BMJ Open. 2023 Jun 22;13(6):e069794. doi: 10.1136/bmjopen-2022-069794.

ABSTRACT

OBJECTIVES: The hepatotoxicity of irinotecan has been widely implicated in the treatment of multiple solid tumours. However, there are few studies on the influencing factors of irinotecan-induced hepatotoxicity. Herein, we investigated the risk factors for irinotecan-induced liver injury among 421 patients receiving irinotecan-based regimens (IBRs).

DESIGN: Retrospective multi-centre cross-sectional study.

SETTING: This study surveyed four hospitals in China.

PARTICIPANTS: After excluding participants with missing variables, we retrospectively collected the demographic, clinical and therapeutic data of 421 patients who received IBRs in four hospitals between January 2020 and December 2021 and divided the patients into two groups: those without liver injury and those with liver injury.

RESULTS: The 421 enrolled patients were grouped (liver injury group: n=92; control group: n=329) according to their hepatic biochemical monitoring parameters. In our study, the multivariate logistic regression results showed that three to four cycles of chemotherapy (OR (95% CI): 2.179 (1.272 to 3.733); p=0.005) and liver metastasis (OR (95% CI): 1.748 (1.079 to 2.833); p=0.023) were independent risk factors for irinotecan-induced liver injury. The Cox proportional hazards model demonstrated that alcohol consumption history (OR (95% CI): 2.032 (1.183 to 3.491); p=0.010) and a cumulative dose of irinotecan ≥1000 mg (OR (95% CI): 0.362 (0.165 to 0.792); p=0.011) were significantly correlated with the onset time of irinotecan-induced liver injury.

CONCLUSIONS: These findings suggest that patients with liver metastasis or who received three to four cycles of chemotherapy should undergo rigorous liver function monitoring to prevent or reduce the incidence of irinotecan-induced liver injury. Moreover, patients with a history of alcohol consumption should also be closely monitored.

PMID:37349101 | DOI:10.1136/bmjopen-2022-069794

Stud Health Technol Inform. 2023 Jun 22;304:91-95. doi: 10.3233/SHTI230378.

ABSTRACT

The COVID-19 pandemic has rapidly increased the possibilities for conducting Decentralized Clinical Trials (DCT). This paper addresses the potential for conducting DCT in Denmark and discusses how this potential can improve equity in digital healthcare. From stakeholder interviews, we learned that DCT has the potential to be implemented, as DCT guidelines are in place in Denmark. DCT can potentially improve equal access and inclusion of diverse populations, home administration of medication, retention and compliance, and monitoring of patients and side effects. While DCT has potential in a Danish context, the challenges regarding DCT need to be considered carefully, particularly concerning equity in digital health.

PMID:37347577 | DOI:10.3233/SHTI230378

Am J Nurs. 2023 Jul 1;123(7):16. doi: 10.1097/01.NAJ.0000944900.69960.ee.

ABSTRACT

Zavegepant (Zavzpret), a nasal spray, is approved to treat adults with acute migraine with or without aura. It should not be used as a preventative.The most common adverse effects of zavegepant are taste disorders, nausea, nasal discomfort, and vomiting. Hypersensitivity reactions are also possible.Patients should avoid coadministration with intranasal decongestants, as these can decrease zavegepant absorption.

PMID:37345774 | DOI:10.1097/01.NAJ.0000944900.69960.ee

Chem Res Toxicol. 2023 Jun 22. doi: 10.1021/acs.chemrestox.3c00047. Online ahead of print.

ABSTRACT

Overdose of acetaminophen, a widely used antipyretic and analgesic drug, is one of the leading causes of drug-induced acute liver injury in the United States and worldwide. Phase-I metabolism of acetaminophen generates the toxic N-acetyl-p-benzoquinone imine (NAPQI) intermediate. Reactions of NAPQI with a wide range of biomolecules cause increased oxidative stress, endoplasmic reticulum (ER) stress, inflammation, and mitochondrial dysfunction, some of the cellular events contributing toward liver toxicity. Previously, we evaluated the potential of an FDA-approved, ER stress-modulating antihypertensive drug, Wytensin (trans-guanabenz, E-GA), as an antidote for acetaminophen hepatotoxicity. E-GA prevented elevation of the liver enzyme alanine aminotransferase (ALT), even when administered up to 6 h after acetaminophen overdose, and exhibited synergistic analgesic interactions. However, the commercially available guanabenz exists solely as a trans-isomer and suffers from sedative side effects resulting from the inhibition of central α2A-adrenergic receptors in locus coeruleus. Here, we studied the utility of the relatively unexplored cis-isomer of guanabenz as a treatment option for acetaminophen-induced liver toxicity. cis(Z)-Guanabenz acetate (Z-GA) lacks interaction with α2A-adrenoreceptors and is thus devoid of sedative, blood-pressure-lowering side effects of E-GA. Treatment of mice with Z-GA (10 mg/kg) before acetaminophen overdose and up to 6 h post APAP administration prevented liver injury and suppressed the elevation of serum ALT levels. Mechanistically, hepatoprotective effects of both isomers are similar and partly attributed to attenuation of the ER stress and oxidative stress in the liver. The results of this study suggest that Z-GA may be a safer, effective antidote for the clinical management of acute liver injury resulting from acetaminophen overdose. It also raises a tantalizing possibility of a prophylactic combination of the geometric isomer of the approved drug guanabenz with acetaminophen in a clinical setting.

