Front Pharmacol. 2022 Oct 28;13:1053356. doi: 10.3389/fphar.2022.1053356. eCollection 2022.

ABSTRACT

Background and objective: Idiopathic pulmonary fibrosis (IPF) is a critical disease, with limited treatments available. Clinical practices show that traditional Chinese medicine (TCM) has certain efficacy. This study was preliminarily to evaluate the efficacy and safety of TCM treatment based on syndrome differentiation in IPF. Methods: A study design of exploratory, multi-centers, randomized, double-blinded, placebo controlled trial has been adopted. A total of 80 IPF patients from four sub-centers were enrolled. All the patients were randomly assigned into TCM group (TCMG) or control group (CG) in 1:1. Patients in TCMG were given CM granules, as patients in CG given with the placebo of CM granule. All the patients received a 26-week treatment. The efficacy was assessed by acute exacerbations (AEs) of IPF, pulmonary function, clinical symptoms, dyspnea scores (mMRC), health-related quality of life (HRQoL), 6-min walk test (6MWT) and all-cause mortality. Safety has also been assessed. Results: A total of 67 patients completed the trial with 35 in TCM group and 32 in control group. Meaningful differences have been observed in mean changes in AEs (-1.56 times; 95% CI, -2.69 to -0.43, p = 0.01), DLco% (5.29; 95% CI, 0.76 to 9.81, p = 0.02), cough scores (-0.38 points; 95% CI, -0.73 to -0.04, p = 0.03), and 6MWT (30.43 m; 95% CI, 2.85 to 58.00, p = 0.03), with no statistical differences in FEV1, FVC, expectoration, chest tightness, Shortness of breath, Fatigue, Cyanosis, mMRC, CAT, SF-36, and SGRQ total scores in 26 weeks after treatment than before treatment. At of the end of follow-up, a total of 10 patients died, including three and seven in the TCM and control group respectively. And the HR (Hazard ratio) for CM granules in all-cause mortality was 0.39 (95% CI, 0.10-1.52). The drug-related adverse events were not observed. Conclusion: CM granules, as compared with placebo, could reduce frequencies of AEs, improve pulmonary function, HRQoL, exercise capacity and symptoms and signs for IPF to some extent with acceptable side-effect.

PMID:36386223 | PMC:PMC9649819 | DOI:10.3389/fphar.2022.1053356

Front Pharmacol. 2022 Oct 25;13:1043828. doi: 10.3389/fphar.2022.1043828. eCollection 2022.

ABSTRACT

GPR40 is a class A G-protein coupled receptor (GPCR) mainly expressed in pancreas, intestine, and brain. Its endogenous ligand is long-chain fatty acids, which activate GPR40 after meal ingestion to induce secretion of incretins in the gut, including GLP-1, GIP, and PYY, the latter control appetite and glucose metabolism. For its involvement in satiety regulation and metabolic homeostasis, partial and AgoPAM (Positive Allosteric Modulation agonist) GPR40 agonists had been developed for type 2 diabetes (T2D) by many pharmaceutical companies. The proof-of-concept of GPR40 for control of hyperglycemia was achieved by clinical trials of partial GPR40 agonist, TAK-875, demonstrating a robust decrease in HbA1c (-1.12%) after chronic treatment in T2D. The development of TAK-875, however, was terminated due to liver toxicity in 2.7% patients with more than 3-fold increase of ALT in phase II and III clinical trials. Different mechanisms had since been proposed to explain the drug-induced liver injury, including acyl glucuronidation, inhibition of mitochondrial respiration and hepatobiliary transporters, ROS generation, etc. In addition, activation of GPR40 by AgoPAM agonists in pancreas was also linked to β-cell damage in rats. Notwithstanding the multiple safety concerns on the development of small-molecule GPR40 agonists for T2D, some partial and AgoPAM GPR40 agonists are still under clinical development. Here we review the most recent progress of GPR40 agonists development and the possible mechanisms of the side effects in different organs, and discuss the possibility of developing novel strategies that retain the robust efficacy of GPR40 agonists for metabolic disorders while avoid toxicities caused by off-target and on-target mechanisms.

