BMC Gastroenterol. 2023 Feb 19;23(1):43. doi: 10.1186/s12876-023-02681-y.

ABSTRACT

BACKGROUND: COVID-19 is widely known to induce a variety of extrapulmonary manifestations. Gastrointestinal symptoms have been identified as the most common extra-pulmonary manifestations of COVID-19, with an incidence reported to range from 3 to 61%. Although previous reports have addressed abdominal complications with COVID-19, these have not been adequately elucidated for the omicron variant. The aim of our study was to clarify the diagnosis of concomitant abdominal diseases in patients with mild COVID-19 who presented to hospital with abdominal symptoms during the sixth and seventh waves of the pandemic of the omicron variant in Japan.

METHODS: This study was a retrospective, single-center, descriptive study. In total, 2291 consecutive patients with COVID-19 who visited the Department of Emergency and Critical Care Medicine, Kansai Medical University Medical Center, Osaka, Japan, between January 2022 and September 2022 were potentially eligible for the study. Patients delivered by ambulance or transferred from other hospitals were not included. We collected and described physical examination results, medical history, laboratory data, computed tomography findings and treatments. Data collected included diagnostic characteristics, abdominal symptoms, extra-abdominal symptoms and complicated diagnosis other than that of COVID-19 for abdominal symptoms.

RESULTS: Abdominal symptoms were present in 183 patients with COVID-19. The number of patients with each abdominal symptom were as follows: nausea and vomiting (86/183, 47%), abdominal pain (63/183, 34%), diarrhea (61/183, 33%), gastrointestinal bleeding (20/183, 11%) and anorexia (6/183, 3.3%). Of these patients, 17 were diagnosed as having acute hemorrhagic colitis, five had drug-induced adverse events, two had retroperitoneal hemorrhage, two had appendicitis, two had choledocholithiasis, two had constipation, and two had anuresis, among others. The localization of acute hemorrhagic colitis was the left-sided colon in all cases.

CONCLUSIONS: Our study showed that acute hemorrhagic colitis was characteristic in mild cases of the omicron variant of COVID-19 with gastrointestinal bleeding. When examining patients with mild COVID-19 with gastrointestinal bleeding, the potential for acute hemorrhagic colitis should be kept in mind.

PMID:36800938 | DOI:10.1186/s12876-023-02681-y

Med Sci (Paris). 2023 Feb;39(2):101-104. doi: 10.1051/medsci/2023001. Epub 2023 Feb 17.

NO ABSTRACT

PMID:36799742 | DOI:10.1051/medsci/2023001

JAMA Netw Open. 2023 Feb 1;6(2):e230023. doi: 10.1001/jamanetworkopen.2023.0023.

ABSTRACT

IMPORTANCE: Respiratory syncytial virus (RSV) is the leading cause of acute lower respiratory infection in children younger than 5 years; effective prevention strategies are urgently needed.

OBJECTIVE: To compare the efficacy and safety of monoclonal antibodies for the prevention of RSV infection in infants and children.

DATA SOURCES: In this systematic review and network meta-analysis, PubMed, Embase, CENTRAL, and ClinicalTrials.gov were searched from database inception to March 2022.

STUDY SELECTION: Randomized clinical trials that enrolled infants at high risk of RSV infection to receive a monoclonal antibody or placebo were included. Keywords and extensive vocabulary related to monoclonal antibodies, RSV, and randomized clinical trials were searched.

DATA EXTRACTION AND SYNTHESIS: The Preferred Reporting Items for Systematic Reviews and Meta-analyses reporting guideline was used. Teams of 2 reviewers independently performed literature screening, data extraction, and risk of bias assessment. The Grading of Recommendations, Assessments, Developments, and Evaluation approach was used to rate the certainty of evidence. A random-effects model network meta-analysis was conducted using a consistency model under the frequentist framework.

MAIN OUTCOMES AND MEASURES: The main outcomes were all-cause mortality, RSV-related hospitalization, RSV-related infection, drug-related adverse events, intensive care unit admission, supplemental oxygen use, and mechanical ventilation use.

RESULTS: Fifteen randomized clinical trials involving 18 395 participants were eligible; 14 were synthesized, with 18 042 total participants (median age at study entry, 3.99 months [IQR, 3.25-6.58 months]; median proportion of males, 52.37% [IQR, 50.49%-53.85%]). Compared with placebo, with moderate- to high-certainty evidence, nirsevimab, palivizumab, and motavizumab were associated with significantly reduced RSV-related infections per 1000 participants (nirsevimab: -123 [95% CI, -138 to -100]; palivizumab: -108 [95% CI, -127 to -82]; motavizumab: -136 [95% CI, -146 to -125]) and RSV-related hospitalizations per 1000 participants (nirsevimab: -54 [95% CI, -64 to -38; palivizumab: -39 [95% CI, -48 to -28]; motavizumab: -48 [95% CI, -58 to -33]). With moderate-certainty evidence, both motavizumab and palivizumab were associated with significant reductions in intensive care unit admissions per 1000 participants (-8 [95% CI, -9 to -4] and -5 [95% CI, -7 to 0], respectively) and supplemental oxygen use per 1000 participants (-59 [95% CI, -63 to -54] and -55 [95% CI, -61 to -41], respectively), and nirsevimab was associated with significantly reduced supplemental oxygen use per 1000 participants (-59 [95% CI, -65 to -40]). No significant differences were found in all-cause mortality and drug-related adverse events. Suptavumab did not show any significant benefits for the outcomes of interest.