PMID:37348131 | DOI:10.1021/acs.chemrestox.3c00047

Am J Health Syst Pharm. 2023 Jun 22:zxad141. doi: 10.1093/ajhp/zxad141. Online ahead of print.

ABSTRACT

DISCLAIMER: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time.

PURPOSE: Glycopyrronium, also known as glycopyrrolate, is an antimuscarinic competitive inhibitor of acetylcholine widely utilized topically for its anticholinergic properties in dermatology. A single topical glycopyrronium tosylate (GT) formulation is available on the market, and prescription of this medication has become increasingly popular among dermatologists. This medication has a relatively notable adverse effect profile and carries risks that patients need to be counseled on before initiation.

SUMMARY: A 22-year-old female presented to our emergency department (ED) with a chief complaint of difficulty urinating for 48 hours and blurred vision for 2 weeks. Over the course of a week, she visited the ED once and urgent care multiple times due to complications associated with combination use of GT and cetirizine. Although these clinical effects were reversible, the patient impact in our case was profound given the time, cost, and invasive nature of these visits.

CONCLUSION: The notable adverse effects of GT should be considered when prescribing this agent.

PMID:37348110 | DOI:10.1093/ajhp/zxad141

Sci Rep. 2023 Jun 21;13(1):10045. doi: 10.1038/s41598-023-35916-9.

ABSTRACT

Unintended side effects linked to the antineoplastic drug cisplatin are a major drawback in its clinical application. The underlying source of these side effects include the generation of reactive oxygen species which are toxic and damaging to tissues and organs. In the present study the anti-inflammatory and antioxidant potential of sodium salicylate was assessed against cisplatin-induced hepatotoxicity in albino rats. Sodium salicylate was used as a model drug and loading into hollow structured porous silica using ultrasound-assisted sol-gel method to produce a nanoemulsion. Transmission Electron Microscopy and Dynamic Light scattering analysis were employed to assess the structural properties and stability of this model. Liver function was assessed by measuring biomarkers including ALT, AST & GGT and oxidant/antioxidant markers including MDA, NO, PON, GSH, MCP1 & AVP in serum or liver tissue. Additionally, blood leukocyte DNA damage was evaluated. Cisplatin significantly altered the normal levels of all biomarkers confirming its hepatotoxic effects. In contrast, treatment with sodium salicylate-loaded silica nanoemulsion significantly restored the levels of these markers. The finding suggests the protective effects of this model drug in preventing cisplatin-induced hepatotoxicity, and therefore may have implications in attenuating cisplatin-induced hepatotoxicity.

PMID:37344526 | PMC:PMC10284791 | DOI:10.1038/s41598-023-35916-9

Front Immunol. 2023 Jun 5;14:1158364. doi: 10.3389/fimmu.2023.1158364. eCollection 2023.

ABSTRACT

BACKGROUND: Parkinson's Disease (PD) is one of the most common neurodegenerative diseases. PD has recently received more attention by researchers in the midst of the COVID-19 pandemic.

OBJECTIVE: Yet to be researched is the effect of the COVID-19 vaccines on PD patients. Several PD patients are still hesitant to the vaccine due to this unaddressed fear. The purpose of this study is to address this gap.

METHODS: Surveys were administered to PD patients 50 years and older at UF Fixel Institute who received at least one dose of the COVID-19 vaccine. Survey questions included patients' severity of PD symptoms before and after the vaccine and extent of worsening PD symptoms post-vaccination. After three weeks of collecting responses, the data was analyzed.

RESULTS: 34 respondents were eligible for data consideration because they fell within the age range being studied. A total of 14 respondents out of 34 (41%, p=0. 0001) reported that their PD symptoms worsened after the COVID-19 vaccine to some extent.

CONCLUSION: There was strong evidence of worsening of PD symptoms post COVID-19 vaccination, however it was mostly mild and limited to a couple of days. The worsening had statistically significant moderate positive correlation with vaccine hesitancy and post-vaccine general side effects. A possible causative mechanism of PD symptom worsening using existing scientific knowledge would be stress and anxiety associated with vaccine hesitancy and the extent of post-vaccine general side effects (fever, chills, pain), likely via simulating a mild systemic infection/inflammation the latter already established causes of PD symptom worsening.