PMID:36386134 | PMC:PMC9640913 | DOI:10.3389/fphar.2022.1043828

CNS Drugs. 2022 Nov 16. doi: 10.1007/s40263-022-00970-w. Online ahead of print.

ABSTRACT

BACKGROUND: Emulsified isoflurane was designed to circumvent the deficiencies of inhalation anesthetics, which have a longer time to onset, result in a higher drug consumption, and for which a specific anesthesia machine is required for clinical use. The aim of this study was to compare the efficacy and safety of emulsified isoflurane with propofol for anesthesia induction in adults patients.

METHODS: This multicenter, randomized, double-blind, positive-controlled, non-inferiority, phase III clinical trial compared the efficacy and safety of emulsified isoflurane with propofol for anesthesia induction. Each patient in the emulsified isoflurane group received a single bolus injection of 12% emulsified isoflurane at a dose of 30 mg/kg, and each patient in the propofol group received a single bolus injection of 0.8% propofol at a dose of 2 mg/kg. The primary outcome of the efficacy evaluation was the proportion of participants with successful anesthesia induction, which was regarded as a Modified Observer's Assessment of Alertness/Sedation (MOAA/S) score of < 1 and lack of use of other sedative drugs. A number of secondary efficacy outcomes were also assessed. Safety was monitored based on (1) adverse events, (2) repeated measurement of vital signs; (3) physical examination, (4) routine laboratory examinations of hematology, biochemistry, urine, coagulation function, and (5) 12-lead electrocardiogram.

RESULTS: A total of 416 patients were enrolled (n = 208 in each group) and 398 patients were administered study drug. The proportion of participants with successful anesthesia induction was 100% with a 95% confidence interval of - 1.9% to + 1.9% for the emulsified isoflurane and propofol groups, which met the predesigned non-inferiority criteria of 5%. The study demonstrated the non-inferiority of sedation produced by emulsified isoflurane compared to propofol. Among the secondary efficacy outcomes, emulsified isoflurane showed a better cardiovascular stability than propofol. The number of patients from the emulsified isoflurane group who experienced drug-related adverse events was significantly higher than that of patients from the propofol group. However, there was no significant difference between the two groups in terms of adverse events or drug-related adverse events of grades 3-5.

CONCLUSIONS: Emulsified isoflurane exhibited non-inferiority of anesthesia/sedation compared to propofol in patients undergoing anesthesia induction.

CLINICAL TRIAL REGISTRATION: ChiCTR2000038185, registered on 12 December, 2020 ( www.chictr.org.cn ).

PMID:36385453 | DOI:10.1007/s40263-022-00970-w

Dtsch Med Wochenschr. 2022 Nov;147(23):1513-1522. doi: 10.1055/a-1810-9275. Epub 2022 Nov 16.

ABSTRACT

Drug-induced cardiovascular side effects have a significant impact on morbidity and mortality. The demographic change and improved long-term survival particularly in cancer patients have caused an increasing number of affected patients, hence emphasizing the importance of the best possible treatment of such complications. This article gives an overview of classic and modern groups of substances with cardiotoxic effects and summarizes the principles of diagnostics and therapy. After characterizing the common cardiovascular side effects caused by anthracycline chemotherapy, we focus on complications caused by modern forms of immunotherapy, considering its significant impact on oncological therapy in the future due to its growing clinical application. In addition to specific cancer therapies, accompanying measures such as blood transfusions in patients with hematologic diseases can also lead to severe cardiovascular complications. In the last section, we classify important features and therapeutic approaches in cardiac involvement of transfusion-related hemochromatosis. A good knowledge of the characteristics of specific cardiovascular side effects can help to improve the management of affected patients.

PMID:36384152 | DOI:10.1055/a-1810-9275

Cureus. 2022 Oct 13;14(10):e30273. doi: 10.7759/cureus.30273. eCollection 2022 Oct.

ABSTRACT

Marijuana is among the most widely used recreational drugs in the United States. The most common side effects of marijuana include mood changes, impaired memory, impaired body movements, and hallucination. Chronic use of marijuana is associated with transaminitis and hepatomegaly. Reported cases of acute hepatitis secondary to heavy marijuana smoking are very rare.

