JAMA Netw Open. 2024 Feb 5;7(2):e240572. doi: 10.1001/jamanetworkopen.2024.0572.

NO ABSTRACT

PMID:38416493 | DOI:10.1001/jamanetworkopen.2024.0572

Cochrane Database Syst Rev. 2024 Feb 28;2:CD007837. doi: 10.1002/14651858.CD007837.pub3.

ABSTRACT

BACKGROUND: Adolescent idiopathic scoliosis (AIS) is a pathology that changes the three-dimensional shape of the spine and trunk. While AIS can progress during growth and cause cosmetic issues, it is usually asymptomatic. However, a final spinal curvature above the critical threshold of 30° increases the risk of health problems and curve progression in adulthood. The use of therapeutic exercises (TEs) to reduce the progression of AIS and delay or avoid other, more invasive treatments is still controversial.

OBJECTIVES: To evaluate the effectiveness of TE, including generic therapeutic exercises (GTE) and physiotherapeutic scoliosis-specific exercises (PSSE) in treating AIS, compared to no treatment, other non-surgical treatments, or between treatments.

SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, four other databases, and two clinical trials registers to 17 November 2022. We also screened reference lists of articles.

SELECTION CRITERIA: Randomised controlled trials (RCTs) comparing TE with no treatment, other non-surgical treatments (braces, electrical stimulation, manual therapy), and different types of exercises. In the previous version of the review, we also included observational studies. We did not include observational studies in this update since we found sufficient RCTs to address our study aims.

DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodology. Our major outcomes were progression of scoliosis (measured by Cobb angle, trunk rotation, progression, bracing, surgery), cosmetic issues (measured by surface measurements and perception), and quality of life (QoL). Our minor outcomes were back pain, mental health, and adverse effects.

MAIN RESULTS: We included 13 RCTs (583 participants). The percentage of females ranged from 50% to 100%; mean age ranged from 12 to 15 years. Studies included participants with Cobb angles from low to severe. We judged 61% of the studies at low risk for random sequence generation and 46% at low risk for allocation concealment. None of the studies could blind participants and personnel. We judged the subjective outcomes at high risk of performance and detection bias, and the objective outcomes at high risk of detection bias in six studies and at low risk of bias in the other six studies. One study did not assess any objective outcomes. Comparing TE versus no treatment, we are very uncertain whether TE reduces the Cobb angle (mean difference (MD) -3.6°, 95% confidence interval (CI) -5.6 to -1.7; 2 studies, 52 participants). Low-certainty evidence indicates PSSE makes little or no difference in the angle of trunk rotation (ATR) (MD -0.8°, 95% CI -3.8 to 2.1; 1 study, 45 participants), may reduce the waist asymmetry slightly (MD -0.5 cm, 95% CI -0.8 to -0.3; 1 study, 45 participants), and may result in little to no difference in the score of cosmetic issues measured by the Spinal Appearance Questionnaire (SAQ) General (MD 0.7 points, 95% CI -0.1 to 1.4; 1 study, 16 participants). PSSE may result in little to no difference in self-image measured by the Scoliosis Research Society - 22 Patient Questionnaire (SRS-22) (MD 0.3 points, 95% CI -0.3 to 0.9; 1 study, 16 participants) and improve QoL slightly measured by SRS-22 Total score (MD 0.3 points, 95% CI 0.1 to 0.4; 2 studies, 61 participants). Only Cobb angle results were clinically meaningful. Comparing PSSE plus bracing versus bracing, low-certainty evidence indicates PSSE plus bracing may reduce Cobb angle (-2.2°, 95% CI -3.8 to -0.7; 2 studies, 84 participants). Comparing GTE plus other non-surgical interventions versus other non-surgical interventions, low-certainty evidence indicates GTE plus other non-surgical interventions may reduce Cobb angle (MD -8.0°, 95% CI -11.5 to -4.5; 1 study, 80 participants). We are uncertain whether PSSE plus other non-surgical interventions versus other non-surgical interventions reduces Cobb angle (MD -7.8°, 95% CI -12.5 to -3.1; 1 study, 18 participants) and ATR (MD -8.0°, 95% CI -12.7 to -3.3; 1 study, 18 participants). PSSE plus bracing versus bracing alone may make little to no difference in subjective measurement of cosmetic issues as measured by SAQ General (-0.2 points, 95% CI -0.9 to 0.5; 1 study, 34 participants), self-image score as measured by SRS-22 Self-Image (MD 0.1 points, 95% CI -0.3 to 0.5; 1 study, 34 participants), and QoL measured by SRS-22 Total score (MD 0.2 points, 95% CI -0.1 to 0.5; 1 study, 34 participants). None of these results were clinically meaningful. Comparing TE versus bracing, we are very uncertain whether PSSE allows progression of Cobb angle (MD 2.7°, 95% CI 0.3 to 5.0; 1 study, 60 participants), changes self-image measured by SRS-22 Self-Image (MD 0.1 points, 95% CI -1.0 to 1.1; 1 study, 60 participants), and QoL measured by SRS-22 Total score (MD 3.2 points, 95% CI 2.1 to 4.2; 1 study, 60 participants). None of these results were clinically meaningful. Comparing PSSE with GTE, we are uncertain whether PSSE makes little or no difference in Cobb angle (MD -3.0°, 95% CI -8.2 to 2.1; 4 studies, 192 participants; very low-certainty evidence). PSSE probably reduces ATR (clinically meaningful) (-MD 3.0°, 95% CI -3.4 to -2.5; 2 studies, 138 participants). We are uncertain about the effect of PSSE on QoL measured by SRS-22 Total score (MD 0.26 points, 95% CI 0.11 to 0.62; 3 studies, 168 participants) and on self-image measured by SRS-22 Self-Image and Walter Reed Visual Assessment Scale (standardised mean difference (SMD) 0.77, 95% CI -0.61 to 2.14; 3 studies, 168 participants). Further, low-certainty evidence indicates that 38/100 people receiving GTE may progress more than 5° Cobb versus 7/100 receiving PSSE (risk ratio (RR) 0.19, 95% CI 0.67 to 0.52; 1 study, 110 participants). None of the included studies assessed adverse effects.

