Pediatr Rev. 2023 Feb 1;44(2):68-80. doi: 10.1542/pir.2022-005641.

ABSTRACT

Food-drug interactions should be suspected when a patient is taking their medications as directed and doses are optimized yet therapy is still not optimal (increased adverse effects, decreased efficacy, new adverse effects, etc). In all individuals with suspected food-drug interactions, diet history, baseline laboratory values, drug concentrations, and prescription history are recommended to assess the patient for a possible food-drug interaction. The 3 types of food-drug interactions are pharmaceutical, pharmacokinetic, and pharmacodynamic. Pharmaceutical interactions occur with delivery devices or enteral feeding products. Pharmacokinetic interactions include the processes of a drug's release, absorption, distribution, metabolism, and/or elimination, ultimately affecting the effectiveness and safety of therapy. Pharmacodynamic interactions occur when food alters a drug's clinical effect on the body. The most common food-drug interactions exist with fruits (especially grapefruit), dairy, vitamin K, tyramine-containing foods, and alcohol. Patient counseling and collaboration between health-care teams can help patients avoid food-drug interactions. As a result, medication therapy can be optimized and adverse effects can be avoided.

PMID:36720679 | DOI:10.1542/pir.2022-005641

Antioxid Redox Signal. 2023 Jan 31. doi: 10.1089/ars.2023.0006. Online ahead of print.

ABSTRACT

SIGNIFICANCE: Cardiovascular disease and drug-induced health side effects are frequently associated with - or even caused by - an imbalance between the concentrations of reactive oxygen and nitrogen species (RONS) and antioxidants respectively determining the metabolism of these harmful oxidants.

RECENT ADVANCES: According to the "kindling radical" hypothesis, initial formation of RONS may further trigger the additional activation of RONS formation under certain pathological conditions. The present review will specifically focus on a dysfunctional, uncoupled endothelial nitric oxide synthase (eNOS) caused by RONS in the setting of transportation noise exposure or chronic treatment with organic nitrates, especially nitroglycerin. We will further describe the various "redox switches" that are proposed to be involved in the uncoupling process of eNOS.

CRITICAL ISSUES: In particular, the oxidative depletion of tetrahydrobiopterin (BH4), and S-glutathionylation of the eNOS reductase domain will be highlighted as major pathways for eNOS uncoupling upon noise exposure or nitroglycerin treatment. In addition, oxidative disruption of the eNOS dimer, inhibitory phosphorylation of eNOS at threonine or tyrosine residues, redox-triggered accumulation of asymmetric dimethylarginine (ADMA) and L-arginine deficiency will be discussed as alternative mechanisms of eNOS uncoupling.

FUTURE DIRECTIONS: The clinical consequences of eNOS dysfunction due to uncoupling on cardiovascular disease will be summarized also providing a template for future clinical studies on endothelial dysfunction caused by pharmacological or environmental risk factors.

PMID:36719770 | DOI:10.1089/ars.2023.0006

Clin J Am Soc Nephrol. 2023 Jan 1;18(1):36-46. doi: 10.2215/CJN.0000000000000022.

ABSTRACT

BACKGROUND: Tolvaptan slows expansion of kidney volume and kidney function decline in adults with autosomal dominant polycystic kidney disease (ADPKD). Progression during childhood could be treated before irreversible kidney damage occurs, but trial data are lacking. We evaluated the safety and efficacy of tolvaptan in children/adolescents with ADPKD.

METHODS: This was the 1-year, randomized, double-blind, portion of a phase 3b, two-part trial being conducted at 20 academic pediatric nephrology centers. Key eligibility criteria were ADPKD and eGFR ≥60 ml/min per 1.73 m2. Participants aged 12-17 years were the target group (group 1, enrollment goal n≥60); participants aged 4-11 years could additionally enroll (group 2, anticipated enrollment approximately 40). Treatments were tolvaptan or placebo titrated by body weight and tolerability. Coprimary end points, change from baseline in spot urine osmolality and specific gravity at week 1, assessed inhibition of antidiuretic hormone activity. The key secondary end point was change in height-adjusted total kidney volume (htTKV) to month 12 in group 1. Additional end points were safety/tolerability and quality of life. Statistical comparisons were exploratory and post hoc.

