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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

Breast cancer is the most frequently diagnosed cancer in the UAE and a leading cause of cancer-related mortality. Although early diagnosis contributes to favorable prognoses, novel treatment modalities like antibody-drug conjugates (ADCs) have significantly broadened the therapeutic landscape for patients in metastatic settings. The recognition of "HER2-low" expression as a targetable category has caused a paradigm shift in the management of breast cancer. Although initially developed to target HER2-positive breast cancer, trastuzumab deruxtecan (T-DXd), an ADC, has now also been approved to treat metastatic or unresectable HER2-low breast cancers. Despite the inherent specificity of an ADC, the risk of off-site toxicity exists and is an essential component while assessing the risk-benefit ratio of the treatment. Developing strategies to balance efficacy and safety is crucial, especially for newly approved therapies like T-DXd. Regional perspectives, cultural beliefs, and demographic factors influence treatment decisions and outcomes. The objective of this paper is to establish a UAE-specific consensus among oncologists on practical T-DXd treatment considerations and management of associated side effects. Establishing a consensus on monitoring and managing T-DXd side effects among experts can promote informed decision-making. [ABSTRACT FROM AUTHOR]

Background: Electroconvulsive therapy (ECT)-induced fever can significantly affect patient experience, treatment adherence, and the course of treatment. However, little is known about the prevalence of ECT-induced fever and its associated risk factors in patients with major mental disorders (MMD). Methods: This retrospective, case-control study included 113 cases and 226 age-matched controls (1:2). The case group comprised patients who exhibited an axillary temperature of ≥37.5°C (99.5°F) at least once within 24 hours post-ECT. Patients diagnosed with MMD underwent ECT between January 1, 2021, and December 31, 2021, at a large psychiatric hospital in China. Demographic and clinical data were extracted from the electronic chart management system (ECMS) for both groups. Results: The prevalence of ECT-induced fever in patients with MMD was 6.8% [113/1,674, 95% confidence interval (CI): 5.6% to 8.0%], with a session-based prevalence of 1.1% (130/11,570, 95% CI: 0.9% to 1.3%). Multivariate logistic regression analysis identified paliperidone [odds ratios (OR)=2.5, 95% CI: 1.2 to 4.9] as a risk factor, while quetiapine (OR=0.4, 95% CI: 0.3 to 0.8) was found to be protective. No significant association between etomidate and ECT-induced fever was observed in univariate analysis (p >0.05). Conclusions: This study found a relatively low prevalence of ECT-induced fever. Paliperidone was identified as a risk factor, while quetiapine had a protective effect. Etomidate was not significantly associated with ECT-induced fever in patients with MMD. [ABSTRACT FROM AUTHOR]

Introduction: Most drugs fail during development and there is a clear and unmet need for approaches to better understand mechanistically how drugs exert both their intended and adverse effects. Gaining traction in this field is the use of disease data linking genes with pathological phenotypes and combining this with drugtarget interaction data. Methods: We introduce methodology to associate drugs with effects, both intended and adverse, using a tripartite network approach that combines drug-target and target-phenotype data, in which targets can be represented as proteins and protein domains. Results: We were able to detect associations for over 140,000 ChEMBL drugs and 3,800 phenotypes, represented as Human Phenotype Ontology (HPO) terms. The overlap of these results with the SIDER databases of known drug side effects was up to 10 times higher than random, depending on the target type, disease database and score threshold used. In terms of overlap with drug-phenotype pairs extracted from the literature, the performance of our methodology was up to 17.47 times greater than random. The top results include phenotype-drug associations that represent intended effects, particularly for cancers such as chronic myelogenous leukemia, which was linked with nilotinib. They also include adverse side effects, such as blurred vision being linked with tetracaine. Discussion: This work represents an important advance in our understanding of how drugs cause intended and adverse side effects through their action on disease causing genes and has potential applications for drug development and repositioning. [ABSTRACT FROM AUTHOR]