AUTHORS' CONCLUSIONS: The evidence on the efficacy of TE is currently sparse due to heterogeneity, small sample size, and many different comparisons. We found only one study following participants to the end of growth showing the efficacy of PSSE over TE. This result was weakened by adding studies with short-term results and unclear preparation of treating physiotherapists. More RCTs are needed to strengthen the current evidence and study other highly clinically relevant outcomes such as QoL, psychological and cosmetic issues, and back pain.

PMID:38415871 | DOI:10.1002/14651858.CD007837.pub3

Cochrane Database Syst Rev. 2024 Feb 28;2:CD007156. doi: 10.1002/14651858.CD007156.pub3.

ABSTRACT

BACKGROUND: Oral submucous fibrosis (OSF) is a chronic disease of the oral cavity that causes progressive constriction of the cheeks and mouth accompanied by severe pain and reduced mouth opening. OSF has a significant impact on eating and swallowing, affecting quality of life. There is an increased risk of oral malignancy in people with OSF. The main risk factor for OSF is areca nut chewing, and the mainstay of treatment has been behavioural interventions to support habit cessation. This review is an update of a version last published in 2008.

OBJECTIVES: To evaluate the benefits and harms of interventions for the management of oral submucous fibrosis.

SEARCH METHODS: We used standard, extensive Cochrane search methods. The latest search date was 5 September 2022.

SELECTION CRITERIA: We considered randomised controlled trials (RCTs) of adults with a biopsy-confirmed diagnosis of OSF treated with systemic, locally delivered or topical drugs at any dosage, duration or delivery method compared against placebo or each other. We considered surgical procedures compared against other treatments or no active intervention. We also considered other interventions such as physiotherapy, ultrasound or alternative therapies.

DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods. Our primary outcomes were 1. participant-reported resumption of normal eating, chewing and speech; 2. change or improvement in maximal mouth opening (interincisal distance); 3. improvement in range of jaw movement; 4. change in severity of oral/mucosal burning pain/sensation; 5.

ADVERSE EFFECTS: Our secondary outcomes were 6. quality of life; 7. postoperative discomfort or pain as a result of the intervention; 8. participant satisfaction; 9. hospital admission; 10. direct costs of medication, hospital bed days and any associated inpatient costs for the surgical interventions. We used GRADE to assess certainty of evidence for each outcome.

MAIN RESULTS: We included 30 RCTs (2176 participants) in this updated review. We assessed one study at low risk of bias, five studies at unclear risk of bias and 24 studies at high risk of bias. We found diverse interventions, which we categorised according to putative mechanism of action. We present below our main findings for the comparison 'any intervention compared with placebo or no active treatment' (though most trials included habit cessation for all participants). Results for head-to-head comparisons of active interventions are presented in full in the main review. Any intervention versus placebo or no active treatment Participant-reported resumption of normal eating, chewing and speech No studies reported this outcome. Interincisal distance Antioxidants may increase mouth opening (indicated by interincisal distance (mm)) when measured at less than three months (mean difference (MD) 3.11 mm, 95% confidence interval (CI) 0.46 to 5.77; 2 studies, 520 participants; low-certainty evidence), and probably increase mouth opening slightly at three to six months (MD 8.83 mm, 95% CI 8.22 to 9.45; 3 studies, 620 participants; moderate-certainty evidence). Antioxidants may make no difference to interincisal distance at six-month follow-up or greater (MD -1.41 mm, 95% CI -5.74 to 2.92; 1 study, 90 participants; low-certainty evidence). Pentoxifylline may increase mouth opening slightly (MD 1.80 mm, 95% CI 1.02 to 2.58; 1 study, 106 participants; low-certainty evidence). However, it should be noted that these results are all less than 10 mm, which could be considered the minimal change that is meaningful to someone with oral submucous fibrosis. The evidence was very uncertain for all other interventions compared to placebo or no active treatment (intralesional dexamethasone injections, pentoxifylline, hydrocortisone plus hyaluronidase, physiotherapy). Burning sensation Antioxidants probably reduce burning sensation visual analogue scale (VAS) scores at less than three months (MD -30.92 mm, 95% CI -31.57 to -30.27; 1 study, 400 participants; moderate-certainty evidence), at three to six months (MD -70.82 mm, 95% CI -94.39 to -47.25; 2 studies, 500 participants; moderate-certainty evidence) and at more than six months (MD -27.60 mm, 95% CI -36.21 to -18.99; 1 study, 90 participants; moderate-certainty evidence). The evidence was very uncertain for the other interventions that were compared to placebo and measured burning sensation (intralesional dexamethasone, vasodilators). Adverse effects Fifteen studies reported adverse effects as an outcome. Six of these studies found no adverse effects. One study evaluating abdominal dermal fat graft reported serious adverse effects resulting in prolonged hospital stay for 3/30 participants. There were mild and transient general adverse effects to systemic drugs, such as dyspepsia, abdominal pain and bloating, gastritis and nausea, in studies evaluating vasodilators and antioxidants in particular.

