Subst Abuse Treat Prev Policy. 2023 Jul 7;18(1):42. doi: 10.1186/s13011-023-00544-z.

ABSTRACT

BACKGROUND: Encephalopathy can occur from a non-fatal toxic drug event (overdose) which results in a partial or complete loss of oxygen to the brain, or due to long-term substance use issues. It can be categorized as a non-traumatic acquired brain injury or toxic encephalopathy. In the context of the drug toxicity crisis in British Columbia (BC), Canada, measuring the co-occurrence of encephalopathy and drug toxicity is challenging due to lack of standardized screening. We aimed to estimate the prevalence of encephalopathy among people who experienced a toxic drug event and examine the association between toxic drug events and encephalopathy.

METHODS: Using a 20% random sample of BC residents from administrative health data, we conducted a cross-sectional analysis. Toxic drug events were identified using the BC Provincial Overdose Cohort definition and encephalopathy was identified using ICD codes from hospitalization, emergency department, and primary care records between January 1st 2015 and December 31st 2019. Unadjusted and adjusted log-binomial regression models were employed to estimate the risk of encephalopathy among people who had a toxic drug event compared to people who did not experience a toxic drug event.

RESULTS: Among people with encephalopathy, 14.6% (n = 54) had one or more drug toxicity events between 2015 and 2019. After adjusting for sex, age, and mental illness, people who experienced drug toxicity were 15.3 times (95% CI = 11.3, 20.7) more likely to have encephalopathy compared to people who did not experience a drug toxicity event. People who were 40 years and older, male, and had a mental illness were at increased risk of encephalopathy.

CONCLUSIONS: There is a need for collaboration between community members, health care providers, and key stakeholders to develop a standardized approach to define, screen, and detect neurocognitive injury related to drug toxicity.

PMID:37420239 | PMC:PMC10329314 | DOI:10.1186/s13011-023-00544-z

BMJ Open. 2023 Jul 7;13(7):e067912. doi: 10.1136/bmjopen-2022-067912.

ABSTRACT

INTRODUCTION: Nurses frequently place a peripheral venous catheter during children's hospitalisation. Many studies suggest treatment of venipuncture-related pain. The administration of an equimolar mixture of oxygen and nitrous oxide (EMONO) is employed for pain control; however, no studies have analysed the association between EMONO and audiovisuals.The purpose of the study is to evaluate the effect of EMONO administration when combined with audiovisuals (EMONO+Audiovisual) versus EMONO alone on perceived pain, side effects and level of cooperation during peripheral venous access placement in children aged 2-5 years.

METHODS AND ANALYSIS: The first 120 eligible children admitted to the paediatric ward of the Lodi Hospital and presenting the indication for peripheral venous access will be enrolled. Sixty children will be randomly assigned to the experimental group (EMONO+Audiovisual) and 60 to the control group (EMONO alone).The Face, Legs, Activity, Cry, Consolability scale will be used to assess pain in the children aged 2-years old; pain in the children aged 3-5 years will be assessed using the Wong-Baker scale. The cooperation throughout the procedure will be measured using the Groningen Distress Rating Scale.

ETHICS AND DISSEMINATION: The Milan Area 1 Ethics Committee approved the study protocol (Experiment Registry No. 2020/ST/295). The trial results will be presented at conferences and published in peer-reviewed journals.

TRIAL REGISTRATION NUMBER: NCT05435118.

PMID:37419632 | DOI:10.1136/bmjopen-2022-067912

Georgian Med News. 2023 May;(338):115-116.

ABSTRACT

The pathogenesis of lichen planus and lichenoid-type reactions remains shrouded in mystery to this day, precisely because of the inability to perform acute/specific tests for reproduction of a particular type of reaction (in this case lichenoid) in order to prove a causal relationship. Nevertheless, the concept of molecular mimicry/antigen mimicry as a possible important pathogenetic inducer for lichen planus and lichenoid-type reactions, is increasingly becoming a topic of discussion and remains more than relevant at present. Disturbances in the integrity of tissue homeostasis- in one form or another, in fact, become a powerful generator of cross-mediated immunity, possibly directed at tissue-localized structures/structural elements/proteins or amino acids. The observation and reporting of this kind of disorders (even in the absence of the mentioned tests), as well as their parallel manifestation with a disease such as lichen planus (or lichenoid-type reaction), has led over the years to the validation of the now universal belief that the disease is multifactorially determined. And the causes of disruption of this integrity can be both external- infectious, meicamentous as well as internal- tumoral, paraneoplastic, etc. Medication induction or triggering of lichen planus by beta blockers has been observed and reported frequently over the years, and the clinical picture can vary and be extremely heterogeneous. We describe the first case in the world literature of a lichen planus after nebivolol administration that developed in the strictly restricted area of the glans penis. According to a reference in the medical literature, this is also the second case in the world literature of penile localized lichen planus after beta blocker intake. The other analogous one was recorded and described back in 1991 after propranolol intake.

