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BACKGROUND: Resurgent psychedelic research has largely supported the safety and efficacy of psychedelic therapy for the treatment of various psychiatric disorders. As psychedelic use and therapy increase in prevalence, so does the importance of understanding associated risks. Cases of prolonged negative psychological responses to psychedelic therapy seem to be rare; however, studies are limited by biases and small sample sizes. The current analytical approach was motivated by the question of whether rare but significant adverse effects have been under-sampled in psychedelic research studies. METHODS: A bottom margin analysis approach was taken to focus on negative responders to psychedelic use in a pool of naturalistic, observational prospective studies (N = 807). We define negative response by a clinically meaningful decline in a generic index of mental health, that is, one standard error from the mean decrease in psychological well-being 4 weeks post-psychedelic use (vs pre-use baseline). We then assessed whether a history of diagnosed mental illness can predict negative responses. RESULTS: We find that 16% of the cohort falls into the negative responder subset. Parsing the sample by self-reported history of psychiatric diagnoses, results revealed a disproportionate prevalence of negative responses among those reporting a prior personality disorder diagnosis (31%). One multivariate regression model indicated a greater than four-fold elevated risk of adverse psychological responses to psychedelics in the personality disorder subsample (b = 1.425, p

IntroductionCannabis has been reported to have both anxiogenic and anxiolytic effects. Habitual cannabis use has been associated with anxiety disorders (AD). The causal pathways and mechanisms underlying the association between cannabis use (CU)/cannabis use disorder (CUD) and anxiety remain unclear. We examined the literature via a systematic review to investigate the link between cannabis and anxiety. The hypotheses studied include causality, the common factor theory, and the self-medication hypothesis.MethodsCritical systematic review of published literature examining the relationship of CU/CUD to AD or state-anxiety, including case reports, literature reviews, observational studies, and preclinical and clinical studies. A systematic MEDline search was conducted of terms including: [anxiety], [anxiogenic], [anxiolytic], [PTSD], [OCD], [GAD], [cannabis], [marijuana], [tetrahydrocannabinol], [THC].ResultsWhile several case-control and cohort studies have reported no correlation between CU/CUD and AD or state anxiety (N = 5), other cross-sectional, and longitudinal studies report significant relationships (N = 20). Meta-analysis supports anxiety correlating with CU (N = 15 studies, OR = 1.24, 95% CI: 1.06-1.45, p = 0.006) or CUD (N = 13 studies, OR = 1.68, 95% CI: 1.23-2.31, p = 0.001). PATH analysis identifies the self-medication hypothesis (N = 8) as the model that best explains the association between CU/CUD and AD or state-anxiety. Despite the support of multiple large cohort studies, causal interpretations (N = 17) are less plausible, while the common factor theory (N = 5), stress-misattribution hypothesis, and reciprocal feedback theory lack substantial evidential support.ConclusionThe association between cannabis and anxiety is best explained by anxiety predisposing individuals toward CU as a method of self-medication. A causal relationship in which CU causes AD incidence is less likely despite multiple longitudinal studies suggesting so.

INTRODUCTION: Subjective improvement in gastrointestinal (GI) symptoms was assessed among patients using medical marijuana (MMJ). METHODS: Participants completed surveys at 0 days, 30 days, 6 months, and 12 months with questions about the severity of their GI symptoms on a scale from 1 (mild) to 3 (severe). RESULTS: In each survey, participants reported a significant decrease in GI symptom severity when using MMJ versus when not using MMJ (p < 0.05). The most common self-reported side effects from using MMJ were increased appetite (12-21.4%), fatigue (6-16.7%), anxiety (4-11.9%), cough (4-11.9%), headache (6-7.9%), and dry mouth (4-7.1%). CONCLUSION: In patients with chronic GI symptoms, MMJ may provide persistent symptom severity improvement. Limited product availability and mild to moderate side effects are factors to consider before trialing MMJ.

BackgroundClinical trials using psilocybin therapy to treat anorexia nervosa (AN) are currently underway. The safety and tolerability of psilocybin is of utmost importance in individuals with AN who may present unique medical vulnerabilities. The purpose of this review is to describe how the common physiologic adverse effects of psilocybin may impact medical complications experienced by individuals with AN in clinical trials of psilocybin therapy.Main bodyThe physiologic underpinnings of common adverse effects following psilocybin administration are described, including tachycardia, hypertension, electrocardiogram changes, nausea, headache, and lightheadedness. These anticipated physiologic changes are described in relation to the common medical correlates seen in individuals with AN. Risk mitigation strategies for each adverse effect are proposed.ConclusionEarly evidence suggests that psilocybin therapy is well-tolerated in individuals with AN. Understanding the unique medical complications of AN, and how they may be impacted by common physiologic adverse effects of psilocybin administration, leads to tailored risk mitigation strategies to enhance safety and tolerability of this novel intervention.

Background: H1-antihistamines are widely used to treat symptoms depending on histamine release in a variety of conditions. However, neurological adverse events have been reported in post-marketing surveillance studies and there are limited literatures comparing the neurological disorders associated with newer-generation H1-antihistamines from real-world datasets. Aims: We performed a comparative analysis of nervous system disorders and several newer-generation H1-antihistamines including: cetirizine, loratadine, levocetirizine, desloratadine and fexofenadine. Methods: Disproportionality analysis was used to identify the suspected drug neurological adverse events associated with H1-antihistamines of interest via the Food and Drug Administration Adverse Event Reporting System. The proportional reporting ratio (PRR), χ2 (chi-square) and the reporting odds ratio (ROR) with 95% confidence interval (CI) were used to estimate the association. Results: AE reports of 43,815 cases from 2017 to 2021 were extracted from FAERS. The H1-antihistamines included in our study were associated with various neurological adverse events that could be classified into 12 aspects, containing 42 preferred terms. The majority of adverse event reports were concentrated at somnolence: cetirizine [N = 1342, ROR (95%CI) = 11.8 (11.2–12.5), PRR = 10.8, χ2 = 11755.4], levocetirizine [N = 1276, ROR(95%CI) = 28.5 (26.7–30.3), PRR = 22.7, χ2 = 26218.4], loratadine[N = 516, ROR(95%CI) = 4.6 (4.2-5.0), PRR = 4.4, χ2 = 1378.1], desloratadine [N = 33, ROR(95%CI) = 6.1 (4.3–8.6), PRR = 5.8, χ2 = 131.9], fexofenadine [N = 498, ROR(95%CI) = 5.0 (4.6–5.5), PRR = 4.8, χ2 = 1519.0]. Conclusion: Neurological AEs associated with individual newer generation H1-antihistamines of interest varies a lot, whereas somnolence was the most common AE reports. Fexofenadine was highly associated with headaches. Sedative effects associated with levocetirizine and cetirizine should arouse more concern. Seizures significantly associated with levocetirizine and desloratadine were infrequently reported, further research is needed to avoid possible serious outcomes. Patients taking cetirizine probably have higher risk of dystonia and anticholinergic syndrome. [ABSTRACT FROM AUTHOR]

Background: Although there have been network meta-analyses (NMAs) regarding the efficacy and safety of targeted immunotherapy for psoriatic arthritis, most of them primarily focus on biologics. However, small molecules and biologics have many differences in properties and onset time. This NMA put emphasis on small molecule drugs and incorporates medications including upadacitinib and deucravacitinib, which have been less compared previously. Objective: To compare the efficacy and safety of small molecule drugs (apremilast, deucravacitinib, tofacitinib, and upadacitinib) in active psoriatic arthritis (PsA) using NMA. Design: This study was conducted and reported following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-analyses Extension Statement for Network Meta-Analyses (PRISMA-NMA), with relevant articles identified through searches across electronic databases. Data sources and methods: Databases including PubMed, Cochrane Library, and ClinicalTrial.gov were searched. Randomized controlled trials (RCTs) of targeted synthetic small molecules for PsA controlled by either placebo or active comparators within weeks 12–16 were eligible. A frequentist framework and a random-effect model were employed for the analysis. The revised Cochrane risk-of-bias tool for RCTs was used to assess the quality of the enrolled studies. Results: A total of 9 RCTs involving 3699 patients were analyzed. Apremilast 30 mg bid, deucravacitinib 6 mg and 12 mg qd, tofacitinib 5 mg bid, and upadacitinib 15 mg qd all demonstrated superior efficacy over placebo in achieving American College of Rheumatology (ACR) 20/50/70, Psoriasis Area and Severity Index (PASI) 75, and Health Assessment Questionnaire-Disability Index (HAQ-DI) scores at weeks 12–16. When compared to adalimumab, upadacitinib achieved borderline superiority in PASI 75 at week 12 (risk ratio (RR) = 1.20, 95% confidence interval (CI): 1.02–1.40). Among the four medications studied, only deucravacitinib showed significantly better HAQ-DI scores compared to apremilast (RR = −0.16, 95% CI: −0.29 to −0.02), with no statistically significant differences observed in other parameters. Conclusion: All four small molecule oral medications exhibited superior efficacy to placebo and comparable safety profiles. Across different assessment criteria, including ACR 50, ACR 70, PASI 75, or HAQ-DI, deucravacitinib 12 mg and upadacitinib consistently ranked in the top two positions. [ABSTRACT FROM AUTHOR]

