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

Anticancer Res. 2023 Feb;43(2):883-891. doi: 10.21873/anticanres.16231.

ABSTRACT

BACKGROUND/AIM: Anemia is one of the dose-limiting toxicities of olaparib. A global randomized controlled trial confirmed that anemia occurrence in Japanese was relatively high. The factors related to anemia in different nationalities remain unknown. Therefore, this study investigated the factors of olaparib-related anemia in real-world settings using an adverse event reporting system database.

PATIENTS AND METHODS: We used data from FDA Adverse Events Reporting System (FAERS) and Japanese Adverse Drug Event Report database (JADER) between 2018 and 2021. FAERS reports from Japan were collected to conduct subgroup analysis, which was defined as FAERS-Japan. The endpoint was the occurrence of olaparib-related anemia. Disproportionality analysis was conducted to calculate reporting odds ratio (ROR), with a confidence interval of 95%. Adjusted ROR (aROR) was calculated to control for sex differences.

RESULTS: In FAERS and JADER, the daily olaparib dose per body weight (DPBW) ≥12 mg/kg was associated with anemia occurrence [aROR; FAERS, 4.483 (3.009-6.680), p<0.001, FAERS-Japan, 1.834 (1.091-3.063), p=0.009, and JADER, 1.628 (1.039-2.551), p=0.034]. Furthermore, FAERS reports confirmed that females with body weight <50 kg, reports from Japan, concomitant use of drugs causing vitamin B12 deficiency, and previous platinum treatment history were associated with olaparib-related anemia. FAERS-Japan also showed that body weight <50 kg and previous platinum treatment history were associated with anemia occurrence.

CONCLUSION: High DPBW constitutes a significant risk of olaparib-related anemia. In addition, information on co-administration of drugs causing vitamin B12 deficiency and previous platinum treatment history is also important for the evaluation of the risk of olaparib-related anemia.

PMID:36697083 | DOI:10.21873/anticanres.16231

Clin Med (Lond). 2023 Jan;23(1):56-60. doi: 10.7861/clinmed.2022-0589.

ABSTRACT

The use of cancer immunotherapies such as immune checkpoint inhibitors (ICIs) has been a paradigm shift in harnessing the immune system to act against cancer cells, and transformed the treatment of several solid and haematological malignancies. Cancer immunotherapies have a unique toxicity profile dependent on their mechanism of action, related to upregulation of immune activity. These can be severe and lead to life-threatening organ toxicity, and therefore identification of at-risk patient groups, early detection and prompt initiation of steroids and other immune-modulating agents is imperative. Acute presentations with toxicity related to these agents comprise a significant proportion of primary and secondary care presentations related to treatment toxicity in oncology. This article will focus on the diagnosis and management of common toxicities associated with immune checkpoint inhibitors, the most commonly utilised cancer immunotherapies.

PMID:36697001 | DOI:10.7861/clinmed.2022-0589

Infect Dis Ther. 2023 Jan 25. doi: 10.1007/s40121-023-00759-4. Online ahead of print.

ABSTRACT

INTRODUCTION: Severe Coronavirus Disease 2019 (COVID-19) progresses with inflammation and coagulation, due to an overactive complement system. Complement component 5a (C5a) plays a key role in the complement system to trigger a powerful "cytokine and chemokine storm" in viral infection. BDB-001, a recombinant human immunoglobulin G4 (IgG4) that specially binds to C5a, has the potential to inhibit the C5a-triggered cytokine storm in treating COVID-19 patients and other inflammation diseases. Here, we have explored its safety, tolerability, pharmacokinetics, and pharmacodynamics in healthy adults. This trial is registered with http://www.chinadrugtrials.org.cn/(CTR20200429 ).

METHODS: Thirty-two enrolled participants were randomized into three single-dose cohorts (2, 4, and 8 mg/kg) and 1 multi-dose cohort (4 mg/kg), and received either BDB-001 or placebo (3:1) double-blindly. The safety and tolerability after administration were evaluated for 21 days for single-dose cohorts and 28 days for the multi-dose cohort. The pharmacokinetics of BDB-001 in plasma and pharmacodynamics as free C5a in plasma were analyzed.