PMID:37419483

PLoS One. 2023 Jul 7;18(7):e0288100. doi: 10.1371/journal.pone.0288100. eCollection 2023.

ABSTRACT

Ghana's rate of reporting adverse drug reaction (ADRs) over the past years has consistently been below the WHO standard despite utilizing the spontaneous or voluntary reporting system. While underreporting undermines the pharmacovigilance system and poses a huge threat to public health safety, there is limited information on the perspectives of healthcare workers directly involved in drug administration. The present study investigated the knowledge, attitude and practice of physicians and nurses at the Cape Coast Teaching Hospital (CCTH) towards spontaneous reporting of ADRs (SR-ADRs). A descriptive cross-sectional survey was employed in the study. Pre-tested (Cronbach's alpha value of 0.72) and validated questionnaires comprising 37 open-ended and close-ended questions were administered to 44 doctors and 116 nurses at the CCTH who had been practicing for at least six months prior to study. Out of the 160 administered questionnaires, 86 was administered face-to-face and the remaining via e-mails. Descriptive analysis was performed and the results were presented in simple frequencies and percentages. Binary logistic regression model was used to test association of the independent variables with SR-ADRs. With a response rate of 86.4% for physicians and 59.5% for nurses, 38 (35.5%) physicians and 69 (64.5%) nurses completed the questionnaires and returned same. Majority (82.3%, 88) of the respondents knew that it is their responsibility to report ADRs although their knowledge levels was found to be inadequate (that is ≤80%) in majority (66.7%) of the text items that assessed knowledge levels. On the attitude of respondents, it was found that 57% (61) of them agreed that under-reporting was due to complacency whereas 80.4% (86) of them agreed that it was due the lack of adequate training. On the issues of practice, the prevalence of encountering, assisting in the management, and reporting of ADRs were 26.1% (28), 17.8% (19) and 7.5% (8) respectively. Also, nurses were 1.22 times more likely to encounter a patient with ADRs and twice more likely to fill and forward ADR form than doctors during management. Respondents with more than six months but less than one year of practice experience were more likely (AOR = 1.38, 95% CI: 2.72-7.3) to encounter a patient with ADRs as compared to those with just six months of practice experience. Furthermore, male respondents were more likely (AOR = 2.42, 95% CI: 1-5.85) to encounter patients with ADRs but less likely (AOR = 0.49, 95% CI: 0.91-2.6) to fill and forward ADR form compared to their female counterparts. In conclusion, doctors and nurses at the CCTH had inadequate knowledge about ADRs and its existing pharmacovigilance systems, thus accounting for the low spontaneous ADRs reporting in the facility.

PMID:37418384 | PMC:PMC10328237 | DOI:10.1371/journal.pone.0288100

Hematology. 2023 Dec;28(1):2231738. doi: 10.1080/16078454.2023.2231738.

ABSTRACT

OBJECTIVE: The remarkable effect of arsenic trioxide (ATO) was verified, but side effects are generally observed in acute promyelocytic leukemia (APL) patients, especially leukocytosis and hepatotoxicity. Our aims are to study predictors and reduce ATO-induced side effects without inhibiting efficacy.

METHODS: Sulfhydryl in ATO-treated APL patients was detected by the Spectra Max M5 microplate reader. And patients were divided into high and low sulfhydryl groups according to median sulfhydryl concentration. The onset time of leukocytosis and the peak value of WBC were compared . Correlations between hepatotoxicity indicators and sulfhydryl concentrations were analysed.

