1136/bcr-2022-251966.

ABSTRACT

Pembrolizumab, a humanised monoclonal antibody and immune checkpoint inhibitor (ICI) that blocks programmed death receptor 1 and its ligands, is an effective immunotherapy for malignancies such as melanoma, lung, head and neck, cancers, and Hodgkin's lymphoma. It has an overall response rate between 73% and 83%, with complete response rate of 27%-30%. It is well tolerated with minor side effects in 70% of cases characterised by fatigue, rash, pruritus and diarrhoea. In rare cases, more serious and life-threatening complications can occur at a rate of 0.3%-1.3%. We report a case of a woman in her 70s with non-small-cell lung cancer treated with ICI. She presented to the emergency department with left-sided ptosis and muscle weakness 3 weeks of her first dose of pembrolizumab infusion as a treatment plan of her cancer. She was diagnosed with myasthenia gravis, myocarditis and myositis as ICI-induced immune-related adverse effects resistant to medical intervention. We wish to raise awareness of the triad of life-threatening complication of ICI therapy that accounts for 30%-50% of fatal complications.

PMID:36593626 | DOI:10.1136/bcr-2022-251966

Trials. 2023 Jan 3;24(1):4. doi: 10.1186/s13063-022-06982-7.

ABSTRACT

BACKGROUND: The prognosis for patients with relapsed and/or refractory (R/R) non-Hodgkin's lymphoma (NHL) or acute lymphoblastic leukaemia (ALL) remains poor, with existing treatments having significant side effects. Developed for the treatment of these cancers, AFM11 is a tetravalent, bispecific humanised recombinant antibody construct (TandAb®) designed to bind to human CD19 and CD3 and lead to the activation of T cells inducing apoptosis and killing of malignant B cells.

METHODS: Two open-label, multicentre, dose-escalation phase 1 studies evaluated the safety, pharmacokinetics and activity of AFM11 in patients with R/R CD19-positive B cell NHL (AFM11-101) and in patients with CD19 + B-precursor Philadelphia-chromosome negative ALL (AFM11-102). Adverse events (AEs) were assessed and recorded; imaging (NHL) or bone marrow assessment (ALL) were used to evaluate response. Additional pharmacodynamic assays undertaken included cytokine release analysis and B-cell and T-cell depletion.

RESULTS: In AFM11-101, 16 patients with R/R NHL received AFM11 in five different dose cohorts. Of which, 14 experienced drug-related treatment-emergent AEs (TEAEs) [including five serious AEs (SAEs)], five patients experienced dose-limiting toxicity (DLT) and ten patients discontinued the study. The high number of neurological events led to a decrease in infusion frequency during the study. No objective response to treatment was observed. In AFM11-102, 17 patients with R/R ALL received AFM11 in six different dose cohorts. Thirteen patients experienced drug-related TEAEs (including four SAEs), DLTs occurred in two patients and five patients discontinued the study. An objective response was recorded in three patients. The maximum tolerated dose could not be determined in either study due to early termination.

CONCLUSIONS: AFM11 treatment was associated with frequent neurological adverse reactions that were severe in some patients. In ALL, some signs of activity, albeit short-lived, were observed whereas no activity was observed in patients with NHL; therefore, further clinical development was terminated.

TRIAL REGISTRATION: NCT02106091 . Safety Study to Assess AFM11 in Patients With Relapsed and/or Refractory CD19 Positive B-cell NHL. Registered April 2014. NCT02848911 . Safety Study to Assess AFM11 in Patients With Relapsed or Refractory Adult B-precursor ALL. Registered July 2016.

PMID:36597128 | DOI:10.1186/s13063-022-06982-7

BMC Psychiatry. 2023 Jan 3;23(1):4. doi: 10.1186/s12888-022-04348-6.