RESULTS: The incidence of drug-related adverse events (AEs) was low, and all AEs were mild or moderate: neither AEs ≥ 3 (NCI-Common Terminology Criteria For Adverse Events, CTCAE 5.0) nor serious adverse events (SAEs) were found. The area under the concentration-time curve from time zero to 480 h (AUC0-480h), that from time zero to infinity (AUCinf), and peak plasma concentration ©max) increased dose-dependently from 2 to 8 mg/kg in the single-dose cohorts and were characterized by a nonlinear pharmacokinetics of target-mediated drug disposal (TMDD). The accumulation index by AUC0-tau after five administrations (4 mg/kg) from the multi-dose cohort was 6.42, suggesting an accumulation effect. Furthermore, inhibition of C5a at the plasma level was observed.

CONCLUSION: The results of this phase I study supported that BDB-001 is a potent anti-C5a inhibitor with safety, tolerability, and no immunogenicity. TRIAL REGISTRATION NUMBER: CTR20200429.

PMID:36697937 | DOI:10.1007/s40121-023-00759-4

Euro Surveill. 2023 Jan;28(3). doi: 10.2807/1560-7917.ES.2023.28.3.2200195.

ABSTRACT

BackgroundPost-authorisation vaccine safety surveillance is well established for reporting common adverse events of interest (AEIs) following influenza vaccines, but not for COVID-19 vaccines.AimTo estimate the incidence of AEIs presenting to primary care following COVID-19 vaccination in England, and report safety profile differences between vaccine brands.MethodsWe used a self-controlled case series design to estimate relative incidence (RI) of AEIs reported to the national sentinel network, the Oxford-Royal College of General Practitioners Clinical Informatics Digital Hub. We compared AEIs (overall and by clinical category) 7 days pre- and post-vaccination to background levels between 1 October 2020 and 12 September 2021.ResultsWithin 7,952,861 records, 781,200 individuals (9.82%) presented to general practice with 1,482,273 AEIs, 4.85% within 7 days post-vaccination. Overall, medically attended AEIs decreased post-vaccination against background levels. There was a 3-7% decrease in incidence within 7 days after both doses of Comirnaty (RI: 0.93; 95% CI: 0.91-0.94 and RI: 0.96; 95% CI: 0.94-0.98, respectively) and Vaxzevria (RI: 0.97; 95% CI: 0.95-0.98). A 20% increase was observed after one dose of Spikevax (RI: 1.20; 95% CI: 1.00-1.44). Fewer AEIs were reported as age increased. Types of AEIs, e.g. increased neurological and psychiatric conditions, varied between brands following two doses of Comirnaty (RI: 1.41; 95% CI: 1.28-1.56) and Vaxzevria (RI: 1.07; 95% CI: 0.97-1.78).ConclusionCOVID-19 vaccines are associated with a small decrease in medically attended AEI incidence. Sentinel networks could routinely report common AEI rates, contributing to reporting vaccine safety.

PMID:36695484 | DOI:10.2807/1560-7917.ES.2023.28.3.2200195

BMJ Open. 2022 Sep 8;12(9):e061457. doi: 10.1136/bmjopen-2022-061457.

ABSTRACT

OBJECTIVE: This study aimed to develop an adverse drug reactions (ADR) antecedent prediction system using machine learning algorithms to provide the reference for security usage of Chinese herbal injections containing Panax notoginseng saponin in clinical practice.

DESIGN: A nested case-control study.

SETTING: National Center for ADR Monitoring and the Electronic Medical Record (EMR) system.

PARTICIPANTS: All patients were from five medical institutions in Sichuan Province from January 2010 to December 2018.

MAIN OUTCOMES/MEASURES: Data of patients with ADR who used Chinese herbal injections containing Panax notoginseng saponin were collected from the National Center for ADR Monitoring. A nested case-control study was used to randomly match patients without ADR from the EMR system by the ratio of 1:4. Eighteen machine learning algorithms were applied for the development of ADR prediction models. Area under curve (AUC), accuracy, precision, recall rate and F1 value were used to evaluate the predictive performance of the model. An ADR prediction system was established by the best model selected from the 1080 models.

RESULTS: A total of 530 patients from five medical institutions were included, and 1080 ADR prediction models were developed. Among these models, the AUC of the best capable one was 0.9141 and the accuracy was 0.8947. According to the best model, a prediction system, which can provide early identification of patients at risk for the ADR of Panax notoginseng saponin, has been established.

CONCLUSION: The prediction system developed based on the machine learning model in this study had good predictive performance and potential clinical application.