CONCLUSIONS AND RELEVANCE: In this study, motavizumab, nirsevimab, and palivizumab were associated with substantial benefits in the prevention of RSV infection, without a significant increase in adverse events compared with placebo. However, more research is needed to confirm the present conclusions, especially for safety and cost-effectiveness.

PMID:36800182 | DOI:10.1001/jamanetworkopen.2023.0023

J Coll Physicians Surg Pak. 2023 Feb;33(2):153-157. doi: 10.29271/jcpsp.2023.02.153.

ABSTRACT

OBJECTIVE: To compare COVID-19 associated mucormycosis cases (CAM) with non-COVID-19 associated mucormycosis (non-CAM) cases followed as in-patients.

STUDY DESIGN: Observational Study.

PLACE AND DURATION OF STUDY: Department of Infectious Diseases and Clinical Microbiology, Adana City Training and Research Hospital, Health Sciences University (HSU), Adana, Turkey, between January 2018 and March 2022.

METHODOLOGY: Patients with a diagnosis of mucormycosis (proven and probable) were dichotomised as COVID-19 associated mucormycosis and non-COVID-19 associated mucormycosis cases. Both groups were compared for underlying malignancy, chemotherapy, antifungal therapy related side effects and overall survival.

RESULTS: Of the 35 cases enrolled in the study, 17 (48.6%) had CAM and 18 (51.4%) had non-CAM. A statistically significant difference was detected between non-CAM and CAM cases in terms of haematological malignancy, receiving chemotherapy, and antifungal therapy-related side effects (p=0.019, p=0.019, and p=0.027 respectively). Steroid use was found as a risk factor for the diabetic CAM cases (p<0.0001). The difference between the CAM and non-CAM cases in terms of overall survival was not statistically significant (p=0.088).

CONCLUSION: Because of the ongoing COVID-19 pandemic and the increasing number of critical patients, treatment of COVID-19 should be performed cautiously in patients who have the risk of developing CAM, particularly those with diabetes and immunosuppression (haematologic malignancy, receiving steroid or chemotherapy, etc.) and these patients should be monitored closely.

KEY WORDS: Mucormycosis, COVID-19, Mucormycosis associated with COVID-19, Diabetes mellitus, Turkey.

PMID:36797623 | DOI:10.29271/jcpsp.2023.02.153

Sci Rep. 2023 Feb 16;13(1):2777. doi: 10.1038/s41598-023-29581-1.

ABSTRACT

We aimed to determine whether knee OA is associated with CVD risk and all-cause death and to evaluate whether the association differs by exercise behavior. We used Korea National Health Insurance Service (KNHIS) database and included 201,466 participants (7572 subjects diagnosed with knee OA) who underwent health screening between 2009 and 2015. Those who had been diagnosed with knee OA or CVD before the index year were excluded. Cox proportional hazard models were used after adjusting for sociodemographic and CVD risk factors to evaluate the association between knee OA and CVD risk and all-cause death. Stratification analysis was further performed to determine the effect of exercise behavior on this relationship. During a median follow-up of 7.06 ± 2.24 years, 8743 CVD (2510 MI and 6553 stroke) cases developed. Individuals with knee OA had increased risks of CVD [hazard ratio (HR) 1.26, 95% confidence interval (CI) 1.15-1.38], myocardial infarction (MI) (HR 1.20, 95% CI 1.00-1.44), and stroke (HR 1.29, 95% CI 1.16-1.43) compared with those without knee OA. Those with knee OA who did not exercise had an increased risk of CVD (HR 1.25, 95% CI 1.11-1.40), whereas no significant increased CVD risk was observed in those with knee OA who exercised at least once a week (HR 1.11, 95% CI 0.96-1.28). There was no association between knee osteoarthritis and all-cause death. Knee OA was independently associated with an increased risk of CVD. Lack of exercise might have a synergistic adverse effect on the association between knee OA and CVD.

PMID:36797339 | PMC:PMC9935498 | DOI:10.1038/s41598-023-29581-1

Front Endocrinol (Lausanne). 2023 Jan 30;14:1098032. doi: 10.3389/fendo.2023.1098032. eCollection 2023.

ABSTRACT

AIM: To identify risk factors predictive of or associated with gastrointestinal side effects (GISE) of liraglutide in patients with type 2 diabetes (T2DM).