RESULTS: Among the 91 randomized (group 1, n=66; group 2, n=25), least squares (LS) mean reduction (±SEM) in spot urine osmolality at week 1 was greater with tolvaptan (-390 [28] mOsm/kg) than placebo (-90 [29] mOsm/kg; P<0.001), as was LS mean reduction in specific gravity (-0.009 [0.001] versus -0.002 [0.001]; P<0.001). In group 1, the 12-month htTKV increase was 2.6% with tolvaptan and 5.8% with placebo (P>0.05). For tolvaptan and placebo, respectively, 65% and 16% of subjects experienced aquaretic adverse events, and 2% and 0% experienced hypernatremia. There were no elevated transaminases or drug-induced liver injuries. Four participants discontinued tolvaptan, and three discontinued placebo. Quality-of-life assessments remained stable.

CONCLUSIONS: Tolvaptan exhibited pharmacodynamic activity in pediatric ADPKD. Aquaretic effects were manageable, with few discontinuations.

CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Safety, Pharmacokinetics, Tolerability and Efficacy of Tolvaptan in Children and Adolescents With ADPKD (Autosomal Dominant Polycystic Kidney Disease) NCT02964273.

PMID:36719158 | DOI:10.2215/CJN.0000000000000022

Int J Clin Pract. 2023 Jan 14;2023:3336736. doi: 10.1155/2023/3336736. eCollection 2023.

ABSTRACT

BACKGROUND: Pharmaceutical care services offered by pharmacists rationalize drug therapy, improve patient quality of life, and save patients' lives. This study was designed to optimize patient drug therapy through pharmaceutical care services offered by a pharmacist in consultation with other health care providers (HCPs) at a tertiary care hospital.

METHODS: This descriptive study was conducted to assess the role and effectiveness of pharmacists in optimizing drug therapy outcomes. The study was carried out at an internal and pulmonary medicine unit of a tertiary care hospital in Srinagar, Jammu and Kashmir, India, with a total of 50 health care providers (HCPs) (24 doctors, 16 nurses, and 10 pharmacists). A total of 182 patients (males and females) of all age groups were recruited into the study over a period of nine months. Patient-specific pharmaceutical care plans initiated by the pharmacist based on drug therapy-related needs and problems were used to address and optimize drug therapy outcomes in consultation with other HCPs.

RESULTS: A total of 388 drug-related problems (DRPs) with an average of 2.29 DRPs per patient were identified, for which 258 pharmaceutical care plans as interventions were proposed, out of which 233 (90.31%) were accepted and implemented. Preassessment and postassessment by HCPs on services rendered by the pharmacist showed a positive change in attitude among HCPs with respect to their endorsement and acceptance of the pharmacist's services in providing direct patient care.

CONCLUSIONS: Pharmaceutical care services offered by pharmacists helped in optimizing drug therapy and patient care.

PMID:36713950 | PMC:PMC9867584 | DOI:10.1155/2023/3336736

Drug Ther Bull. 2023 Jan 30:dtb-2023-000003. doi: 10.1136/dtb.2023.000003. Online ahead of print.

ABSTRACT

Overview of: Baunwall SMD, Andreasen SE, Hansen MM, et al Faecal microbiota transplantation for first or second Clostridioides difficile infection (EarlyFMT): a randomised, double-blind, placebo-controlled trial. Lancet Gastroenterol Hepatol 2022;7:1083-91.

PMID:36717202 | DOI:10.1136/dtb.2023.000003

Z Orthop Unfall. 2023 Jan 30. doi: 10.1055/a-1994-7500. Online ahead of print.

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) is one of the major and potentially life-threatening complications following major orthopedic surgeries. Research evidence comparing the effectiveness of rivaroxaban and enoxaparin for thromboprophylaxis specific to total hip arthroplasty (THA) has been limited. Hence, this review was done to compare the efficacy and safety of rivaroxaban against enoxaparin for thromboprophylaxis after THA.

MATERIALS AND METHODS: We conducted a search in databases including Medline, EMBASE, ScienceDirect, Google Scholar, and Cochrane Library from inception until May 2021. Randomized controlled trials directly comparing the effectiveness of rivaroxaban and enoxaparin for thromboprophylaxis among patients undergoing THA were eligible for inclusion. Outcome parameters assessed were efficacy in terms of total VTE and all-cause mortality, major VTE, deep vein thrombosis, symptomatic VTE, and safety in terms of major bleeding events, clinically relevant nonmajor bleeding events, minor bleeding events, total bleeding events, drug-related adverse events, and wound infection. We performed a meta-analysis with a random effects model and reported a pooled risk ratio (RR) with a 95% confidence interval (CI).