PMID:37342344 | PMC:PMC10278957 | DOI:10.3389/fimmu.2023.1158364

Front Immunol. 2023 Jun 5;14:1197364. doi: 10.3389/fimmu.2023.1197364. eCollection 2023.

ABSTRACT

During the past decade, there has been a revolution in cancer therapeutics by the emergence of antibody-based immunotherapies that modulate immune responses against tumors. These therapies have offered treatment options to patients who are no longer responding to classic anti-cancer therapies. By blocking inhibitory signals mediated by surface receptors that are naturally upregulated during activation of antigen-presenting cells (APC) and T cells, predominantly PD-1 and its ligand PD-L1, as well as CTLA-4, such blocking agents have revolutionized cancer treatment. However, breaking these inhibitory signals cannot be selectively targeted to the tumor microenvironment (TME). Since the physiologic role of these inhibitory receptors, known as immune checkpoints (IC) is to maintain peripheral tolerance by preventing the activation of autoreactive immune cells, IC inhibitors (ICI) induce multiple types of immune-related adverse effects (irAEs). These irAEs, together with the natural properties of ICs as gatekeepers of self-tolerance, have precluded the use of ICI in patients with pre-existing autoimmune diseases (ADs). However, currently accumulating data indicates that ICI might be safely administered to such patients. In this review, we discuss mechanisms of well established and newly recognized irAEs and evolving knowledge from the application of ICI therapies in patients with cancer and pre-existing ADs.

PMID:37342323 | PMC:PMC10277501 | DOI:10.3389/fimmu.2023.1197364

Continuum (Minneap Minn). 2023 Jun 1;29(3):903-922. doi: 10.1212/CON.0000000000001236.

ABSTRACT

OBJECTIVE: Advances in cancer treatment have led to extended survival and increased risk of neurologic complications in an aging population. This review summarizes potential neurologic complications in patients who have undergone treatment for neurologic and systemic malignancies.

LATEST DEVELOPMENTS: Radiation and cytotoxic chemotherapy along with other targeted therapies continue to be the mainstay of cancer treatment. These advances in cancer care have led to improved outcomes and increased the need to understand the spectrum of neurologic complications that may arise from treatment. While radiation and older therapies including cytotoxic chemotherapies have side effect profiles that are widely known and well understood, this article serves as a review of the more commonly associated neurologic complications of both traditional and newer treatments being offered to this patient population.

ESSENTIAL POINTS: Neurotoxicity is a common complication of cancer-directed treatment. In general, neurologic complications of radiation therapy are more common in central nervous system malignancies, and neurologic complications of chemotherapy are more common in non-neurologic malignancies. Attempts at prevention, early detection, and intervention remain paramount in the reduction of neurologic morbidity.

PMID:37341335 | DOI:10.1212/CON.0000000000001236

Cochrane Database Syst Rev. 2023 Jun 21;6:CD014788. doi: 10.1002/14651858.CD014788.pub2.

ABSTRACT

BACKGROUND: Endometriosis is a common gynaecological condition affecting 6 to 11% of reproductive-age women and may cause dyspareunia, dysmenorrhoea, and infertility. One treatment strategy is medical therapy with gonadotrophin-releasing hormone analogues (GnRHas) to reduce pain due to endometriosis. One of the adverse effects of GnRHas is a decreased bone mineral density. In addition to assessing the effect on pain, quality of life, most troublesome symptom and patients' satisfaction, the current review also evaluated the effect on bone mineral density and risk of adverse effects in women with endometriosis who use GnRHas versus other treatment options.

OBJECTIVES: To assess the effectiveness and safety of GnRH analogues (GnRHas) in the treatment of painful symptoms associated with endometriosis and to determine the effects of GnRHas on bone mineral density of women with endometriosis.

SEARCH METHODS: We searched the Cochrane Gynaecology and Fertility (CGF) Group trials register, CENTRAL, MEDLINE, Embase, PsycINFO and the trial registries in May 2022 together with reference checking and contact with study authors and experts in the field to identify additional studies.

SELECTION CRITERIA: We included randomised controlled trials (RCTs) which compared GnRHas with other hormonal treatment options, including analgesics, danazol, intra-uterine progestogens, oral or injectable progestogens, gestrinone and also GnRHas compared with no treatment or placebo. Trials comparing GnRHas versus GnRHas in conjunction with add-back therapy (hormonal or non-hormonal) or calcium-regulation agents were also included in this review. DATA COLLECTION AND ANALYSIS: We used standard methodology as recommended by Cochrane. Primary outcomes are relief of overall pain and the objective measurement of bone mineral density. Secondary outcomes include adverse effects, quality of life, improvement in the most troublesome symptoms and patient satisfaction. Due to high risk of bias associated with some of the studies, primary analyses of all review outcomes were restricted to studies at low risk of selection bias. Sensitivity analysis including all studies was then performed.