Background: Myelin oligodendrocyte glycoprotein (MOG) IgG related optic neuritis (ON) which manifests as recurrent episodes and severe visual impairment remains a challenging issue in relapse prevention. Tocilizumab (TCZ), a human monoclonal antibody against IL-6R, may be an alternative treatment for the prevention of relapse in refractory MOG-ON patients. Objectives: To investigate the efficacy and safety of Tocilizumab (TCZ) in patients with recurrent myelin oligodendrocyte glycoprotein IgG related optic neuritis (MOG-ON). Design: We conducted an open-label, single-arm, nonrandomized, uncontrolled clinical trial at a tertiary neuro-ophthalmology center between April 1, 2021, and April 1, 2022. Methods: Participants with relapsed MOG-ON, whose disease had been resistant to previous immunotherapies, received tocilizumab as monotherapy or as an add-on therapy and were followed up for at least 12 months. Annual recurrence rate (ARR), best corrected visual acuity (BCVA), and adverse events were recorded for analyses. Result: Ten patients (7 females and 3 males) with relapsed MOG-ON were included with a mean (SD) ages of 28.6 (20.5) years old at disease onset and 30.9 (19.7) years at first TCZ administration, with a mean disease duration of 26.6 (11.3) months. Seven (70%) patients remained relapse-free, and the median (range) ARR dropped significantly from 1.9 (0.4–3.5) to 0.0 (0–4.0) during TCZ treatment (p = 0.006). Three patients experienced a relapse of ON at 2, 3, and 7 months after TCZ therapy. The median BCVA improved from 2.7 (2.0–3.0) logMAR at the nadir to 0.2 (0–2.0) logMAR at the last follow-up. Adverse effects included transient diarrhea (n = 1) and upper respiratory infection (n = 1). Conclusion: This study supports that Tocilizumab therapy, with or without concomitant immunosuppression, is safe and effective in reducing relapses in MOG-ON patients who have failed immunosuppressive therapy or targeted B-cell therapy. Trial registration: This trial is registered with the Chinese Clinical Trial Registry, number ChiCTR2100045273. (URL: https://www.chictr.org.cn/showproj.html?proj=124810) [ABSTRACT FROM AUTHOR]

Background: Sex disparities are known modifiers of health and disease. In neuroendocrine neoplasms (NENs), sex-based differences have been observed in the epidemiology and treatment-related side effects. Objectives: To examine sex differences in demographics, diagnoses present during hospital admission, comorbidities, and outcomes of hospital course among hospitalized patients with NENs. Design: Retrospective analysis. Methods: A descriptive analysis of sex differences was performed on patients with NENs discharged from U.S. community hospitals in 2019 from the National Inpatient Sample (NIS), Healthcare Cost and Utilization Project, and Agency for Healthcare Research and Quality. Results: A total of 7334 patients with NENs were identified; 4284 patients had primary NENs, and 3050 patients had metastatic NENs. In total, 48.7% were males and 51.3% were females. Distributions of race and ethnicity, and payer types differed by sex (p < 0.001 and p = 0.027, respectively). For race and ethnicity, there were more females in White, Black, and Native American races, and Hispanic ethnicity. For payer types, female predominance was seen with Medicare, Medicaid, private insurance, and self-pay groups. Sex differences were seen in diagnosis made during hospital stay. In all NENs, oral (p = 0.036) and neurologic (p < 0.001) diagnoses were more common in females; ascites (p = 0.002), dysphagia (p = 0.002), biliary ductal obstruction (p = 0.014), and jaundice (p = 0.048) were more common in males. In primary NENs, ascites (p < 0.001) was male predominant. In metastatic NENs, dysphagia (p = 0.003) and jaundice (p = 0.034) were male predominant, whereas females had more headaches (p < 0.001). Nausea and vomiting were female predominant in all NENs (p < 0.001), primary (p = 0.044), and metastatic (p < 0.001) NENs. For comorbidities, arthropathies (p < 0.001), depression (p < 0.001), hypothyroidism (p < 0.001), other thyroid disorders (p < 0.001), chronic pulmonary disease (p = 0.002), and obesity (p < 0.001) were female predominant. Conclusion: There were sex differences in the race and ethnicity, payer types, diagnoses present during hospital admission, and comorbidities among the 2019 NIS hospital discharge sample of patients with NENs. Plain language summary: Sex differences in patients with neuroendocrine tumors during hospital admission This study explored sex differences in neuroendocrine neoplasms (NENs) using 2019 hospital discharge data. There were variations in demographics, diagnoses, and comorbidities between males and females. Female patients had higher rates of oral and neurologic issues, while males had more ascites, dysphagia, and jaundice. Certain comorbidities like arthritis, depression, hypothyroidism, and obesity were more common in females. Hospital stays and mortality rates did not differ significantly based on sex. In summary, this research highlights distinct sex-related patterns in NENs, shedding light on potential areas for tailored interventions or further investigation. [ABSTRACT FROM AUTHOR]

Phototoxicity is a significant problem that occurs in a large part of the population and is often caused by commonly used pharmaceuticals, including over-the-counter drugs. Therefore, testing drugs with photosensitizing potential is very important. The aim of this study is to analyze the cytotoxicity and phototoxicity of ketoprofen towards human melanocytes and fibroblasts in three different treatment schemes in order to optimize the study. Cytometric tests (studies of viability, proliferation, intracellular thiol levels, mitochondrial potential, cell cycle, and DNA fragmentation), Western blot analysis (cytochrome c and p44/p42 protein levels), and confocal microscopy imaging were performed to assess the impact of the developed treatments on skin cells. Research on experimental schemes may help reduce or eliminate the risk of phototoxic reactions. In the case of ketoprofen, we found that the strongest phototoxic potential was exhibited in the treatment where the drug was present in the solution during the irradiation of cells, both pigmented and non-pigmented cells. These results indicate that the greatest risk of photosensitivity reactions related to ketoprofen occurs after direct contact with the drug and UV exposure. [ABSTRACT FROM AUTHOR]

Background/Objectives: Vestibular schwannomas (VSs), also called acoustic neuromas, are benign tumors affecting the vestibulocochlear nerve, often leading to hearing loss and balance issues. This condition is particularly challenging in patients with neurofibromatosis type 2 (NF2), where VSs tend to develop bilaterally. Conventional treatments, such as surgery and radiotherapy, although effective, carry risks like hearing loss and nerve damage. Bevacizumab, a VEGF-targeting monoclonal antibody, has emerged as a less invasive treatment option, showing potential for tumor volume reduction and hearing preservation. This systematic review aims to assess the efficacy of bevacizumab in controlling tumor volume, preserving hearing, and identifying associated adverse events. Methods: A comprehensive systematic review was performed using PRISMA guidelines. PubMed and Cochrane Library databases were searched for studies evaluating the effects of bevacizumab on VS, focusing on key outcomes like tumor volume reduction, hearing preservation, and adverse events. Data extraction and quality assessment were independently conducted by two reviewers using the Newcastle-Ottawa Scale. Results: Nine studies involving 176 patients were included. Bevacizumab showed a partial tumor volume reduction (≥20%) in 40% of cases and disease stabilization in 50%, while 10% experienced tumor progression. Hearing outcomes revealed improvement in 36% of patients, stabilization in 46%, and deterioration in 18%. Severe adverse effects, including hypertension and thromboembolic events, occurred in 13% of patients, while 18% reported no side effects. Tumor regrowth was observed in some patients after treatment discontinuation, emphasizing the need for long-term monitoring. Conclusions: Bevacizumab demonstrates effectiveness in managing VS, particularly in NF2 patients, by reducing tumor size and preserving hearing in a substantial proportion of cases. However, the variability in patient response and the risk of adverse events underscore the need for individualized treatment approaches and further research, including randomized controlled trials, to optimize its clinical application. [ABSTRACT FROM AUTHOR]