AUTHORS' CONCLUSIONS: We found moderate-certainty evidence that antioxidants administered systemically probably improve mouth opening slightly at three to six months and improve burning sensation VAS scores up to and beyond six months. We found only low/very low-certainty evidence for all other comparisons and outcomes. There was insufficient evidence to make an informed judgement about potential adverse effects associated with any of these treatments. There was insufficient evidence to support or refute the effectiveness of the other interventions tested. High-quality, adequately powered intervention trials with a low risk of bias that compare biologically plausible treatments for OSF are needed. It is important that relevant participant-reported outcomes are evaluated.

PMID:38415846 | DOI:10.1002/14651858.CD007156.pub3

Clin Epigenetics. 2024 Feb 28;16(1):36. doi: 10.1186/s13148-024-01648-4.

ABSTRACT

BACKGROUND: Metabolic side effects of psychotropic medications are a major drawback to patients' successful treatment. Using an epigenome-wide approach, we aimed to investigate DNA methylation changes occurring secondary to psychotropic treatment and evaluate associations between 1-month metabolic changes and both baseline and 1-month changes in DNA methylation levels. Seventy-nine patients starting a weight gain inducing psychotropic treatment were selected from the PsyMetab study cohort. Epigenome-wide DNA methylation was measured at baseline and after 1 month of treatment, using the Illumina Methylation EPIC BeadChip.

RESULTS: A global methylation increase was noted after the first month of treatment, which was more pronounced (p < 2.2 × 10-16) in patients whose weight remained stable (< 2.5% weight increase). Epigenome-wide significant methylation changes (p < 9 × 10-8) were observed at 52 loci in the whole cohort. When restricting the analysis to patients who underwent important early weight gain (≥ 5% weight increase), one locus (cg12209987) showed a significant increase in methylation levels (p = 3.8 × 10-8), which was also associated with increased weight gain in the whole cohort (p = 0.004). Epigenome-wide association analyses failed to identify a significant link between metabolic changes and methylation data. Nevertheless, among the strongest associations, a potential causal effect of the baseline methylation level of cg11622362 on glycemia was revealed by a two-sample Mendelian randomization analysis (n = 3841 for instrument-exposure association; n = 314,916 for instrument-outcome association).

CONCLUSION: These findings provide new insights into the mechanisms of psychotropic drug-induced weight gain, revealing important epigenetic alterations upon treatment, some of which may play a mediatory role.

PMID:38419113 | DOI:10.1186/s13148-024-01648-4

Drug Ther Bull. 2024 Feb 28:dtb-2024-000013. doi: 10.1136/dtb.2024.000013. Online ahead of print.

NO ABSTRACT

PMID:38417949 | DOI:10.1136/dtb.2024.000013

Sci Rep. 2024 Feb 27;14(1):4819. doi: 10.1038/s41598-024-55664-8.

ABSTRACT

One of the significant worldwide health problems associated with pharmacovigilance is the under-reporting of adverse drug reactions (ADRs). Reporting suspected ADRs is essential to ensure patient safety, medicine safety, and healthcare quality. The new policy in Saudi Arabia emphasizes pharmacists taking a new clinical role, which may facilitate and improve the documentation of ADRs. Therefore, this study aimed to assess the knowledge and perception of community pharmacists towards the ADRs and their reporting practice in Saudi Arabia. A cross-sectional study using a structured self-administered questionnaire was administered to community pharmacists working in Saudi Arabia. Data were analyzed using descriptive and inferential statistics to identify the association between perceptions and ADR reporting practices. A P value < of 0.05 was considered statistically significant. A response rate of 43% (n = 163) was achieved, of whom 55.2% demonstrated knowledge of PV. Only 16% of community pharmacists were aware of the responsible center for monitoring and collecting ADRs in Saudi Arabia. The key facilitator was offering incentives to pharmacists, and the lack of time was found to be a key barrier among reporter community pharmacists. Positive attitudes toward pharmacovigilance and ADR reporting were expressed by community pharmacists. The findings of this study emphasize the further need for education and training programs and simplifying the ADR reporting process used in Saudi Arabia to enhance the reporting practice.

PMID:38413787 | PMC:PMC10899240 | DOI:10.1038/s41598-024-55664-8

Sci Rep. 2024 Feb 27;14(1):4785. doi: 10.1038/s41598-024-54886-0.