RESULTS: Eleven studies, including 9057 participants, were analyzed. Amongst efficacy outcomes, VTE and all-cause mortality pooled an RR of 0.58 (95% CI: 0.34-0.99), major VTE pooled an RR of 0.37 (95% CI: 0.15-0.90), deep vein thrombosis pooled an RR of 0.57 (95% CI: 0.32-1.02), and symptomatic VTE pooled an RR of 0.51 (95% CI: 0.30-0.87). Amongst safety outcomes, major bleeding events pooled an RR of 1.18 (95% CI: 0.77-1.80), total bleeding events pooled an RR of 1.12 (95% CI: 0.93-1.34), drug-related adverse event pooled an RR of 0.99 (95% CI: 0.87-1.12), and wound infection pooled an RR of 1.11 (95% CI: 0.58-2.14).

CONCLUSION: Rivaroxaban is a more efficacious drug in terms of VTE and all-cause mortality compared to enoxaparin following THA, and rivaroxaban was non-inferior in terms of safety profiles such as wound infection, bleeding, and drug-related adverse events.

PMID:36716770 | DOI:10.1055/a-1994-7500

Livers. 2023 Mar;3(1):33-53. doi: 10.3390/livers3010003. Epub 2023 Jan 12.

ABSTRACT

The epidemic of obesity, type 2 diabetes and nonalcoholic liver disease (NAFLD) favors drug consumption, which augments the risk of adverse events including liver injury. For more than 30 years, a series of experimental and clinical investigations reported or suggested that the common pain reliever acetaminophen (APAP) could be more hepatotoxic in obesity and related metabolic diseases, at least after an overdose. Nonetheless, several investigations did not reproduce these data. This discrepancy might come from the extent of obesity and steatosis, accumulation of specific lipid species, mitochondrial dysfunction and diabetes-related parameters such as ketonemia and hyperglycemia. Among these factors, some of them seem pivotal for the induction of cytochrome P450 2E1 (CYP2E1), which favors the conversion of APAP to the toxic metabolite N-acetyl-p-benzoquinone imine (NAPQI). In contrast, other factors might explain why obesity and NAFLD are not always associated with more frequent or more severe APAP-induced acute hepatotoxicity, such as increased volume of distribution in the body, higher hepatic glucuronidation and reduced CYP3A4 activity. Accordingly, the occurrence and outcome of APAP-induced liver injury in an obese individual with NAFLD would depend on a delicate balance between metabolic factors that augment the generation of NAPQI and others that can mitigate hepatotoxicity.

PMID:36713231 | PMC:PMC9879315 | DOI:10.3390/livers3010003

bioRxiv. 2023 Jan 4:2023.01.04.522664. doi: 10.1101/2023.01.04.522664. Preprint.

ABSTRACT

An increasing number of preclinical and clinical studies are exploring the use of receptor-engineered cells that can respond to disease states for the treatment of cancer, infectious disease, autoimmunity, and regeneration. However, receptor-based cell therapies, including chimeric antigen receptor (CAR), face many critical issues including target recognition escape, adverse side effects, and lack of in vivo control. Drug-controllable receptors offer a promising solution to overcome these issues through precise in vivo tuning of cells via enhanced sensing and therapeutic efficacy. Here we develop a novel class of modular and tunable receptors, termed valency-controlled receptors (VCRs), which can leverage customized small molecules to mediate cell signaling strength via controlled spatial clustering. We first develop DNA origami activated VCRs to demonstrate that receptor valency is a core mechanism that modulates immune cell activation. We design a series of customized valency-control ligands (VCLs) by transforming small molecule drugs into a multivalency format and modularly fusing VCR onto the CAR architecture. We demonstrate that VCL induction allows enhanced target sensitivity of engineered cells. Using medicinal chemistry, we develop programmable bioavailable VCL drugs to demonstrate that the VCR system enables drug-induced highly potent responses towards low antigen cancers in vitro and in vivo . Valency controlled receptors and customizable drug ligands provide a new synthetic biology platform to precisely tune engineered cell therapeutic potency, which can address existing safety and efficacy barriers in cell therapy.

