Drug Ther Bull. 2022 Nov 9:dtb-2022-000061. doi: 10.1136/dtb.2022.000061. Online ahead of print.

ABSTRACT

Overview of: Zeng C, Rosenberg L, Li X, et al Sodium-containing acetaminophen and cardiovascular outcomes in individuals with and without hypertension. Eur Heart J 2022;43:1743-55.

PMID:36351781 | DOI:10.1136/dtb.2022.000061

BMC Geriatr. 2022 Nov 7;22(1):841. doi: 10.1186/s12877-022-03536-z.

ABSTRACT

BACKGROUND: Polypharmacy can be defined as using five or more medications simultaneously. "Medication-related problems", an extension of polypharmacy, includes inappropriate prescribing, poor adherence, overdosage, underdosage, inappropriate drug selection, inadequate monitoring, adverse drug effects, and drug interactions. Polypharmacy and the high risk of medication-related problems among older people are associated with adverse health consequences due to drug-drug interactions, drug-disease interactions, and adverse drug effects. This study aims to assess the factors associated with polypharmacy and the high risk of medication-related problems among community-dwelling older people in the Netherlands, Greece, Croatia, Spain, United Kingdom.

METHOD: This longitudinal study used baseline and follow-up data from 1791 participants of the Urban Health Center European project. Polypharmacy and the risk of medication-related problems were evaluated at baseline and follow-up using the Medication Risk Questionnaire. We studied factors in the domains (a) sociodemographic characteristics, (b) lifestyle and nutrition, and (c) health and health care use. Hierarchical logistic regression analyses were used to examine the factors associated with polypharmacy and the high risk of medication-related problems.

RESULTS: Mean age was 79.6 years (SD ± 5.6 years); 60.8% were women; 45.2% had polypharmacy, and 41.8% had a high risk of medication-related problems. Women participants had lower odds of polypharmacy (OR = 0.55;95%CI:0.42-0.72) and a high risk of medication-related problems (OR = 0.50; 95%CI:0.39-0.65). Participants with a migration background (OR = 1.67;95%CI:1.08-2.59), overweight (OR = 1.37; 95%CI:1.04-1.79) and obesity (OR = 1.78;95%CI:1.26-2.51) compared to 'normal weight', with lower physical HRQoL (OR = 0.96, 95%CI:0.95-0.98), multi-morbidity (OR = 3.73, 95%CI:2.18-6.37), frailty (OR = 1.69, 95%CI:1.24-2.30), visited outpatient services (OR = 1.77, 95%CI: 1.09-2.88) had higher odds of polypharmacy. The associations with the high risk of medication-related problems were similar.

CONCLUSIONS: Multiple factors in demography, lifestyle, nutrition, and health care use are associated with polypharmacy and the high risk of medication-related problems. Polypharmacy is a single element that may reflect the number of medications taken. The broader content of medication-related problems should be considered to assess the context of medication use among older people comprehensively. These provide starting points to improve interventions to reduce polypharmacy and high risk of medication-related problems. In the meantime, health professionals can apply these insights to identify subgroups of patients at a high risk of polypharmacy and medication-related problems.

TRIAL REGISTRATION: The intervention of the UHCE project was registered in the ISRCTN registry as ISRCTN52788952. The date of registration is 13/03/2017.

PMID:36344918 | DOI:10.1186/s12877-022-03536-z

Front Immunol. 2022 Oct 21;13:1013186. doi: 10.3389/fimmu.2022.1013186. eCollection 2022.

ABSTRACT

OBJECTIVE: To study the incidence and distribution of adverse events in immune checkpoint inhibitors (ICI) for digestive system cancers and to provide a reference for the safe, rational, and effective use of immune detection site inhibitors.

METHODS: We searched for articles published in English between January 1, 2010, and May 18, 2022. All clinical trials of ICI-based therapies for digestive system cancers were investigated, including only randomized controlled trials that reported data on the overall incidence of treatment-related adverse events (trAEs) or immune-related adverse reactions (irAEs) or tables.