METHODS: T2DM patients treated with liraglutide for the first time were obtained and grouped into patients without GSEA and patients with GSEA. Baseline variables, including age, sex, body mass index (BMI), glycemia profiles, alanine aminotransferase, serum creatinine, thyroid hormones, oral hypoglycemic drugs and history of gastrointestinal diseases, were tested for possible associations with GSEA outcome. Significant variables were entered into univariate and multivariate logistic regression (forward LR) analyses. Receiver operating characteristic (ROC) curves to determine clinically useful cutoff values.

RESULTS: A total of 254 patients (95 female) were included in this study. 74 cases (29.13%) reported GSEA and 11 cases (4.33%) discontinued treatment. The results of univariate analyses showed that sex, age, thyroid stimulating hormone (TSH), free triiodothyronine, α-glucosidase inhibitor (AGI), and concomitant gastrointestinal diseases were associated with GSEA occurrence (all p <0.05). In the final regression model, AGI use (adjusted OR=4.01, 95%CI: 1.90-8.45, p<0.001), gastrointestinal diseases (adjusted OR=3.29, 95%CI: 1.51-7.18, p=0.003), TSH (adjusted OR=1.79, 95%CI: 1.28-2.50, p=0.001) and male sex (adjusted OR=0.19, 95%CI: 0.10-0.37, p<0.001) were independently associated with GSEA. Furthermore, ROC curve analysis confirmed that TSH values of 1.33 and 2.30 in females and males, respectively, were useful thresholds for predicting GSEA.

CONCLUSION: This study suggests that the combination of AGI, concomitant gastrointestinal diseases, female sex and higher TSH levels are independent risk factors of GSEA of liraglutide treatment in patients with T2DM. Further research is warranted to elucidate these interactions.

PMID:36793278 | PMC:PMC9922750 | DOI:10.3389/fendo.2023.1098032

Pediatr Rheumatol Online J. 2023 Feb 15;21(1):18. doi: 10.1186/s12969-023-00800-3.

ABSTRACT

OBJECTIVE: To evaluate the efficacy of levofolinic acid (LVF) administered 48 h before methotrexate (MTX) in reducing gastrointestinal side effects without interference with drug efficacy.

METHODS: A prospective observational study was performed including patients with Juvenile Idiopathic Arthritis (JIA) reporting significant gastrointestinal discomfort after MTX despite taking a dose of LVF 48 h after MTX. Patients with anticipatory symptoms were excluded. A LVF supplemental dose was added 48 h before MTX and patients were followed every 3-4 months. At each visit data on gastrointestinal symptoms, disease activity (JADAS, ESR, CRP values) and treatment changes were collected. Friedman test for repeated measures analyzed differences between these variables over time.

RESULTS: Twenty-one patients were recruited and followed for at least 12 months. All patients received MTX subcutaneously (mean 9.54 mg/m2) and LVF 48 h before and after MTX (mean 6.5 mg/dose), 7 received a biological agent too. Complete remission of gastrointestinal side effects was reported in 61.9% of study patients at first visit (T1) and increased over time (85.7%, 95.2%, 85.7% and 100% at T2, T3, T4, T5, respectively). MTX efficacy was maintained as showed by significant reduction of JADAS and CRP (p = 0.006 and 0.008) from T1 to T4 and it was withdrawn for remission in 7/21.

CONCLUSIONS: LVF given 48 h before MTX significantly reduced gastrointestinal side effects and did not reduce drug's efficacy. Our results suggest that this strategy may improve compliance and quality of life in patients with JIA and other rheumatic diseases treated with MTX.

PMID:36793106 | DOI:10.1186/s12969-023-00800-3

Zhonghua Yu Fang Yi Xue Za Zhi. 2023 Feb 6;57(2):273-280. doi: 10.3760/cma.j.cn112150-20220808-00798.