Objectives: Risk factors for post-endoscopic retrograde cholangiopancreatography (ERCP) complications have been extensively studied and are well established; most complications are mild and self-limiting. This study aims to identify patients at risk of severe early post-ERCP complications. Methods: We conducted a retrospective cohort study with data from 2810 ERCP procedures performed at Ghent University Hospital between 2016 and 2022. Patient records and a maintained ERCP registry were used to identify all ERCP-related complications and possible risk factors. The AGREE classification was used to determine the severity of the complication. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of severe complications. Results: Out of 2810 procedures, 223 cases (7.9%) had post-ERCP complications, with severe complications occurring in 20.3% of cases. The most common severe complication was haemorrhage (22/49 severe complications, 44.9%), with perforation having the highest probability of being severe (10/15 cases, 67%). Independent predictors of severe complications included anticoagulative therapy (OR 6.3, 95% CI 1.4–28.3, p = 0.016) and high procedural difficulty (Schutz category 3: OR 11.5, 95% CI 2.4–54.6, p = 0.002; category 4: OR 5.9, 95% CI 1.4–23.5, p = 0.012). Conclusions: Patients on anticoagulation and those undergoing complex ERCP procedures (Schutz 3 or 4) are at particular risk of severe procedure-related complications. [ABSTRACT FROM AUTHOR]

Background/Objectives: The current study aimed to characterize the adverse reactions associated with dry needling (DN) treatments reported by Polish physiotherapists, with a secondary objective of investigating whether the level of DN experience influences the occurrence of these adverse effects. Methods: A total of 102 Polish physiotherapists, all with regular DN practice, participated in an ad hoc online survey. The participants were categorized by their level of experience in DN treatment: 44 with 0–2 years, 43 with 3–6 years, and 15 with more than 7 years of experience. The survey consisted of 27 questions focused on both mild and severe adverse effects resulting from DN treatments. Results: The results showed that in the short term (over the past week), minor bleeding was the most commonly reported mild adverse effect (70%), followed closely by slightly pain during treatment (68%). Slight pain following treatment was also reported by 52% of respondents. No significant relationship was found between experience with dry needling (DN) and the reporting of mild adverse effects, with the exception of tingling (X(2) = 10.958; p = 0.004). In the retrospective analysis of the past month, most respondents reported experiencing bleeding between one and three times (49%), while bruising occurred one to three times in 44% of cases. Similarly, 44% of respondents noted pain after treatment one to three times, and 47% experienced pain during DN at this frequency. A significant interaction with DN experience was observed in the frequency of drowsiness reported over the past month (X(10) = 19.735; p = 0.032). Conclusions: Severe adverse effects were extremely rare in clinical practice: pneumothorax and shock were each reported by 3% of respondents, nerve palsy by 14%, infection by 2%, and hospitalization by 1%. In conclusion, this study suggests that most adverse effects are mild, typically involving bleeding and slight pain during or after treatment. Additionally, DN experience does not appear to be a significant factor influencing the type or prevalence of these adverse effects. [ABSTRACT FROM AUTHOR]

Drugs for the treatment of obesity show significant effectiveness, but the adverse effects (ADRs) of these drugs are numerous and varied, and some of them are highly cost-generating. Our research aimed to define the health care utilization pattern in treating ADRs of antiobesity therapy, to compare the costs of treating these ADRs among selected European countries, and to identify the key cost drivers. A comparative analysis of the costs of treating the ADRs of antiobesity drugs in 10 European countries (seven EU members and three from the Western Balkans) was conducted, and the impact of parameters of global health expenditures on them was assessed. There are considerable differences in costs of treating adverse antiobesity drug reactions among European countries: costs of treating gastroesophageal reflux disease varied almost 20 times between North Macedonia (12.6 EUR) and Estonia (202.9 EUR). The Gross Domestic Product per capita was an important cost driver in treating the majority of the ADRs studied (p <.001), except for retinopathy, anaphylaxis, and respiratory disorders. The Domestic Private Health Expenditure increased the costs of treating depression (p =.012), upper respiratory tract infection (p =.008), melanocytic naevus (p =.027), and drug-induced hepatitis (p =.023). Investment in pharmaceuticals, medical goods, and preventive care tended to reduce the costs of treating several ADRs, which are seemingly unrelated to the body site or mechanism. Healthcare utilization and costs of treating ADRs to antiobesity drugs vary significantly among European countries. These differences should be considered when creating inputs for cost-effectiveness and budget impact models to decrease their uncertainty. [ABSTRACT FROM AUTHOR]

A severe and progressive interstitial lung disease (ILD) known as idiopathic pulmonary fibrosis (IPF) has an unknown etiology with poorly defined mechanisms of development. Among the currently prescribed pharmacological interventions for IPF, nintedanib demonstrates the ability to decelerate the deterioration of lung function and yield positive clinical outcomes. Multiple randomized placebo-controlled trials have confirmed the efficacy and acceptable safety profile of nintedanib. Real-world evidence studies also support the use of nintedanib in IPF, being an efficient and well-tolerated treatment option. It has the potential to stabilize the disease progression in patients with ILD. Patients with IPF frequently have comorbidities like diabetes and hypertension, which can exacerbate the course of disease, reduce quality of life, and decrease treatment adherence. For well-informed decision-making, it is important for healthcare professionals to recognize the position of nintedanib therapy in IPF with comorbidities. The gastrointestinal adverse effects, notably diarrhea, dominate the nintedanib safety profile. These can be effectively controlled by closely monitoring side effects, administering anti-diarrheal and anti-emetic drugs, reducing the nintedanib dose, and discontinuing it in case of severe symptoms with an option to reintroduce the treatment after side effects subside. Symptomatic interventions and monitoring of liver enzymes may reduce the occurrence of permanent treatment discontinuations. [ABSTRACT FROM AUTHOR]

Objective: Antipsychotics remain the first‐line treatment for people diagnosed with psychotic disorders despite adverse effects which lead many people to stop their medication. Many stop without the support of the prescriber, who may fear relapse. The objective of this study is to better understand the process of withdrawal from antipsychotics, from the perspective of people taking antipsychotics. Design: Online survey. Methods: An international online survey elicited quantitative responses about pre‐withdrawal planning (560) and qualitative responses about what was helpful and unhelpful when withdrawing from antipsychotics (443). Responses came from users of antipsychotics in 29 countries. Results: Forty‐seven per cent did not consult their psychiatrist before discontinuing. Only 40% made preparations, most commonly making a plan, gathering information and informing family. The most frequently reported helpful factors were focussing on the benefits of getting off the drugs (including ending adverse effects and feeling more alive), information about withdrawal symptoms and how to withdraw safely, withdrawing slowly, and support from psychologists, counsellors and psychotherapists. The most common unhelpful factor was the psychiatrist/doctor, largely because of their lack of knowledge, refusal to support the patient's wishes and the threat or use of coercion. Conclusions: Evidence‐based, respectful, collaborative responses to patients' concerns about adverse effects and desires to withdraw would probably reduce relapse rates and improve long‐term outcomes. It would definitely help end pervasive breaching of the principle of informed consent and human rights legislation. [ABSTRACT FROM AUTHOR]