This is a literature review about the major adverse effects of the use of the novel drug alpelisib in PIK3CA -mutated metastatic breast cancer. Alpelisib is a direct PIK3CA inhibitor that has proven remarkably beneficial for the treatment of this cancer subtype; however, it comes with many adverse effects, hyperglycemia being the most common. This review explains the predisposing factors, management, and prevention of alpelisib-associated hyperglycemia. Alpelisib is a phosphatidylinositol 3-kinase inhibitor approved by the US Food and Drug Administration for the treatment of hormone receptor–positive metastatic breast cancer with PIK3CA (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α) mutation. In recent years a number of adverse effects have been observed to be associated with this therapy, the most notable of which is hyperglycemia. A literature search was conducted to include case studies, case series, systematic reviews, and meta-analyses within the last 10 years that evaluated patients with PIK3CA- mutated hormone receptor–positive, human epidermal growth factor receptor 2 negative metastatic breast cancer. Hyperglycemia was a notable adverse effect that was found in the majority of patients without preexisting diabetes mellitus. Patients with hyperglycemia were in the high-risk groups of advanced age, prediabetes mellitus or history of insulin resistance, increased body mass index, increased blood monocyte count, and increased hemoglobin A1c (glycated hemoglobin). Hyperglycemia was manageable with antihyperglycemic agents and dose modification/discontinuation of alpelisib with no severe progression. Other notable adverse effects were rash, stomatitis, diarrhea, pneumonitis, reduced appetite, elevated liver enzymes, nausea, fatigue, and rare reports of diabetic ketoacidosis. This literature review aims to highlight the incidence and risk factors of alpelisib-induced hyperglycemia in greater depth. [ABSTRACT FROM AUTHOR]

Numerous studies have shown that topical timolol is effective in treating infantile hemangioma (IH) with minimal adverse events. However, consensus is lacking on optimal timing, dosage, frequency, and safety parameters for this treatment. This study aims to explore the timing and safety of topical timolol treatment for superficial IH. A retrospective analysis included pediatric IH patients who underwent topical timolol treatment at the Department of Pediatric Surgery of Sichuan Provincial People’s Hospital between January 2019 and January 2023. Medical records were reviewed for patient information, lesion characteristics, outcomes, and complications. Topical timolol was administered to 666 IH patients. Median follow-up was 10 months. 480 cases had excellent or good outcomes, while 186 had fair or poor outcomes. Patients ≤ 3 months had better outcomes than those > 3 months (Z = 4.713, P < 0.001). Small IH had better outcomes than large IH (Z = 1.991, P = 0.046). Lesion locations did not significantly affect outcomes (H = 10.252, P = 0.114). Respiratory problems occurred in 58 (8.7%) cases, localized skin irritation occurred in 48 (7.2%) cases, sleep disturbance occurred in 30 (4.5%) cases, and residual skin lesions occurred in 26 (3.9%) cases. In 59 (8.8%) cases the IH had relapses. Conclusions: Topical timolol is safe and effective for IH. Patients who are aged 1 < months ≤ 3 or have small (1.5 cm < max diameter ≤ 5 cm) IH are more likely to experience better outcomes. It also may reduce the incidence of residual skin lesions and relapse. Therefore it may be a useful alternative therapy option for superficial IH. What is Known: • β-blockers are now considered to be first-line treatment of infantile hemangioma. • Topical timolol treatment is safe and effective for infantile hemangioma. What is New: • Patients who are aged ≤ 3 months or have a max diameter ≤ 5 cm infantile hemangioma are likely to experience better outcomes by topical timolol treatment. • Topical timolol treatment may reduce the incidence of residual skin lesions and infantile hemangioma relapses. [ABSTRACT FROM AUTHOR]

Objective: In this perspective, we investigate how the Royal Australian and New Zealand College of Psychiatrists' (RANZCP) position statement on psychotherapy takes the potential for adverse effects into account. Conclusions: Psychotherapy has two critical outcomes – efficacy and adverse effects. Evidence-based psychotherapy is significantly more effective than care-as-usual for about one in 10 psychotherapy patients. However, a similar proportion also reports adverse effects. Despite this, the RANZCP position statement on psychotherapy focuses on efficacy with minimal discussion of the adverse effects. This is an oversight because psychiatrists have legal and ethical obligations to consider the adverse effects as well as the benefits of any treatment. We therefore reflect on the RANZCP's six recommendations in light of the adverse effects of psychotherapy. [ABSTRACT FROM AUTHOR]