PMID:36712002 | PMC:PMC9881924 | DOI:10.1101/2023.01.04.522664

Eur J Gastroenterol Hepatol. 2023 Mar 1;35(3):261-269. doi: 10.1097/MEG.0000000000002506. Epub 2022 Dec 22.

ABSTRACT

BACKGROUND: Real-world data showed that ustekinumab is an effective treatment for Crohn's disease for up to 52 weeks. Yet, long-term effectiveness and safety outcomes beyond 52 weeks are limited. This study aimed to evaluate the corticosteroid-free clinical remission for up to 104 weeks. Secondary aims were focused on biochemical disease, dosing adjustments and safety outcomes.

METHODS: This multicentre prospective cohort study enrolled Crohn's disease patients who started ustekinumab between May 2016 and September 2019. Participants had scheduled outpatient visits at week 0, 13, 26, 52 and 104. Data on clinical disease [Harvey Bradshaw Index (HBI) = 4 points = remission], biochemical disease (faecal calprotectin = 200 µg/g or C-reactive protein = 10 mg/l = remission), dose adjustments and adverse drug reactions (ADRs) were recorded.

RESULTS: We included 101 Crohn's disease patients. In all patients, the proportion of patients in corticosteroid-free clinical remission was 35 and 36% at week 52 and 104. Of patients achieving corticosteroid-free remission at week 52, more than half maintained corticosteroid-free remission throughout week 104. Biochemical remission rates were 25 and 30% at week 52 and 104, respectively. In the first year of treatment, 33% required their first dose escalation, and 15% in the second year. Overall, 7% of patients discontinued ustekinumab due to ADRs. Ustekinumab persistency rates were 68% at week 52 and 59% at week 104.

CONCLUSION: Ustekinumab is an effective and well-tolerated treatment for Crohn's disease. More than half of all patients continued ustekinumab treatment after 104 weeks whereas one-third achieved corticosteroid-free remission.

PMID:36708296 | DOI:10.1097/MEG.0000000000002506

Alzheimers Res Ther. 2023 Jan 28;15(1):24. doi: 10.1186/s13195-023-01163-3.

ABSTRACT

BACKGROUND: This phase II proof-of-concept study assessed the efficacy and safety of BI 425809, a novel selective glycine transporter-1 inhibitor, for the treatment of cognitive impairment associated with probable Alzheimer's disease dementia.

METHODS: This 12-week, multicenter, double-blind, placebo-controlled, parallel-group study randomized (1:1:1:1:1) patients with mild-to-moderate probable Alzheimer's disease dementia to BI 425809 2, 5, 10, and 25 mg or placebo once daily. The primary efficacy endpoint was the change from baseline in Alzheimer's Disease Assessment Scale-Cognitive Subscale 11-item total score after 12 weeks of treatment. Safety was also assessed.

RESULTS: Six hundred and ten male and female patients were randomized to BI 425809 2 mg (n = 123), 5 mg (n = 122), 10 mg (n = 122), and 25 mg (n = 123) or placebo (n = 120). Approximately 47% (n = 286) were male; the mean (standard deviation) age was 72.9 (7.7) years. Treatment compliance was above 97% for all dose groups. The Mini-Mental State Examination category on the median score was < 22 in 47% (n = 287) of patients and ≥ 22 in 53% (n = 322) of patients. No significant, non-flat dose-response relationship was detected for the primary endpoint (adjusted p-value > 0.76 for all models). BI 425809 was generally well-tolerated. Overall, 47.9% (n = 292) of patients reported at least one adverse event during the trial; the frequency of patients with investigator-defined drug-related adverse events was similar in all treatment groups, ranging from 15.4 to 19.5% across the BI 425809 treatment groups and 15.8% for placebo.

CONCLUSIONS: No clinically meaningful changes from baseline were observed following treatment with BI 425809 in patients with mild-to-moderate probable Alzheimer's disease dementia.

TRIAL REGISTRATION: ClinicalTrials.gov NCT02788513 (1346-0023). Registered on June 2, 2016. EU Clinical Trials Register 2015-005438-24. Registered on May 6, 2016.