RESULTS: We searched 2048 records, of which 21 studies (7108 patients) were eligible for inclusion. The incidence of ICI trAEs of any grade was 82.7% (95% CI 73.9-90.0), and the incidence of grade 3 or higher trAEs was 27.5% (95% CI 21.3-34.1). The pooled rate of ICI irAEs of any grade was 26.3% (95% CI 11.8-44.0), and the incidence of grade 3 or higher irAEs was 9.4% (95% CI 1.1-24.6). In multivariate analysis, the incidence, characteristics, and distribution of AEs varied by cancer type, combination therapy modality (single/two-drug), and different agent types.

CONCLUSION: Our meta-analysis summarizes AEs associated with ICI in digestive system cancers. The incidence, characteristics, and distribution of AEs vary by cancer type, combination therapy modality, and different agent types. These findings can be considered for the early identification of AEs and provide effective interventions to reduce the severity of these patients. It can provide a clinical reference and may contribute to clinical practice.

PMID:36341450 | PMC:PMC9634077 | DOI:10.3389/fimmu.2022.1013186

Front Public Health. 2022 Oct 20;10:996179. doi: 10.3389/fpubh.2022.996179. eCollection 2022.

ABSTRACT

BACKGROUND: Semaglutide was approved for treatment of type 2 diabetes mellitus (T2DM) and chronic weight management in obesity or overweight adults. However, real-world data regarding its long-term gastrointestinal safety and tolerability in large sample population are incomplete. We evaluated semaglutide-associated gastrointestinal safety signals by data mining of the FDA pharmacovigilance database.

METHODS: Reporting odds ratio (ROR) was employed to quantify the signals of semaglutide-related gastrointestinal adverse events (AEs) from 2018 to 2022. Serious and non-serious cases were compared by Mann-Whitney U test or Chi-squared (χ2) test, and signals were prioritized using a rating scale.

RESULTS: We identified 5,442 cases of semaglutide-associated gastrointestinal AEs, with 45 signals detected, ranging from a ROR025 of 1.01 (hypoaesthesia oral) to 42.03 (eructation), among which 17 AEs were identified as new and unexpected signals. Patient age (p < 0.001) and body weight (p = 0.006) rather than sex (p = 0.251) might be associated with an increased risk of gastrointestinal AEs severity. Notably, the association between semaglutide and gastrointestinal disorders remained when stratified by age, body weight, sex and reporter type. One strong, 22 moderate and 22 weak clinical priority signals were defined. The median time-to-onset (TTO) for strong clinical priority signal was 23 days, while for moderate and weak, they were 6 and 7 days, respectively. All of the disproportionality signals had early failure type features, suggesting that the risk of gastrointestinal AEs occurrence gradually decreased over time.

CONCLUSION: Our study provided a deeper and broader understanding of semaglutide's gastrointestinal safety profiles, which would help healthcare professionals to mitigate the risk of gastrointestinal AEs in clinical practice.

PMID:36339230 | PMC:PMC9631444 | DOI:10.3389/fpubh.2022.996179

Sci Rep. 2022 Nov 7;12(1):18844. doi: 10.1038/s41598-022-23795-5.