Background: A growing body of evidence suggests a potential link between the SARS-CoV-2 vaccine and menstrual changes in women who were menstruating at the time of vaccination. Nevertheless, the prevalence of this event in those with secondary amenorrhea for different causes, i.e. formerly menstruating women, remains unclear. It is plausible that, analogous to those observed in currently menstruating women, they experienced some degree of alteration in their reproductive health, defined here as menstrual-related disturbances. Objective: The aim was to analyze this phenomenon and identify the factors associated with the occurrence of menstrual-related disturbances in this subpopulation. Study design: A retrospective observational cross-sectional study was conducted among adult Spanish in December 2021 using an online survey (N = 17,512). The present analysis includes a subpopulation of vaccinated and formerly menstruating women (N = 548). General characteristics, medical history, and adverse events following COVID-19 vaccination were recorded. Chi-square, Mann-Whitney U and McNemar mid-P tests were performed. Bivariate logistic regression was then used to identify the key factors influencing this unexpected event. Results: In comparison with the first dose, significantly higher percentages of respondents experienced menstrual-related disturbances (dose 1: 38.5 percent vs. dose 2: 44.8 percent) after receiving the second one. Among them, those related to the length and flow stand out, being of long-term nature in about 17–20 percent of cases. Interindividual factors influencing this unexpected event after receiving the dose 1 may include weight, perimenopause, preexisting diagnoses of non-autoimmune rheumatic/articular conditions, use of hormonal contraceptives, suffering from other vaccine side effects − such as arm pain and the number of previous pregnancies; for dose 2, these factors may include suffering from menstrual-related alterations after receiving dose 1, as well as the use of hormonal contraceptives and perimenopause. Conclusion: Formerly menstruating women might experience long-term menstrual-related disturbances following COVID-19 vaccination. Potential influencing factors include weight, perimenopause, rheumatic/articular conditions, hormonal contraceptives, vaccine side effects and previous pregnancies. [ABSTRACT FROM AUTHOR]

Background: Treatment-related skin reactions (TRSRs) induced by enfortumab vedotin (EV) targeting nectin-4 are among the most common adverse events. However, their association with survival and treatment response is poorly understood. Methods: We retrospectively identified patients who received EV from December 2021 to April 2023 at Nagoya University Hospital and its affiliated facilities and extracted clinical data from their medical records. We evaluated cancer-specific survival (CSS) and progression-free survival (PFS) as survival outcomes and overall response rate (ORR) and disease control rate (DCR) as treatment responses between patients with and without TRSRs. Results: In total, 67 eligible patients were identified. Thirty-four patients experienced TRSRs, and the remaining 33 did not experience TRSRs. The median follow-up period was 8 months. Patients in the TRSRs group demonstrated significantly longer median CSS (15 vs. 8 months; p = 0.003) and median PFS (10 vs. 5 months; p < 0.001) than the non-TRSRs. Regarding treatment response, the patients in the TRSRs group showed a favorable, albeit nonsignificant, treatment response trend compared with those in the non-TRSRs group (ORR, 73.5% vs. 51.5%; p = 0.107; DCR, 91.2 % vs. 81.8%; p = 0.444). Conclusions: Patients with TRSRs demonstrated more prolonged survival and superior treatment responses to EV treatment. The role of TRSR as a surrogate marker of EV's efficacy should be further explored in prospective and sufficiently powered studies. [ABSTRACT FROM AUTHOR]

Background: Antipsychotic medications (APs) are used for people with psychosis diagnoses and, increasingly for other problems and groups. Aims: This study examines how APs are prescribed, from the perspective of recipients. Methods: 757 people, from 30 countries, responded to questions about their experiences with APs, in an online survey. Results: Most (70%) were told nothing about adverse effects. Fewer than 2% recalled being told about the risks of diabetes, suicidality, sexual dysfunction, or reduced life span. None recalled being told about reduced brain volume or withdrawal effects. Only 28% recalled being offered other treatments; with only 14% offered talking therapies. 46% were not told how long to take the APs; and, of those who were told something, 48% were told to take them forever. Most respondents (76%) were not told how APs work. Only 19% were satisfied with the prescribing process, and only 25% reported a good, or very good, relationship with the prescriber. Information, satisfaction with the process, and the prescriber relationship were all positively related to three self-reported outcomes: reduction of problems the drugs were prescribed for, general helpfulness, and quality of life. Conclusions: Steps need to be taken to ensure people prescribed antipsychotics are fully informed, especially about adverse effects and alternatives. [ABSTRACT FROM AUTHOR]