PMID:36709275 | DOI:10.1186/s13195-023-01163-3

BMC Cancer. 2023 Jan 27;23(1):94. doi: 10.1186/s12885-022-10489-4.

ABSTRACT

BACKGROUND: PRECONNECT was an international, phase IIIb trial evaluating the safety and efficacy of trifluridine/tipiracil (FTD/TPI) for metastatic colorectal cancer (mCRC).

METHODS: Patients with mCRC received FTD/TPI 35 mg/m2 twice-daily on days 1-5 and 8-12 of each 28-day cycle for third- or later-line treatment.

PRIMARY ENDPOINT: safety and time to deterioration of Eastern Cooperative Oncology Group performance status [ECOG PS] to ≥2). Secondary endpoints included progression-free survival (PFS). Potential prognostic factors for PFS were explored.

RESULTS: Of 914 patients, 69% completed 0-3, 24% completed 4-7, and 7% completed ≥8 cycles of FTD/TPI. Drug-related grade ≥ 3 adverse events included neutropenia (38.1%), anaemia (7.2%) and asthenia (3.4%). Median [95% CI] time to ECOG PS deterioration was 8.7 [8.1-not calculable] months and increased with duration of treatment (DoT). Median PFS was 2.8 [2.7-3.0] months and increased with duration of treatment DoT. Prognostic factors associated with longer PFS included time since diagnosis of first metastasis, number of metastatic sites, baseline ECOG PS, presence/absence of liver metastasis or previous regorafenib treatment, and laboratory variables.

CONCLUSIONS: No new safety concerns for FTD/TPI were identified and PFS increased with DoT. These data provide confidence for the use of FTD/TPI, including the use of multiple cycles, in routine practice.

TRIAL REGISTRATION: EudraCT Number: 2016-002311-18; registered 19/09/2016. https://clinicaltrials.gov/ct2/show/NCT03306394 ; registered 11/10/2017.

PMID:36707808 | DOI:10.1186/s12885-022-10489-4

Cancer Chemother Pharmacol. 2023 Feb;91(2):103-119. doi: 10.1007/s00280-023-04504-z. Epub 2023 Jan 27.

ABSTRACT

Natural products, also referred to as dietary supplements, complementary and alternative medicines, and health or food supplements are widely used by people living with cancer. These products are predominantly self-selected and taken concurrently with cancer treatments with the intention of improving quality of life, immune function and reducing cancer symptoms and treatment side effects. Concerns have been raised that concurrent use may lead to interactions resulting in adverse effects and unintended treatment outcomes. This review provides an overview of the mechanisms by which these interactions can occur and the current evidence about specific clinically important natural product-drug interactions. Clinical studies investigating pharmacokinetic interactions provide evidence that negative treatment outcomes may occur when Hypericum perforatum, Grapefruit, Schisandra sphenanthera, Curcuma longa or Hydrastis canadensis are taken concurrently with common cancer treatments. Conversely, pharmacodynamic interactions between Hangeshashinto (TJ-14) and some cancer treatments have been shown to reduce the side effects of diarrhoea and oral mucositis. In summary, research in this area is limited and requires further investigation.

PMID:36707434 | PMC:PMC9905199 | DOI:10.1007/s00280-023-04504-z

Mycoses. 2023 Jan 27. doi: 10.1111/myc.13571. Online ahead of print.

ABSTRACT

BACKGROUNDS: Onychomycosis was an ignored condition in children, and the prevalence was still unknown worldwide.

OBJECTIVES: This study was conducted to investigate the prevalence and treatment regimens of onychomycosis in children younger than 18 years old.

METHODS: We systemically reviewed all publications by searching the key terms to reveal the onychomycosis in children from 1990 to 2022.

RESULTS: A total of 44 articles including 2,382 children with onychomycosis were enrolled in this study. The male to female ratio was 1.29:1. The youngest child was 35 days old and the average age was 9.8 years old. The duration of disease usually ranged from 7 days to 4 years. Onychomycosis in children was more prevalent in toenails compared to fingernails (77.6% vs. 18.4%), and 4% patients had both. A total of 527 children (22.12%) had concomitant tinea pedis infection, and in 267 patients (11.21%), their family members had onychomycosis or tinea pedis. The most common clinical type of onychomycosis was DLSO (67.74%) and the predominant isolates were T. rubrum (66.13%), followed by C. albicans (9.08%) and T mentagrophytes complex (5.34%). There were 419 children (74.03%) receiving systematic treatment only, 74 patients (13.07%) receiving topical treatment only, and 73 patients (12.90%) receiving both systematic and topical treatment. Twelve patients (2.12%) had mild drug-related side effects. During the follow-up, 71.25% children were cured, 17.50% symptoms improved, and 4.17% failed treatment.