ABSTRACT

To observe the efficacy and safety of solifenacin and/or mirabegron as a medical expulsive therapy (MET) in patients with double-J stent-related overactive bladder (OAB) symptoms. A total of 219 patients with double-J stent-related OAB symptoms were prospectively randomized into two groups. One-hundred and nine cases in the combination group accepted mirabegron and solifenacin therapy and 110 cases as control only accepted solifenacin therapy. The lower urinary tract symptoms and overactive bladder questionnaire (OAB-q) health-related quality of life (HRQol) and symptom bother score between two groups were compared at the 1st, 2nd and 4th week ends. All of 219 patients were randomly assigned to two groups, of which 109 patients were included in the combination group and 110 in the solifenacin group. The incidences of LUTS, including urgency, frequent urination, and incontinence episodes, in the 2nd week (44.9% vs. 64.5%, P = 0.028; 48.6% vs. 62.7%, P = 0.036; and 40.4% vs. 56.4%, P = 0.018) and the 4th week (14.7% vs. 30.9%, P = 0.004; 16.5% vs. 33.6%, P = 0.003; and 11.9% vs. 26.4%, P = 0.007) after combination treatment were significantly lower than those in the solifenacin group. The incidence of drug-related adverse events in the solifenacin group was higher than that in the combination group, but there was no statistically significant difference (P > 0.05). In terms of secondary variables, the OAB-q HRQol score in the combination group was statistically superior in comparison with that in the solifenacin group between the second and fourth week (77.9 vs. 76.4, P = 0.020; and 87.9 vs. 85.6, P = 0.001). The OAB-q symptom bother score was higher in the solifenacin group than in the combination group (37.6 vs. 36.4, P = 0.016; and 26.2 vs. 24.8, P = 0.003). Combination therapy of solifenacin and mirabegron demonstrated significant improvements over solifenacin monotherapy in reducing OAB symptoms associated with double-J stents, and providing a higher quality of life without increasing bothersome adverse effects.

PMID:36344629 | DOI:10.1038/s41598-022-23795-5

Exp Clin Endocrinol Diabetes. 2022 Nov 7. doi: 10.1055/a-1932-3136. Online ahead of print.

ABSTRACT

OBJECTIVE: To assess safety, tolerability, pharmacokinetics, and pharmacodynamics of treatment with the selective 11beta-hydroxysteroid dehydrogenase-1 (11beta-HSD1) inhibitor BI 187004 in male and female patients with type 2 diabetes and overweight or obesity.

METHODS: Randomized, double-blind, parallel-group, placebo-controlled multiple rising dose study, with 10-360 mg BI 187004 once daily over 14 days in 71 patients. Assessments included 11beta-HSD1 inhibition in the liver and subcutaneous adipose tissue ex vivo (clinical trial registry number NCT01874483).

RESULTS: BI 187004 was well tolerated and safe in all tested dose groups. The incidence of drug-related adverse events was 51.8% (n=29) for BI 187004 and 35.7% (n=5) for placebo. There were no clinically relevant deviations in laboratory or electrocardiogram parameters besides one patient on 360 mg discontinuing treatment due to moderate supraventricular tachycardia.BI 187004 was rapidly absorbed within 2 h; exposure increased non-proportionally. The oral clearance was low, apparent volume of distribution was moderate to large, and terminal half-life with 106-124 h was rather long. Urinary tetrahydrocortisol/tetrahydrocortisone ratio decreased, indicating liver 11beta-HSD1 inhibition. Median inhibition of 11beta-HSD1 in subcutaneous adipose tissue biopsies was 87.9-99.4% immediately after the second dose and 73.8-97.5% 24 h after the last dose of BI 187004.

CONCLUSIONS: BI 187004 was safe and well tolerated over 14 days and could be dosed once daily. Targeted 11beta-HSD1 enzyme inhibition of≥80% could be shown for BI 187004 doses≥40 mg. This dose should be targeted in further studies to test blood glucose lowering in patients with type 2 diabetes and overweight or obesity.

PMID:36343645 | DOI:10.1055/a-1932-3136

Ann Intern Med. 2022 Nov 8. doi: 10.7326/M22-1438. Online ahead of print.

ABSTRACT

BACKGROUND: Parkinson disease (PD) is associated with α-synuclein (αS) aggregation within enteric neurons. ENT-01 inhibits the formation of αS aggregates and improved constipation in an open-label study in patients with PD.

OBJECTIVE: To evaluate the safety and efficacy of oral ENT-01 for constipation and neurologic symptoms in patients with PD and constipation.

DESIGN: Randomized, placebo-controlled phase 2b study. (ClinicalTrials.gov: NCT03781791).

SETTING: Outpatient.

PATIENTS: 150 patients with PD and constipation.

INTERVENTION: ENT-01 or placebo daily for up to 25 days. After baseline assessment of constipation severity, daily dosing was escalated to the prokinetic dose, the maximum dose (250 mg), or the tolerability limit, followed by a washout period.