Vincristine sulphate, a microtubule inhibitor, is used extensively in veterinary oncology for treating lymphoma. Neutropenia during multiagent protocols is a common reason for treatment delay and reduced dose intensity. This study evaluated toxicities associated with treating systemically well neutropenic lymphoma patients with vincristine. Lymphoma patients undergoing CHOP were evaluated retrospectively for instances of vincristine administration when absolute neutrophil counts (ANC) were 1.5 × 109/L or below. Instances of vincristine administration when ANC was equal to or less than 1.5 × 109/L were compared to vincristine administration where ANC was greater than 1.5 × 109/L in the same patient. Univariate and multivariate modelling compared VCOG‐CTCAE v1.1 grading of vomiting, diarrhoea, anorexia and 7‐day neutrophil nadir between groups. The median dose of vincristine administered was 0.7 mg/m2 for both study groups. A total of 112 doses of vincristine were administered to neutropenic patients (grade 2 n: 76, grade 3 n: 26, and grade 4 n: 10). These were compared to 223 doses of vincristine administered to the same patients when ANC was above 1.5 × 109/L. Neutropenic administration was most prevalent 7 days following cyclophosphamide administration. Day 7 post‐administration neutropenia was more prevalent in patients with ANC greater than 1.5 × 109/L at the time of vincristine administration (neutropenic 9%; non‐neutropenic 18%). Relative risk of 7‐day neutropenia, vomiting, diarrhoea, and anorexia was similar between groups on multivariate analysis. Patients with lymphoma who receive vincristine when ANC is 1.5 × 109/L or below are at no greater risk of adverse effects than the same patient who receives vincristine when neutrophil counts are greater than 1.5 × 109/L. [ABSTRACT FROM AUTHOR]

Introduction: Methadone has shown effectiveness in pain control in patients with cancer who are intolerant to other opioids in China. However, the optimal strategy for methadone conversion from previous high doses of opioids in refractory cancer pain remains debatable. This study aimed to describe the efficacy and safety of a 3-day switch (3DS) strategy for methadone conversion in patients with refractory cancer pain on high doses of opioids. Methods: We retrospectively reviewed 30-day medical records of 70 patients with refractory cancer pain who used a 3DS strategy for methadone conversion from previous high doses of opioids from July 2018 to December 2022. The 3DS strategy indicated that the methadone dose was increased by one third every day for 3 days. Data on the rate of successful conversion, the time to stable analgesia after conversion, the conversion efficiency, the corrected QT (QTc) interval, the actual conversion ratios, adverse events (AEs), and quality of life were analyzed. Results: Seventy patients received 3DS methadone conversion and 64 patients were eligible for analysis. Fifty patients (78%) achieved stable analgesia, and the median time to stable analgesia was 8.14 ± 2.70 (range 6–14) days. The average dose of methadone was 77.94 ± 42.74 mg. The most common AEs (≥ 10%) included constipation, dry mouth, nausea, and cold sweats. The incidence of constipation was reduced post-methadone conversion, and a statistically significant but asymptomatic prolongation of the QTc interval was observed. Additionally, the actual conversion ratios were lower than Ayonrinde's recommended ratios. Conclusions: The 3DS strategy for methadone conversion is applicable in Chinese patients with refractory cancer pain on high doses of opioids. [ABSTRACT FROM AUTHOR]

Background: Proton pump inhibitors (PPIs) are used for various conditions and are generally considered safe drugs; however, there has been a surge in their usage over time, partially related to their safety and overprescription. Purpose: This study is aimed to assess how much the public of Lahore knows about PPI, and how they use it, and if they follow their physician's instructions or not. Methods: A cross-sectional study was planned to attain the objective of the study. Respondents visiting various community pharmacies were inquired about their willingness to participate in this study. Chi-square was used to find the association between sociodemographic parameters and awareness of PPIs. p value less than 0.05 was considered statistically significant. Results: There were mostly university students (73.7%), with 82.2% having heard of PPIs. Prevalent use (86.85%) is observed, often after a medical condition. Notably, 60.1% use PPIs as needed, but only 52.3% complete the prescribed course. PPIs were taken before meals only by 69.3% of participants. Associations exist between having heard of PPIs, and age with younger participants (p < 0.001) exhibiting less awareness. Females also have heard lesser of PPIs (p = 0.011). Education correlates with unawareness (p < 0.001), and many participants are unaware of PPI side effects (51.04%). Conclusion: The study contributes valuable insights to the understanding of PPI usage perspectives, offering implications for healthcare practices and public health awareness campaigns. Overall, the public shows signs of awareness but those are not enough to eliminate the misuse of PPIs in Lahore. [ABSTRACT FROM AUTHOR]

Objective: This study aimed at ascertaining the efficacy and safety of hepatic arterial infusion chemotherapy (HAIC) combined with donafenib versus HAIC alone in the treatment of unresectable hepatocellular carcinoma (HCC). Methods: Seventy HCC patients were enrolled for our study, and they were randomized by simple randomization using computer‐generated random numbers into two groups: control group and observation group. Regular follow‐up reviews were conducted to assess the efficacy of treatments. The levels of apoptotic factors, the levels of hepatic fibrosis indices, the levels of serum tumor vascular factors and tumor markers, and the occurrence of adverse reactions in the two groups were recorded and compared. Results: Disease control rate, objective response rate, and progression‐free survival (PFS) of patients in the observation group were higher in contrast to the control group. After 12 weeks of treatment, lower mRNA expression of c‐mesenchymal‐epithelial transition factor, telomerase, and Fas Ligand and higher mRNA expression of Fas and Caspase‐3 were observed in HCC tissues of the observation group versus the control group (p < 0.05); lower detection values of serum laminin, hyaluronic acid, collage type IV, vascular endothelial growth factor receptor 2, and alpha‐fetal protein (AFP) were noted in HCC patients of the observation group in comparison to the control group (p < 0.05); there was no difference in the incidence of adverse reactions between the two groups. Conclusion: Donafenib combined with HAIC in the treatment of unresectable HCC patients can notably reduce serum AFP levels, improve hepatic fibrosis, enhance short‐term efficacy, prolong PFS, and have a favorable safety profile. [ABSTRACT FROM AUTHOR]

Cognitive impairment affects around 19% of community‐dwelling older adults in the United States. Pharmacists can play a significant role in identifying and deprescribing cognitive‐impairing medications through cognitive‐focused medication reviews or as part of comprehensive medication management. Multiple tools exist to help pharmacists and other practitioners identify these medications, yet a comprehensive description of these tools has not been undertaken. We searched EBSCO MEDLINE, PubMed, EMBASE, CINAHL, and PsycInfo from inception to August 4, 2023, using search terms relative to medications and cognition. Studies were included if they detailed a tool to assess the cognitive burden of a medication regimen. Abstracts and full texts were screened independently and in duplicate. Any disagreements at the level of full‐text screening were resolved by consensus. Eligible studies underwent data extraction by two authors independently and in duplicate using a data extraction form. Our search identified 13 126 articles of which only four tools were initially included. Additionally, we identified seven articles from the reference lists of excluded review articles for a final inclusion count of 11 tools. Articles were published between 2001 and 2017. Nine of 11 tools (82%) were focused solely on anticholinergic medications, while only one tool indicated a clinically relevant cutoff value and alternative medication recommendations. While there are many tools to assess the cognitive burden from medications, many are limited by the development date, focus on anticholinergic medications, or lack clinically useful information. Further research is needed to develop more comprehensive, up‐to‐date, and readily implementable tools that clinical pharmacists can utilize to assess medication‐induced cognitive risks. Such as tool could be applied by pharmacists in many settings to optimize medication use and improve patient outcomes. [ABSTRACT FROM AUTHOR]

Platinum-based chemotherapy has been the standard first-line (1L) treatment for advanced urothelial carcinoma (UC) for decades, based on the proven efficacy and established safety profiles of cisplatin- and carboplatin-based regimens. With the emergence of novel regimens, it is important to reevaluate and contextualize the role of 1L platinum-based chemotherapy. Platinum-based chemotherapy followed by avelumab 1L maintenance in patients without disease progression following platinum-based chemotherapy was established as a standard 1L regimen based on the JAVELIN Bladder 100 phase III trial. More recently, the EV-302 phase III trial showed the superiority of 1L enfortumab vedotin (EV) + pembrolizumab versus platinum-based chemotherapy, and the Checkmate 901 phase III trial showed the superiority of 1L nivolumab + cisplatin/gemcitabine versus cisplatin/gemcitabine alone. These 2 regimens have now been included as standard 1L options in treatment guidelines for advanced UC. EV + pembrolizumab is now the preferred 1L treatment, and in locations where EV + pembrolizumab is not available or individual patients are not considered suitable, recommended options are platinum-based chemotherapy followed by avelumab maintenance or nivolumab + cisplatin-based chemotherapy. In this review, we discuss current treatment options for advanced UC recommended in guidelines, practical considerations with platinum-based chemotherapy, the role of avelumab 1L maintenance, recent phase III trials of EV + pembrolizumab and nivolumab + cisplatin/gemcitabine, safety profiles of recommended 1L treatments, and second-line treatment options. [ABSTRACT FROM AUTHOR]