CONCLUSION: Onychomycosis was no longer a rare finding in children, for children with nail disorders, the diagnosis of onychomycosis should be considered. For mild patients, topical treatment can be a good choice, while for severe patients, oral antifungal drugs should be added under monitoring.

PMID:36707404 | DOI:10.1111/myc.13571

Front Pharmacol. 2023 Jan 10;13:1014410. doi: 10.3389/fphar.2022.1014410. eCollection 2022.

ABSTRACT

Background: Duzhong [DZ (Eucommia ulmoides Oliv.)] is regarded as a traditional Chinese medicine with a history dating back more than 2000 years. This herb is considered a nourishing herb in China and is commonly used as a tonic to strengthen muscles and bones, nourish the kidneys and liver, and soothe miscarriages. Moreover, there is evidence that DZ is capable of regulating blood pressure (BP), and several compounds isolated from DZ have been shown to have a BP-lowering effect. Quanduzhong capsules contain an extract of DZ [Eucommia ulmoides Oliv. (Eucommiaceae; Eucommiae cortex)] that is effective in treating hypertension. This multicenter, randomized, double-blind, placebo-controlled clinical trial sought to evaluate the clinical efficacy of Quanduzhong capsules in the treatment of low-to-moderate risk grade 1 hypertension patients. Materials and methods: A total of 60 patients from 3 centers with documented low-to-moderate risk grade 1 hypertension were randomly assigned in a 1:1 ratio to the test group or the control group. After a 1 week lead-in period using sham Quanduzhong capsules, all patients who met the entry criteria (29 cases in the test group and 29 cases in the control group) entered the 4 week test period. The test group took Quanduzhong capsules, and the control group continued to take sham Quanduzhong capsules. The primary endpoints [24-h mean systolic blood pressure (SBP) and diastolic blood pressure (DBP) determined via 24-h ambulatory blood pressure monitoring (ABPM); office SBP and DBP] and secondary endpoints [mean arterial pressure; mean pulse; daytime mean SBP and DBP; nocturnal mean SBP and DBP; SBP and DBP load; area under the blood pressure (BP) curve; morning peak BP; early morning SBP and DBP; smoothness index of SBP and DBP; 24 h BP mean coefficient of variation (CV); percentage of patients with circadian restoration in ABPM; home BP; quality of life evaluated by WHO Quality of Life-BREF questionnaire; grading and quantitative evaluation of hypertension symptoms; values of plasmatic renin activity, angiotensin II, aldosterone, β-2 microglobulin and homocysteine] were assessed following the treatment. Drug-related adverse events and adverse drug reactions were also compared. Results: After a 4 week test period, a significant difference in the DBP CV between the two groups was observed (-2.49 ± 4.32 vs. 0.76 ± 4.3; p < .05). Moreover, the mean office SBP change was -7.62 ± 9.32 mmHg, and the mean DBP change was -4.66 ± 6.03 (p < .05). Among the three subjects with abnormal homocysteine levels in the test group, homocysteine levels decreased by 6.23 ± 9.15 μmol/L after treatment. No differences were observed between the two groups in any other indicators. After 4 weeks of treatment, there were no significant differences between the groups in terms of safety indicators (p > .05). No abnormal vital signs (except BP) or severe liver or renal function impairment were observed during the treatment periods; in addition, adverse events and drug reactions were mild. Conclusion: Treatment with Quanduzhong capsules reduced office SBP and DBP as well as DBP CV determined by 24-h ambulatory BP monitoring in patients with grade 1 hypertension at low-to-moderate risk. Clinical Trial Registration: https://www.chictr.org.cn/showproj.aspx?proj=32531, identifier ChiCTR1900021699.

PMID:36703729 | PMC:PMC9871381 | DOI:10.3389/fphar.2022.1014410

Medicine (Baltimore). 2023 Jan 20;102(3):e31478. doi: 10.1097/MD.0000000000031478.