RESULTS: The concentration of sulfhydryl before treatment was significantly higher in the high sulfhydryl group. Leukocytosis ((7.0 ± 5.5) vs. (14.6 ± 8.5) day) and the peak value of WBC occurred earlier in the low sulfhydryl group ((10.8 ± 5.9) vs. (19.3 ± 5.5) day) than in the high group, and the peak value was significantly lower in the low sulfhydryl group ((24.04 ± 15.05) × 109/L) than in the high group ((42.95 ± 25.57) × 109/L). The elevated liver enzymes were smaller in the higher sulfhydryl group between time points before treatment and the treatment one week later (ΔALT 66.57 vs. 9.85 U/L, ΔAST 59.52 vs. 17.76 U/L), as between time points before treatment and peak value. There was a negative correlation between sulfhydryl and elevated liver enzymes.

CONCLUSIONS: Higher sulfhydryl compounds contribute to ameliorating ATO-induced leukocytosis and hepatotoxicity in APL patients. The low sulfhydryl before treatment can advance the onset of leukocytosis. For patients with higher sulfhydryl in the early stage, close monitoring of liver enzymes is warranted instead of prophylactic applying any hepatoprotective intervention, to maintain ATO efficacy.

PMID:37417768 | DOI:10.1080/16078454.2023.2231738

Reg Anesth Pain Med. 2023 Jul 6:rapm-2023-104482. doi: 10.1136/rapm-2023-104482. Online ahead of print.

ABSTRACT

BACKGROUND: Ketamine has garnered increased interest for its promising applications in chronic pain treatment, particularly in cases where conventional therapies have proven insufficient. Nevertheless, despite its potential advantages, ketamine remains classified as a third-line medication for pain management. While there are well-documented reactions to ketamine such as hypertension and tachycardia, not much is known about its relationship to cortisol. In this case report, we explicate the administration of ketamine in a patient presenting with atypical facial pain, examining its multifaceted effects on cortisol levels and concurrent pain management.

CASE PRESENTATION: A patient with a history of Cushing's disease underwent multiple resections of a pituitary tumor. Afterwards, the patient began experiencing a burning-like pain on the left side of the face. The discomfort was initially treated with a variety of neuromodulatory and anti-inflammatory medications, which caused intolerable side effects and were not effective for pain. As a final recourse, we initiated a regimen of oral compounded ketamine at 5-10 mg three times daily as needed. The patient exhibited marked amelioration in their pain symptoms; however, there was an elevation in their baseline cortisol. In view of the potential risk of inducing Cushing's syndrome, the administration of daily ketamine was discontinued.

CONCLUSION: While ketamine is primarily known to control pain through the antagonization of N-methyl-D-aspartate receptors, its effects on cortisol may also contribute to its analgesic properties. Physicians should be aware of the potential for these interactions, particularly when treating patients with a predisposition to hormonal imbalances.

PMID:37419510 | DOI:10.1136/rapm-2023-104482

Prehosp Emerg Care. 2023 Jul 7:1-21. doi: 10.1080/10903127.2023.2234491. Online ahead of print.

ABSTRACT

Objective: Varying rates of complications have been reported for prehospital sedation with ketamine, and the relationship to dosing has not been studied on a large scale. We evaluated the association between prehospital ketamine dosing and rates of intubations and other adverse events in patients with behavioral emergencies.Methods: Using the 2018/2019 ESO public-use research datasets, we included all non-traumatic, adult behavioral and drug-related EMS encounters with ketamine administration. Based on consensus guidelines, we stratified patients into "above" and "at/below" the maximum dosing for sedation (2 mg/kg IV/IO or 5 mg/kg IM) using the highest single dose of ketamine given. We created propensity scores for matched subjects using 1:1 propensity score matching. Using logistic regression, we compared rates of intubation and other airway interventions, antipsychotic coadministration, improvement reported by EMS, hypoxia, hypotension, and cardiac arrest between the two groups.Results: We included 2,383 patients: 478 in the above and 1,905 in the at/below dose group. Above dose ketamine was associated with a higher rate of intubation or supraglottic airway placement (6.4% v 3.3%, OR 2.0, 95% CI 1.00-3.90). Other airway interventions were similar (40.0% v 40.0%, OR 1, 95% CI 0.80-1.30). The above dose group also showed a higher rate of improvement noted by EMS clinicians (92.5% v 88.7%, OR 1.6, 95% CI 1.01-2.40). The rates of antipsychotic coadministration, hypoxia, hypotension, and cardiac arrest were similar between the cohorts.Conclusions: Patients given ketamine doses above consensus recommendations for sedation appeared more likely to receive prehospital intubation, but not more likely to experience other adverse events.