ABSTRACT

BACKGROUND: Creating appropriate and sustainable treatment plans for patients with concurrent disorders presents a challenge to psychiatrists and addiction medicine specialists alike. Although varenicline has been found to be the most effective medication for smoking cessation and abstinence when compared to results from placebo medications, nicotine patches and bupropion, caution is needed when starting patients on this medication. With the high prevalence of concurrent mental health and substance use disorders in vulnerably-housed populations in Canada, it becomes increasingly important to advocate for increased guidance and research into treating concurrent disorders.

CASE PRESENTATION: In this case, a young female patient provisionally diagnosed with bipolar I disorder was hospitalized for a manic episode in the context of substance use and medication noncompliance. She also endorsed a long history of tobacco, alcohol, cocaine, cannabis and ketamine use. Perceptual abnormalities, including auditory hallucinations, were not recorded at admission. In addition to being stabilized for bipolar diagnosis, the patient was started on nicotine replacement therapy on Day 7 of admission followed by initiation of varenicline for smoking cessation on Day 14 of admission. Soon after the varenicline treatment was started, the patient developed auditory hallucinations, paranoia and referential beliefs. However, her insight was intact, and she had minimal thought form disorganization. In this case, these symptoms were thought to be secondary to varenicline after the consideration of potential alternative contributors.

CONCLUSION: The occurrence of side effects as a result of varenicline use in patients with diagnosed mental health conditions is rare and underlying psychiatric illness is not labeled as an absolute contraindication in the prescription of varenicline. However, it is important to advocate for increased guidance and research on the treatment of substance use disorders in patients with bipolar I disorder. Patients may also benefit from increased collaboration between psychiatric and addiction services as that may allow for earlier recognition and intervention of symptoms to minimize distress.

PMID:36597062 | DOI:10.1186/s12888-022-04348-6

Reg Anesth Pain Med. 2023 Jan 3:rapm-2022-104193. doi: 10.1136/rapm-2022-104193. Online ahead of print.

NO ABSTRACT

PMID:36596581 | DOI:10.1136/rapm-2022-104193

BMJ Open Qual. 2023 Jan;12(1):e002002. doi: 10.1136/bmjoq-2022-002002.

ABSTRACT

INTRODUCTION: Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used for their analgesic and anti-inflammatory action, but the gastrointestinal (GI) adverse effects are a known cause of preventable harm. A medication safety audit was incentivised for community pharmacies in England in 2 successive years as part of the Pharmacy Quality Scheme (PQS) to address GI safety of NSAIDs.

AIMS: To evaluate community pharmacy's contributions to NSAID safety and determine any change between audit 1 (2018-2019) and audit 2 (2019-2020).

METHOD: Patients aged 65 years or over prescribed an NSAID were included in both audits. The audit tool assessed compliance with national standards relating to co-prescribed gastroprotection, referrals to the prescriber and patient advice on long-term NSAID use and effects, with responses submitted via an online portal. Descriptive analyses were performed to explore differences between the years and tested for significance using Χ2 tests. Qualitative data were analysed using an inductive thematic approach.

KEY FINDINGS: Data from 91 252 patients in audit 1 and 73 992 in audit 2 were analysed. More patients were prescribed gastroprotection in audit 2 (85.0%) than audit 1 (80.7%, p<0.001). More patients without gastroprotection in audit 2 had a current or recent referral (67.5%) than in audit 1 (58.8%, p<0.001). Verbal or other communications between pharmacists and patients about their NSAID medication were reported more frequently in audit 2 (76.0% vs 63.5%, p<0.001).

CONCLUSION: During two audits, community pharmacists in England reported referring more than 15 000 patients at risk of preventable harm from NSAIDs to prescribers for review. The audits demonstrated significant potential for year-on-year improvement in GI safety for a large cohort of older patients prescribed NSAIDs. This evaluation provides evidence of how the PQS can effectively address a specific aspect of medicines safety and the place of community pharmacy more broadly in improving medicines safety.

PMID:36593072 | PMC:PMC9809222 | DOI:10.1136/bmjoq-2022-002002

In Vivo. 2023 Jan-Feb;37(1):345-356. doi: 10.21873/invivo.13085.