ABSTRACT

Objective: To investigate the clinical efficacy and safety of anti-IgE monoclonal antibody (omazumab) in the treatment of allergic united airway disease (UAD) in the real-wold. Methods: Retrospective cohort study summarizes the case data of patients with allergic united airway disease who were treated with anti IgE monoclonal antibody (omalizumab) for more than 16 weeks from March 1, 2018 to June 30, 2022 in the Peking University First Hospital.The allergic UAD is defined as allergic asthma combined with allergic rhinitis (AA+AR) or allergic asthma combined with chronic sinusitis with nasal polyps (AA+CRSwNP) or allergic asthma combined with allergic rhinitis and nasal polyps (AA+AR+CRSwNP). The control of asthma was evaluated by asthma control test (ACT), lung function test and fractional exhaled nitric oxide (FeNO). The AR was assessed by total nasal symptom score (TNSS). The CRSwNP was evaluated by nasal visual analogue scale (n-VAS), sino-nasal outcome test-22 (SNOT-22), nasal polyps score (TPS) and Lund-Mackay sinus CT grading system. The global evaluation of omalizumab for the treatment of allergic UADwas performed by Global Evaluation of Treatment Effectiveness(GETE).The drug-related side effects were also recorded. Matched t test and Wilcoxon signed-rank test were used to compare the score changes of IgE monoclonal antibody (omazumab) before and after treatment, and multivariate logistic regression analysis was used to determine the influencing factors of IgE monoclonal antibody (omazumab) response. Results: A total of 117 patients with UAD were enrolled, ranging in age from 19 to 77 years; The median age of patients was 48.7 years; Among them, 60 were male, ranging from 19 to 77 years old, with a median age of 49.9 years; There were 57 females, ranging from 19 to 68 years old, with a median age of 47.2 years. There were 32 cases in AA+AR subgroup, 59 cases in AA+CRSwNP subgroup, and 26 cases in AA+AR+CRSwNP subgroup. The total serum IgE level was 190.5 (103.8,391.3) IU/ml. The treatment course of anti IgE monoclonal antibody was 24 (16, 32) weeks. Compared with pre-treatment, omalizumab increased ACT from 20.0 (19.5,22.0) to 24.0 (23.0,25.0) (Z=-8.537, P<0.001), increased pre-bronchodilator FEV1 from 90.2 (74.8,103.0)% predicted value to 95.4 (83.2,106.0)% predicted value (Z=-5.315,P<0.001), increased FEV1/FVC from 80.20 (66.83,88.38)% to 82.72 (71.26,92.25)% (Z=-4.483,P<0.001), decreased FeNO from(49.1±24.8) ppb to (32.8±24.4) ppb (t=5.235, P<0.001), decreased TNSS from (6.5±2.6)to (2.4±1.9) (t=14.171, P<0.001), decreased n-VAS from (6.8±1.2) to (3.4±2.0)(t=14.448, P<0.001), decreased SNOT-22 from (40.0±7.9) to (21.3±10.2)(t=15.360, P<0.001), decreased TPS from (4.1±0.8) to (2.4±1.0)(t=14.718, P<0.001) and decreased Lund-Mackay CT score from (6.0±1.3) to (3.1±1.6)(t=17.012, P<0.001). The global response rate to omalizumab was 67.5%(79/117). The response rate in AA+AR (90.6%,29/32) was significantly higher than that in AA+CRSwNP (61.0%,36/59) and AA+AR+CRSwNP (53.8%,14/26) subgroups (χ2=11.144,P=0.004). Only 4 patients (3.4%,4/117) had mild side effects. Conclusion: The real-world study showed favorable effectiveness and safety of anti-IgE monoclonal antibody for treatment of allergic UAD. To provide basis for preventing the progress and precise treatment of allergic UAD.

PMID:36797588 | DOI:10.3760/cma.j.cn112150-20220808-00798

Phytomedicine. 2023 Feb 5;112:154704. doi: 10.1016/j.phymed.2023.154704. Online ahead of print.

ABSTRACT

BACKGROUND: Yishen Tongbi decoction (YSTB) which is an herbal formula, has been used for the treatment of rheumatoid arthritis (RA) for more than ten years with a better curative effect. Methotrexate (MTX) is an effective anchoring agent used to treat rheumatoid arthritis. There were, however, no head-to-head comparative randomized controlled trials comparing traditional Chinese medicine (TCM) to MTX, Therefore, we performed this double-blind, double-model, randomized controlled trial of the efficacy and safety of YSTB and MTX in the treatment of active RA for 24 weeks.

METHODS: Patients who met the enrollment criteria were randomly selected (1:1) to receive either YSTB therapy (YSTB 150 ml once daily + MTX placebo 7.5-15 mg once weekly) or MTX therapy (MTX 7.5-15 mg once weekly + YSTB placebo 150 ml once daily) in treatment cycles lasting 24 weeks. The percentage of patients who achieve a clinical disease activity index (CDAI) response at week 24 is the primary efficacy outcome. A 10% risk differential non-inferiority margin was previously defined. The Chinese Clinical Trials Registry has recorded this trial (ChiCTR-1,900,024,902, registered on August 3rd 2019, http://www.chictr.org.cn/index.aspx).

RESULTS: Out of 118 patients whose eligibility was determined from September 2019 to May 2022, 100 patients (n = 50 for each group) were enrolled in the research overall. The 24-week trial was completed by 82% (40/49) of the YSTB group's patients and 86% (42/49) of the MTX group's patients. In the intention-to-treat analysis, 67.4% (33/49) of patients in the YSTB group met the main outcome of CDAI response criteria at week 24, compared to 57.1% (28/49) in the MTX group. The risk difference was 0.102 (95% CI -0.089 to 0.293), which demonstrated the non-inferiority of YSTB to MTX. After further testing for superiority, the ratio of CDAI responses achieved by the YSTB and MTX groups was not statistically significant (p = 0.298). At the same time, in week 24, secondary outcomes such as the ACR 20/50/70 response, the European Alliance of Associations for Rheumatology good or moderate response, remission rate, simplified disease activity index response, and low disease activity rate all showed similar statistically significant patterns. There was statistically significant attainment of ACR20 (p = 0.008) and EULAR good or moderate response (p = 0.009) in two groups at week 4. The intention-to-treat analysis results and the per-protocol analysis results were in agreement. The incidence of drug-related adverse events was not statistically different between the two groups (p = 0.487).