PMID:37418327 | DOI:10.1080/10903127.2023.2234491

Expert Opin Drug Saf. 2023 Jul 7. doi: 10.1080/14740338.2023.2234825. Online ahead of print.

ABSTRACT

BACKGROUND: Drug-induced seizures are a common occurrence in clinical practice, with research indicating that around 6% of initial seizures are due to drug toxicity. The use of antibiotics is one such cause of drug-related seizures. Previous systematic review has identified specific antibiotics that pose a risk of seizures, but a comprehensive analysis of a large patient sample is needed to determine the risk associated with various drugs.

OBJECTIVE: This study aimed to evaluate the association between seizures and various antibiotics that are presently accessible.

METHODS: To identify potential risk signals from the US Food and Drug Administration adverse event reporting system (FAERS) database, a disproportionality analysis was conducted. The reporting odds ratio (ROR) using the frequency approach and the information component (IC) using the Bayesian approach were used to detect signals. The median time-to-onset of seizure, as well as the Weibull distribution parameters were calculated to analyze the onset time.

RESULTS: A total of 14,407,157 FAERS reports were analyzed.10 antibiotics were associated with seizures that were defined by 41 preferred terms. Onset time were aligned with the wear out failure type profile.

CONCLUSION: This study identified 10 antibiotics that showed significant associations with seizures. Imipenem-cilastatin had the highest seizure ROR.

PMID:37417744 | DOI:10.1080/14740338.2023.2234825

Signal Transduct Target Ther. 2023 Jul 7;8(1):262. doi: 10.1038/s41392-023-01469-6.

ABSTRACT

Since their invention in the early 2000s, tyrosine kinase inhibitors (TKIs) have gained prominence as the most effective pathway-directed anti-cancer agents. TKIs have shown significant utility in the treatment of multiple hematological malignancies and solid tumors, including chronic myelogenous leukemia, non-small cell lung cancers, gastrointestinal stromal tumors, and HER2-positive breast cancers. Given their widespread applications, an increasing frequency of TKI-induced adverse effects has been reported. Although TKIs are known to affect multiple organs in the body including the lungs, liver, gastrointestinal tract, kidneys, thyroid, blood, and skin, cardiac involvement accounts for some of the most serious complications. The most frequently reported cardiovascular side effects range from hypertension, atrial fibrillation, reduced cardiac function, and heart failure to sudden death. The potential mechanisms of these side effects are unclear, leading to critical knowledge gaps in the development of effective therapy and treatment guidelines. There are limited data to infer the best clinical approaches for the early detection and therapeutic modulation of TKI-induced side effects, and universal consensus regarding various management guidelines is yet to be reached. In this state-of-the-art review, we examine multiple pre-clinical and clinical studies and curate evidence on the pathophysiology, mechanisms, and clinical management of these adverse reactions. We expect that this review will provide researchers and allied healthcare providers with the most up-to-date information on the pathophysiology, natural history, risk stratification, and management of emerging TKI-induced side effects in cancer patients.

PMID:37414756 | PMC:PMC10326056 | DOI:10.1038/s41392-023-01469-6

Science. 2023 Jul 7;381(6653):18-19. doi: 10.1126/science.adj5607. Epub 2023 Jul 6.

ABSTRACT

Details emerge for uncommon cases of neurologic complications, blood pressure swings, and other side effects.

PMID:37410823 | DOI:10.1126/science.adj5607

J Infect Dev Ctries. 2023 Jun 30;17(6):812-818. doi: 10.3855/jidc.17136.

ABSTRACT

INTRODUCTION: Coronavirus disease-19 (COVID-19) is known to cause severe disease in chronic kidney disease and maintenance dialysis patients. We aim to report the outcome of COVID-19 and the adverse effects of Remdesivir (RDV) in patients with renal failure.