PMID:36381892 | PMC:PMC9653216 | DOI:10.7759/cureus.30273

Cureus. 2022 Oct 4;14(10):e29921. doi: 10.7759/cureus.29921. eCollection 2022 Oct.

ABSTRACT

Background KLS-1 is zinc (Zn) aspartate enriched with isotope 64Zn to 99.2% mass fraction of total zinc. KLS-1 is intended as a novel therapeutic approach for patients with a variety of diseases including but not limited to different forms of cancer and neurodegenerative diseases. The purpose of this first-in-human study was to determine the maximum tolerated dose (MTD), safety, and pharmacokinetics (PK) in patients with medical disorders. Methods The study was designed as consisting of two consecutive parts: the dose escalation part and the dose expansion part. Adult patients with refractory glioblastoma, primary progressive aphasia/dementia, amyotrophic lateral sclerosis, Parkinson's disease (PD), and type 1 diabetes were included. KLS-1 formulated as a 10 mL water solution containing 26.42 mg/mL of 64zinc aspartate (that is equivalent to 5.184 mg/mL of 64Zn) was administered twice weekly in two-week cycles via two-hour intravenous (IV) infusion at various dose levels during the dose escalation part and twice weekly during five subsequent weeks in the dose expansion part. The study was conducted at Pan American Cancer Treatment Center (Tijuana, Mexico) in 2020 and had a duration of 10 months. Results A total of eight patients (all white/Caucasian) were enrolled in both parts of the study. A total of four patients who participated in the dose escalation part were dosed twice weekly at 1, 2, and 4 mg/kg in two-week cycles for each dose level with the dose increased to the next higher level in the subsequent cycle. Dose-limiting toxicities (DLTs) were defined at dose level 4 mg/kg due to treatment-emergent reversible adverse events that required medications for symptomatic relief. The most common drug-related toxicities that occurred in two or more patients (≥25%) were weakness (five patients), fatigue (four patients), dizziness (three patients), nausea (two patients), poor sleep (two patients), and abdominal discomfort (two patients). In the dose expansion part, a dose of 2 mg/kg administered twice weekly was investigated for five continuous weeks in four patients and was established as recommended phase 1b/2 dose. Systemic exposure to KLS-1 (area under the curve (AUC) and maximum serum concentration (Cmax)) increased from 1 to 4 mg/kg and showed a linear relationship. Conclusions Multiple doses of KLS-1 ranging from 1 to 2 mg/kg administered twice a week via intravenous infusion for up to five continuous weeks were safe and well tolerated in patients with different types of therapeutic conditions including but not limited to a few forms of cancer and Parkinson's disease, and the evaluated pharmacokinetic parameters exhibited favorable profile.

PMID:36381721 | PMC:PMC9637427 | DOI:10.7759/cureus.29921

Health Sci Rep. 2022 Nov 14;5(6):e931. doi: 10.1002/hsr2.931. eCollection 2022 Nov.

ABSTRACT

BACKGROUND AND AIMS: Doxycycline is recommended for use in rickettsial diseases. The available evidence regarding its safety for rickettsial infection in pregnancy is limited. Our study aimed to describe the adverse events of doxycycline when used during pregnancy for any indication, in terms of adverse maternal and/or neonatal outcomes, using the United States Food and Drug Administration Adverse Event Reporting System (FAERS).

METHODS: We used the OpenVigil software for extracting the safety reports from the United States submitted to the FAERS from 2004 to 2021. We manually reviewed reports of doxycycline use resulting in adverse pregnancy outcomes or congenital anomalies to describe the patient and safety event characteristics.

RESULTS: From 2004 to 2021, 59 individual case safety reports containing preferred terms indicative of drug exposure during pregnancy or drug-induced adverse fetal outcomes were identified in the FAERS database. Following deduplication and manual review, 20 relevant adverse event reports were obtained. Doxycycline was the suspect medication in 13/20 (65%) reports. The common adverse event terms reported were premature delivery/baby in 6 reports, spontaneous abortion in 6, intrauterine death in 2, and various congenital anomalies in the rest. Fifty percent of the safety reports contained other medications which could have potentially caused the outcome.