CONCLUSIONS: Previous studies have used TCM as an adjunct to conventional therapy, and few of them have directly compared it with MTX. In order to lessen disease activity in RA patients, this trial demonstrated that YSTB compound monotherapy was non-inferior to MTX monotherapy and had superior efficacy following short-term treatment. This study provided evidence-based medicine in the treatment of RA with compound prescriptions of TCM and contributed to promoting phytomedicine use in RA patients.

PMID:36796186 | DOI:10.1016/j.phymed.2023.154704

Oral Dis. 2023 Feb 16. doi: 10.1111/odi.14539. Online ahead of print.

ABSTRACT

OBJECTIVE: To determine the prevalence of potential drug-drug interactions involving psychotropics prescribed by dentists, and dispensed by the public healthcare system, as well as to describe the severity and level of evidence of those interactions in the state of Minas Gerais, Brazil.

MATERIALS AND METHODS: We conducted data analysis from pharmaceutical claims in which dental patients received systemic psychotropics in 2017. Data from the Pharmaceutical Management System provided the drug dispensing history of the patients, allowing the identification of those on concomitant medication use. The outcome was the occurrence of potential drug-drug interactions, which were detected according to IBM Micromedex®. Independent variables were the patient's sex, age, and the number of drugs used. Descriptive statistics was performed using SPSS v. 26.

RESULTS: Overall, 1,480 individuals were prescribed psychotropic drugs. The prevalence of potential drug-drug interactions was 24.8% (n=366). The total of 648 interactions was observed and, most of which were of major severity (n=438, 67.6%). Most interactions occurred in female individuals (n=235; 64.2%), with 46.0 (±17.3) years-old, concurrently taking 3.7 (±1.9) drugs.

CONCLUSION: A substantial proportion of dental patients presented potential drug-drug interactions, mostly of major severity, which might be life-threatening.

PMID:36794905 | DOI:10.1111/odi.14539

Acta Derm Venereol. 2023 Feb 14;103:adv00867. doi: 10.2340/actadv.v103.3364.

NO ABSTRACT

PMID:36789755 | DOI:10.2340/actadv.v103.3364

Ital J Pediatr. 2023 Feb 14;49(1):20. doi: 10.1186/s13052-023-01427-6.

ABSTRACT

BACKGROUND: This study aimed to analyze all the patients who contacted the hospital's pediatric poison control center (PPCC) for exposure to ibuprofen and acetaminophen, in order to assess the incidence of any adverse reactions.

METHODS: We retrospectively reported the clinical data of children who accessed the PPCC of the Bambino Gesù Children's Hospital, IRCCS, Rome, from January 1, 2018 to September 30, 2022 due to wrong, accidental or intentional intake of inappropriate doses of acetaminophen and/or ibuprofen. In addition, we compared patients according to the intake of one of the two drugs and reported the trimestral distribution of cases during the study period.

RESULTS: A total of 351 patients accessed the PPCC during the study period. The median age was 3.0 years. Most patients were females (57.8%). The most common reason for inappropriate oral intake of paracetamol or ibuprofen was a wrong use or an accidental intake (78.6%), with a fifth of patients taking the drug with suicidal intent (21.1%). According to the PPCC evaluation, most patients were not intoxicated (70.4%). Hospitalization was required for 30.5% of patients. Adverse reactions were reported in 10.5% of cases, with a similar incidence in patients who took paracetamol or ibuprofen. Nausea and vomiting were the most commonly reported adverse reactions. A higher frequency of moderate intoxication was found in patients who took paracetamol compared to ibuprofen (p = 0.001). The likelihood of intoxication was also higher in the paracetamol cohort. A spike of cases was registered at the end of 2021.

CONCLUSIONS: We analyze exposures to the two most commonly used pediatric molecules, paracetamol and ibuprofen, to assess the frequency of adverse reactions. We demonstrated that these relatively "safe" drugs may be associated with intoxications and adverse reactions when inappropriately administered.

PMID:36788576 | DOI:10.1186/s13052-023-01427-6

BMC Med Inform Decis Mak. 2023 Feb 14;23(1):35. doi: 10.1186/s12911-023-02133-3.

ABSTRACT

BACKGROUND: The measurement of drug similarity has many potential applications for assessing drug therapy similarity, patient similarity, and the success of treatment modalities. To date, a family of computational methods has been employed to predict drug-drug similarity. Here, we announce a computational method for measuring drug-drug similarity based on drug indications and side effects.