Pemphigus vulgaris (PV) is a severe autoimmune bullous dermatosis that is characterized by autoantibodies against epidermal adhesion proteins causing painful mucosal and skin blistering. Standard treatments for PV include corticosteroids, steroid‐sparing immunosuppressants, or intravenous monoclonal anti–CD20‐antibody therapy. The European guidelines suggest high‐dose intravenous immunoglobulin (IVIg) therapy as a promising approach for severe or treatment‐resistant cases. We report on a 65‐year‐old woman with severe and recurrent disease who achieved long‐term disease stabilization with IVIg treatment. Because of recurrent fatigue and headache, the patient was switched to an alternative IVIg preparation with a novel manufacturing process, thus ensuring high purity and better tolerability. We observed excellent efficacy, yet side effects remained largely unchanged. Further studies are necessary to evaluate the long‐term efficacy and tolerability of this new IVIg preparation. [ABSTRACT FROM AUTHOR]

Purpose of review: This review presents the risks and benefits of very low LDL cholesterol and the safety of using lipid-lowering therapy to achieve these levels. Recent findings: A growing body of literature suggests that lower LDL cholesterol levels are associated with a reduced risk of cardiovascular disease. Further, achieving these levels with pharmaceuticals is remarkably safe. Although statins may slightly increase the risk of diabetes mellitus and hemorrhagic stroke, the benefits outweigh the risks. Summary: While recommendations from professional societies are increasingly aggressive, additional risk reduction could be achieved by setting more even ambitious LDL cholesterol goals. [ABSTRACT FROM AUTHOR]

Background: Mephentermine is a sympathomimetic drug widely used by professional athletes and bodybuilders for muscle-building and enhancing physical performance. This study evaluated the evidence of adverse effects associated with mephentermine use among athletes. Methods: A systematic search was performed in PubMed and Embase from inception to December 2022. The bibliographies of the included studies were examined for additional studies. Quality assessment of the included studies were done using an appropriate scale. Results: From 905 studies, 13 met the eligibility criteria. Fourteen male athletes aged 20 to 35 years experienced adverse effects. Parenteral administration of mephentermine was the most preferred route among users. The daily administered dose of mephentermine varied from 30 mg to 1200 mg. All athletes consumed mephentermine at the advice of their trainers or peers. The most common adverse effects experienced by athletes were dependence and psychosis, which developed among chronic users (used for more than 1 year). Other adverse effects were decompensated heart failure, hepatic and renal injury, and resistance to ephedrine therapy. Conclusions: Mephentermine use is associated with numerous health complications. The lack of data supporting its performance-enhancing effects, combined with its substantial toxicities, questions the usefulness of this drug in athletes. [ABSTRACT FROM AUTHOR]

Lenvatinib, a multi-target inhibitor of receptor tyrosine kinases, has been increasingly used in the treatment of advanced hepatocellular carcinoma (HCC). However, its association with renal adverse effects, including proteinuria and renal microvascular complications, was not fully understood in HCC patients. We reported a case of a 68-year-old male with a history of hypertension, diabetes mellitus, and hepatitis C virus (HCV) infection, diagnosed with primary HCC in 2015. Despite previous treatments, he was started on lenvatinib due to tumor recurrence. Initially, he had mild proteinuria, which significantly worsened post-lenvatinib initiation, accompanied by fluctuating renal function and severe edema. The diagnosis of lenvatinib-induced renal microvascular damage was confirmed through renal biopsy, which showed glomerular sclerosis, tubulointerstitial changes, and arteriolosclerosis. Discontinuation of lenvatinib led to significant improvements in proteinuria and edema. Subsequent cancer recurrence was managed with microwave ablation and immunotherapy, with satisfactory recovery. The potential for lenvatinib to induce significant renal microvascular disease, as demonstrated in this case, emphasizes the importance of vigilant renal monitoring and personalized therapeutic strategies in patients treated with lenvatinib for HCC. Early intervention and dose adjustment may be crucial in preventing severe renal impairment, highlighting the significance of tailored treatment plans in the management of advanced HCC patients especially with pre-existing risk factors. [ABSTRACT FROM AUTHOR]

In the context of drug-resistant epilepsy, deep brain stimulation (DBS) has received FDA approval. However, there have been reports of potential adverse effects, such as depression and memory impairment associated with DBS.This systematic review and meta-analysis aimed to investigate the impact of DBS on the quality of life (QoL), and seizure frequency of patients who had DRE, and assess its potential adverse events. The study followed PRISMA guidelines and thoroughly assessed databases, including Pubmed, Scopus, Embase, Web of Science, and the Cochrane Library, up to 31 July. Statistical analysis, fixed effect model analysis, performed by the Comprehensive Meta-analysis software (CMA) version 3.0. Additionally, Cochran's Q test was conducted to determine the statistical heterogeneity. The systematic review encompassed 54 studies, with 38 studies included in the subsequent meta-analysis. The total number of patients included in the studies was 999. The findings indicated a significant decrease in the mean seizure frequency of subjects following DBS (SMD: 0.609, 95% CI: 0.519 to 0.700, p-value < 0.001). Moreover, patients' QoL significantly improved after DBS (SMD: -0.442, 95% CI: -0.576 to -0.308, p-value < 0.001). The hippocampus displayed the most notable effect size among the different DBS targets. Subgroup analysis based on follow-up duration revealed increased DBS efficacy after two years. There are few reports of adverse events, such as insertional-related complications, infection, and neuropsychiatric complications, but the majority of these were temporary and non-fatal. DBS emerged as an effective and safe procedure for reducing seizure frequency and enhancing the quality of life in DRE patients, with minimal adverse events. Furthermore, the efficacy of DBS was observed to improve over time. [ABSTRACT FROM AUTHOR]

Studies of psychedelic-assisted therapy with LSD, psilocybin, MDMA, and related substances show clinical promise but inadequately assess side effects. Measuring side effects is challenging because they are not always easily differentiated from treatment effects or disease symptoms and show high heterogeneity, variable duration and impact, and sensitivity to context. A systematic questionnaire describing important characteristics of side effects of psychedelics and MDMA would greatly improve on previous methods. We aimed to create a standardized tool for recording clinically relevant side effects of psychedelics and MDMA, including their severity, duration, impact, and treatment-relatedness. We constructed the Swiss Psychedelic Side Effects Inventory (SPSI) based on insights from previous research. It was pilot tested in 145 participants from three studies. Structured feedback from an expert panel was used to improve validity and feasibility. The final SPSI contains 32 side effects and standardized follow-up questions about their severity, impact, treatment-relatedness, and duration. It is compatible with any study design and can be administered as an interview or self-report at any timepoint after treatment with psychedelics or MDMA. The SPSI omits relatively unimportant side effects for brevity's sake, though space for additional symptoms is given. Future studies are needed to confirm its validity in different contexts. The SPSI is available in English and German for collecting systematic data on side effects from psychedelics and MDMA. This information is vital for improving clinical decisions, informed consent, and patient safety. • Psychedelics and MDMA can cause a unique profile of side effects which are not well-captured by the methods used in previous studies. • Psychedelic side effects vary in their severity, duration, and subjective impact. • Using previous studies, pilot data, and expert feedback, we developed the Swiss Psychedelic Side Effects Inventory (SPSI). • The SPSI contains 32 side effects and assesses their severity, impact, duration, and treatment-relatedness. • The SPSI can be used at any timepoint after psychedelic administration in any study of psychedelics or MDMA. [ABSTRACT FROM AUTHOR]