CONCLUSIONS: The number of reported events in the FAERS database of adverse pregnancy/neonatal outcomes following doxycycline use is small, similar to the numbers reported from large cohort or surveillance studies. Given the presence of concomitant medications that could have contributed to the outcome, there does not seem to be a strong signal of harm, although this needs to be confirmed by surveillance studies.

PMID:36381408 | PMC:PMC9662692 | DOI:10.1002/hsr2.931

Sci Rep. 2022 Nov 15;12(1):19555. doi: 10.1038/s41598-022-23834-1.

ABSTRACT

Osimertinib was a third-generation, irreversible epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), which approved by the US Food and Drug Administration (FDA) in 2015 for treatment of non-small cell lung cancer (NSCLC). Our study was to explore the adverse events (AEs) caused by osimertinib through data mining of the US FDA Adverse Event Reporting System (FAERS), and provide reference for clinical safety. Data of osimertinib were collected from the FAERS database covering the period from first quarter of 2016 to the fourth quarter of 2021. Disproportionality analyses was employed to quantify the associated AE signals of osimertinib and detect the risk signals from the data in the FAERS database. Reporting odds ratio (ROR) was used to detect the risk signals from the data in the FAERS database. The definition relied on system organ class (SOCs) and preferred terms (PTs) by the Medical Dictionary for Regulatory Activities (MedDRA). Totally, 9,704,33 reports were collected from the FAERS database, 10,804 reports of osimertinib were identified as the 'primary suspected (PS)' AEs. Osimertinib induced AEs occurred in 27 organ systems. 68 significant disproportionality PTs satisfying with the four algorithms were retained at the same time. Unexpected significant AEs such as scrotal volvulus, hepatic function abnormal, venous thromboembolisms might also occur. The median onset time of osimertinib-associated AEs was 58 days (interquartile range [IQR] 14-212 days), and the majority of the AEs occurred within the first 30 days after osimertinib initiation. Our study found significant new AEs signals of osimertinib and might provide support for clinical monitoring and risk identification of osimertinib.

PMID:36380085 | DOI:10.1038/s41598-022-23834-1

Saudi Med J. 2022 Nov;43(11):1248-1253. doi: 10.15537/smj.2022.43.11.20220493.

ABSTRACT

OBJECTIVES: To investigate the side effects of Pizer- BioNTech mRNA (BNT162b2) and Spikevax (mRNA- 1273) Coronavirus disease 2019 (COVID-19) vaccines on adolescents in Riyadh, Saudi Arabia.

METHODS: A cross-sectional study using an online questionnaire was carried out among COVID-19 vaccine adolescent recipients in Riyadh, Saudi Arabia. After receiving at least one dose of each vaccine, general and demographic data were collected, and vaccine-related side effects were evaluated.

RESULTS: The final sample consisted of 604 participants with a majority age group of 16-17 years old. Approximately 89.1% of the study participants were female. Most participants reported pain at the injection site (85.1% 1st dose, 79.8% 2nd dose), feeling tired, and headache (58.6% 1st dose, 64.2% 2nd dose). Moreover, we found that patients who took the first dose and had a chronic disease had 2.4 times higher odds of having menstrual disorder (females) than non-chronic disease patients (p=0.03) and 4.5 times higher odds of exhibiting breathing congestion (p=0.01). In addition, patients with chronic disease had 2.4 times higher odds of exhibiting muscle and joint pain and dizziness than non-chronic disease patients (p=0.01, p=0.02). Males were less likely to have dizziness after the first dose than females (OR=0.26, p=0.01).

CONCLUSION: This study investigates the adverse effects of COVID-19 vaccines among adolescents in Riyadh. As a result, this study creates a database to inform people about the risk of experiencing side effects based on their gender, age, and the vaccine type; more investigation is needed to better understand the link between risk factors and the development of adverse effects.

PMID:36379531 | DOI:10.15537/smj.2022.43.11.20220493

J Clin Oncol. 2022 Nov 15:JCO2200575. doi: 10.1200/JCO.22.00575. Online ahead of print.

ABSTRACT

PURPOSE: To investigate efficacy and safety of trastuzumab deruxtecan (T-DXd) in human epidermal growth factor receptor 2 (HER2)-low gastric or gastroesophageal junction (GEJ) adenocarcinoma.