METHODS: The model was applied for 2997 drugs in the side effects category and 1437 drugs in the indications category. The corresponding binary vectors were built to determine the Drug-drug similarity for each drug. Various similarity measures were conducted to discover drug-drug similarity.

RESULTS: Among the examined similarity methods, the Jaccard similarity measure was the best in overall performance results. In total, 5,521,272 potential drug pair's similarities were studied in this research. The offered model was able to predict 3,948,378 potential similarities.

CONCLUSION: Based on these results, we propose the current method as a robust, simple, and quick approach to identifying drug similarity.

PMID:36788528 | DOI:10.1186/s12911-023-02133-3

J Clin Oncol. 2023 Feb 20;41(6):1162-1171. doi: 10.1200/JCO.22.02499.

ABSTRACT

PURPOSE: To evaluate the efficacy and tolerability of two doses of gefitinib (Iressa [ZD1839]; AstraZeneca, Wilmington, DE), a novel epidermal growth factor receptor tyrosine kinase inhibitor, in patients with pretreated advanced non-small-cell lung cancer (NSCLC).

PATIENTS AND METHODS: This was a randomized, double-blind, parallel-group, multicenter phase II trial. Two hundred ten patients with advanced NSCLC who were previously treated with one or two chemotherapy regimens (at least one containing platinum) were randomized to receive either 250-mg or 500-mg oral doses of gefitinib once daily.

RESULTS: Efficacy was similar for the 250- and 500-mg/d groups. Objective tumor response rates were 18.4% (95% confidence interval [CI], 11.5 to 27.3) and 19.0% (95% CI, 12.1 to 27.9); among evaluable patients, symptom improvement rates were 40.3% (95% CI, 28.5 to 53.0) and 37.0% (95% CI, 26.0 to 49.1); median progression-free survival times were 2.7 and 2.8 months; and median overall survival times were 7.6 and 8.0 months, respectively. Symptom improvements were recorded for 69.2% (250 mg/d) and 85.7% (500 mg/d) of patients with a tumor response. Adverse events (AEs) at both dose levels were generally mild (grade 1 or 2) and consisted mainly of skin reactions and diarrhea. Drug-related toxicities were more frequent in the higher-dose group. Withdrawal due to drug-related AEs was 1.9% and 9.4% for patients receiving gefitinib 250 and 500 mg/d, respectively.

CONCLUSION: Gefitinib showed clinically meaningful antitumor activity and provided symptom relief as second- and third-line treatment in these patients. At 250 mg/d, gefitinib had a favorable AE profile. Gefitinib 250 mg/d is an important, novel treatment option for patients with pretreated advanced NSCLC.

PMID:36791474 | DOI:10.1200/JCO.22.02499

Gut Liver. 2023 Feb 15. doi: 10.5009/gnl220457. Online ahead of print.

ABSTRACT

BACKGROUND/AIMS: Fexuprazan is a novel potassium-competitive acid blocker that could be of benefit to patients with gastric mucosal injury. The aim of this study was to assess the 2-week efficacy and safety of fexuprazan in patients with acute or chronic gastritis.

METHODS: In this study, 327 patients with acute or chronic gastritis who had one or more gastric erosions on endoscopy and subjective symptoms were randomized into three groups receiving fexuprazan 20 mg once a day (q.d.), fexuprazan 10 mg twice a day (b.i.d.), or placebo for 2 weeks. The posttreatment assessments were the primary endpoint (erosion improvement rate), secondary endpoints (cure rates of erosion and edema and improvement rates of redness, hemorrhage, and subjective symptoms), and drug-related adverse events.

RESULTS: Among the patients, 57.8% (59/102), 65.7% (67/102), and 40.6% (39/96) showed erosion improvement 2 weeks after receiving fexuprazan 20 mg q.d., fexuprazan 10 mg b.i.d., and placebo, respectively. Both fexuprazan 20 mg q.d. and 10 mg b.i.d. showed superior efficacy to the placebo (p=0.017 and p<0.001, respectively). Likewise, both fexuprazan 20 mg q.d. and 10 mg b.i.d. also showed higher erosion healing rates than the placebo (p=0.033 and p=0.010, respectively). No difference was noted in the edema healing rate and the improvement rates for redness, hemorrhage, and subjective symptoms between the fexuprazan and placebo groups. No significant difference was noted in the incidence of adverse drug reactions.

CONCLUSIONS: Fexuprazan 20 mg q.d. and 10 mg b.i.d. for 2 weeks showed therapeutic efficacy superior to that of placebo in patients with acute or chronic gastritis (ClinicalTrials.gov identifier NCT04341454).

PMID:36789577 | DOI:10.5009/gnl220457

BMC Prim Care. 2023 Feb 14;24(1):48. doi: 10.1186/s12875-023-02004-w.