ABSTRACT

BACKGROUND: Nausea and vomiting are among the most common adverse effects experienced by cancer patients undergoing treatment worldwide. Their treatment with pharmacologic therapy can often be complicated by medication interactions and other unwanted side effects. The aim of this systematic review and meta-analysis protocol is to assess the effectiveness and safety of acupuncture therapy for treating nausea and vomiting in patients with cancer.

METHODS: Three electronic databases and 2 clinical registry platforms will be searched from inception to May 2022: the MEDLINE via PubMed, Embase via Ovid, the Cochrane Central Register of Controlled Trials via the Cochrane Library, the World Health Organisation International Clinical Trials Registry Platform, and National Institutes of Health Clinical trials.gov. Search terms will include nausea, vomiting, cancer, and acupuncture. Two researchers will independently select studies, extract data and assess the risk of bias. The primary outcome will be the incidence of nausea and/or vomiting or other validated outcome measures. Meta-analysis will be carried out using RevMan V.5.4. The quality of evidence from randomized clinical trials will be evaluated with the Grading of Recommendations Assessment, Development and Evaluation System tool.

RESULTS: The results will provide a high-quality synthesis of evidence for clinicians in the field of oncology.

CONCLUSION: The conclusion is expected to provide evidence to determine whether acupuncture is an effective and safe treatment for cancer patients with nausea and vomiting.

PMID:36701706 | PMC:PMC9857488 | DOI:10.1097/MD.0000000000031478

Rev Soc Bras Med Trop. 2023 Jan 23;56:S0037-86822023000100305. doi: 10.1590/0037-8682-0384-2022. eCollection 2023.

ABSTRACT

BACKGROUND: Chagas disease (CD) treatment is commonly associated with a high incidence of adverse effects. It is crucial to study and update these adverse effects to improve the existing knowledge of which drugs to use and to clarify the information presented to patients.

METHODS: We analyzed the adverse effects of benznidazole in two cohorts of patients: a large retrospective study and a small prospective study.

RESULTS: This large retrospective study described the most and least common adverse effects in our area and characterized our Chagas disease population. This prospective study, along with a close follow-up of the treatment, detected more adverse effects and enhanced the patients' perception of the disease and treatment.

CONCLUSIONS: This information is important for preventing non-medical-related withdrawals and for removing baseless fears. Better knowledge of patients could help us provide better care.

PMID:36700605 | DOI:10.1590/0037-8682-0384-2022

Clin Microbiol Infect. 2023 Jan 23:S1198-743X(23)00039-3. doi: 10.1016/j.cmi.2023.01.017. Online ahead of print.

ABSTRACT

OBJECTIVES: Chronic active Epstein-Barr virus infection (CAEBV) is a prototype of EBV-associated T-or NK-cell lymphoproliferative diseases. It is a disease with poor outcome. Almost all current therapies are ineffective except of allogeneic hematopoietic stem cell transplantation.

METHODS: We investigated the efficacy and safety of programmed death 1 (PD-1) blockade (Sintilimab), combined with lenalidomide, which is an immunomodulatory drug, in an open-label, single-center, prospective study involving CAEBV patients. PD1 blockade 2mg/kg was given every two weeks by intravenous infusion on day 1, and lenalidomide 5mg (age<18 years)/10mg (age>=18 years) was given orally once a day on day 1-14.

RESULTS: As of Nov 15, 2020, 34 patients were enrolled. As of the Feb 1, 2021 analysis cut-off date, 24 cases completed at least 3 courses and were assessed for efficacy. The overall response rate is 54.2% (13/24, 45.8% complete response; 8.3% partial response). EBV-DNA copies in PBMC decreased significantly (p=0.002). The proportion of CD8+T cells in lymphocytes increased (p=0.007). The comparative analysis between response group and non-response group showed the proportion of Effector Memory CD8+ T cells and cytokines of CTLs activation (IFN-γ, CD27, CD30, MIG, IP-10) increased significantly in Response-group after treatment. Whole-exome sequencing generated from peripheral blood and saliva samples reveal that Non-Response group had a higher somatic mutational load of copy number variation in background. With a median follow-up time of 17.8 months, 22 of 24 patients were alive with an estimated survival probability of 91.3% at 1 year. All 34 patients were assessed for safety evaluation. The possible drug-related adverse events were reported in 17 (50%) patients.