METHODS: Patients with locally advanced or metastatic HER2-low (cohort 1, immunohistochemistry 2+/in situ hybridization-negative; cohort 2, immunohistochemistry 1+) gastric/GEJ adenocarcinoma treated with at least two prior regimens, including fluoropyrimidine and platinum, but anti-HER2 therapy naive, received T-DXd 6.4 mg/kg intravenously once every 3 weeks. The primary end point was confirmed objective response rate by independent central review.

RESULTS: Among 21 patients enrolled in cohort 1 and 24 enrolled in cohort 2, 19 and 21 patients, respectively, had central HER2 confirmation, received T-DXd, and had measurable tumors at baseline. The confirmed objective response rate was 26.3% (95% CI, 9.1 to 51.2) from five partial responses in cohort 1 and 9.5% (95% CI, 1.2 to 30.4) from two partial responses in cohort 2. Thirteen patients (68.4%) in cohort 1 and 12 (60.0%) in cohort 2 experienced reduced tumor size. The median overall survival was 7.8 months (95% CI, 4.7 to nonevaluable) in cohort 1 and 8.5 months (95% CI, 4.3 to 10.9) in cohort 2; the median progression-free survival was 4.4 months (95% CI, 2.7 to 7.1) and 2.8 months (95% CI, 1.5 to 4.3), respectively. The most common grade ≥ 3 treatment-emergent adverse events in cohorts 1 and 2 were anemia (30.0% and 29.2%), decreased neutrophil count (25.0% and 29.2%), and decreased appetite (20.0% and 20.8%). Drug-related interstitial lung disease/pneumonitis occurred in one patient in each cohort (grade 1 or 2). No drug-related deaths occurred.

CONCLUSION: This study provides preliminary evidence that T-DXd has clinical activity in patients with heavily pretreated HER2-low gastric/GEJ adenocarcinoma.

PMID:36379002 | DOI:10.1200/JCO.22.00575

J Int AIDS Soc. 2022 Nov;25(11):e25970. doi: 10.1002/jia2.25970.

ABSTRACT

INTRODUCTION: Globally about 1.7 million children were living with HIV in 2020. Two integrase strand transfer inhibitors, dolutegravir and raltegravir, are increasingly used in children. We conducted a systematic review to assess the effectiveness and safety of dolutegravir and raltegravir in children and adolescents living with HIV, aged 0-19 years.

METHODS: Sources included MEDLINE, Embase, the Cochrane Library, clinical trial registries, abstracts from key conferences and reference list searching. Observational studies and clinical trials published January 2009-March 2021 were eligible. Outcomes included efficacy/effectiveness (CD4 counts and viral load) and/or safety outcomes (mortality, grade 3/4 adverse events and treatment discontinuation) through 6 months or more post-treatment initiation. Risk of bias was assessed using previously published tools appropriate for the study design. Narrative syntheses were conducted.

RESULTS AND DISCUSSION: In total, 3626 abstracts and 371 papers were screened. Eleven studies, including 2330 children/adolescents, reported data on dolutegravir: one randomized controlled trial (RCT; low risk of bias), one single-arm trial (unclear risk of bias) and nine cohort studies (three low risk of bias, two unclear risk and four high risk). Ten studies, including 649 children/adolescents receiving raltegravir, were identified: one RCT (low risk of bias), one single-arm trial (low risk of bias) and eight cohort studies (four low risk of bias, three unclear risk and one high risk). Viral suppression levels in children/adolescents at 12 months were high (>70%) in most studies assessing dolutegravir (mostly second- or subsequent-line, or mixed treatment lines), and varied from 42% (5/12) to 83% (44/53) at 12 months in studies assessing raltegravir (mostly second- or subsequent-line). Across all studies assessing dolutegravir or raltegravir, grade 3/4 adverse events (clinical and/or laboratory) were reported in 0-50% of subjects, few resulted in discontinuation, few were drug related and no deaths were attributed to either drug.