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic has been a major challenge worldwide for the past years with high morbidity and mortality rates. While vaccination was the cornerstone to control the pandemic and disease spread, concerns regarding safety and adverse events (AEs) have been raised lately. A cross-sectional study was conducted between January 1st and January 22nd, 2022, in six Arabic countries namely Saudi Arabia, Egypt, Syria, Libya, Iraq, and Algeria. We utilized a self-administered questionnaire validated in Arabic which encompassed two main parts. The first was regarding sociodemographic data while the second was about COVID-19 vaccination history, types, doses, and experienced AEs. A multistage sampling was employed in each country, involving the random selection of three governorates from each country, followed by the selection of one urban area and one rural area from each governorate. We included the responses of 1564 participants. The most common AEs after the first and second doses were local AEs (67.9% and 46.6%, respectively) followed by bone pain and myalgia (37.6% and 31.8%, respectively). After the third dose, the most common AEs were local AEs (45.7%) and fever (32.4%). Johnson and Johnson, Sputnik Light, and Moderna vaccines showed the highest frequency of AEs. Factors associated with AEs after the first dose included an increase in age (aOR of 61-75 years compared to the 12-18 years group: 2.60, 95% CI: 1.59-4.25, p = 0.001) and male gender (OR: 0.72, 95% CI: 0.63-0.82, p < 0.001). The cumulative post-vaccination COVID-19 disease was reported with Sinovac (16.1%), Sinopharm (15.8%), and Johnson and Johnson (14.9) vaccines. History of pre-vaccination SARS-CoV-2 infection significantly increases the risk of post-vaccination COVID-19 after the first, second, and booster doses (OR: 3.09, CI: 1.9-5.07, p < 0.0001; OR: 2.56, CI: 1.89-3.47, p < 0.0001; and OR: 2.94, CI: 1.6-5.39, p = 0.0005 respectively). In conclusion, AEs were common among our participants, especially local AEs. Further extensive studies are needed to generate more generalizable data regarding the safety of different vaccines.

PMID:38413637 | PMC:PMC10899622 | DOI:10.1038/s41598-024-54886-0

Front Immunol. 2024 Feb 12;15:1292122. doi: 10.3389/fimmu.2024.1292122. eCollection 2024.

ABSTRACT

Immunotherapy has revolutionized the cancer treatment landscape by opening up novel avenues for intervention. As the use of immune checkpoint inhibitors (ICIs) has exponentially increased, so have immune-related adverse events (irAEs). The mechanism of irAEs may involve the direct damage caused by monoclonal antibodies and a sequence of immune responses triggered by T cell activation. Common side effects include dermatologic toxicity, endocrine toxicity, gastrointestinal toxicity, and hepatic toxicity. While relatively rare, neurotoxicity, cardiotoxicity, and pulmonary toxicity can be fatal. These toxicities pose a clinical dilemma regarding treatment discontinuation since they can result in severe complications and necessitate frequent hospitalization. Vigilant monitoring of irAEs is vital in clinical practice, and the principal therapeutic strategy entails the administration of oral or intravenous glucocorticoids (GSCs). It may be necessary to temporarily or permanently discontinue the use of ICIs in severe cases. Given that irAEs can impact multiple organs and require diverse treatment approaches, the involvement of a multidisciplinary team of experts is imperative. This review aims to comprehensively examine the pathogenesis, clinical manifestations, incidence, and treatment options for various irAEs.

PMID:38410506 | PMC:PMC10895024 | DOI:10.3389/fimmu.2024.1292122

Reg Anesth Pain Med. 2024 Feb 27:rapm-2023-105261. doi: 10.1136/rapm-2023-105261. Online ahead of print.

ABSTRACT

BACKGROUND AND OBJECTIVES: Perioperative psychological stress and pharmacological anxiolysis can negatively affect the quality of recovery after total knee arthroplasty. We aimed to assess whether hypnosis combined with virtual reality could reduce intraoperative pharmacological sedation and improve quality of recovery after total knee arthroplasty surgery.

METHODS: In this prospective randomized clinical trial, 60 patients scheduled for total knee arthroplasty with spinal anesthesia were randomly divided into 2 groups of 30 patients each. Intraoperatively, intermittent boluses of midazolam 1 mg were administered at 5 min intervals at the patient's request, with a maximum driven by the clinical assessment of sedation depth. During surgery, patients received standard care (group control) or virtual reality hypnosis (group VRH). An unblinded observer recorded the total dose of midazolam administered during surgery, and changes in the Quality-of-Recovery 15-item score, comfort, fatigue, pain and anxiety before and 1, 3 and 7 days after surgery.

RESULTS: Patients in the VRH group required a lower dose of midazolam (mg; median (range)) intraoperatively (group VRH: 0 (0-4) and group control: 2 (0-9), p<0.001). Quality-of-Recovery 15-item, anxiety, and pain were similar between groups.

CONCLUSIONS: In total knee arthroplasty with spinal anesthesia, VRH reduces the requirement for intraoperative pharmacological sedation, without a change in the quality of recovery.

TRIAL REGISTRATION NUMBER: NCT05707234.