MAIN RESULTS: Seventy-two studies involving 7355 patients were included. The evidence was very low to low quality: the main limitations of all studies were serious risk of bias due to poor reporting of study methods, and serious imprecision. Trials comparing GnRHas versus no treatment We did not identify any studies. Trials comparing GnRHas versus placebo There may be a decrease in overall pain, reported as pelvic pain scores (RR 2.14; 95% CI 1.41 to 3.24, 1 RCT, n = 87, low-certainty evidence), dysmenorrhoea scores (RR 2.25; 95% CI 1.59 to 3.16, 1 RCT, n = 85, low-certainty evidence), dyspareunia scores (RR 2.21; 95% CI 1.39 to 3.54, 1 RCT, n = 59, low-certainty evidence), and pelvic tenderness scores (RR 2.28; 95% CI 1.48 to 3.50, 1 RCT, n = 85, low-certainty evidence) after three months of treatment. We are uncertain of the effect for pelvic induration, based on the results found after three months of treatment (RR 1.07; 95% CI 0.64 to 1.79, 1 RCT, n = 81, low-certainty evidence). Besides, treatment with GnRHas may be associated with a greater incidence of hot flushes at three months of treatment (RR 3.08; 95% CI 1.89 to 5.01, 1 RCT, n = 100, low-certainty evidence). Trials comparing GnRHas versus danazol For overall pain, for women treated with either GnRHas or danazol, a subdivision was made between pelvic tenderness, partly resolved and completely resolved. We are uncertain about the effect on relief of overall pain, when a subdivision was made for overall pain (MD -0.30; 95% CI -1.66 to 1.06, 1 RCT, n = 41, very low-certainty evidence), pelvic pain (MD 0.20; 95% CI -0.26 to 0.66, 1 RCT, n = 41, very low-certainty evidence), dysmenorrhoea (MD 0.10; 95% CI -0.49 to 0.69, 1 RCT, n = 41, very low-certainty evidence), dyspareunia (MD -0.20; 95% CI -0.77 to 0.37, 1 RCT, n = 41, very low-certainty evidence), pelvic induration (MD -0.10; 95% CI -0.59 to 0.39, 1 RCT, n = 41, very low-certainty evidence), and pelvic tenderness (MD -0.20; 95% CI -0.78 to 0.38, 1 RCT, n = 41, very low-certainty evidence) after three months of treatment. For pelvic pain (MD 0.50; 95% CI 0.10 to 0.90, 1 RCT, n = 41, very low-certainty evidence) and pelvic induration (MD 0.70; 95% CI 0.21 to 1.19, 1 RCT, n = 41, very low-certainty evidence), the complaints may decrease slightly after treatment with GnRHas, compared to danazol, for six months of treatment. Trials comparing GnRHas versus analgesics We did not identify any studies. Trials comparing GnRHas versus intra-uterine progestogens We did not identify any low risk of bias studies. Trials comparing GnRHas versus GnRHas in conjunction with calcium-regulating agents There may be a slight decrease in bone mineral density (BMD) after 12 months treatment with GnRHas, compared to GnRHas in conjunction with calcium-regulating agents for anterior-posterior spine (MD -7.00; 95% CI -7.53 to -6.47, 1 RCT, n = 41, very low-certainty evidence) and lateral spine (MD -12.40; 95% CI -13.31 to -11.49, 1 RCT, n = 41, very low-certainty evidence). AUTHORS' CONCLUSIONS: For relief of overall pain, there may be a slight decrease in favour of treatment with GnRHas compared to placebo or oral or injectable progestogens. We are uncertain about the effect when comparing GnRHas with danazol, intra-uterine progestogens or gestrinone. For BMD, there may be a slight decrease when women are treated with GnRHas, compared to gestrinone. There was a bigger decrease of BMD in favour of GnRHas, compared to GnRHas in conjunction with calcium-regulating agents. However, there may be a slight increase in adverse effects when women are treated with GnRHas, compared to placebo or gestrinone. Due to a very low to low certainty of the evidence, a wide range of outcome measures and a wide range of outcome measurement instruments, the results should be interpreted with caution.

PMID:37341141 | DOI:10.1002/14651858.CD014788.pub2

Brief Bioinform. 2023 Jun 21:bbad228. doi: 10.1093/bib/bbad228. Online ahead of print.

ABSTRACT

Adverse drug events (ADEs) are common in clinical practice and can cause significant harm to patients and increase resource use. Natural language processing (NLP) has been applied to automate ADE detection, but NLP systems become less adaptable when drug entities are missing or multiple medications are specified in clinical narratives. Additionally, no Chinese-language NLP system has been developed for ADE detection due to the complexity of Chinese semantics, despite ˃10 million cases of drug-related adverse events occurring annually in China. To address these challenges, we propose DKADE, a deep learning and knowledge graph-based framework for identifying ADEs. DKADE infers missing drug entities and evaluates their correlations with ADEs by combining medication orders and existing drug knowledge. Moreover, DKADE can automatically screen for new adverse drug reactions. Experimental results show that DKADE achieves an overall F1-score value of 91.13%. Furthermore, the adaptability of DKADE is validated using real-world external clinical data. In summary, DKADE is a powerful tool for studying drug safety and automating adverse event monitoring.