MEASUREMENTS: The primary efficacy end point was the number of complete spontaneous bowel movements (CSBMs) per week. Neurologic end points included dementia (assessed using the Mini-Mental State Examination [MMSE]) and psychosis (assessed using the Scale for the Assessment of Positive Symptoms adapted for PD [SAPS-PD]).

RESULTS: The weekly CSBM rate increased from 0.7 to 3.2 in the ENT-01 group versus 0.7 to 1.2 in the placebo group (P < 0.001). Improvement in secondary end points included SBMs (P = 0.002), stool consistency (P < 0.001), ease of passage (P = 0.006), and laxative use (P = 0.041). In patients with dementia, MMSE scores improved by 3.4 points 6 weeks after treatment in the ENT-01 group (n = 14) versus 2.0 points in the placebo group (n = 14). Among patients with psychosis, SAPS-PD scores improved from 6.5 to 1.7 six weeks after treatment in the ENT-01 group (n = 5) and from 6.3 to 4.4 in the placebo group (n = 6). ENT-01 was well tolerated, with no deaths or drug-related serious adverse events. Adverse events were predominantly gastrointestinal, including nausea (34.4% [ENT-01] vs. 5.3% [placebo]; P < 0.001) and diarrhea (19.4% [ENT-01] vs. 5.3% [placebo]; P = 0.016).

LIMITATION: Longer treatment periods need to be investigated in future studies.

CONCLUSION: ENT-01 was safe and significantly improved constipation.

PRIMARY FUNDING SOURCE: Enterin, Inc.

PMID:36343348 | DOI:10.7326/M22-1438

Breathe (Sheff). 2022 Sep;18(3):220164. doi: 10.1183/20734735.0164-2022. Epub 2022 Oct 11.

ABSTRACT

Treatment of obstructive sleep apnoea in adults is evolving, from a "one treatment fits all" to a more individualised approach. The spectrum of treatment options is broad and heterogeneous, including conservative, technological and pharmaceutical modalities. This raises the questions of which patients these modalities might be useful for, and if there are specific criteria for single or combined treatment. The most commonly used non-CPAP treatment is a mandibular advancement device. Furthermore, it appears from the available evidence that upper airway surgery, bariatric surgery, and maxillomandibular advancement can be effective in particular patient groups and should be indicated more readily in clinical practice. Technically, a tracheotomy is the most effective surgical treatment, but is not socially acceptable and is associated with major side-effects. Other treatment options are emerging, like positional therapy, hypoglossal nerve stimulation, and myofunctional exercises. Drug therapy is also promising when pathophysiological traits are considered. The range of currently available treatment options will be discussed in this review, with emphasis on the selection of appropriate patients, therapeutic efficacy and compliance, and reference to recent guidelines. In the selection process, routine application of drug-induced sleep endoscopy to assess the site(s) of collapse during sleep can increase the success rate of both surgical interventions and oral appliance therapy.

EDUCATIONAL AIMS: To outline recommendations concerning the proper management of obstructive sleep apnoea (OSA) patients that cannot be treated adequately with continuous positive airway pressure (CPAP) due to intolerance, poor adherence or compliance, or CPAP refusal.To provide information about the selection of appropriate patients for alternative non-CPAP treatment options.To better understand the different aspects of OSA treatment with noninvasive approaches, such as oral appliances, positional therapy, drug treatment and myofunctional therapy, including indications, contraindications, and expected short- and long-term results.To discuss the different surgical options for the treatment of OSA and to provide information on the important issue of proper patient selection for surgery, as most OSA surgical outcomes are associated with the pre-operative assessment of the level(s) of upper airway collapse.

PMID:36340820 | PMC:PMC9584565 | DOI:10.1183/20734735.0164-2022

Drugs Context. 2022 Oct 21;11:2022-6-3. doi: 10.7573/dic.2022-6-3. eCollection 2022.