ABSTRACT

BACKGROUND/AIM: The COVID-19 prophylactic vaccine for the prevention of coronavirus infection was approved in Japan on February 14, 2021. Adverse event reports for the vaccine were collected from the Japan Adverse Drug Event Relief (JADER) database, similar to those for drugs. Reported odds ratios (RORs) and proportional reporting ratios (PRRs) are commonly used in disproportionality analysis to detect safety signals. Therefore, adverse event reports from the vaccinated population may affect the detection of safety signals for the registered drugs. This study determined the impact of adverse event reports on the detection of safety signals for a COVID-19 prophylactic vaccine by analyzing the JADER database using disproportionality analysis.

PATIENTS AND METHODS: We extracted data from the JADER dataset, in which the COVID-19 vaccine was reported as a suspected drug, and selected the top 10 adverse events in terms of the number of reports. We then extracted the top 30 drugs by the amount of information in the selected 10 adverse events and compared the changes in the number of signal detections with and without the COVID-19 vaccine report data.

RESULTS: The total number of adverse events reported in the JADER database during the study period was 2,002,564. Of the total number of reports, 85,489 (4.3%) reported adverse events related to the COVID-19 vaccine. Of the top 30 drugs reported in the 10 selected adverse events, the ROR and PRR were found to be lower with the inclusion of COVID-19 vaccine data than without. Detection by ROR excluded 23 out of 245 drugs, and detection by PRR excluded 34 out of 204 drugs.

CONCLUSION: The rapid increase in the number of adverse event reports for the COVID-19 vaccine in JADER may affect the detection of safety signals by disproportionality analysis.

PMID:36593055 | DOI:10.21873/invivo.13085

Pathol Oncol Res. 2022 Dec 16;28:1610752. doi: 10.3389/pore.2022.1610752. eCollection 2022.

ABSTRACT

Introduction: Olanzapine (OLZ) is one of the second-generation antipsychotics drugs (APDs) used to treat several psychiatric illnesses. Olanzapine treatment is often associated with many metabolic side effects in a dose dependent manner such as obesity, dyslipidemia and insulin resistance, induction of type II diabetes and acute pancreatitis in some patients. Methods: Hyperbaric Oxygen therapy (HBOT) was investigated as a tool to mitigate olanzapine metabolic side effects in rats. Thirty-six female Sprague Dawley (SD) rats were divided into 4 groups; rats on olanzapine treatment either exposed to hyperbaric oxygen therapy (HBOOLZ) or left without exposure (OLZ) then non-treated rats that either exposed to hyperbaric oxygen therapy or left without exposure (control). Rats received Hyperbaric Oxygen therapy for 35 days at 2.4 atmospheres absolute (ATA) for 2.5 h daily followed by intraperitoneal injection of olanzapine at 10 mg/kg or placebo. Results: Rats on either hyperbaric oxygen therapy or olanzapine had a significant loss in body weight. Olanzapine treatment showed a decrease in serum insulin level, triglyceride, highdensity lipoprotein (HDL) cholesterol, and lipase level but an increase in fasting blood sugar (FBS), insulin resistance index (HOMA-IR) and amylase, while rats' exposure to hyperbaric oxygen therapy reversed these effects. The Pancreatic Langerhans islets were up-regulated in both hyperbaric oxygen therapy and olanzapine treatments but the combination (HBOOLZ) doubled these islets number. Discussion: This study advocated that hyperbaric oxygen therapy can be an alternative approach to control or reverse many metabolic disorders (MDs) associatedwith olanzapine treatment. In addition, it seems that hyperbaric oxygen therapy positively affect the pancreatic Langerhans cells activity and architecture.

PMID:36590387 | PMC:PMC9801520 | DOI:10.3389/pore.2022.1610752

Indian J Ophthalmol. 2023 Jan;71(1):235-240. doi: 10.4103/ijo.IJO_945_22.