AbstractPsychedelics have shown early evidence for a range of benefits and low harm profiles in extant research. However, adverse effects (AEs) research in psychedelics has been limited, leading to underspecified AE profiles, inconsistent measurement, and potential undercounting of AEs. The development of safe, effective psychedelic therapies and treatments for AEs when they occur requires a thorough assessment of psychedelic-related AEs, their phenomenology, risk factors, and longitudinal duration. This article proposes that research on meditation-related AEs, which overlap in important ways with the phenomenological and contextual characteristics of psychedelic-related AEs, has engaged many methodological challenges present in the study of psychedelic-related AEs. Thus, meditation-related AE research offers thematic and methodological insights that are valuable to psychedelic AE research. An integrative review of extant AE research in both psychedelics and meditation is provided, and an agenda for leveraging meditation research to advance the investigation of psychedelic AEs is recommended. This includes the utility of meditation-related AEs as a comparator condition for psychedelic-related AEs, as well as recommendations for the adoption of (1) detailed and comprehensive, (2) user-informed, (3) impact-based, (4) standardized, (5) unbiased, and (6) representative measures of AEs and (7) examining factors that influence their impacts and trajectories. [ABSTRACT FROM AUTHOR]

(1) Background: Growth in the use of video games has spurred innovations in the health sector, especially through exergames, which promote physical activity using interactive technologies like augmented reality. Exergames are shown to enhance exercise motivation and engagement, yet enjoyment remains inconsistent across studies. This pilot study aims to provide evidence on how different exergaming doses affect exercise heart rate, perceived exertion, adverse effects, and enjoyment in older adults. (2) Methods: A pilot randomized controlled trial was conducted to compare different doses of exercise through video games (13 vs. 28 min) in older adults living in a nursing home. A single bout of exergaming was provided to assess the outcomes: heart rate, rate of perceived exertion, physical activity enjoyment scale score, and adverse effects. (3) Results: Thirty-two older adults were recruited. This study revealed no significant differences in heart rate between groups (p = 0.1). There is a weak correlation between the rate of perceived exertion and the level of enjoyment (rs = −0.193) and between the total time of the intervention and the incidence of adverse effects (rs = 0.295). (4) Conclusions: The use of a higher dose of exergaming is effective in achieving moderate physical intensity. Also, the results suggest the intervention was generally well tolerated and enjoyed by older adults, with no serious adverse effects reported. [ABSTRACT FROM AUTHOR]

Background/Objectives: Titanium dental implants are considered to be the most modern and effective solution for replacing lost teeth. These medical devices not only restore the chewing and aesthetic functionality of the smile but also provide a stable support for crowns, bridges or dentures. The aim of this study was to identify the perceptions of patients about titanium dental implants and their effects on the human body. Methods: A structural equation model (SEM) was conducted to study how a series of independent variables have the ability to influence the perception and intention of the patients regarding these medical devices. A data analysis was performed using WarpPLS 8.0 software. This research was conducted on a sample of 162 respondents. Results: The results illustrated that patients' perception of titanium dental implants is explained by 71% of the independent variables analysed, and their intention to have a new implant in the next period is explained by 61%. The proposed econometric model was validated, with seven hypotheses accepted out of nine. Conclusions: Although titanium has long been used in implant dentistry, in recent years, experts have identified a number of adverse effects that can arise from its use. This study has added value both at the practical and theoretical level. Perception is influenced by respondents' perceived advantages, by the problems perceived by the respondents regarding titanium dental implants, by the degree of awareness of the risks of titanium dental implants, and by the adverse effects experienced by respondents regarding titanium dental implants. [ABSTRACT FROM AUTHOR]

Background/Objectives: The use of dietary supplements (DSs) has become common among fitness enthusiasts, aiming to enhance performance, recovery, and overall well-being. Methods: A cross-sectional study was conducted in the city of Beni Mellal from April to July 2024, assessed dietary practices, motivations for supplement use, and associated adverse effects among 420 survey participants. Results: The majority of dietary supplement users were aged 25–64 and had higher education levels. Colopathy (67.38%) was the most common eating disorder, followed by digestive (59.46%), inflammatory, and rheumatic diseases (53.50%). Dietary supplementation prevalence was 88.1%, with proteins (60.81%), medicinal plants (45.13%), and vitamins (42.70%) being the most consumed. Key motivations included supporting muscle, bone, and joint strength (musculoskeletal) (83.78%) and enhancing heart and lung function for cardiorespiratory health (82.43%). However, 28% of protein users experienced adverse effects, such as myalgia, gastralgia, palpitations, and insomnia. Multivariate linear regression indicated a significant negative association of creatine with effectiveness (β = −0.485, p = 0.001). Conclusions: Overall, while the benefits of dietary and sports practices are evident, the adverse effects associated with protein supplements highlight the necessity for enhanced nutrivigilance and nutritional education to ensure safe supplements. [ABSTRACT FROM AUTHOR]

Background: Chronic subdural hematoma (CSDH) is an important medical condition characterized by the accumulation of blood in the subdural space. Several methods have been explored, including surgical intervention and administration of tranexamic acid, which is a conservative treatment option. This meta-analysis aimed to assess the effectiveness and safety of tranexamic acid in CSDH management. Methods: A systematic literature search was performed according to the PRISMA and MOOSE guidelines. This study included cohort and randomized controlled trials involving adults with chronic subdural hematoma (CSDH) who were treated with intravenous tranexamic acid. The primary outcome measures were recurrence and adverse events. Results: Six studies encompassing 2024 participants were included. Studies have shown that tranexamic acid reduced recurrence rates (OR, 0.32; 95% CI: 0.27–0.38, p = 0.16; I2 = 0%), although the result was non-significant. However, the analysis of adverse events indicated a moderate level of heterogeneity (OR, 1.14; 95% CI: 0.60–2.15, p = 0.07; I2 = 57%), suggesting a potential safety concern. Conclusion: In conclusion, this meta-analysis suggests tranexamic acid (TXA) may reduce chronic subdural hematoma (CSDH) recurrence, though significance varied across studies. Adverse effects with TXA were similar to controls. Larger trials are needed to confirm TXA's role in CSDH management. [ABSTRACT FROM AUTHOR]

Introduction: Systematic collection of diverse adverse events during herbal medicine administration is crucial. The Korea Adverse Event Reporting System (KAERS) compiles spontaneously reported adverse event data for medicinal products including herbal medicines. This study focused on extracting and analyzing adverse event data specifically related to herbal medicine products from the KAERS database. Methods: Individual case safety reports (ICSRs) encompassing 84 types of herbal medicine products, identified by item codes from 2012 to 2021, were extracted from the KAERS database. Descriptive statistics were employed to analyze the characteristics of the extracted reports, and adverse event information was systematically categorized and analyzed based on the MedDRA System Organ Class and preferred term classification. Results: In total, 1,054 ICSRs were extracted, with some documenting multiple adverse events in a single ICSR, resulting in 1,629 extracted adverse events. When categorized by the MedDRA System Organ Class, gastrointestinal disorders were the most prevalent (28.7%), followed by skin and subcutaneous tissue disorders (20.1%). Based on the preferred terms, the most frequently reported adverse events were diarrhea (5.8%), urticaria (5.3%), pruritus (4.7%), rash (4.4%), and abdominal discomfort (4.2%). The most frequently reported herbal medicines were Bangpungtongseong-san (297 cases), Kyeongok-go (144 cases), and Eunkyo-san (108 cases). Conclusion: Spontaneously reported adverse events associated with herbal medicine products were systematically documented using the KAERS database. This study, which focused on voluntarily reported adverse reactions, underscores the need for additional research to estimate the incidence rate of adverse events and assess causality. [ABSTRACT FROM AUTHOR]