PMID:38413184 | DOI:10.1136/rapm-2023-105261

J Med Case Rep. 2024 Feb 27;18(1):76. doi: 10.1186/s13256-024-04390-w.

ABSTRACT

INTRODUCTION: Hydroxychloroquine and azathioprine have been routinely used to control and treat primary and secondary Sjögren's syndrome, which potentially triggered some overdoses by these drugs. Toxicity from hydroxychloroquine and azathioprine manifests in the form of cardiac conduction abnormalities, nausea, vomiting, and muscle weakness. Recognizing these unique drug overdoses and management of these toxicities is important. This case report aims to expand our current understanding of these drug overdoses and their management and also underscores the importance of anticipating and identifying fewer common complications, such as hypocalcemia.

CASE REPORT: A 34-year-old Persian woman with a history of Sjögren's syndrome presented to the emergency department 3.5-4 hours after an intentional overdose of hydroxychloroquine and azathioprine and severe hypotension and loss of consciousness. Although the patient was regularly taking other medications, such as fluoxetine, naproxen, and prednisolone, she explicitly clarified that these were not the substances involved in her overdose. Early investigations showed hypokalemia (2.4 mEq/L), hypocalcemia (7.5 mg/dL), and hypoglycemia (65 mg/dL). She was also diagnosed with metabolic acidosis and respiratory alkalosis. The electrocardiogram showed changes in favor of hypokalemia; other lab tests were run on the patient. Supportive treatments were applied, including rapid intravenous fluid dextrose 5%, normal saline, potassium chloride 30 mEq, and calcium gluconate 100 mg. The patient was managed and monitored overnight in the emergency room and recovered without residual side effects.

CONCLUSION: Hydroxychloroquine and azathioprine toxicity are considered rare, but it is likely to increase in frequency given the prevalence and increase in autoimmune diseases and the increasing usage of these drugs in treating such diseases. We found hypocalcemia as the presentation to this patient, which needs further investigation into the probable mechanism. Clinicians need to consider the unique effects of hydroxychloroquine and azathioprine poisoning and initiate appropriate emergency interventions to improve the outcomes in similar patients.

PMID:38409169 | PMC:PMC10897995 | DOI:10.1186/s13256-024-04390-w

BMJ. 2024 Feb 26;384:q488. doi: 10.1136/bmj.q488.

NO ABSTRACT

PMID:38408769 | DOI:10.1136/bmj.q488

iScience. 2024 Feb 7;27(3):109148. doi: 10.1016/j.isci.2024.109148. eCollection 2024 Mar 15.

ABSTRACT

Drug-drug interactions (DDIs) can produce unpredictable pharmacological effects and lead to adverse events that have the potential to cause irreversible damage to the organism. Traditional methods to detect DDIs through biological or pharmacological analysis are time-consuming and expensive, therefore, there is an urgent need to develop computational methods to effectively predict drug-drug interactions. Currently, deep learning and knowledge graph techniques which can effectively extract features of entities have been widely utilized to develop DDI prediction methods. In this research, we aim to systematically review DDI prediction researches applying deep learning and graph knowledge. The available biomedical data and public databases related to drugs are firstly summarized in this review. Then, we discuss the existing drug-drug interactions prediction methods which have utilized deep learning and knowledge graph techniques and group them into three main classes: deep learning-based methods, knowledge graph-based methods, and methods that combine deep learning with knowledge graph. We comprehensively analyze the commonly used drug related data and various DDI prediction methods, and compare these prediction methods on benchmark datasets. Finally, we briefly discuss the challenges related to drug-drug interactions prediction, including asymmetric DDIs prediction and high-order DDI prediction.

PMID:38405609 | PMC:PMC10884936 | DOI:10.1016/j.isci.2024.109148

Explor Res Clin Soc Pharm. 2024 Feb 14;13:100421. doi: 10.1016/j.rcsop.2024.100421. eCollection 2024 Mar.

ABSTRACT

BACKGROUND: The problem with substandard and falsified (SF) medical products may grow in high-income countries when e-commerce of medicines increases. Unauthorized websites offer medicines of insufficient quality. This underscores the importance of evaluating how the problem with SF medical products can be prevented from escalating. However, little is known about what knowledge and experience professionals working primarily with medicines have about the phenomenon.

OBJECTIVE: This study was conducted to explore purposively selected pharmacists' experience and knowledge about SF medical products.

METHODS: Twelve individual interviews were conducted with purposively selected pharmacists between May 2021 and September 2021. An interview guide was used with specific questions about e-commerce, which focused on exploring pharmacists' experience and knowledge about SF medical products. The interviews lasted, on average, 49 min and were analyzed using inductive qualitative content analysis.

RESULTS: A main theme 'Pharmacists as guardians of safe medicines' emerged. This theme consisted of three categories pinpointing 'risk factors', 'protective factors', and 'opportunities for improvement' regarding SF medical products. Findings suggest that pharmacists can play a role in preventing the problem with SF medical products from escalating. Participants emphasized they were in this line of work to help patients and increase patient safety.

CONCLUSIONS: Pharmacists have the opportunity to empower the public with knowledge about SF medical products since they discuss medicines with many people every day. Awareness of risk factors for SF medical products enables pharmacists to guide patients to avoid risky purchases from unauthorized websites. To do this, better communication, and cooperation with patients and other healthcare professionals are needed.