METHODOLOGY: A retrospective observational study included all admitted patients with COVID-19 who received Remdesivir. Clinical characteristics and outcomes were compared in patients with renal failure (RF) and non-renal failure (NRF). We also evaluated RDV-associated nephrotoxicity and observed renal functions during antiviral treatment.

RESULTS: A total of 142 patients received RDV, 38 (26.76%) in RF and 104 (73.23%) in the non-RF group. The median absolute lymphocyte count was low while C-reactive protein, ferritin, and D-dimer were significantly high on admission in the RF group. A significant number of patients in the RF group required ICU admission (58% vs. 35% p = 0.01) and expired (29% vs. 12.5 p = 0.02). Among survivors and non-survivors in the RF group, raised inflammatory markers and low platelet count on presentation were significantly associated with high mortality. Median serum creatinine (mg/dL) was 0.88 on admission, remained at 0.85 in the NRF group, and improved from 4.59 to 3.87 (mg/dL) after receiving five days of RDV in the RF group.

CONCLUSIONS: COVID-19 in renal failure has a high risk for ICU admissions leading to increased mortality. Multiple comorbidities and raised inflammatory markers are predictors of poor outcomes. We observed no significant drug-related adverse effects, and none of our patients required discontinuation of RDV due to worsening renal function.

PMID:37406071 | DOI:10.3855/jidc.17136

Front Immunol. 2023 Jun 19;14:1190850. doi: 10.3389/fimmu.2023.1190850. eCollection 2023.

ABSTRACT

PD-1 inhibitors, as one of commonly used immune checkpoint inhibitors, enable T-cell activation and prevent immune escape by blocking the PD-1/PD-L1 signaling pathway. They have transformed the treatment landscape for cancer in recent years, due to the advantages of significantly prolonging patients' survival and improving their life quality. However, the ensuing unpredictable immune-related adverse effects (irAEs) plague clinicians, such as colitis and even potentially fatal events like intestinal perforation and obstruction. Therefore, understanding the clinical manifestations and grading criteria, underlying mechanisms, available diverse therapies, accessible biomarkers, and basis for risk stratification is of great importance for the management. Current evidence suggests that irAEs may be a marker of clinical benefit to immunotherapy in patients, so whether to discontinue PD-1 inhibitors after the onset of irAEs and rechallenge after remission of irAEs requires further evaluation of potential risk-reward ratios as well as more data from large-scale prospective studies to fully validate. At the end, the rare gastrointestinal toxicity events caused by PD-1 inhibitors are also sorted out. This review provides a summary of available data on the gastrointestinal toxicity profile caused by PD-1 inhibitors, with the aim of raising clinicians' awareness in daily practice, so that patients can safely benefit from therapy.

PMID:37404814 | PMC:PMC10315615 | DOI:10.3389/fimmu.2023.1190850

Cancer Diagn Progn. 2023 Jul 3;3(4):498-503. doi: 10.21873/cdp.10246. eCollection 2023 Jul-Aug.

ABSTRACT

BACKGROUND/AIM: Immune-checkpoint inhibitors have recently shown great promise in treating various cancers, but often cause immune-related adverse events (irAEs). Simultaneous drug-induced hypothyroidism and isolated adrenocorticotropic hormone (ACTH) deficiency are rare irAEs. This combination of irAEs is associated with paradoxical endocrine dysfunction characterized by large amounts of thyroid-stimulating hormone (TSH) and small amounts of ACTH in the anterior lobe of the pituitary. We herein report a case of hypothyroidism with isolated ACTH deficiency during pembrolizumab therapy for recurrent lung cancer.

CASE REPORT: Our patient was a 66-year-old man with recurrence of squamous cell lung carcinoma. Four months after chemotherapy that included pembrolizumab, the patient presented with general fatigue and laboratory tests showed high concentrations of TSH with low concentrations of free-T4. He was diagnosed with hypothyroidism and levothyroxine was prescribed. His ACTH concentration was found to be low 1 week later when he developed an acute adrenal crisis with associated hyponatraemia. We then changed his diagnosis to concurrent hypothyroidism with isolated ACTH deficiency. His condition improved after 3 weeks of administration of cortisol.

CONCLUSION: It is difficult to diagnose a concurrent paradoxical endocrine disorder, such as hypothyroidism with isolated ACTH deficiency, as in the present case. Physicians should pay attention to symptoms and laboratory data to identify various types of endocrine disorders as irAEs.