ABSTRACT

BACKGROUND: Service gaps exist in oral anticoagulant (OAC) use among patients with atrial fibrillation (AF) in primary care. The purpose of this study was to explore the clinical effectiveness of a community dwelling Atrial Fibrillation Special Clinic (AFSC) run by primary care physicians by evaluating its impact on OAC use and the control of modifiable cardiovascular disease (CVD) risk factors in high risk AF patients.

METHOD: Quasi-experimental study was conducted in AFSC run by public primary care physicians in Hong Kong. Study subjects were high risk AF patients with CHA2DS2-VASc scores ≥ 2, who had been followed up (FU) at AFSC for at least one year from 01 August, 2019 to 31 October, 2020. OAC usage and modifiable CVD risk factor control were compared before and after one year of FU at AFSC. Drug-related adverse events, emergency attendance or hospitalisation episodes, survival and mortality rates after one year FU at AFSC were also reviewed.

RESULTS: Among the 299 high risk AF patients included in the study, significant increase in OAC use was observed from 58.5% at baseline to 82.6% after one year FU in AFSC (P < 0.001). Concerning CVD risk factor control, the average diastolic blood pressure level was significantly reduced (P = 0.009) and the satisfactory blood pressure control rate in non-diabetic patients was markedly improved after one year FU (P = 0.049). However, the average HbA1c and LDL-c levels remained static. The annual incidence rate of ischaemic stroke/systemic embolism was 0.4%, intra-cranial haemorrhage was 0.4%, major bleeding episode was 3.2% and all-cause mortality was 4.3%, all of which were comparable to reports in the literature.

CONCLUSION: AFSC is effective in enhancing OAC use and maintaining optimal modifiable CVD risk factor control among high risk AF patients managed in primary care setting, and therefore may reduce AF-associated morbidity and mortality in the long run.

PMID:36788489 | DOI:10.1186/s12875-023-02004-w

BMC Pediatr. 2023 Feb 13;23(1):77. doi: 10.1186/s12887-023-03891-9.

ABSTRACT

BACKGROUND: The characteristics and incidence of adverse drug events (ADEs) among pediatric cancer patients in developing countries have not been well characterized. ADEs & medication errors associated with cancer chemotherapy in children need to be analyzed on their incidence and severity. The purpose of this study was hence, to assess the incidence of adverse drug events and contributing factors among pediatric cancer patients at Jimma university medical center, Jimma, Ethiopia.

METHOD: A prospective observational method was used to study adverse drug events in pediatrics admitted to the pediatric oncology unit of Jimma University medical center between October and December 2020. The ADEs were identified using multifaceted approaches involving daily chart review, interviews of Parents/caregivers (and/or children themselves), attendance at ward rounds, and voluntary staff reports. Both univariate and multivariate logistic regression were used to assess the predictors of the identified ADEs. Those factors that showed association at p-value < 0.25 in the univariate analysis were added to the backward multivariate logistic regression model and the significant association was checked at p-value < 0.05.

RESULT: A total of 73 (46 male and 27 female) patients were included in the study. A total of 466 ADEs were identified with an incidence of 638.36 ADEs per 100 patients, 38.35 ADEs per 100 patient days, and 2.34 ADEs per chemotherapy cycle. The most common ADEs were hematologic toxicities (anemia 55(11.8%), neutropenia 52(11.16%) & thrombocytopenia 31(6.65%)), and gastrointestinal effects (nausea 46(9.87%), vomiting 46(9.87%), anorexia 41(8.8%). Out of 466 ADEs, 150 (32.19%) were classified as common terminology criteria for adverse events (CTCAE) as Grade 1, 199 (42.70%) as Grade 2, 64(13.73%) as Grade 3, 48(10.30%) as grade 4 and 5(1.07%) as Grade 5. Severe acute malnutrition (SAM) is the most common comorbidity present, 20(27.40%) followed by pneumonia, 4(5.50%). Presence of comorbidity (AOR 12.700, CI 1.978-81.549), cancer type (AOR 13.332, CI 3.288-54.059), use of 4 or more chemotherapy drugs (AOR 6.179, CI 1.894-20.165) and length of hospital stay more than 8 days (AOR 5.367, CI 1.167-24.684) were associated with the risk of developing grades 3 and 4 ADEs.

CONCLUSION: Adverse drug events were common in the pediatric oncology ward of JUMC. In particular, children with multiple chemotherapy drugs and those with the comorbid condition were at greater risk for adverse drug events.

PMID:36782170 | DOI:10.1186/s12887-023-03891-9

Eur J Hosp Pharm. 2023 Feb 14:ejhpharm-2022-003669. doi: 10.1136/ejhpharm-2022-003669. Online ahead of print.

ABSTRACT

OBJECTIVES: Optimal perioperative success in cardiac surgery requires precise management of drug treatment. This study aimed to determine the prevalence, types and associated factors of drug-related problems (DRPs) during the entire hospital stay.