PMID:38405083 | PMC:PMC10885592 | DOI:10.1016/j.rcsop.2024.100421

BioDrugs. 2024 Mar;38(2):275-285. doi: 10.1007/s40259-024-00651-8. Epub 2024 Feb 25.

ABSTRACT

INTRODUCTION: Anti-calcitonin gene-related peptide monoclonal antibodies (anti-CGRP-mAbs) have recently been approved for the prevention of migraine, and their safety profile is not fully characterized.

OBJECTIVE: The aim of this study was to evaluate the adverse drug reactions (ADRs) of anti-CGRP-mAbs through the analysis of individual case safety reports (ICSRs) collected in the EudraVigilance (EV) database, with a specific focus on cardiovascular (CV) ADRs.

METHODS: Data on ICSRs recorded between July 2018 and December 2022 in the EV database, involving one of the anti-CGRP-mAbs for migraine prevention-erenumab (ERE), galcanezumab (GMB), fremanezumab (FMB), and eptinezumab (EPT)-were included in the analysis. All ICSRs reporting at least one CV ADR, as identified within the MedDRA® System Organ Classes (SOCs) "cardiac disorders" or "vascular disorders," were selected for the analysis. The frequency of disproportionate reporting was expressed as the reporting odds ratio (ROR) with its 95% confidence interval (CI), to evaluate the frequency of reporting of CV ADRs for each anti-CGRP-mAb compared with all other monoclonal antibodies (mAbs). A case-by-case analysis was conducted paying particular attention to serious CV ADR reports, focusing on the type of seriousness, age group, sex, and concomitant drugs.

RESULTS: A total of 9441 ICSRs were recorded in the EV database from 2018 to 2022, of which more than half were related to ERE (58.9%), followed by GMB (21.4%), FMB (19.0%), and EPT (0.7%). CV ICSRs accounted for 1205 cases (12.8%), with a total of 1599 CV ADRs. The CV ICSRs were mainly related to female patients (82.6%) aged 18-64 years (73.4%). Of the reported CV ADRs, 67.5% were considered serious. Among the total number of ICSRs related to each anti-CGRP-mAb, those associated with FMB had a higher percentage of CV ADRs (n = 253; 14.1%), followed by ERE (n = 707; 12.7%), EPT (n = 8; 12.7%), and GMB (n = 237; 11.7%). A higher frequency of reporting hypertension was shown for ERE (ROR = 1.45; 95% CI = 1.14-1.85). Pallor was mainly observed with FMB (5.00; 1.68-14.89), as well as deep vein thrombosis (3.86; 1.57-9.51), hot flush (2.16; 1.43-3.25), and palpitations (1.48; 1.05-2.08). Atrial fibrillation (2.36; 1.02-5.46) and myocardial infarction (2.21; 1.37-3.58) were mostly reported for GMB.

CONCLUSION: The analysis of anti-CGRP-related CV ADRs was consistent with the information reported in the literature. However, hypertension with ERE, atrial fibrillation and myocardial infarction with GMB, as well as pallor, deep vein thrombosis, hot flush, and palpitations with FMB were not reported in the Summary of Product Characteristics (SmPCs). Considering this, more post-marketing analyses are needed to improve knowledge on the CV safety profiles of anti-CGRP-mAbs, especially for the last approved medication, EPT.

PMID:38402495 | DOI:10.1007/s40259-024-00651-8

Lancet. 2024 Feb 22:S0140-6736(23)02554-0. doi: 10.1016/S0140-6736(23)02554-0. Online ahead of print.

ABSTRACT

BACKGROUND: No randomised controlled trial has ever been done in patients with metastatic phaeochromocytomas and paragangliomas. Preclinical and first clinical evidence suggested beneficial effects of sunitinib. We aimed to evaluate the safety and efficacy of sunitinib in patients with metastatic phaeochromocytomas and paragangliomas.

METHODS: FIRSTMAPPP is a multicentre, international, randomised, placebo-controlled, double-blind, phase 2 trial done at 14 academic centres across four European countries. Eligible participants were adults (aged ≥18 years) with sporadic or inherited progressive metastatic phaeochromocytomas and paragangliomas. Patients were randomly assigned (1:1) to receive either oral sunitinib (37·5 mg per day) or placebo. Randomisation was stratified according to SDHB status (mutation present vs wild type) and number of previous systemic therapies (0 vs ≥1). Primary endpoint was the rate of progression-free survival at 12 months according to real-time central review (Response Evaluation Criteria in Solid Tumours version 1.1). On the basis of a two-step Simon model, we aimed for the accrual of 78 patients, assuming a 20% improvement of the 12-month progression-free survival rate from 20% to 40%, to conclude that sunitinib is effective. Crossover from the placebo group was allowed. This trial is registered with ClinicalTrials.gov, number NCT01371201, and is closed for enrolment.