ABSTRACT

PURPOSE: Our study aims to evaluate the effectiveness of intravenous erythropoietin (EPO) in patients with indirect traumatic optic neuropathy (TON), assess the side effects, and compare the visual function results among three groups of patients who had received different treatment options - EPO, steroids, and observation.

METHODS: : Patients with indirect TON presenting to the neuro-ophthalmology clinic from August 2019 to March 2020, were assigned to three groups, with six patients in each group. In group 1, patients were recruited prospectively and received recombinant human erythropoietin, whereas, in groups 2 and 3, patients were recruited retrospectively and received intravenous methylprednisolone followed by oral steroids and multivitamins, respectively. Groups 1 and 2 included patients presenting within 2 weeks of trauma, whereas group 3 included those presenting beyond that. Best-corrected visual acuity, pupillary reaction, color vision, and visual fields following treatment were measured.

RESULTS: Initial visual acuity in the EPO group ranged from 20/80 to no perception of light (No PL). The mean initial BCVA (1.82 logMAR, standard deviation [SD] = 0.847) improved to 1.32, SD = 0.93 logMAR after treatment recorded at the third month (P = 0.0375), with no significant adverse effects. The initial BCVA of group 2 ranged from 20/120 to No PL. The mean initial BCVA (1.95, SD = 0.77 logMAR) improved to 1.45 logMAR, SD = 0.97 after treatment (P = 0.0435) but three patients had side effects of steroids. Initial visual acuity in Group 3 ranged from 20/40 to no PL. The mean initial BCVA (1.09 logMAR, SD = 1.10) worsened to 1.19 logMAR, SD = 1.06 after treatment after treatment (P = 0.0193). The improvement in BCVA when compared between the three groups was not significant.

CONCLUSION: Both erythropoietin and steroids are effective in the management of traumatic optic neuropathy. However, erythropoietin shows lesser or no side effects when compared to steroids.

PMID:36588242 | DOI:10.4103/ijo.IJO_945_22

Front Vet Sci. 2022 Dec 14;9:1056408. doi: 10.3389/fvets.2022.1056408. eCollection 2022.

ABSTRACT

Activation of one or both the Ras/MAPK and PI3K/Akt/mTOR signal transduction pathways are known to mediate oncogenicity of several canine and human cancers, including mucosal melanomas. Reciprocal cross activation between the two pathways can be a source of drug resistance. Consequently, oral dosing for plasma pharmacokinetic (PK) analysis and tolerability to a combination of sapanisertib, a dual TORC1/2 inhibitor, and trametinib, a MEK inhibitor, was evaluated in nontumor-bearing laboratory dogs for its potential application in parallel pathway targeting. Twelve dogs, divided into three equal cohorts, received either the combination or single agents. Animals were monitored for PK following single dose and 17-day repeat dosing, and by clinical observations, hematology, serum biochemistry, coagulation studies and urinalyses. A single trametinib dose (0.025 mg/kg), sulfated as dimethyl sulfoxide which enhanced its absorption, reached mean maximum concentration (Cmax) 0.64 ng/mL [18% coefficient of variation (CV)] at a median time to maximum concentration (Tmax) of 1.5 h (hr), and mean area under the concentration-time curve (AUC) 16.8 hr*ng/mL (14%CV), which were similar when given alone or in combination with sapanisertib. A prolonged half-life afforded 3-4-fold plasma accumulation of trametinib with daily dosing, analogous to humans. Trametinib PK mirrored previous regulatory data in dogs, while exposure approximated some published human values but generally not all patients. Sapanisertib-alone in canine plasma following single 0.1 mg/kg dose [mean Cmax 26.3 ng/mL (21%CV), median Tmax 2.0 hr, and mean AUC 248 hr*ng/mL (41%CV)] resembled levels in human therapeutic trials; whereas canine sapanisertib exposure was reduced when combined with trametinib, a known cytochrome P450 CYP3A4 inducer. Sex differences were not observed for either drug. Side effects upon repeat dosing with either or both drugs may include body weight loss, maldigestion, and cutaneous discoloration. The combination was tolerated without dose limiting toxicity, although clinical laboratory analyses revealed drug-induced acute-phase inflammation, proteinuria, and decreased blood reticulocytes, mild changes not necessitating intervention. Short-term results in dogs with this combination would appear to hold translational promise for clinical trial evaluation to target canine and possibly human melanoma, as well as other cancers having one or both signal transduction pathway activations.