PMID:36691200 | PMC:PMC9462100 | DOI:10.1136/bmjopen-2022-061457

BMC Neurol. 2023 Jan 23;23(1):35. doi: 10.1186/s12883-023-03063-3.

ABSTRACT

BACKGROUND: Spinal muscular atrophy (SMA) is a progressive degenerative neuromuscular disease. Nusinersen, with its quick onset of action, can benefit patients early in the treatment course. However, there are currently no clinical studies regarding the improvement in motor function and nutritional status of patients after loading period treatment with nusinersen. Here, we aimed to determine the efficacy of nusinersen in improving motor function and nutritional status in children with SMA treated with nusinersen after loading period in Western China.

METHODS: In this retrospective study, data for all pediatric patients (aged < 18 years), with genetically confirmed diagnosis of SMA who were treated with nusinersen, were collected before initiation of treatment and after 2 months of treatment. We assessed motor function using standardized scales and nutritional status of patients with SMA as well as side effects of nusinersen.

RESULTS: Forty-six pediatric patients aged < 18 years were enrolled in this study. After 2 months of treatment, the motor function of patients with SMA type 1, 2, and 3 improved. The difference in Revised Upper Limb Module scores from M0 to M2 was significant in patients with SMA type 2 and 3 (P = 0.004, P = 0.042, respectively). The difference in Hammersmith Functional Motor Scale Expanded scores from M0 to M2 in patients with SMA type 2 was also significant (P = 0.000). No significant differences were found for Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorder (CHOP-INTEND), Hammersmith Infant Neurologic Examination-Part 2 (HINE-2), and 6-Minute Walking Test (6MWT) scores between M0 and M2, but the scores of CHOP-INTEND, HINE-2, and 6MWT were all increased after loading period treatment. The overall improvement in nutritional status was not statistically significant. No serious adverse effects were observed.

CONCLUSIONS: Our study provides evidence for the efficacy and safety of nusinersen and the nutritional status of pediatric patients with SMA after the loading period treatment. Motor function of all patients improved after 2 months of loading period nusinersen treatment. Patients with a shorter disease duration showed better response to treatment. Careful surveillance of nutritional status is needed in patients with SMA.

PMID:36690929 | DOI:10.1186/s12883-023-03063-3

Pediatr Infect Dis J. 2023 Jan 23. doi: 10.1097/INF.0000000000003832. Online ahead of print.

ABSTRACT

BACKGROUND: Ceftolozane/tazobactam, a cephalosporin-β-lactamase inhibitor combination, active against multidrug-resistant gram-negative pathogens, is approved for treatment of adults with complicated urinary tract infections (cUTI). Safety and efficacy of ceftolozane/tazobactam in pediatric participants with cUTI, including pyelonephritis, were assessed.

METHODS: This phase 2 study (NCT03230838) compared ceftolozane/tazobactam with meropenem for treatment of cUTI in participants from birth to <18 years of age. The primary objective was safety and tolerability. Key secondary end points included clinical cure and per-participant microbiologic response rates at end of treatment (EOT) and test of cure (TOC) visits.

RESULTS: The microbiologic modified intent-to-treat (mMITT) population included 95 participants (ceftolozane/tazobactam, n = 71; meropenem, n = 24). The most common diagnosis and pathogen were pyelonephritis (ceftolozane/tazobactam, 84.5%; meropenem, 79.2%) and Escherichia coli (ceftolozane/tazobactam, 74.6%; meropenem, 87.5%); 5.7% (ceftolozane/tazobactam) and 4.8% (meropenem) of E. coli isolates were extended-spectrum β-lactamase-producers. Rates of adverse events were similar between treatment groups (any: ceftolozane/tazobactam, 59.0% vs. meropenem, 60.6%; drug-related: ceftolozane/tazobactam, 14.0% vs. meropenem, 15.2%; serious: ceftolozane/tazobactam, 3.0% vs. meropenem, 6.1%). Rates of clinical cure for ceftolozane/tazobactam and meropenem at EOT were 94.4% and 100% and at TOC were 88.7% and 95.8%, respectively. Rates of microbiologic eradication for ceftolozane/tazobactam and meropenem at EOT were 93.0% and 95.8%, and at TOC were 84.5% and 87.5%, respectively.