CONCLUSIONS: These reassuring findings suggest that dolutegravir and raltegravir are effective and safe as preferred regimens in children and adolescents living with HIV. With the rollout of dolutegravir in paediatric populations already underway, it is critical that data are collected on safety and effectiveness in infants, children and adolescents, including on longer-term outcomes, such as weight and metabolic changes.

PMID:36377082 | DOI:10.1002/jia2.25970

BMC Neurol. 2022 Nov 14;22(1):427. doi: 10.1186/s12883-022-02949-y.

ABSTRACT

BACKGROUND: Vaccination is an important public health strategy; however, many neurological adverse effects are associated with COVID-19 vaccination, being encephalitis a rare manifestation.

CASE PRESENTATION: We present the case of a 33-year-old woman who received the first dose of the BBIBP-CorV vaccine against COVID-19 on April 4 and the second dose on April 28, 2021. Three days after receiving the second dose, she experienced a subacute episode of headache, fever, insomnia, and transient episodes of environment disconnection. We obtained negative results for infectious, systemic, and oncological causes. Brain magnetic resonance imaging showed lesions in the bilateral caudate nucleus and nonspecific demyelinating lesions at the supratentorial and infratentorial compartments. The results of the neuronal autoantibodies panel were negative. She had an adequate response to immunoglobulin and methylprednisolone; however, she experienced an early clinical relapse and received a new cycle of immunosuppressive treatment followed by a satisfactory clinical evolution.

CONCLUSIONS: We report the first case of severe encephalitis associated with BBIBP-CorV (Sinopharm) vaccination in Latin America. The patient had atypical imaging patterns, with early clinical relapse and a favorable response to corticosteroid therapy.

PMID:36376863 | DOI:10.1186/s12883-022-02949-y

Sci Data. 2022 Nov 14;9(1):699. doi: 10.1038/s41597-022-01825-1.

ABSTRACT

The data currently described was generated within the EU/FP7 HeCaToS project (Hepatic and Cardiac Toxicity Systems modeling). The project aimed to develop an in silico prediction system to contribute to drug safety assessment for humans. For this purpose, multi-omics data of repeated dose toxicity were obtained for 10 hepatotoxic and 10 cardiotoxic compounds. Most data were gained from in vitro experiments in which 3D microtissues (either hepatic or cardiac) were exposed to a therapeutic (physiologically relevant concentrations calculated through PBPK-modeling) or a toxic dosing profile (IC20 after 7 days). Exposures lasted for 14 days and samples were obtained at 7 time points (therapeutic doses: 2-8-24-72-168-240-336 h; toxic doses 0-2-8-24-72-168-240 h). Transcriptomics (RNA sequencing & microRNA sequencing), proteomics (LC-MS), epigenomics (MeDIP sequencing) and metabolomics (LC-MS & NMR) data were obtained from these samples. Furthermore, functional endpoints (ATP content, Caspase3/7 and O2 consumption) were measured in exposed microtissues. Additionally, multi-omics data from human biopsies from patients are available. This data is now being released to the scientific community through the BioStudies data repository ( https://www.ebi.ac.uk/biostudies/ ).

PMID:36376331 | DOI:10.1038/s41597-022-01825-1

Am J Manag Care. 2022 Nov;28(11):566-571. doi: 10.37765/ajmc.2022.89259.

ABSTRACT

OBJECTIVES: Drug-drug interactions (DDIs) are among the most common causes of adverse drug reactions and are further complicated by genetic variants of drug-metabolizing enzymes. The aim of this study is to quantify and describe potential DDIs, drug-gene interactions (DGIs), and drug-drug-gene interactions (DDGIs) in a community-based population.

STUDY DESIGN: This was an analysis of deidentified retail pharmacy prescription data for 4761 individuals.

METHODS: Data were first assessed for DDIs, and individuals were stratified to a risk category using the logic of a commercially available digital DDGI tool. To calculate the frequency of potential DGIs and DDGIs, genotypes were imputed and randomly allocated to the cohort 100 times via Monte Carlo simulation according to each variant's frequency in the general population.