ABSTRACT

The differential diagnosis of non-coeliac enteropathies (NCEs) is challenging and includes a wide range of aetiologies. Drug-induced NCEs are relatively common and characterized by duodenal villous atrophy, which resolves upon suspension of the offending drug. Immune-checkpoint inhibitors (ICIs), targeting molecules involved in the activation of cytotoxic T cells by targeting, for example, PD-1, PD-L1 and CTLA4, are increasingly used for many types of cancers. Adverse events occurring in the gastrointestinal tract have been described, predominantly in the form of immune-mediated colitis mimicking inflammatory bowel disease. Small bowel involvement whilst on ICI therapy is also possible, though less well described. Herein, we describe two cases of enteropathy with villous atrophy and negative coeliac serology due to ICIs: a 65-year-old man affected by stage IV pulmonary adenocarcinoma under treatment with pembrolizumab and an 18-year-old woman affected by stage IV auricular melanoma who was treated with nivolumab. We also provide a review of the current literature describing small bowel involvement during therapy with ICIs, alone or in combination, for different types of solid tumours. Implications for clinical practice include considering the possibility of small bowel involvement in oncological patients treated with ICIs and the inclusion of ICIs amongst the iatrogenic causes of NCE with villous atrophy. Enteropathies due to ICIs may also represent a pathogenetic model for the understanding of the molecular mechanisms leading to villous atrophy in NCE.

PMID:36339292 | PMC:PMC9616105 | DOI:10.7573/dic.2022-6-3

Cureus. 2022 Oct 3;14(10):e29857. doi: 10.7759/cureus.29857. eCollection 2022 Oct.

ABSTRACT

Bupropion is one of the most commonly prescribed antidepressant medications by physicians all over the world. Because of its favorable sexual profile, it is used as an alternative to serotonin reuptake inhibitors (SSRIs). Its significance in smoking cessation is also well recognized. However, it is associated with a few side effects, such as dizziness, anxiety, tremors, nausea, and insomnia. We present the case of a 54-year-old chronic smoker who developed acute facial dystonia involving the temporomandibular joint (TMJ) after being prescribed 300 mg of bupropion. The Naranjo scale was used to assess the probability of bupropion-induced dystonia. Following the diagnosis, the drug was stopped, and the dystonia completely resolved within one week. At her follow-ups, the patient was found to have no recurrence of dystonia.

PMID:36337825 | PMC:PMC9627898 | DOI:10.7759/cureus.29857

Cureus. 2022 Oct 1;14(10):e29809. doi: 10.7759/cureus.29809. eCollection 2022 Oct.

ABSTRACT

Beta-blockers are well-known for their wide range of therapeutic applications, particularly in patients with cardiac diseases. Physicians worldwide are aware of their potential side effects, including hypoglycemia, dizziness, slow heart rate, fatigue, and heart block. We report a case of erythrodermic psoriasis caused by beta-blockers in a 61-year-old woman with no prior history of the skin condition. The diagnosis was made based on the characteristic histopathological picture and a Naranjo score of 6. She was administered 15 mg of methotrexate weekly and received supportive care. She recovered completely within two months and exhibited no recurrence of symptoms.

PMID:36337823 | PMC:PMC9621099 | DOI:10.7759/cureus.29809

Crit Care Nurs Clin North Am. 2022 Dec;34(4):361-371. doi: 10.1016/j.cnc.2022.08.005.

ABSTRACT

Medications are a common cause of injury to the kidney and can contribute to the increased progression of disease, poorer outcomes, and increased health care costs. Improved prescribing practices can decrease the risk for the development of acute kidney injury and the progression to end-stage kidney disease. KDIGO Clinical Practice Guidelines recommend the use of caution when prescribing potentially nephrotoxic medications for patients with kidney disease. More than 50-72% of individuals across all stages of kidney disease utilized potentially nephrotoxic medications contributing to poorer outcomes. Annually, 1.5 million adverse drug events causing medication-induced nephrotoxicity occur in the US. Medication-induced nephrotoxicity accounts for 14-26% of cases of AKI in adults and 16% of hospitalized children. It is imperative that nurses and all health care providers are practicing nephrotoxic stewardship to prevent medication-induced nephrotoxicity.