FINDINGS: From Dec 1, 2011, to Jan 31, 2019, a total of 78 patients with progressive metastatic phaeochromocytomas and paragangliomas were enrolled (39 patients per group). 25 (32%) of 78 patients had germline SDHx variants and 54 (69%) had used previous therapies. The primary endpoint was met, with a 12-month progression-free survival in 14 of 39 patients (36% [90% CI 23-50]) in the sunitinib group. In the placebo group, the 12-month progression-free survival in seven of 39 patients was 19% (90% CI 11-31), validating the hypotheses of our study design. The most frequent grade 3 or 4 adverse events were asthenia (seven [18%] of 39 and one [3%] of 39), hypertension (five [13%] and four [10%]), and back or bone pain (one [3%] and three [8%]) in the sunitinib and placebo groups, respectively. Three deaths occurred in the sunitinib group: these deaths were due to respiratory insufficiency, amyotrophic lateral sclerosis, and rectal bleeding. Only the latter event was considered drug related. Two deaths occurred in the placebo group due to aspiration pneumonia and septic shock.

INTERPRETATION: This first randomised trial supports the use of sunitinib as the medical option with the highest level of evidence for anti-tumour efficacy in progressive metastatic phaeochromocytomas and paragangliomas.

FUNDING: French Ministry of Health, through the National Institute for Cancer, German Ministry of Education and Research, and the German Research Foundation within the CRC/Transregio 205/2, EU Seventh Framework Programme, and a private donator grant.

PMID:38402886 | DOI:10.1016/S0140-6736(23)02554-0

Int J Mol Sci. 2024 Feb 6;25(4):1993. doi: 10.3390/ijms25041993.

ABSTRACT

Nonalcoholic fatty liver disease, recently re-named metabolic dysfunction-associated steatotic fatty liver disease, is considered the most prevalent liver disease worldwide. Its molecular initiation events are multiple and not always well-defined, comprising insulin resistance, chronic low-grade inflammation, gut dysbiosis, and mitochondrial dysfunction, all of them acting on genetic and epigenetic grounds. Nowadays, there is a growing public health threat, which is antibiotic excessive use and misuse. This widespread use of antibiotics not only in humans, but also in animals has led to the presence of residues in derived foods, such as milk and dairy products. Furthermore, antibiotics have been used for many decades to control certain bacterial diseases in high-value fruit and vegetables. Recently, it has been emphasised that antibiotic-induced changes in microbial composition reduce microbial diversity and alter the functional attributes of the microbiota. These antibiotic residues impact human gut flora, setting in motion a chain of events that leads straight to various metabolic alterations that can ultimately contribute to the onset and progression of NAFLD.

PMID:38396671 | PMC:PMC10888279 | DOI:10.3390/ijms25041993

Cancer Med. 2024 Feb;13(3):e7024. doi: 10.1002/cam4.7024.

ABSTRACT

OBJECTIVES: The use of immune checkpoint inhibitors, particularly PD-1 inhibitors, has revolutionized the treatment of advanced tumors and shown significant improvements in patient survival rates. However, which PD-1 inhibitor is more effective and safer for a specific indication remains unclear. To address this problem, our study aimed to evaluate the effectiveness and safety of different PD-1 inhibitors in combination with chemotherapy as first-line therapy for individuals with advanced non-small-cell lung cancer (NSCLC) without driver genes in the real world.

MATERIALS AND METHODS: We conducted a retrospective study of individuals diagnosed with aNSCLC who received immune checkpoint inhibitors (ICIs) with modified PD-1 inhibitors, including Sintilimab, Toripalimab, Tislelizumab, Camrelizumab, or Pembrolizumab as first-line treatment between March 5th, 2016 and October 20th, 2022. We assessed demographic and clinical information and analyzed clinical response, survival outcomes, and safety profiles. The primary endpoint was overall survival (OS), and the secondary endpoints included progression-free survival (PFS), objective response rate (ORR), disease control rate (DCR), and safety.

RESULTS: As of the date cut-off on October 20th, 2022, the median follow-up time was 20.62 months. A total of 204 patients were enrolled in the study, including 56 (27.5%) patients receiving modified PD-1 inhibitors (Sintilimab, Toripalimab, Tislelizumab, or Camrelizumab) in combination with chemotherapy and 148 (72.5%) patients receiving Pembrolizumab in combination with chemotherapy. In the overall cohort, the median overall survival (OS) was 26.9 months (95%CI, 22.3-31.6), the median progression-free survival (PFS) was 8.4 months (95%CI, 6.9-9.8), and the objective response rate (ORR) and disease control rate (DCR) were 47.6% (95%CI, 29.9-43.6) and 84.3% (95%CI, 78.4-88.9). The mOS of modified PD-1 inhibitors group and Pembrolizumab group were 30.7 (95%CI, 17.3-44.4) months and 26.8 (95%CI, 22.2-31.4) months. The mPFS of two groups were 8.3(95%CI, 6.9-9.6) months and 8.8 (95%CI, 6.9-10.7) months, respectively. There was no statistical difference between the two groups in terms of OS or PFS. The ORR for the two groups was 48.2% (95%CI, 34.8-61.8) and 47.3% (95%CI, 39.1-5.6), respectively. However, due to the limited sample size, the difference was not statistically significant. On the other hand, the DCR tended to be higher in the Pembrolizumab group (86.5%; 95%CI, 79.7-91.4) compared to the modified PD-1 inhibitors group (78.6%; 95%CI, 65.2-87.9), and this difference was statistically significant (p = 0.006). In terms of safety, both groups exhibited favorable clinical safety profiles. The only two types of potentially immune-related adverse events reported were pneumonitis and reactive cutaneous capillary endothelial proliferation (RCCEP).