PMID:37405219 | PMC:PMC10316054 | DOI:10.21873/cdp.10246

Front Surg. 2023 Jun 19;10:1151327. doi: 10.3389/fsurg.2023.1151327. eCollection 2023.

ABSTRACT

INTRODUCTION: Haemorrhoidal disease (HD) affects a considerable portion of the adult population. The aim of this study is to confirm the safety and efficacy of the treatments and to report the long-term outcomes of Sclerotherapy (ST) and Mucopexy and Haemorrhoidal Dearterialization (MHD) performed over the last 4 years in a single tertiary centre. The secondary outcome is to evaluate the usefulness of both techniques and to demonstrate how those can be associated as a bridge to surgery.

MATERIALS AND METHODS: Patients affected by second-third-degree haemorrhoids and undergoing ST or non-Doppler guided MHD between 2018 and 2021 were enrolled. Safety and efficacy, recurrence rate, Haemorrhoid Severity Score (HSS) and pain resulting from both techniques were evaluated.

RESULTS: Out of 259 patients, 150 underwent ST. Further, 122 (81.3%) patients were male and 28 (18.7%) were female. The mean age was 50.8 (range 34-68) years. Most of the patients (103, 68.6%) were affected by second-degree HD, while 47 (31.4%) were affected by third-degree HD. The overall success rate was 83.3%. The median pre-operative HSS score was 3 (IQR 0-4, p = 0.04) and at 2 year the median HSS was 0 (IQR 0-1, p = 0.03). No intraoperative complications and no drug-related side effects occurred. The mean follow-up for ST was 2 years (range 1-4; SD ±0.88). MHD was performed on 109 patients. In detail, 80 patients (73.4%) were male while 29 patients (26.6%) were female. The mean age in this group was 51.3 (range 31-69). Further, 72 patients (66.1%) were affected by third-degree HD and 37 (33.9%) by second-degree HD. The median HSS score was 9 (IQR 8-10, p = 0.001) preoperatively two years after treatment was 0 (IQR 0-1, p = 0.004). Major complications occurred in three patients (2.75%). The overall success rate was 93.5% (second degree 89.2% vs. third degree 95.8%). The mean follow-up for MHD was 2 years (range 1-4; SD ±0.68).

CONCLUSIONS: The results confirm the usefulness of those techniques, which can be considered safe and easily repeatable procedures, with a low recurrence rate after 2 years of median follow-up.

PMID:37405058 | PMC:PMC10317504 | DOI:10.3389/fsurg.2023.1151327

J Transl Med. 2023 Jul 4;21(1):432. doi: 10.1186/s12967-023-04272-7.

ABSTRACT

OBJECTIVE: Despite advances in pharmacology, the treatment of schizophrenia (SZ) remains a challenge due to relapse after antipsychotic discontinuation and multiple adverse effects of antipsychotics. We hypothesized that a low dose of risperidone in combination with sertraline would reduce serious adverse effects without decreasing treatment response. This study aimed to examine the efficacy, safety, and tolerability of low-dose risperidone combined with sertraline to reduce risperidone dose and serious adverse effects in first-episode and medication-naive (FEMN) SZ patients.

METHODS: A total of 230 patients with FEMN SZ were randomly assigned to receive low-dose risperidone in combination with sertraline (RS group) or regular-dose risperidone (control group). The Positive and Negative Syndrome Scale (PANSS), Hamilton Depression Rating Scale (HAMD), and Personal and Social Performance Scale (PSP) were assessed at baseline and the end of the first, second, third, and sixth months. In addition, serum prolactin levels and extrapyramidal symptoms were measured at baseline and follow-up.

RESULTS: Repeated measures ANCOVA showed significant interaction effects of treatment by time on psychotic symptoms, as well as HAMD, PSP scores, prolactin levels, and extrapyramidal symptoms (all p < 0.05). Compared with the control group, the RS group had greater decreases in PANSS total score and its subscores and HAMD score (all p < 0.01) and a greater increase in PSP total score (p < 0.01). Notably, side effects were lower in the RS group relative to the control group. Improvements in HAMD and PANSS total scores, changes in prolactin levels and gender predicted improvements in PSP from baseline to month 6.