CONCLUSIONS: PD-1 blockade combined with lenalidomide was an effective and safe therapy for CAEBV patients. The significant therapeutic effect and the different characteristics between response and non-response group, provides a possible predictive value for CAEBV treatment option.

PMID:36702399 | DOI:10.1016/j.cmi.2023.01.017

Front Pharmacol. 2023 Jan 9;13:1077468. doi: 10.3389/fphar.2022.1077468. eCollection 2022.

ABSTRACT

In recent years, cancer immunotherapy has made remarkable achievements. Immune checkpoint inhibitors (ICIs) have been used successfully in several types of cancer in the past decade. However, expanded indication and increased use of Immune checkpoint inhibitors have resulted in increased reports of toxicity called immune-related adverse events (irAEs). Due to the unique immunological characteristics of the liver, a hepatic immune-related adverse events has also been reported, which is usually termed Immune-mediated hepatitis (IMH). So far, it is generally considered that the mechanism of IMH induced by Immune checkpoint inhibitors is mainly the overactivation of T cells. It has been reported that the incidence of IMH ranges from 1% to 15%. Because of the lack of specific markers, a diagnosis of exclusion of IMH is critical. Although most IMH is mild and recoverable, several death cases have been reported, which has been increasingly concerned. This review summarizes the current understanding of the pathophysiology, epidemiology, diagnosis, management and prognosis of IMH caused by Immune checkpoint inhibitors. It also discusses the controversial issues in IMH, such as the role of liver biopsy, grading criteria, risk factors, rational treatment strategies with steroids, and the timing of Immune checkpoint inhibitors rechallenging, which may provide helpful information for IMH in future clinical practice.

PMID:36699050 | PMC:PMC9868416 | DOI:10.3389/fphar.2022.1077468

Nervenarzt. 2023 Feb;94(2):149-158. doi: 10.1007/s00115-022-01434-8. Epub 2023 Jan 25.

ABSTRACT

Pharmacotherapy is the most important pillar in the treatment of epilepsies. In approximately 50% of epilepsy patients monotherapy with anti-seizure medications (ASM) is insufficient. The knowledge of specific drug interactions in combination therapies is essential to recognize and avoid adverse side effects up to relevant therapy risks, including loss of efficiency and intoxication. Interactions can be of a pharmacokinetic or pharmacodynamic nature. Some effects of interactions in combination therapies can also be advantageous. Therapeutic drug monitoring in serum is not necessary for all ASMs and should be used rationally: however, it should be performed consistently if the indications are present. This review article provides fundamental knowledge about the most relevant interactions between ASMs and the indications for therapeutic drug monitoring.

PMID:36695895 | DOI:10.1007/s00115-022-01434-8

BMC Pediatr. 2023 Jan 25;23(1):43. doi: 10.1186/s12887-023-03860-2.

ABSTRACT

BACKGROUND AND OBJECTIVES: Pulmonary hypertension (PH) is a rare, but serious disease among children. However, PH has been primarily evaluated among adults. Consequently, treatment therapies have not been fully evaluated among pediatric populations and are used in an 'off label' manner. The purpose of this study was to estimate the side effect profiles of the most commonly prescribed pediatric PH therapies and to understand the burdens placed upon families caring for children living with PH.

METHODS: Participants were recruited online through the "Families of children with pulmonary hypertension" Facebook group and asked to complete a survey about PH treatments.

RESULTS: A total of 139 parents of a child living with PH completed the survey. Almost all children used ≥ 1 medication to treat PH, with 52% using ≥ 3 medications. The highest average number of side effects was reported by users of Treprostinil, Selexipag and type-5 phosphodiesterase (PDE5) inhibitors. The most common side effects were skin flushing, headache, nasal congestion, joint/muscle pain, and nausea. In terms of accessing care, 81% travel ≥ 20 miles and 68% travel for ≥ 60 min to receive care.

CONCLUSIONS: We found an array of treatment combinations employed to mitigate symptoms of PH in children, with a wide range of side effects. We also found a large, unseen economic, emotional, and time burden of caring for a child living with PH. Further research is warranted to understand the clinical implications of these side effects to move towards labeled usage of these therapies rather than post-hoc off-label usage.

PMID:36698086 | DOI:10.1186/s12887-023-03860-2