PMID:36336427 | DOI:10.1016/j.cnc.2022.08.005

BMC Cancer. 2022 Nov 5;22(1):1136. doi: 10.1186/s12885-022-10199-x.

ABSTRACT

BACKGROUND: Immune checkpoint inhibitors (ICIs) has shown remarkable benefit in the treatment of a range of cancer types, although it may initiate immune related adverse events (irAEs) in patients. Some studies have shown that there is a close relationship between the occurrence of irAEs and prognosis. In present study, we have attempted to establish whether the occurrence of irAEs after the use of anti PD-1 antibodies is associated with treatment efficacy in people with advanced gastric cancer (AGC).

METHODS: This study included patients treated with the anti-PD-1 antibodies for AGC patients at The Fourth Hospital of Hebei Medical University. IrAEs were identified clinically and graded as per the National Cancer Institute Common Terminology Criteria for Adverse Events ver. 4.03. Efficacy was evaluated with objective response rate (ORR), disease control rate (DCR), progression free survival (PFS) and overall survival (OS). The analysis was performed to determine the association between irAEs and clinical outcomes.

RESULT: Of the 74 AGC patients in our study, 24 developed irAEs. The DCR of the irAE displayed a trend better than that of non-irAE group but without statistical difference (41.70% VS 6.0%, p = 0.118). Median PFS in the irAE group was superior to that in the non-irAE group (176 days VS 94 days, p = 0.001). Median OS also showed this trend of difference at borderline statistical level (292 days VS 239 days, p = 0.057). Multivariate analysis also demonstrated irAE (HR = 0.269, 95%CI: 0.088 to 0.822, p = 0.021) were associated independently with the better prognosis for AGC patients.

CONCLUSION: In advanced gastric cancer treated with anti PD-1 antibodies, the occourence of irAEs might contribute to the improved prognosis.

PMID:36335320 | PMC:PMC9636611 | DOI:10.1186/s12885-022-10199-x

Ann Clin Psychiatry. 2022 Nov;34(4):217-219. doi: 10.12788/acp.0084.

NO ABSTRACT

PMID:36331562 | DOI:10.12788/acp.0084

Drug Ther Bull. 2022 Sep 6:dtb-2022-000049. doi: 10.1136/dtb.2022.000049. Online ahead of print.

ABSTRACT

Overview of: Tita AT, Szychowski JM, Boggess K, et al Treatment for mild chronic hypertension during pregnancy. N Engl J Med 2022;386:1781-92.

PMID:36332943 | DOI:10.1136/dtb.2022.000049

J Infect Dev Ctries. 2022 Oct 31;16(10):1660-1663. doi: 10.3855/jidc.16594.

ABSTRACT

INTRODUCTION: Drug-induced liver injury (DILI) is one of the most common causes of liver damage. A large number of drugs, dietary supplements, and herbal medications can cause hepatotoxicity. In some situations, it is difficult to distinguish between DILI and autoimmune hepatitis, especially when the mechanism is immune-mediated. Albendazole is a drug that has been used for decades for the treatment of parasitic infections in humans. One of the side effects is liver enzyme elevation, but rarely requires the discontinuation of therapy. Previous experience has shown that hypersensitivity is the most common mechanism of albendazole hepatotoxicity.

CASE REPORT: Here we presented a paediatric patient in whom albendazole induced severe liver injury. In laboratory analyses, in addition to markedly elevated transaminases and parameters of cholestasis, there was also a significant increase in IgG, so autoimmune hepatitis was considered. Even though the liver histology indicated toxic liver disease, prednisolone was started. Corticosteroid therapy resulted in the complete normalization of liver function, as well as IgG. With the cessation of corticosteroid therapy, transaminases, bilirubin and gamma-glutamyl transferase (GGT) remained within normal levels, but an increase in anti-smooth muscle antibodies (SMA) was noted in immunological analyses after one year of follow-up.