CONCLUSIONS: Our study suggests that low-dose risperidone in combination with sertraline was more effective for psychotic symptoms and psychosocial functioning, with significantly fewer adverse effects in patients with FEMN SZ.

TRIAL REGISTRATION NUMBER: ClinicalTrials.gov, NCT04076371.

PMID:37403159 | DOI:10.1186/s12967-023-04272-7

Syst Rev. 2023 Jul 3;12(1):112. doi: 10.1186/s13643-023-02273-7.

ABSTRACT

BACKGROUND: Systematic reviews that assess the benefits of interventions often do not completely capture all dimensions of the adverse effects. This cross-sectional study (part 1 of 2 studies) assessed whether adverse effects were sought, whether the findings on these effects were reported, and what types of adverse effects were identified in systematic reviews of orthodontic interventions.

METHODS: Systematic reviews of orthodontic interventions on human patients of any health status, sex, age, and demographics, and socio-economic status, in any type of setting assessing any type of adverse effect scored at any endpoint or timing were eligible. The Cochrane Database of Systematic Reviews and 5 leading orthodontic journals were manually searched for eligible reviews between August 1 2009 and July 31 2021. Study selection and data extraction was conducted by two researchers independently. Prevalence proportions were calculated for four outcomes on seeking and reporting of adverse effects of orthodontic interventions. Univariable logistic regression models were used to determine the association between each one of these outcomes and the journal in which the systematic review was published using the eligible Cochrane reviews as reference.

RESULTS: Ninety-eight eligible systematic reviews were identified. 35.7% (35/98) of reviews defined seeking of adverse effects as a research objective, 85.7% (84/98) sought adverse effects, 84.7% (83/98) reported findings related to adverse effects, and 90.8% (89/98) considered or discussed potential adverse effects in the review. Reviews in the journal Orthodontics and Craniofacial Research compared with Cochrane reviews had approximately 7 times the odds (OR 7.20, 95% CI 1.08 to 47.96) to define seeking of adverse effects in the research objectives. Five of the 12 categories of adverse effects accounted for 83.1% (162/195) of all adverse effects sought and reported.

CONCLUSIONS: Although the majority of included reviews sought and reported adverse effects of orthodontic interventions, end-users of these reviews should beware that these findings do not give the complete spectrum on these effects and that they could be jeopardized by the risk of non-systematically assessing and reporting of adverse effects in these reviews and in the primary studies that feed them. Much research is ahead such as developing core outcome sets on adverse effects of interventions for both primary studies and systematic reviews.

PMID:37400925 | PMC:PMC10318679 | DOI:10.1186/s13643-023-02273-7

Zhonghua Gan Zang Bing Za Zhi. 2023 Jun 20;31(6):659-663. doi: 10.3760/cma.j.cn501113-20230418-00174.

ABSTRACT

Statins are a kind of prescription drug that is widely used to treat hyperlipidemia, coronary artery disease, and other atherosclerotic diseases. A common side effect of statin use is a mild rise in liver aminotransferases, which occurs in less than 3% of patients. Statin-related liver injury is most commonly caused by atorvastatin and simvastatin, but severe liver injury is uncommon. Therefore, understanding and evaluating hepatotoxicity and weighing the benefits and risks is of great significance to better realize the protective effect of statins.

PMID:37400395 | DOI:10.3760/cma.j.cn501113-20230418-00174

Zhonghua Gan Zang Bing Za Zhi. 2023 Jun 20;31(6):653-658. doi: 10.3760/cma.j.cn501113-20230418-00172.

ABSTRACT

Drug-induced liver injury (DILI) risk prediction, diagnosis establishment, clinical management, and all other aspects are facing great challenges. Although the current understanding of its pathogenesis is still incomplete, research over the past 20 years has shown that genetic susceptibility may play an important role in the occurrence and development of DILI. In recent years, pharmacogenomics studies have further revealed the association between human leukocyte antigen (HLA) genes, some non-HLA genes, and hepatotoxicity from certain drugs. However, due to the lack of well-designed, prospective, large-sample cohort validation and low positive predictive values, there may still be some way to go before the current results can be truly translated into clinical practice for precise prediction and prevention of DILI risk.