PMID:37344167 | DOI:10.1093/bib/bbad228

Exp Hematol Oncol. 2023 Jun 21;12(1):55. doi: 10.1186/s40164-023-00415-0.

ABSTRACT

Ropeginterferon alfa-2b represents a new-generation pegylated interferon-based therapy and is administered every 2-4 weeks. It is approved for polycythemia vera (PV) treatment in the United States and Europe with a starting dose of 100 µg (50 µg for patients receiving hydoxyurea) and intra-patient dose titrations up to 500 µg at 50 µg increments, which took approximately 20 or more weeks to reach a plateau dose level. This study aimed to assess ropeginterferon alfa-2b at an alternative dosing regimen with a higher starting dose and quicker intra-patient dose titrations, i.e., the 250-350-500 μg schema, in 49 Chinese patients with PV with resistance or intolerance to hydroxyurea. The primary endpoint of the complete hematologic response rate at treatment weak 24 was 61.2%, which was notably higher than 43.1% at 12 months with the approved dosing schema. The JAK2V617F allele burden decreased from baseline to week 24 (17.8% ± 18.0%), with one patient achieving a complete molecular response. Ropeginterferon alfa-2b was well-tolerated and most adverse events (AEs) were mild or moderate. Common AEs included alanine aminotransferase and aspartate aminotransferase increases mostly at grade 1 or 2 levels. Patients did not present with jaundice or significant bilirubin level increase. No grade 4 or 5 AEs occurred. Seven patients (14.3%) experienced reversible, drug-related grade 3 AEs. No AEs led to treatment discontinuation. Ropeginterferon alfa-2b at the 250-350-500 μg regimen is highly effective and well-tolerated and can help patients achieve greater and rapid complete hematologic and molecular responses.Clinical Trial Registration: This trial is registered at ClinicalTrials.gov (Identifier: NCT05485948) and in China (China National Medical Products Administration Registration Number: CTR20211664).

PMID:37344895 | DOI:10.1186/s40164-023-00415-0

Eur J Nucl Med Mol Imaging. 2023 Jun 21. doi: 10.1007/s00259-023-06301-5. Online ahead of print.

ABSTRACT

PURPOSE: Primary objective was to compare the per-patient detection rates (DR) of [18F]DCFPyL versus [18F]fluoromethylcholine positron emission tomography/computed tomography (PET/CT), in patients with first prostate cancer (PCa) biochemical recurrence (BCR). Secondary endpoints included safety and impact on patient management (PM).

METHODS: This was a prospective, open label, cross-over, comparative study with randomized treatment administration of [18F]DCFPyL (investigational medicinal product) or [18F]fluoromethylcholine (comparator). Men with rising prostate-specific antigen (PSA) after initial curative therapy were enrolled. [18F]DCFPyL and [18F]fluoromethylcholine PET/CTs were performed within a maximum time interval of 12 days. DR was defined as the percentage of positive PET/CT scans identified by 3 central imaging readers. PM was assessed by comparing the proposed pre-PET/CT treatment with the local treatment", defined after considering both PET/CTs.

RESULTS: A total of 205 patients with first BCR after radical prostatectomy (73%; median PSA = 0.46 ng/ml [CI 0.16;27.0]) or radiation therapy (27%; median PSA = 4.23 ng/ml [CI 1.4;98.6]) underwent [18F]DCFPyL- and/or [18F]fluoromethylcholine -PET/CTs, between July and December 2020, at 22 European sites. 201 patients completed the study. The per-patient DR was significantly higher for [18F]DCFPyL- compared to [18F]fluoromethylcholine -PET/CTs (58% (117/201 patients) vs. 40% (81/201 patients), p < 0.0001). DR increased with higher PSA values for both tracers (PSA ≤ 0.5 ng/ml: 26/74 (35%) vs. 22/74 (30%); PSA 0.5 to ≤ 1.0 ng/ml: 17/31 (55%) vs. 10/31 (32%); PSA 1.01 to < 2.0 ng/ml: 13/19 (68%) vs. 6/19 (32%);PSA > 2.0: 50/57 (88%) vs. 39/57 (68%) for [18F]DCFPyL- and [18F]fluoromethylcholine -PET/CT, respectively). [18F]DCFPyL PET/CT had an impact on PM in 44% (90/204) of patients versus 29% (58/202) for [18F]fluoromethylcholine. Overall, no drug-related nor serious adverse events were observed.

CONCLUSIONS: The primary endpoint of this study was achieved, confirming a significantly higher detection rate for [18F]DCFPyL compared to [18F]fluoromethylcholine, in men with first BCR of PCa, across a wide PSA range. [18F]DCFPyL was safe and well tolerated.