Introduction: Systematic collection of diverse adverse events during herbal medicine administration is crucial. The Korea Adverse Event Reporting System (KAERS) compiles spontaneously reported adverse event data for medicinal products including herbal medicines. This study focused on extracting and analyzing adverse event data specifically related to herbal medicine products from the KAERS database. Methods: Individual case safety reports (ICSRs) encompassing 84 types of herbal medicine products, identified by item codes from 2012 to 2021, were extracted from the KAERS database. Descriptive statistics were employed to analyze the characteristics of the extracted reports, and adverse event information was systematically categorized and analyzed based on the MedDRA System Organ Class and preferred term classification. Results: In total, 1,054 ICSRs were extracted, with some documenting multiple adverse events in a single ICSR, resulting in 1,629 extracted adverse events. When categorized by the MedDRA System Organ Class, gastrointestinal disorders were the most prevalent (28.7%), followed by skin and subcutaneous tissue disorders (20.1%). Based on the preferred terms, the most frequently reported adverse events were diarrhea (5.8%), urticaria (5.3%), pruritus (4.7%), rash (4.4%), and abdominal discomfort (4.2%). The most frequently reported herbal medicines were Bangpungtongseong-san (297 cases), Kyeongok-go (144 cases), and Eunkyo-san (108 cases). Conclusion: Spontaneously reported adverse events associated with herbal medicine products were systematically documented using the KAERS database. This study, which focused on voluntarily reported adverse reactions, underscores the need for additional research to estimate the incidence rate of adverse events and assess causality. [ABSTRACT FROM AUTHOR]

Résumé: Nous avons vu dans une première partie [1] les raisons de la rapidité remarquable de production des vaccins anti-Covid-19 et les résultats des premiers essais randomisés sur ces vaccins. Nous verrons ici les conséquences qu'ils ont entrainées sur les données de santé publique, et nous analyserons les effets indésirables (EI) relevés en reprenant les accusations, hâtives, et parfois mensongères, qui ont été soulevées à leur propos. [ABSTRACT FROM AUTHOR]

Cannabis is the most used drug worldwide with an estimated 219 million users. This narrative review aims to explore the adverse effects and therapeutic applications of cannabis and cannabinoids on the eye, given its growing clinical and non-clinical uses. The current literature reports several adverse ocular effects of cannabis and cannabinoids, including eyelid tremor, ptosis, reduced corneal endothelial cell density, dry eyes, red eyes, and neuro-retinal dysfunction. Cannabinoids may transiently impair night vision, depth perception, binocular and monocular contrast sensitivity, and dynamic visual acuity. Cannabinoids are not currently considered a first-line treatment option for any ocular conditions. Δ-9-tetrahydrocannabinol been shown to result in short-term intraocular pressure reduction, but insufficient evidence to support its use in treating glaucoma exists. Potential therapeutic applications of cannabinoids include their use as a second-line agent for treatment-refractory blepharospasm, for dry eye disease given corneal anti-inflammatory properties, and for suppression of pendular nystagmus in individuals with multiple sclerosis, which all necessitate further research for informed clinical practices. [ABSTRACT FROM AUTHOR]

Background Cannabinoid-based medicines (CBMs) are being used widely in older people. However, information on the incidence of adverse events (AEs) is limited. Objective To quantify the incidence rate difference (IRD) of AEs in middle aged and older adults of age ≥50 years receiving CBMs and also examine associations with weekly doses. Design Systematic review and meta-analysis. Data sources MEDLINE, PubMed, EMBASE, CINAHL, PsychInfo, Cochrane Library and ClinicalTrials.gov (1st Jan 1990–12th June 2023). Methods We included randomised clinical trials (RCTs) using CBMs with mean participant age ≥50 years for medicinal purposes for all clinical indications. Paired reviewers independently screened studies, extracted data and appraised risk of bias. We estimated pooled effect-sizes IRD under the random-effects model. Results Data from 58 RCTs (37 moderate-high quality studies, pooled n = 6611, mean age range 50–87 years, 50% male, n = 3450 receiving CBMs) showed that compared with controls, the incidence of all-cause and treatment-related AEs attributable to delta-9-tetrahydrocannabinol (THC)-containing CBMs were: THC alone [IRD:18.83(95% Confidence Interval [CI], 1.47–55.79) and 16.35(95% CI, 1.25–48.56)] respectively; THC:cannabidiol (CBD) combination [IRD:19.37(95% CI, 4.24–45.47) and 11.36(95% CI, 2.55–26.48)] respectively. IRDs of serious AEs, withdrawals and deaths were not significantly greater for CBMs containing THC with or without CBD. THC dose-dependently increased the incidence of dry mouth, dizziness/lightheadedness, mobility/balance/coordination difficulties, dissociative/thinking/perception problems and somnolence/drowsiness. The interaction of weekly THC:CBD doses played a role in mostly neurological, psychiatric and cardiac side-effects. Conclusions Although CBMs in general are safe and acceptable in middle aged and older adults, one needs to be mindful of certain common dose-dependent side-effects of THC-containing CBMs. [ABSTRACT FROM AUTHOR]

Background: The light spectrum of intense pulsed light (IPL) comprises visible to near‐infrared light. It has been widely employed in the field of aesthetics for approximately 30 years. However, several studies have demonstrated the appearance of various undesirable biomarkers on the skin after IPL irradiation, which remain elucidated. Methods: We reviewed the evolving concepts and explored the potentially harmful effects of IPL that may have been neglected in the past. Results: Increased levels of reactive oxidative stress, p53, p16, proliferating cell nuclear antigen, interleukin‐6, C‐reactive protein, and cleaved caspase 3 and decreased albumin levels in human or mouse skin have been observed after IPL treatment. Visible and infrared light can exert harmful and beneficial effects on human skin. Conclusion: If perform improperly, IPL treatment may lead to cellular senescence, photoaging, photocarcinogenesis, thermal aging, and inflammaging. Further studies are required to verify the significance of the changes in the relevant biomarkers. The selection of treatment candidates, optimal parameters, and standardized protocols for IPL therapy are necessary. [ABSTRACT FROM AUTHOR]

Background: Currently, it remains unknown whether there is an association between body mass index (BMI) and complications during screening colonoscopy; hence, it remains unclear whether BMI should be considered a risk factor in pre-procedural assessments. The aim of this study was to compare mortality and unplanned hospitalization rates before and after colonoscopy stratified by patients' BMI. Material and methods: This was a retrospective cohort study of individuals who underwent screening colonoscopy as part of the Polish Colonoscopy Screening Program (PCSP). The included individuals were followed up for mortality and hospitalization episodes from 42 days prior to colonoscopy to 30 days after the procedure. Rates for the endpoints were calculated, compared, and adjusted for available data. Weighted averages of stratum-specific rates were calculated. Additional subanalyses were performed for sex and procedure type (screening colonoscopy without biopsy, colonoscopy with biopsy, or colonoscopy with polypectomy). Results: A total of 55390 individuals who underwent colonoscopy between years 2012–2015 were included. Obese individuals had significantly more hospitalizations than non-obese patients (1.94% versus 0%, p =.038). Analysis of adjusted hospitalization rates stratified by sex revealed that obese males had significantly higher related hospitalizations' rates before or after and after colonoscopy. Unadjusted and adjusted mortality rates after screening colonoscopy did not reveal significant differences between BMI categories. Conclusions: Overweight and obesity are not clinically relevant risk factors for mortality and hospitalization six weeks before or 30 days after screening colonoscopy. Obese males may be more likely to require hospital care after colonoscopy. [ABSTRACT FROM AUTHOR]

Background: Drug-induced adverse symptoms affect patients' quality of life (QoL) during treatment. Understanding the underlying mechanisms of drug-induced adverse effects could help prevent them. As current drugs have limited effects in halting the progress of Alzheimer's disease (AD), patients are required to take these drugs over a long period. The main obstacles to long-term compliance are drug-elicited side effects that deteriorate patient QoL. Objective: Donepezil, the most popular acetylcholinesterase inhibitor (AChEI) drug for AD, induces various side effects, especially at high doses. This study aimed to identify a drug that can attenuate the side effects of donepezil and investigate the underlying mechanisms. Methods: Five-week-old Sprague-Dawley rats received daily oral donepezil and N-acetylcysteine (NAC) for four weeks. General symptoms following administration were monitored daily to address drug-related adverse effects. Cytosolic calcium influx and generation of reactive oxygen species (ROS) after drug treatment were measured in vitro using C2C12 myotubes. Results: High-dose donepezil induced numerous adverse symptoms in male and female rats, which were markedly attenuated by co-treatment with NAC. NAC significantly reduced both acute and chronic muscle-related symptoms caused by donepezil. Additionally, in vitro studies showed that high-dose donepezil increased ROS and intracellular calcium ([Ca2+]i) levels in muscle cells, contributing to these adverse effects. NAC co-treatment dramatically reduced ROS and [Ca2+]i levels in muscle cells. Conclusions: Combined treatment with NAC effectively diminishes the adverse effects elicited by donepezil by regulating ROS and [Ca2+]i levels in the skeletal muscle, which could contribute to improving donepezil treatment in patients. [ABSTRACT FROM AUTHOR]