PMID:37400394 | DOI:10.3760/cma.j.cn501113-20230418-00172

BMC Med. 2023 Jul 3;21(1):230. doi: 10.1186/s12916-023-02927-2.

ABSTRACT

BACKGROUND: Surgery is a common treatment strategy for patients with neurofibromatosis type 1 (NF1)-related plexiform neurofibroma (PN) and has limited efficacy. FCN-159 is a novel anti-tumorigenic drug via selective inhibition of MEK1/2. This study assesses the safety and efficacy of FCN-159 in patients with NF1-related PN.

METHODS: This is a multicenter, open-label, single-arm, phase I dose-escalation study. Patients with NF1-related PN that was non-resectable or unsuitable for surgery were enrolled; they received FCN-159 monotherapy daily in 28-day cycles.

RESULTS: Nineteen adults were enrolled in the study, 3 in 4 mg, 4 in 6 mg, 8 in 8 mg, and 4 in 12 mg. Among patients included in dose-limiting toxicity (DLT) analysis, DLTs (grade 3 folliculitis) were reported in 1 of 8 patients (16.7%) receiving 8 mg and 3 of 3 (100%) patients receiving 12 mg. The maximum tolerated dose was determined to be 8 mg. FCN-159-related treatment-emergent adverse events (TEAEs) were observed in 19 patients (100%); most of which were grade 1 or 2. Nine (47.4%) patients reported grade 3 study-drug-related TEAEs across all dose levels, including four experiencing paronychia and five experiencing folliculitis. Of the 16 patients analyzed, all (100%) had reduced tumor size and six (37.5%) achieved partial responses; the largest reduction in tumor size was 84.2%. The pharmacokinetic profile was approximately linear between 4 and 12 mg, and the half-life supported once daily dosing.

CONCLUSIONS: FCN-159 was well tolerated up to 8 mg daily with manageable adverse events and showed promising anti-tumorigenic activity in patients with NF1-related PN, warranting further investigation in this indication.

TRIAL REGISTRATION: ClinicalTrials.gov, NCT04954001. Registered 08 July 2021.

PMID:37400844 | DOI:10.1186/s12916-023-02927-2

Med J Aust. 2023 Jul 3. doi: 10.5694/mja2.52019. Online ahead of print.

ABSTRACT

OBJECTIVE: To estimate the effectiveness of vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for protecting people in a largely coronavirus disease 2019 (COVID-19)-naïve regional population from hospitalisation with symptomatic COVID-19.

DESIGN: Retrospective cohort study; analysis of positive SARS-CoV-2 polymerase chain reaction (PCR) test results linked with Central Queensland hospitals admissions data and Australian Immunisation Register data.

SETTING, PARTICIPANTS: Adult residents of Central Queensland, 1 January - 31 March 2022.

MAIN OUTCOME MEASURES: Vaccine effectiveness (1 - relative risk of hospitalisation for vaccinated and unvaccinated people) with respect to protecting against hospitalisation with symptomatic COVID-19 after primary vaccination course only (two doses of an approved SARS-CoV-2 vaccine) and after a booster vaccine dose.

RESULTS: Positive SARS-CoV-2 test results were recorded during 1 January - 31 March 2022 for 9682 adults, 7244 of whom had been vaccinated (75%); 5929 people were aged 40 years or younger (62%), 5180 were women (52%). Forty-seven people were admitted to hospital with COVID-19 (0.48%), four required intensive care (0.04%); there were no in-hospital deaths. Vaccine effectiveness was 69.9% (95% confidence interval [CI], 44.3-83.8%) for people who had received only a primary vaccination course and 81.8% (95% CI, 39.5-94.5%) for people who had also received a booster. Of the 665 Aboriginal and Torres Strait Islander adults with positive SARS-CoV-2 test results, 401 had been vaccinated (60%). Six Indigenous people were hospitalised with symptomatic COVID-19 (0.9%); vaccine effectiveness was 69.4% (95% CI, -56.5% to 95.8%) for Indigenous people who had received a primary vaccination course only or the primary course and a booster.

CONCLUSION: The hospitalisation rate for Central Queensland people with PCR-confirmed Omicron variant SARS-CoV-2 infections during the first quarter of 2022 was low, indicating the protection afforded by vaccination and the value of booster vaccine doses.

PMID:37400415 | DOI:10.5694/mja2.52019