PMID:36590793 | PMC:PMC9794608 | DOI:10.3389/fvets.2022.1056408

Front Pharmacol. 2022 Dec 15;13:1039867. doi: 10.3389/fphar.2022.1039867. eCollection 2022.

ABSTRACT

Triazole antifungal drugs (TAD) are widely used to treat invasive fungal infections due to their broad antifungal spectrum and low toxicity. Despite their preference in the clinic, multiple Adverse Events (AE) are still reported each year.

OBJECTIVE: We aimed to characterize the distribution of Adverse Events associated with Triazole antifungal drugs in different systems and to identify Important Medical Events (IME) signals for Triazole antifungal drugs.

METHODS: The U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) was queried for Adverse Events related to Triazole antifungal drugs from 2012 to 2022. The Adverse Events caused by all other drugs and non-TAD antifungal drugs were analyzed as references. Reporting odds ratio and Bayesian confidence propagation neural network of information components were used to evaluate the association between Triazole antifungal drugs and Important Medical Events. Visual signal spectrum is mapped to identify potential adverse reaction signals.

RESULTS: Overall, 10,262 Adverse Events were reported to be associated with Triazole antifungal drugs, of which 5,563 cases were defined as Important Medical Events. Common adverse drug reactions (ADR) mentioned in the instructions such as delirium and hypokalemia were detected, as well as unlabeled ADRs such as rhabdomyolysis and hepatitis fulminant. Cholestasis, drug-induced liver injury, QT interval prolongation and renal impairment have notable signals in all Triazole antifungal drugs, with 50 percent of patients developing a severe clinical outcome. Isavuconazole had the lowest signal intensity and demonstrated a superior safety profile.

CONCLUSION: Most results are generally consistent with previous studies and are documented in the prescribing instructions, but some IMEs are not included, such as hepatitis fulminant. Additional pharmaco-epidemiological or experimental studies are required to validate the small number of unlabeled ADRs. TAD-related Important Medical Eventshave a considerable potential to cause clinically serious outcomes. Clinical use of Triazole antifungal drugs requires more attention.

PMID:36588707 | PMC:PMC9798094 | DOI:10.3389/fphar.2022.1039867

Lipids Health Dis. 2022 Dec 31;21(1):150. doi: 10.1186/s12944-022-01766-z.

ABSTRACT

BACKGROUND: Cholesterol is crucial for tumor immune microenvironment (TIME) remodeling. Serum lipoprotein cholesterol is closely associated with gastric cancer (GC) progression, but whether it affects TIME remodeling is unknown.

METHODS: GC patients with differential serum high-density lipoprotein (HDL) or low-density lipoprotein (LDL) cholesterol levels were collected. After balancing the baseline, immunohistochemical staining was performed on serial whole-tissue sections to detect B-cell and T-cell subsets, macrophages, and PD-L1. Features of tertiary lymphoid structures (TLSs) and the extra-TLS zone, including TLS distribution and maturation, immune cell density, and PD-L1 expression, were measured by annotating TLSs or regions of interest (ROIs) in the extra-TLS zone.

RESULTS: A total of 9,192 TLSs and over 300 ROIs from 61 patients were measured. Compared to HDL-normal patients, HDL-low patients had a decreased secondary-TLS fraction or density but an elevated NK-cell density in the extra-TLS zone. Compared to LDL-normal patients, LDL-low patients had a higher ratio of PD-1 + T follicular helper cells to CD20 + B cells in TLSs, a higher ratio of PD-1 + T cells to CD8 + T cells and increased PD-1 + T-cell density in the extra-TLS zone. Different correlations were found in groups with differential HDL or LDL levels. Cell dynamics in the immune response were weaker in patients with low lipoprotein cholesterol. TLS parameters reached their peak earlier than those of the extra-TLS zone along with tumor progression.