RESULTS: The probability of a DDI of any impact was 26.0% and increased to 49.6% (95% CI, 48.4%-50.7%) when drug-metabolizing phenotypes were ascribed according to the distribution of variants of 11 genes as found in a Caucasian population. There was a 7.8% probability of major DDIs, which increased to a 10.1% (95% CI, 9.5%-10.8%) probability with the addition of genetic contributions. The probability of DDGIs of any impact was correlated with the number of medications. Antidepressants, antiemetics, blood products and modifiers, analgesics, and antipsychotics had the highest probability of DDGIs.

CONCLUSIONS: The probability of drug interaction risk increased when phenotypes associated with genetic polymorphisms were attributed to the population. These data suggest that pharmacogenomic assessment may be useful in predicting drug interactions and severity when evaluating patient medication profiles.

PMID:36374614 | DOI:10.37765/ajmc.2022.89259

Reprod Sci. 2022 Nov 14. doi: 10.1007/s43032-022-01121-8. Online ahead of print.

ABSTRACT

The objective of this study is to perform a meta-analysis of all randomized controlled trials (RCTs) that surveyed the efficacy and safety of preoperative misoprostol versus placebo during abdominal hysterectomy. Six databases were screened from inception until 3 August 2022. The eligible studies were assessed for risk of bias. The outcomes were summarized as mean difference (MD) and risk ratio (RR) with 95% confidence intervals (CI) in a random-effects model. Ten RCTs with 1076 patients (misoprostol = 537, placebo = 539 patients) were analyzed. Six and four RCTs had an overall low and high risk of bias (single-blinded), respectively. The mean intraoperative blood loss (n = 10 RCTs, MD = - 78.97 ml, 95% [- 130.89, - 27.06], p = 0.003), mean difference in hemoglobin drop (n = 10 RCTs, MD = - 0.42 g/dl, 95% CI [- 0.69, - 0.14], p = 0.003), and mean length of hospital stay (n = 5 RCTs, MD = - 0.2 d, 95% CI [- 0.24, - 0.16], p < 0.001) were significantly reduced in favor of the misoprostol group compared with the placebo group. However, there were no significant differences between both groups regarding the mean operative time (n = 8 RCTs, MD = - 0.63 min, 95% CI [- 5.07, 3.81], p = 0.78), rate of perioperative blood transfusion (n = 7 RCTs, RR = 0.83, 95% CI [0.53, 1.3], p = 0.42), and rate of drug-related adverse events (i.e., nausea, vomiting, diarrhea, headache, chills, and fever). Leave-one-out sensitivity analyses revealed stability for all endpoints, except hospitalization stay. There was no publication bias for all endpoints, except perioperative blood transfusion. Among patients undergoing abdominal hysterectomy, preoperative administration of misoprostol was largely safe and linked to substantial decrease in blood loss-related morbidities.

PMID:36376614 | DOI:10.1007/s43032-022-01121-8

Drug Ther Bull. 2022 Nov 14:dtb-2022-000062. doi: 10.1136/dtb.2022.000062. Online ahead of print.

ABSTRACT

Overview of: British Association of Dermatologists. Guidance on minimising risk of harm from potassium permanganate soaks. April 2022.

PMID:36376055 | DOI:10.1136/dtb.2022.000062

Drug Ther Bull. 2022 Nov 14:dtb-2022-000063. doi: 10.1136/dtb.2022.000063. Online ahead of print.

ABSTRACT

Overview of: Butler J, Anker SD, Lund LH, et al Patiromer for the management of hyperkalemia in heart failure with reduced ejection fraction: the DIAMOND trial. Eur Heart J 2022. doi:10.1093/eurheartj/ehac401 [Epub ahead of print, 2022 Jul 28].

PMID:36376054 | DOI:10.1136/dtb.2022.000063

Ann Pharm Fr. 2022 Nov 11:S0003-4509(22)00149-3. doi: 10.1016/j.pharma.2022.11.006. Online ahead of print.

ABSTRACT

OBJECTIVES: Proton pump inhibitors (PPI) are the most effective drugs in the treatment of acid-related gastrointestinal disorders. Yet, many studies reported potential adverse drug reactions associated with long-term use. In order to reduce the rates of inappropriate PPI prescriptions and to improve patient safety, a tool aimed at guiding pharmacists to analyze PPI prescriptions was designed. It results in a thesaurus of clinical situations designed to argue about the inappropriateness of some PPI prescriptions and to highlight the risk associated with them.