PMID:37341747 | DOI:10.1007/s00259-023-06301-5

Syst Rev. 2023 Jun 20;12(1):99. doi: 10.1186/s13643-023-02269-3.

ABSTRACT

BACKGROUND: It is critical that abstracts of systematic reviews transparently report both the beneficial and adverse effects of interventions without misleading the readers. This cross-sectional study assessed whether adverse effects of interventions were reported or considered in abstracts of systematic reviews of orthodontic interventions and whether spin on adverse effects was identified when comparing the abstracts with what was sought and reported in these reviews.

METHODS: This cross-sectional study (part 2 of 2) used the same sample of 98 systematic reviews orthodontic interventions as used in part 1. Eligible reviews were retrieved from the Cochrane Database of Systematic Reviews and the 5 leading orthodontic journals between August 1 2009 and July 31 2021. Prevalence proportions were sought for 3 outcomes as defined in the published protocol. Univariable logistic regression models were built to explore associations between the presence of spin in the abstract and a series of predictors. Odds ratios (OR) 95% confidence intervals (95% CI) were used to quantify the strength of associations and their precision.

RESULTS: 76.5% (75/98) of eligible reviews reported or considered (i.e., discussed, weighted etc.) potential adverse effects of orthodontic interventions in the abstract and the proportion of spin on adverse effects was 40.8% (40/98) in the abstract of these reviews. Misleading reporting was the predominant category of spin, i.e., 90% (36/40). Our explorative analyses found that compared to the Cochrane Database of Systematic Reviews all 5 orthodontic journals had similar odds of the presence of spin on adverse effects in abstracts of systematic reviews of orthodontic interventions. The odds of the presence of spin did not change over the sampled years (OR: 1.03, 95% CI: 0.9 to 1.16) and did not depend on the number of authors (OR: 0.93, 95% CI: 0.71 to 1.21), or on the type of orthodontic intervention (OR: 1.1, 95% CI: 0.45 to 2.67), or whether conflicts of interests were reported (OR: 0.74, 95% CI: 0.32 to 1.68).

CONCLUSION: End users of systematic reviews of orthodontic interventions have to be careful when interpreting results on adverse effects in the abstracts of these reviews, because they could be jeopardized by uncertainties such as not being reported and misleading reporting as a result of spin.

PMID:37340504 | PMC:PMC10280878 | DOI:10.1186/s13643-023-02269-3

Eur J Hosp Pharm. 2023 Jun 20:ejhpharm-2023-003729. doi: 10.1136/ejhpharm-2023-003729. Online ahead of print.

ABSTRACT

OBJECTIVES: Evidence on the effectiveness of remdesivir when used in real-life clinical practice is controversial. This study aims to analyse its effectiveness and the factors associated with increased mortality in non-critically ill patients with COVID-19 pneumonia who require supplemental low-flow oxygen and received remdesivir.

METHODS: A retrospective cohort study was conducted at Ramón y Cajal University Hospital (Madrid, Spain) which included all patients treated with remdesivir in our institution during the second pandemic breakout in Spain, from August to November 2020. Treatment with remdesivir was limited to non-critically ill patients with COVID-19 pneumonia requiring low-flow supplemental oxygen, with a treatment duration of 5 days.

RESULTS: A total of 1757 patients were admitted with COVID-19 pneumonia during the study period, of which 281 non-critically ill patients were treated with remdesivir and included in the analysis. Mortality at 28 days after initiation of treatment was 17.1%. The median (IQR) time to recovery was 9 days (6-15). 104 (37.0%) patients had complications during hospitalisation, with renal failure being the most frequent (31 patients; 36.5%). After adjustment for confounding factors, high-flow oxygen therapy was associated with increased 28-day mortality (HR 2.77; 95% CI 1.39 to 5.53; p=0.004) and decreased 28-day clinical improvement (HR 0.54; 95% CI 0.35 to 0.85; p=0.008). A significant difference in survival and clinical improvement was identified between patients treated with high and low-flow oxygen.

CONCLUSION: The 28-day mortality rate in patients treated with remdesivir needing low-flow oxygen therapy was higher than that published in clinical trials. Age and increased oxygen therapy needed after the beginning of treatment were the main risk factors associated with mortality.

PMID:37339865 | DOI:10.1136/ejhpharm-2023-003729

Front Endocrinol (Lausanne). 2023 Jun 1;14:1172089. doi: 10.3389/fendo.2023.1172089. eCollection 2023.

ABSTRACT

AIMS: Diabetes mellitus (DM), one of the most common chronic diseases in China, is a risk factor for SARS-COV-2 infection and poor prognosis of COVID-19. The COVID-19 vaccine is one of the key measures to control the pandemic. However, the actual coverage of COVID-19 vaccination and associated factors remain unclear among DM patients in China. We conducted this study to investigate the COVID-19 vaccine coverage, safety, and perceptions among patients with DM in China.