CONCLUSIONS: Immune-mediated hepatotoxicity from albendazole is one possible mechanism of liver injury. The use of albendazole in the treatment of parasitic infections, especially in children, requires close monitoring. The question remains as to whether albendazole is a drug that can induce autoimmune hepatitis in the paediatric population.

PMID:36332223 | DOI:10.3855/jidc.16594

Ann Med. 2022 Dec;54(1):3085-3095. doi: 10.1080/07853890.2022.2139411.

ABSTRACT

OBJECTIVES: Extensive application of anti-HER2 targeted therapy improves significantly the HER2-positive advanced breast cancer (BC) prognosis, however, it is still difficult to treat brain metastasis. In current study, we explored effective approaches via combining pyrotinib to treat brain metastasis in patients with HER2-positive advanced BC based upon clinical data.

MATERIALS AND METHODS: Current study included 61 HER2-positive BC patients with brain metastases (BM) who were treated by pyrotinib-based regimens. The systemic regimens included pyrotinib combined with capecitabine, pyrotinib combined with nab-paclitaxel, and pyrotinib combined with vinorelbine. Patients' progression-free survival (PFS), overall survival (OS), clinical benefit rate (CBR) and objective response rate (ORR), as well as drug-related adverse events (AEs) in regard of each combination regimen were analyzed.

RESULTS: Pyrotinib-based systemic therapy resulted in 8.6 months median PFS (mPFS) and 18.0 months median OS (mOS) among the BM patients. Regarding different regimens, the combination of pyrotinib with nab-paclitaxel was superior to the combination with capecitabine and vinorelbine with respect to PFS and OS. The central nervous system (CNS) ORR did not showcase significant difference among 3 regimens, however, nab-paclitaxel combined regimen obtained the best peripheral ORR (84.6%) (p ≤ .05).

CONCLUSIONS: Pyrotinib-based combination therapy is safe for HER2-positive brain metastasis treatment. Compared with vinorelbine or capecitabine, pyrotinib combined with nab-paclitaxel is more effective with less toxicity, which is the preferable regimen for HER2-positive brain metastasis.KEY MESSAGESPresent investigation investigated effective methods through combining pyrotinib to treat brain metastasis with HER2-positive advanced brain cancer. The outcomes verified that pyrotinib-based combination therapy was safe and efficient to treat HER2-positive brain metastasis. Therefore, it is effective to treat brain metastasis applying anti-HER2 targeted therapies although pyrotinib showcases efficiency regarding its treatments for the metastasis.

PMID:36331291 | DOI:10.1080/07853890.2022.2139411

Rev Esp Salud Publica. 2022 Nov 3;96:e202211085.

ABSTRACT

OBJECTIVE: Energy drinks generally contain caffeine and other stimulants, commercially aimed at young people. Previous research suggests that its effects on adolescents health are dangerous. The aim of the study was to evaluate the effect of taurine and caffeine consumption from energy drinks on adolescent health and to identify patterns of consumption and, their association with physiological symptoms.

METHODS: A cross-sectional study of a convenience sample of students (n=135) aged 16 to 17 years was conducted in the State of Hidalgo, Mexico. A self-administered online questionnaire was used from September to November 2020 to report energy drink consumption patterns, perceived effects, and psychophysiological symptoms. The statistical analysis of questionnaire content was made by interjudges evaluation. A concordance index (Cohen-Fleiss Kappa coefficient) was applied for consumption patterns, bivariate correlation tests, Pearson correlation coefficients for levels (very high, moderate, low) of caffeine and taurine were used in the items applied to the target population and Spearmans rho for physiological and psychological effects.

RESULTS: The participants (mean age: 16 years; 57.8% of women) reported having consumed energy drinks at least once. Only 26.7% of adolescents (n=36) reported that they had never consumed. The average consumption of energy drinks was once per month (24.4%). A statistically significant correlation was found between the consumption of drinks with taurine and the physical effects (tremors and chest pain) and caffeinated beverages with psychophysiological (fatigue, excessive urination, insomnia, and feeling of lack of rest).