Since the reports of the first cases of COVID-19, in less than 5 years, a huge number of documents regarding that disease and the coronavirus (SARS-CoV-2), responsible for the infection, have been published. The tremendous number of scientific documents covers many topics on different issues directly related to COVID-19/SARS-CoV-2. The number of articles—including reviews—reporting adverse/side effects of the approved COVID-19 vaccines is considerable. A wide range of adverse/side effects have been reported in humans after COVID-19 vaccination: thrombotic events/thrombocytopenia, myocarditis/pericarditis, cutaneous reactions, immune-mediated effects, psychiatric adverse events, systemic lupus erythematosus, reproductive toxicity, and other miscellaneous adverse effects. In contrast, information on nonclinical studies conducted to assess the potential toxicity/adverse effects of the COVID-19 vaccines in laboratory animals, is comparatively very scarce. The present review was aimed at revising the scientific literature regarding the studies in laboratory animals on the toxic/adverse effects of COVID-19 vaccines. In addition, the investigations reported in those specific toxicology journals with the highest impact factors have been examined one by one. The results of the present review indicate that most nonclinical/experimental studies on the adverse/toxic effects of the COVID-19 vaccines and/or potential candidates showed—in general terms—a good safety profile. Only in some animal studies were certain adverse effects found. However, a rather surprising result has been the limited number of available (in the databases PubMed and Scopus) nonclinical studies performed by the companies that have been the largest manufacturers of mRNA vaccines in the world. It is assumed that these studies have been conducted. However, they have not been published in scientific journals, which does not allow the judgment of the international scientific community, including toxicologists. [ABSTRACT FROM AUTHOR]

Aim: We aimed to investigate the long‐term impact of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) on thyroid function, cardiovascular health, renal outcomes and adverse events in individuals with obesity and without type 2 diabetes (T2D). Materials and Methods: In this observational cohort study, we used propensity score matching to construct comparable cohorts of individuals with obesity and without T2D who were new to GLP‐1 RA treatment and those who did not receive glucose‐lowering medications. In total, 3,729,925 individuals with obesity were selected from the TriNetX Global Network, with an index event between 1 January 2016 and 31 March 2024. The primary outcomes were safety, cardiovascular, thyroid and clinical biochemical profile outcomes occurring within 5 years following the index event. Results: After propensity score matching, the study included 12,123 individuals in each group. GLP‐1 RA treatment was associated with a significantly lower risk of all‐cause mortality (hazard ratio 0.23; 95% confidence interval 0.15–0.34) and several cardiovascular complications, including ischaemic heart disease, heart failure, arrhythmias, hypertension, stroke and atrial fibrillation (all p < 0.05). GLP‐1 RAs were also associated with a lower risk of acute kidney injury and allergic reactions. These protective effects were consistent across various subgroups and regions. Conclusions: In this large observational study, GLP‐1 RAs showed long‐term protective effects on cardiovascular health, renal outcomes and adverse events in individuals with obesity and without T2D. Our findings suggest that GLP‐1 RAs may offer a comprehensive approach to managing obesity and its related comorbidities, potentially improving overall health and survival in this population. [ABSTRACT FROM AUTHOR]

Background and objective: Systemic sclerosis (SSc) is a highly heterogeneous disease whose treatment is based mainly on immunosuppressants, antifibrotics, and vasodilators. Intravenous immunoglobulin (IVIG) have proved effective in other autoimmune diseases. The objective of this study is to evaluate the efficacy and safety of IVIG in SSc. Methods: The systematic review was conducted according to the PRISMA Statement. Medline, Embase and Cochrane Library databases were searched until March 2024. We assessed the quality of included studies using the Cochrane Risk of Bias 2.0 tool (RoB 2) for randomised clinical trials and the Cochrane Risk in non-randomized studies (ROBINS-I) tool for observational studies. Results: From 1242 studies identified, 15 studies were included, of which 14 were observational studies. In total, 361 patients with SSc were included, and 295 received treatment with IVIG. Most of the studies used a dose of 2 g/kg IVIG. Ten studies, including the clinical trial, showed high risk of bias, and five had a critical risk. Skin involvement was assessed using modified Rodnan skin score, in 11 studies and the authors reported cutaneous efficacy in 9 of them. The 6 studies that assessed muscle involvement reported an improvement. Six studies reported data on gastrointestinal efficacy. Other domains such as lung and joint involvement and steroid-sparing effect were evaluated. The most frequent adverse events were mild, including headache, abdominal pain, fever, and skin rash. Conclusion: Treatment with IVIG in SSc patients could be helpful and safe in patients with cutaneous, muscular, or digestive manifestations. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) vaccination has been offered in over a hundred countries worldwide (including the United Kingdom, since September 2008). Controversy around adverse effects persists, with inconsistent evidence from follow-up of randomized controlled trials and confounding by indication limiting the conclusions drawn from larger-scale observational studies. This study aims to estimate the association between receiving a quadrivalent HPV vaccine and the reporting of short-term adverse effects and to demonstrate the utility of regression discontinuity design for examining side effects in routine data. Methods: We applied a novel regression discontinuity approach to a retrospective population-based cohort using primary care data from the UK Clinical Practice Research Datalink linked to hospital and social deprivation data. We examined the new onset of gastrointestinal, neuromuscular, pain, and headache/migraine symptoms using READ and International Classification of Diseases, tenth revision diagnostic codes. For each year between 2012 and 2017, we compared girls in school year 8 (born July/August) who were eligible to receive the vaccine with girls in year 7 (born September/October) who were not eligible. Results: Of the 21,853 adolescent girls in the cohort, 10,881 (50%) were eligible for HPV vaccination. There was no evidence of increased new gastrointestinal symptoms (adjusted odds ratio [OR]: 0.99; 95% confidence interval [CI]: 0.85, 1.15), headache/migraine symptoms (OR: 0.84; 95% CI: 0.70, 1.01), or pain symptoms (OR: 1.05; 95% CI: 0.95, 1.16) when comparing those eligible and ineligible for HPV vaccination. Conclusion: This study found no evidence that HPV vaccination eligibility is associated with reporting short-term adverse effects among adolescent girls. [ABSTRACT FROM AUTHOR]

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Background: Clozapine-induced inflammation, such as myocarditis and pneumonia, can occur during initial titration and can be fatal. Fever is often the first sign of severe inflammation, and early detection and prevention are essential. Few studies have investigated the effects of clozapine titration speed and concomitant medication use on the risk of clozapine-induced inflammation. Aims: We evaluated the risk factors for clozapine-associated fever, including titration speed, concomitant medication use, gender and obesity, and their impact on the risk of fever and the fever onset date. Method: We conducted a case-control study. The medical records of 539 Japanese participants with treatment-resistant schizophrenia at 21 hospitals in Japan who received clozapine for the first time between 2010 and 2022 were retrospectively investigated. Of these, 512 individuals were included in the analysis. Individuals were divided into three groups according to the titration rate recommended by international guidelines for East Asians: the faster titration group, the slower titration group and the ultra-slower titration group. The use of concomitant medications (such as antipsychotics, mood stabilisers, hypnotics and anxiolytics) at clozapine initiation was comprehensively investigated. Logistic regression analysis was performed to identify the explanatory variables for the risk of a fever of 37.5°C or higher lasting at least 2 days. Results: Fever risk significantly increased with faster titration, male gender and concomitant use of valproic acid or quetiapine. No increased fever risk was detected with the use of other concomitant drugs, such as olanzapine, lithium or orexin receptor antagonists. Fever onset occurred significantly earlier with faster titration. Multivariate analysis identified obesity as being a factor that accelerated fever onset. Conclusion: A faster titration speed and concomitant treatment with valproic acid and quetiapine at clozapine initiation increased the risk of clozapine-associated fever. Clinicians should titrate clozapine with caution and consider both the titration speed and concomitant medications. [ABSTRACT FROM AUTHOR]