METHODS: Clinical situations in which PPIs are inappropriate were identified by four pharmacists in one gastroenterological, one surgery/liver transplantation, one internal medicine and one oncology units. A scientific literature search was performed for each clinical situation in order to corroborate the pharmacist interventions.

RESULTS: The thesaurus comprises two parts, the first one is dedicated to 12 clinical situations in which a PPI is not required (acute pancreatitis, cholecystectomy etc.), while the second one focus on 22 situations in which PPIs are associated with specific adverse drug reactions (Clostridium difficile infection, vitamin deficiency etc.). Eighty-one articles were used to support the pharmacist interventions.

CONCLUSION: This thesaurus is an analysis tool aimed at guiding pharmacists identify and argue about the inappropriateness of some PPI prescriptions in order to convince doctors to discontinue or not to initiate PPI prescriptions.

PMID:36375534 | DOI:10.1016/j.pharma.2022.11.006

Ann Pharm Fr. 2022 Nov 11:S0003-4509(22)00146-8. doi: 10.1016/j.pharma.2022.11.003. Online ahead of print.

ABSTRACT

OBJECTIVES: The objective of this study was to assess the relevance of proton pump inhibitors prescribing in patients entering a ward with a clinical pharmacist and therefore identifying inappropriate prescribing.

METHODS: A prospective study was conducted for 4 months. Patients admitted to the hospital for elective or emergency surgery, who had medication reconciliation performed by the clinical pharmacy team and who were prescribed proton pump inhibitors before admission were included. The indication for the proton pump inhibitors was collected from the patient or inferred from the medical history. The compliance of the prescriptions with the marketing authorization indications and the duration of treatment and dose was analyzed. The indications were classified into 3 groups: compliant with marketing authorization, off label but relevant use, and strictly off label use.

RESULTS: During the study period, 100 patients were included among whom only 29% had a PPI prescription that did fully comply with the recommendations. Among the twenty-three prescriptions that did not comply with the recommendations in terms of indication, 15 were not relevant at all. Among the 65 prescriptions relevant for indication, 36 were not compliant with dose or duration recommendations. 59% of the total number of patients reported that they had never tried to stop treatment.

CONCLUSIONS: Our study highlights the need for regular reassessment of proton pump inhibitors prescriptions. Multi-disciplinary collaboration on the appropriate use of this class of medication as well as increased awareness among general practitioners and hospital doctors is essential.

PMID:36375532 | DOI:10.1016/j.pharma.2022.11.003

Korean J Intern Med. 2022 Nov;37(6):1153-1166. doi: 10.3904/kjim.2021.216. Epub 2022 Nov 1.

ABSTRACT

BACKGROUND/AIMS: Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly-used medications, and ailments such as arthritis or heart disease, require long-term use of these drugs, which can induce gastroenteropathy with bleeding and ulcers. This study investigated the associations between efficacy, safety, and gastrointestinal symptoms linked to rebamipide and proton pump inhibitor administration in patients requiring long-term NSAID use.

METHODS: This study was a multi-center, randomized, open-labeled, pilot design.

RESULTS: Thirty-three patients were included. Of these, 15 were included in the study group and 18 were in the control group. NSAID-induced gastric ulcers, which were the primary outcome of this study, did not occur in either the study or control group. Changes in the number of small bowel erosions and ulcers were -0.6 ± 3.06 in the study group and 1.33 ± 4.71 in the control group. The number of subjects with mucosal breaks (defined as multiple erosions and/or ulcers) was three (20%) in the study group and six (40%) in the control group (p = 0.427). No serious adverse events occurred in either group. However, dyspepsia and skin rashes occurred in six patients (31.58%) in the study group and 13 (65%) in the control group (p = 0.036).

CONCLUSION: Although statistically significant differences were not generated, possibly as a result of the small sample size, mucosal breaks observed via capsule endoscopy revealed that rebamipide was likely to be more effective than lansoprazole in preventing small intestine damage caused by NSAIDs. Furthermore, fewer side-effects emerged with rebamipide.

PMID:36375487 | DOI:10.3904/kjim.2021.216