CONCLUSIONS: The study findings indicate associations between energy drink consumption and the presence of adverse psychological and physical symptoms in adolescents.

PMID:36325955

Oral Oncol. 2022 Oct 31;135:106231. doi: 10.1016/j.oraloncology.2022.106231. Online ahead of print.

ABSTRACT

OBJECTIVES: Molecular targeted therapies against vascular endothelial growth factor (VEGF) receptor (VEGFR) have been explored in the treatment of recurrent or metastatic nasopharyngeal carcinoma (rmNPC). We conducted a meta-analysis to evaluate the efficacy and safety of VEGF/VEGFR inhibitors for treating rmNPC.

MATERIALS AND METHODS: Electronic databases were searched for eligible literature. Data on the objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), PFS rate, OS rate, and drug-related adverse events (AEs) were extracted.

RESULTS: A total of 10 studies (published in 9 articles) that involved 357 patients were included. The pooled ORR was 37 % (95 % confidence interval [CI]: 17-60 %), the DCR was 70 % (95 % CI: 51-85 %), the mPFS was 5.69 months (95 % CI: 4.52-6.86), the mOS was 12.61 months (95 % CI: 10.23-14.99), the 1-year PFS rate was 34 % (95 % CI: 25-44 %), and the 1-year OS rate was 62 % (95 % CI: 38-83 %). The pooled incidence of grade 3/4 drug-related AEs was 27 %, while that of grade 5 AEs was 0.22 %. Further subgroup analysis showed that the pooled ORR and DCR for first-line VEGF inhibitors were 80 % (95 % CI: 74-86 %) and 94 % (CI: 82-100 %), respectively.

CONCLUSION: Our meta-analysis is the first report to demonstrate the efficacy and safety of VEGF/VEGFR inhibitors in patients with rmNPC. Targeting VEGF/VEGFR therapy added to first-line chemotherapy achieved an excellent ORR and DCR, while the improvement in response rates did not translate to a prominent OS benefit.

PMID:36327674 | DOI:10.1016/j.oraloncology.2022.106231

Front Pediatr. 2022 Oct 12;10:982179. doi: 10.3389/fped.2022.982179. eCollection 2022.

ABSTRACT

OBJECTIVES: To assess and summarize current evidence on the effectiveness and safety of ertapenem for treatment of childhood infections, in consideration of high infection prevalence in children and wide use of ertapenem.

METHODS: The following 8 databases were searched on 13th May 2021: Web of Science, Embase via Ovid SP, PubMed, The Cochrane Library (CENTRAL), Chinese BioMedical Literature Database (CBM), China National Knowledge Infrastructure (CNKI), VIP and Wanfang. The primary outcome was treatment success rate. Risk ratios (RRs) and 95% confidence interval (CI) were estimated using random-effect models. Subgroup analysis was conducted where heterogeneity was found.

RESULTS: Fifteen studies (8 randomized controlled trials, 1 observational comparative study, and 6 before and after studies) involving 2,528 patients were included in the final review. Ertapenem had similar treatment success rates with β-lactam antibiotics [relative risk (RR) = 1.08, 95% CI: 0.99-1.19]. In a subgroup analysis, similar efficacy (RR = 1.08, 95% CI: 0.97-1.20) between ertapenem and other carbapenems. Compared with β-lactam antibiotics, ertapenem did not increase the risk of any adverse events (RR = 1.02, 95%CI: 0.71-1.48), drug-related diarrhea (all non-Asian children, RR = 0.62, 95%CI: 0.31-1.25), or injection site pain (all non-Asian children, RR = 1.66, 95%CI: 0.59-4.68). Subgroup analysis showed no obvious difference between ertapenem group and carbapenems or non-carbapenems group on risk of adverse events.

CONCLUSION: Our findings suggest that ertapenem is effective and safe in treatment for children with infection. Further comparative real-world data is needed to supplement clinical evidence on the overall benefits of ertapenem in this population.

PMID:36324821 | PMC:PMC9620802 | DOI:10.3389/fped.2022.982179