CONCLUSIONS: The modified PD-1 inhibitors showed comparable survival outcomes and manageable safety profiles in NSCLC compared to Pembrolizumab. Moreover, these inhibitors exhibited improved accessibility and economic outcomes compared to Pembrolizumab. While there were similarities in drug-related and immunotherapy-related adverse reactions between the modified PD-1 inhibitors and Pembrolizumab, there were some slight differences. Further prospective and retrospective studies would be necessary to validate these findings beyond the scope of the CTONG1901 study.

PMID:38400661 | DOI:10.1002/cam4.7024

Cancers (Basel). 2024 Feb 15;16(4):795. doi: 10.3390/cancers16040795.

ABSTRACT

Immune-mediated hepatotoxicity (IMH) is not-so-rare complication during treatment with immune checkpoint inhibitors (ICIs). This narrative review aims to report the current knowledge on hepatic immune-related adverse events (irAEs) during immunotherapy from pathogenesis to multidisciplinary management. The majority of cases of IMH are asymptomatic and only a few patients may have clinical conditions. The severity of IMH is usually stratified according to Common Terminology for Clinical Adverse Events (CTCAE) criteria, but these scores may overestimate the clinical severity of IMH compared to the Drug-Induced Liver Injury Network (DILIN) scale. The differential diagnosis of IMH is challenging because the elevated liver enzymes can be due to a number of etiologies such as viral infection, autoimmune and metabolic diseases, liver metastases, biliary diseases, and other drugs. The cornerstones of IMH management are represented by withholding or delaying ICI administration and starting immunosuppressive therapy. A multidisciplinary team, including oncologists, hepatologists, internists, and emergency medicine physicians, is essential for the management of IMH.

PMID:38398187 | DOI:10.3390/cancers16040795

Medicine (Baltimore). 2024 Feb 23;103(8):e35549. doi: 10.1097/MD.0000000000035549.

ABSTRACT

Coronavirus disease 2019 (COVID-19) vaccines are the most effective tools in managing the pandemic. However, the concern about these vaccines is the occurrence of unwanted adverse events (AEs). This study aimed to evaluate the short-term AEs of COVID-19 vaccines (Sputnik V, Astrazenka, and Sinopharm). A cross-sectional study using an online questionnaire was conducted among 321 vaccinated individuals. Demographic information, history of drug use, prior infection with COVID-19, the type of vaccine, vaccination stage, local injection site complication, systemic complication, and allergic reactions were collected and evaluated. Local complications, including pain and swelling at the injection site, and systemic complications, including fever, fatigue, lethargy, lymphadenopathy, and diarrhea, were reported after the injection of the AstraZeneca vaccine was more than the other 2 vaccines; The prevalence of fatigue and lethargy was higher than other systemic complications. The least reported complication was due to lymphadenopathy. The Sinopharm vaccine showed a lower prevalence of AEs than the other 2. The rare AEs, such as facial paralysis, nasal bleeding, and urticarial, were further reported after injection of the AstraZeneca vaccine. In general, the severity of systemic complications after the second dose of the vaccine was also higher than the first dose. All 3 vaccines were safe and tolerable. The most commonly reported AEs were injection site pain (local) and fatigue and lethargy (systemic). These expected AEs occurred shortly after vaccination and indicated an early immune response after vaccination.

PMID:38394514 | DOI:10.1097/MD.0000000000035549

Medicine (Baltimore). 2024 Feb 23;103(8):e36834. doi: 10.1097/MD.0000000000036834.

ABSTRACT

RATIONALE: Rhabdomyolysis is a serious complication of status epilepticus (SE) caused by muscle cell damage and can lead to a life-threatening acute kidney injury (AKI).

PATIENT CONCERNS: A 35-year-old man with a history of seizures treated with 3 different antiepileptic drugs (carbamazepine, lamotrigine, and levetiracetam) presented with SE. The patient received 5 doses of diazepam to control the SE in another hospital and was transferred to our emergency due to AKI.

DIAGNOSES: Laboratory tests corresponded with rhabdomyolysis-induced AKI and disseminated intravascular coagulation. Thereafter, the decrease in renal excretion of both drugs (diazepam and carbamazepine) caused acute liver injury and neurotoxicity. The carbamazepine concentration was 16.39 mcg/mL, which considered in toxic level, despite using the usual dose.

INTERVENTIONS: The patient was treated with hydration and sodium bicarbonate, however; severe AKI mandated a hemodialysis session.

OUTCOMES: The diuresis started to increase, kidney and liver functions improved, and altered mental status reversed.

LESSONS: This case alerts physicians to consider the synergistic drug side effects and interactions, especially when patients present with impaired liver or kidney functions. The reduction in metabolism or excretion of drugs can cause an increase in serum concentrations and induce toxicity, even when the drug intake at the usual dose.

PMID:38394513 | DOI:10.1097/MD.0000000000036834