CONCLUSION: Low serum lipoprotein cholesterol caused adverse effects on antitumor immunity in GC. Lipid management or immunometabolic drugs deserve more attention.

PMID:36585674 | PMC:PMC9805280 | DOI:10.1186/s12944-022-01766-z

J Clin Psychopharmacol. 2023 Jan-Feb 01;43(1):81-83. doi: 10.1097/JCP.0000000000001647.

NO ABSTRACT

PMID:36584260 | DOI:10.1097/JCP.0000000000001647

J Cardiovasc Med (Hagerstown). 2023 Feb 1;24(2):154-158. doi: 10.2459/JCM.0000000000001419. Epub 2022 Dec 22.

NO ABSTRACT

PMID:36583987 | DOI:10.2459/JCM.0000000000001419

Eur J Hosp Pharm. 2022 Dec 30:ejhpharm-2022-003454. doi: 10.1136/ejhpharm-2022-003454. Online ahead of print.

ABSTRACT

BACKGROUND: There is a high prevalence of multimorbidity and polypharmacy among older people, especially in people living with HIV (PLWH) with an increased life expectancy due to effective antiretroviral therapy (ART). Consequently, there is a higher risk of potentially inappropriate medications (PIM), potential drug-drug interactions (DI), and problems of non-adherence to treatment (NAC) in older PLWH. PIMDINAC criteria (potentially inappropriate medications (PIM), drug-drug interactions (DI), and non-adherence to treatment (NAC)) purport to jointly analyse these problems. The purpose of the study was to compare the prevalence of PIMDINAC criteria among elderly PLWH and non-infected patients with chronic diseases, and to determine whether HIV infection constitutes a predictor of the presence of PIMDINAC criteria, totally or partially.

METHODS: A cross sectional study was conducted between February and June 2020. HIV positive patients aged ≥65 years were compared with a group of patients with chronic conditions attending the outpatient hospital pharmacy service.

RESULTS: The study involved 140 patients: 47 HIV positive and 93 HIV negative, and mean age was 69 versus 73 years, respectively (p=0.062). The prevalence of total PIMDINAC criteria was similar between the groups (12.5 vs 10.8%, p=0.505). In relation to inappropriate medication, no differences were observed between groups (48.9 vs 55.9%, p=0434). Drug-drug interactions were higher in patients with chronic conditions (52.7 vs 25.5%, p=0.002) compared with non-adherence, which was higher in people with HIV (22.6 vs 65.6%, p<0.001). No differences in polypharmacy (≥6 and 11 drugs) rates were observed.

CONCLUSIONS: PIMDINAC criteria were highly prevalent in older PLWH, similar to non-infected patients. HIV infection in older people was associated with a lower risk of drug-drug interactions. However, non-adherence was a risk factor compared with age matched controls. Deprescribing strategies, including a capability-motivation-opportunity pharmaceutical care model based intervention should be implemented in clinical routines.

PMID:36585218 | DOI:10.1136/ejhpharm-2022-003454

Infect Dis Ther. 2022 Dec 30. doi: 10.1007/s40121-022-00746-1. Online ahead of print.

ABSTRACT

Cytomegalovirus (CMV) infection can have both direct and indirect effects after solid-organ transplantation, with a significant impact on transplant outcomes. Prevention strategies decrease the risk of CMV disease, although CMV still occurs in up to 50% of high-risk patients. Ganciclovir (GCV) and valganciclovir (VGCV) are the main drugs currently used for preventing and treating CMV. Emerging data suggest that letermovir is as effective as VGCV with fewer hematological side effects. Refractory and resistant CMV also still occur in solid-organ-transplant patients. Maribavir has been shown to be effective and have less toxicity in the treatment of refractory and resistant CMV. In this review paper, we discuss prevention strategies, refractory and resistant CMV, and drug-related side effects and their impact, as well as optimal use of novel anti-CMV therapies.