CONCLUSIONS: Ceftolozane/tazobactam had a favorable safety profile in pediatric participants with cUTI; rates of clinical cure and microbiologic eradication were high and similar to meropenem. Ceftolozane/tazobactam is a safe and effective new treatment option for children with cUTI, especially due to antibacterial-resistant gram-negative pathogens.

PMID:36689671 | DOI:10.1097/INF.0000000000003832

Ann Pharmacother. 2023 Jan 23:10600280221148031. doi: 10.1177/10600280221148031. Online ahead of print.

ABSTRACT

BACKGROUND: Colchicine has a narrow therapeutic index. Its toxicity can be increased due to concomitant exposure to drugs inhibiting its metabolic pathway; these are cytochrome P450 3A4 (CYP3A4) and P-glycoprotein (P-gp).

OBJECTIVE: To examine clinical outcomes associated with colchicine drug interactions using the spontaneous reports of the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).

METHODS: We conducted a disproportionality analysis using FAERS data from January 2004 through June 2020. The reporting odds ratio (ROR) and observed-to-expected ratio (O/E) with shrinkage for adverse events related to colchicine's toxicity (ie, rhabdomyolysis/myopathy, agranulocytosis, hemorrhage, acute renal failure, hepatic failure, arrhythmias, torsade de pointes/QT prolongation, and cardiac failure) were compared between FAERS reports.

RESULTS: A total of 787 reports included the combined mention of colchicine, an inhibitor of both CYP3A4 and P-gp drug, and an adverse event of interest. Among reports that indicated the severity, 61% mentioned hospitalization and 24% death. A total of 37 ROR and 34 O/E safety signals involving colchicine and a CYP3A4/P-gp inhibitor were identified. The strongest ROR signal was for colchicine + atazanavir and rhabdomyolysis/myopathy (ROR = 35.4, 95% CI: 12.8-97.6), and the strongest O/E signal was for colchicine + atazanavir and agranulocytosis (O/E = 3.79, 95% credibility interval: 3.44-4.03).

CONCLUSION AND RELEVANCE: This study identifies numerous safety signals for colchicine and CYP3A4/P-gp inhibitor drugs. Avoiding the interaction or monitoring for toxicity in patients when co-prescribing colchicine and these agents is highly recommended.

PMID:36688283 | DOI:10.1177/10600280221148031

J Epilepsy Res. 2022 Dec 30;12(2):68-70. doi: 10.14581/jer.22012. eCollection 2022 Dec.

ABSTRACT

Perampanel is a novel antiepileptic drug that has been used as an adjunctive treatment for focal-onset seizures. No reports to date have documented respiratory suppression as a side effect of perampanel in adults. Herein, we report a 51-year-old man with focal epilepsy presented with type 2 respiratory failure after accidently consuming of 66 mg of perampanel. Clinicians should consider the possibility of respiratory compromise whenever a high dose of perampanel needs to be administered to patients.

PMID:36685743 | PMC:PMC9830032 | DOI:10.14581/jer.22012

Expert Opin Drug Saf. 2023 Jan 23. doi: 10.1080/14740338.2023.2172160. Online ahead of print.

ABSTRACT

BACKGROUND: - The Food and Drug Administration (FDA)'s Adverse Event Reporting System (FAERS) is a post-marketing surveillance system which relies on spontaneous reports of adverse drug reactions (ADRs). Our objective was to evaluate how black box warning (BBW) updates impact ADR reporting rates.

RESEARCH DESIGN AND METHODS: - We searched MEDWATCH for all BBW updates issued between 01/2014-12/2016 and categorized them as new, major and minor. Rates of relevant ADR reports from the FAERS database in the four years preceding and following a BBW update were assessed amongst the different BBW categories.

RESULTS: - Forty BBW updates were included (16 major, 3 new and 21 minor). A meaningful increase in the proportion of relevant ADRs of all ADRs reported following BBW updates was documented for 53% of new or major updates and 24% of minor updates (p=0.06). The median percentage of reported relevant ADRs increased by 5% following new and major BBW updates and decreased by 30% following minor BBW updates (p=0.3).

CONCLUSIONS: - Reporting of adverse events to the FAERS database is affected by the severity and timing of related BBW updates, highlighting the drawbacks of spontaneous reporting systems. Regulators should promote proactive pharmacovigilance strategies to cope with these limitations.

PMID:36683587 | DOI:10.1080/14740338.2023.2172160