METHODS: A prospective observational study was conducted at the department of cardiovascular surgery in a university hospital between November 2019 and March 2020. Patients with planned elective cardiac surgery, aged ≥18 years, were included. A clinical pharmacist collaboratively reviewed medications on a daily basis and identified DRPs.

RESULTS: A total of 100 patients (60 male) were included; median (range) age was 62 (19-86) years, and median (IQR) length of stay in hospital was 15 (9) days. A total of 275 DRPs were identified (median (IQR) 3 (2-4)). The number of patients who had at least one DRP was 47 preoperatively, 55 in the postoperative intensive care unit, 100 in the postoperative ward, and 16 at discharge. In order to reduce bias because of the small sample size, Firth's logistic regression analysis was conducted. Statistically significant variables according to univariate analysis were included into a logistic regression model. Therefore the length of hospital stay (OR 1.14, 95% CI 1.03 to 1.26, p=0.008), living arrangements (living alone) (OR 4.24, 95% CI 1.41 to 12.73, p=0.009), number of medications at admission (OR 1.32, 95% CI 1.09 to 1.59, p=0.002), and having coronary artery bypass graft surgery (OR 2.87, 95% CI 1.07 to 7.70, p=0.03) were associated with an increased risk for DRPs in the final model.

CONCLUSION: Hospital stay carries an increased risk for DRPs, especially at the postoperative stage. Modifiable risk factors for DRPs can be managed by required interventions performed by a multidisciplinary healthcare team.

PMID:36788008 | DOI:10.1136/ejhpharm-2022-003669

Reg Anesth Pain Med. 2023 Feb 14:rapm-2022-104166. doi: 10.1136/rapm-2022-104166. Online ahead of print.

ABSTRACT

INTRODUCTION: The ultrasound-guided interpectoral-pectoserratus plane block is a fascial plane block for superficial surgery of the anterolateral chest wall. This technique involves injecting a relatively large volume of local anesthetics (typically 30 mL of 0.25%-0.50%, ie, 75-150 mg ropivacaine) underneath the major and minor pectoral muscles of the anterior thoracic wall. There is a potential risk of toxic serum concentrations of local anesthetics due to systemic absorption.

METHODS: 22 patients scheduled for elective unilateral breast cancer surgery were included in this study. All surgery was performed with general anesthesia and an ultrasound-guided interpectoral-pectoserratus plane block with 2.5 mg/kg ropivacaine. Ten venous blood samples were collected at 0 (two samples) 10, 20, 30, 45, 60, 90 and 120 min and at 4 hours after performing the block. Free and total ropivacaine levels were measured at each time point. Albumin and alpha-1-acid-glycoprotein were measured to monitor shifts between the free and bound fraction of ropivacaine.

RESULTS: Samples of 20 patients were analyzed. The mean dose of ropivacaine was 172.8 (22.5) mg. In 50% of the patients, the potentially toxic threshold of 0.15 µg/mL free ropivacaine concentration was exceeded. Mean peak serum concentration occurred at 20 min postinjection.

CONCLUSIONS: This pharmacokinetic study demonstrated that a 2.5 mg/kg ropivacaine interpectoral-pectoserratus plane block may result in exceeding the threshold for local anesthetic systemic toxicity.

PMID:36787951 | DOI:10.1136/rapm-2022-104166

Proc Natl Acad Sci U S A. 2023 Feb 21;120(8):e2205186120. doi: 10.1073/pnas.2205186120. Epub 2023 Feb 14.

ABSTRACT

Chemiluminescence (CL) with the elimination of excitation light and minimal autofluorescence interference has been wieldy applied in biosensing and bioimaging. However, the traditional emission of CL probes was mainly in the range of 400 to 650 nm, leading to undesired resolution and penetration in a biological object. Therefore, it was urgent to develop CL molecules in the near-infrared window [NIR, including NIR-I (650 to 900 nm) and near-infrared-II (900 to 1,700 nm)], coupled with unique advantages of long-time imaging, sensitive response, and high resolution at depths of millimeters. However, no NIR-II CL unimolecular probe has been reported until now. Herein, we developed an H2S-activated NIR-II CL probe [chemiluminiscence donor 950, (CD-950)] by covalently connecting two Schaap's dioxetane donors with high chemical energy to a NIR-II fluorophore acceptor candidate via intramolecular CL resonance energy transfer strategy, thereby achieving high efficiency of 95%. CD-950 exhibited superior capacity including long-duration imaging (~60 min), deeper tissue penetration (~10 mm), and specific H2S response under physiological conditions. More importantly, CD-950 showed detection capability for metformin-induced hepatotoxicity with 2.5-fold higher signal-to-background ratios than that of NIR-II fluorescence mode. The unimolecular NIR-II CL probe holds great potential for the evaluation of drug-induced side effects by tracking its metabolites in vivo, further facilitating the rational design of novel NIR-II CL-based detection platforms.

PMID:36787363 | DOI:10.1073/pnas.2205186120