PMID:36583845 | DOI:10.1007/s40121-022-00746-1

Cureus. 2022 Nov 27;14(11):e31949. doi: 10.7759/cureus.31949. eCollection 2022 Nov.

ABSTRACT

Anaphylaxis is a sudden onset of systemic hypersensitivity caused by mast cell and basophil degranulation. Food, Hymenoptera venom, and drug allergy are among the leading causes of anaphylaxis, particularly in adults. We can consider anaphylaxis caused by swallowing food or medication as a form of poisoning. Because in anaphylaxis, just like in poisoning, an allergen entering the body poses a life-threatening risk. Therefore, the allergen should be removed from the digestive system immediately. However, the decontamination of the gastrointestinal tract is not routinely used to prevent further absorption of allergens from the intestine into the systemic circulation. Among the gastrointestinal decontamination methods is the use of activated charcoal. In this article, we present four patients who developed anaphylaxis due to drug and food intake and were administered oral activated charcoal after their primary treatment (on average, 15-45 minutes after the first presentation) was completed. The youngest of the patients was 22 years old, and the oldest was 40. No side effects, prolonged anaphylactic state, and biphasic reactions were observed in the follow-up of the patients. All patients were discharged after 48-72 hours of hospitalization. The routine approach to poisoning treatment includes patient stabilization, toxidrome recognition, antidote administration, and supportive care, as well as measures to enhance toxin elimination. In anaphylaxis caused by oral allergens, the substance that initiates the reaction can be compared to a kind of toxin. Eliminating the allergen and reducing its absorption could be achieved by administering activated charcoal. Activated charcoal should be considered adjunctive therapy in treating food and oral drug-induced anaphylaxis. This treatment, when administered in a timely manner, might prevent the development of biphasic reactions and the prolongation of the allergic process in anaphylaxis.

PMID:36582570 | PMC:PMC9794912 | DOI:10.7759/cureus.31949

BMJ Open. 2022 Sep 1;12(9):e060967. doi: 10.1136/bmjopen-2022-060967.

ABSTRACT

INTRODUCTION: Esketamine is the S-enantiomer of racemic ketamine and has been approved by the Food and Drug Administration for the management of treatment resistant depression, demonstrating effective and long-lasting benefits. The objective of this observational study is to elucidate the association of intranasal (IN) esketamine with beneficial and negative outcomes in the management of treatment resistant major depressive disorder.

METHODS AND ANALYSIS: This is a multicentre prospective cohort observational study of naturalistic clinical practice. We expect to recruit 10 patients per research centre (6 centres, total 60 subjects). After approval to receive IN esketamine as part of their standard of care management of moderate to severe treatment resistant depression, patients will be invited to participate in this study. Association of esketamine treatment with outcomes in the management of depression will be assessed by measuring the severity of depression symptoms using the Montgomery-Åsberg Depression Rating Scale (MADRS), and tolerability by systematically tracking common side effects of ketamine treatment, dissociation using the simplified 6-Item Clinician Administered Dissociative Symptom Scale and potential for abuse using the Likeability and Craving Questionnaire (LCQ). Change in depressive symptoms (MADRS total scores) over time will be evaluated by within-subject repeated measures analysis of variance. We will calculate the relative risk associated with the beneficial (reduction in total scores for depression) outcomes, and the side effect and dropout rates (tolerability) of adding IN esketamine to patients' current pharmacological treatments. Covariate analysis will assess the impact of site and demographic variables on treatment outcomes.

ETHICS AND DISSEMINATION: Approval to perform this study was obtained through the Health Sciences Research Ethics Board at Queen's University. Findings will be shared among collaborators, through departmental meetings, presented on different academic venues and publishing our manuscript.

PMID:36581972 | PMC:PMC9438206 | DOI:10.1136/bmjopen-2022-060967