METHODS: A cross-sectional study of a sample of 2200 DM patients from 180 tertiary hospitals in China was performed using a questionnaire developed through the Wen Juan Xing survey platform to collect information regarding their coverage, safety, and perceptions of COVID-19 vaccination. A multinomial logistic regression analysis model was performed to determine any independent relationships with COVID-19 vaccination behavior among DM patients.

RESULTS: In total, 1929 (87.7%) DM patients have received at least one dose COVID-19 vaccine, and 271 (12.3%) DM patients were unvaccinated. In addition, 65.2% (n = 1434) were booster vaccinated against COVID-19, while 16.2% (n = 357) were only fully vaccinated and 6.3% (n = 138) were only partially vaccinated. The prevalence of adverse effects after the first dose of vaccine, the second dose of vaccine, and the third dose of vaccine were 6.0%, 6.0%, and 4.3% respectively. Multinomial logistic regression analysis showed that DM patients complicated with immune and inflammatory diseases (partially vaccinated: OR = 0.12; fully vaccinated: OR = 0.11; booster vaccinated: OR = 0.28), diabetic nephropathy (partially vaccinated: OR = 0.23; fully vaccinated: OR = 0.50; booster vaccinated: OR = 0.30), and perceptions on the safety of COVID-19 vaccine (partially vaccinated: OR = 0.44; fully vaccinated: OR = 0.48; booster vaccinated: OR = 0.45) were all associated with the three of vaccination status.

CONCLUSION: This study showed that higher proportion of COVID-19 vaccine coverage among patients with DM in China. The concern about the safety of the COVID-19 vaccine affected the vaccine behavior in patients with DM. The COVID-19 vaccine was relatively safe for DM patients due to all side effects were self-limiting.

PMID:37334292 | PMC:PMC10270113 | DOI:10.3389/fendo.2023.1172089

Am J Perinatol. 2023 Jun 19. doi: 10.1055/s-0043-1770161. Online ahead of print.

ABSTRACT

OBJECTIVE: This study aimed to conduct a systematic review and meta-analysis of all randomized and nonrandomized controlled trials (RCTs and NCTs, respectively) that explored the maternal-neonatal outcomes of cervical osmotic dilators versus dinoprostone in promoting cervical ripening during labor induction.

STUDY DESIGN: Six major databases were screened until August 27, 2022. The quality of included studies was evaluated. The data were summarized as mean difference or risk ratio (RR) with 95% confidence interval (CI) in a random-effects model.

RESULTS: Overall, 14 studies with 15 arms were analyzed (n = 2,380 patients). Ten and four studies were RCTs and NCTs, respectively. The overall quality for RCTs varied (low risk n = 2, unclear risk n = 7, and high risk n = 1), whereas all NCTs had good quality (n = 4). For the primary endpoints, there was no significant difference between both groups regarding the rate of normal vaginal delivery (RR = 1.04, 95% CI: 0.95-1.14, p = 0.41) and rate of cesarean delivery (RR = 1.04, 95% CI: 0.93-1.17, p = 0.51). Additionally, there was no significant difference between both groups regarding the mean change in Bishop score and mean time from intervention to delivery. The rate of uterine hyperstimulation was significantly lower in the cervical osmotic dilator group. For the neonatal outcomes, during cervical ripening, the rate of fetal distress was significantly lower in the cervical osmotic dilator group. There was no significant difference between both groups regarding the mean Apgar scores, rate of meconium-stained amniotic fluid, rate of umbilical cord metabolic acidosis, rate of neonatal infection, and rate of neonatal intensive care unit admission.

CONCLUSION: During labor induction, cervical ripening with cervical osmotic dilators and dinoprostone had comparable maternal-neonatal outcomes. Cervical osmotic dilators had low risk of uterine hyperstimulation compared with dinoprostone. Overall, cervical osmotic dilators might be more preferred over dinoprostone in view of their analogous cervical ripening effects, comparable maternal-neonatal outcomes, and lack of drug-related adverse events.

KEY POINTS: · This is the first analysis of cervical osmotic dilators versus PGE2 for cervical ripening during labor.. · There was no difference between both arms regarding the rates of normal vaginal/cesarean deliveries.. · There was no difference between both arms regarding the rates of neonatal adverse events.. · Cervical osmotic dilators had significant lower risk of uterine hyperstimulation compared with PGE2.. · Cervical osmotic dilators may be superior to PGE2 in view of their similar efficacy and better safety..

PMID:37336231 | DOI:10.1055/s-0043-1770161

Int Immunopharmacol. 2023 Jun 17;121:110465. doi: 10.1016/j.intimp.2023.110465. Online ahead of print.

ABSTRACT

5-Fluorouracil (5-Fu) is the preferred drug in colorectal cancer treatment. Although 5-Fu treatment contributes to the increase in survival rates, long-term use of 5-Fu causes severe intestinal damage, eventually decreasing long-term survival. There is no standardtreatmentfor intestinal damage induced by 5-Fu. Our previous study found that 5-Fu-induced intestinal damage was connected to an increase in senescent cells, and antiaging drugs could relieve some adverse side effects caused by 5-Fu. Hence, it is essential to discover novel, potential antiaging therapeutic drugs for 5-Fu side effect treatment. According to the current study, Atorvastatincalcium (Ator) alleviated cellular senescence in human intestinal epithelial cells (HUVECs) and human umbilical vein endothelial cells (HIECs) caused by oxidative stress and 5-Fu. 5-Fu resulted in an increase in SA-β-Gal-positive cells, synchronously increased expression of aging-related proteins (p16), aging-related genes (p53, p21), and the senescence-associated secretory phenotype (SASP: IL-1β, IL-6, TNF-α), while Atorvastatincalcium (Ator) reversed the increase in these indicators. In the BALB/c mouse model, we confirmed that intestinal damage caused by 5-Fu is related to the increase in senescent cells and drug-induced inflammation, with the therapeutic effects of Ator. In addition, Ator increased the sensitivity of 5-Fu to chemotherapy in vitro and in vivo. Combination therapy significantly reduced HCT116 cell viability. Furthermore, Ator and 5-Fu present a cooperative effect on preventing the growth of tumors in CRC xenograft nude mice. In conclusion, our study demonstrates the value of Ator for treating intestinal damage. Moreover, Ator combined with 5-Fu increased the antitumor ability in CRC cells. Additionally, we provide a novel therapeutic protocol for CRC.

PMID:37336074 | DOI:10.1016/j.intimp.2023.110465

Circ Arrhythm Electrophysiol. 2023 Jun 19:e011574. doi: 10.1161/CIRCEP.122.011574. Online ahead of print.

ABSTRACT

BACKGROUND: Drug-induced or acquired long QT syndrome occurs as a result of the unintended disruption of cardiac repolarization due to drugs that block cardiac ion channels. These side effects have been responsible for the withdrawal of a range of drugs from market and are a common reason for termination of the development of new drugs in the preclinical stage. Existing approaches to risk prediction are expensive and overly sensitive meaning that recently there have been renewed efforts, largely driven by the comprehensive proarrhythmic assay initiative, to develop more accurate methods for allocation of proarrhythmic risk.

METHODS: In this study, we aimed to quantify changes in the morphology of the repolarization phase of the cardiac action potential as an indicator of proarrhythmia, supposing that these shape changes might precede the emergence of ectopic depolarizations that trigger arrhythmia. To do this, we describe a new method of quantifying action potential morphology by measuring the radius of curvature of the repolarization phase both in simulated action potentials, as well as in action potentials measured from induced pluripotent stem cell-derived cardiomyocytes. Features derived from the curvature signal were used as inputs for logistic regressions to predict proarrhythmic risk.

RESULTS: Optimal risk classifiers based on morphology were able to correctly classify risk to drugs in the comprehensive proarrhythmic assay initiative panels with very high accuracy (0.9375) and outperformed conventional metrics based on action potential duration at 90% repolarization, triangulation, and charge movement (qNet).

CONCLUSIONS: Analysis of action potential morphology in response to proarrhythmic drugs improves prediction of torsadogenic risk. Furthermore, morphology metrics can be measured directly from the action potential, potentially eliminating the burden of undertaking complex screens of potency and drug-binding kinetics against multiple cardiac ion channels. As such, this method has the potential to improve and streamline regulatory assessment of proarrhythmia in preclinical drug development.

PMID:37334695 | DOI:10.1161/CIRCEP.122.011574

Proc (Bayl Univ Med Cent). 2023 May 11;36(4):521-523. doi: 10.1080/08998280.2023.2205811. eCollection 2023.

ABSTRACT

An 8-year-old boy presented with his mother for evaluation of an erythematous rash 3 weeks after the start of dual BRAF-MEK inhibition with dabrafenib and trametinib for treatment of progression of low-grade glioma. Panniculitis has been reported as a rare adverse cutaneous event induced by BRAF inhibitors, MEK inhibitors, and the combined dual BRAF-MEK therapy. Based on the patient's history, clinical presentation, and histopathological findings, a diagnosis of drug-induced neutrophilic panniculitis was made. This case describes neutrophilic panniculitis as a potential cutaneous manifestation of dual BRAF-MEK inhibitor therapy and describes the management of such side effects. Neutrophilic panniculitis is a relatively rare manifestation, characterized by neutrophilic inflammation in the subcutaneous tissue. Additionally, this case serves as a reminder to consider the cutaneous side effects of such therapies, given that MEK and BRAF inhibitors are increasingly used to treat primary brain tumors in the pediatric population. Routine inspection and early management may improve patients' quality of life and enable continuation of anticancer therapy.

PMID:37334075 | PMC:PMC10269401 | DOI:10.1080/08998280.2023.2205811