Background: Atypical antipsychotics are a common treatment for serious mental illness, but many are associated with adverse effects, including weight gain and cardiovascular issues, and real-world experience may differ from clinical trial data. Cariprazine has previously demonstrated a favorable safety and tolerability profile in clinical trials. Here, we evaluated the effects of cariprazine on body weight and blood pressure for bipolar I disorder (BP-I), schizophrenia, or as adjunctive treatment for major depressive disorder (MDD) using real-world data. Methods: Symphony Health's Integrated Dataverse® with electronic medical record access (3/1/2015–10/31/2018) was used to identify adults (≥ 18 years) diagnosed with BP-I depression, BP-I mania/mixed, schizophrenia, or MDD, with ≥ 2 cariprazine dispensings (first dispensing = index) and continuous clinical activity for ≥ 12 months pre-index (baseline) and ≥ 3 months post-index. The on-treatment period spanned from index to cariprazine discontinuation, exposure to another atypical or long-acting injectable antipsychotic, or end of clinical activity/data availability. Outcomes included estimated annual linear trajectories for weight, body mass index (BMI), systolic blood pressure (SBP), and diastolic blood pressure (DBP) during baseline and on treatment. Changes were estimated using linear mixed-effects models fitted over measurements pre-index and on treatment; 95% CIs were derived from nonparametric bootstrap procedures. Results: The body weight analysis included 612 patients (BP-I, n = 331 [BP-I depression, n = 172; BP-I mania/mixed, n = 159]; schizophrenia, n = 75; MDD, n = 206). The mean patient age was 43.4 years, 75.2% were female, and the mean (SD) on-treatment period was 219 (185) days. Among patients with measurements before and during cariprazine treatment, estimated annual weight trajectories were + 3.55 (95% CI 2.38, 4.59) kg/year before cariprazine initiation and + 0.91 (− 1.17, 2.82) kg/year during cariprazine treatment. Additionally, annual linear trajectories evaluated across the on-treatment period were + 0.31 (− 0.42, 1.01) kg/m2/year for BMI, − 2.38 (− 4.27, − 0.76) mmHg/year for SBP, and − 0.57 (− 1.75, 0.61) mmHg/year for DBP. Conclusion: In this real-world analysis, cariprazine was associated with an estimated weight gain of + 0.91 kg/year and had minimal impact on BMI and blood pressure when evaluated up to 12 months. [ABSTRACT FROM AUTHOR]

Background: This study reports a case of severe cutaneous toxicity in a patient with metastatic gastric cancer induced by disitamab vedotin, emphasizing the need for careful monitoring and management in such treatments. Case presentation: A 71-year-old female was admitted to hospital complaining of serious rashes following the first cycle of disitamab vedotin regimen for metastatic gastric cancer. The doctor diagnosedtoxic epidermal necrolysis (TEN) induced by the drug. The patient received high-dose methylprednisolone due to the side effects. This resulted in a gradual improvement of symptoms. Conclusion: During the use of disitamab vedotin, patients need to be monitored for severe skin toxicity. [ABSTRACT FROM AUTHOR]

Background/Objectives: Owing to the growing use of immune checkpoint inhibitors (ICIs) in the treatment of cancer, a wide spectrum of toxicity has arisen among cancer patients. Yet, limited ICI toxicity-related research is currently conducted in our region. Methods: This is a retrospective observational study conducted on adult cancer patients who received at least one cycle of ICI single therapy. Toxicity profiles of different ICI monotherapies were described and compared, and their association with different risk factors was assessed. SPSS version 28 was used for statistical analyses, and p < 0.05 was considered statistically significant. Results: A total of 428 patients were treated with anti-PD1 (nivolumab [n = 221, 51.6%] and pembrolizumab [n = 126, 29.5%]) or anti-PD-L1 (atezolizumab [n = 78, 18.2%] and durvalumab [n = 3, 0.7%]). Pneumonia was the most common complication (10%), followed by acute kidney injury (AKI; 8.2%) and hepatitis (7.9%). The proportion of hepatitis cases was significantly higher among atezolizumab compared to nivolumab-, pembrolizumab-, and durvalumab-treated patients (17.95% vs. 7.7% vs. 2.4% vs. 0.0%, respectively; p < 0.001). Gastrointestinal complication (colitis) was detected in 3.3% of patients with a significant difference between treatment groups (4.5%, 1.6%, 1.3%, and 33.3% in nivolumab, pembrolizumab, atezolizumab, and durvalumab, respectively; p = 0.008). Cardiac complications occurred in 1.2% of patients with a significant difference between treatment groups (0.5% in the nivolumab, 3.8% in the atezolizumab, 33.3% in the durvalumab, and none in the pembrolizumab groups (p < 0.001)). Musculoskeletal side effects, including both arthralgia and fatigue, were the most-reported side effects by 39.5% of patients, with significantly higher arthralgia complainers only in nivolumab (7.7%) compared to other treatment groups (0%, 2.6%, and 0% in pembrolizumab, atezolizumab, and durvalumab, respectively, p = 0.007). Hepatic, cardiovascular, hematological, respiratory, renal, gastrointestinal complications, thyroid complications, and dermatological side effects were found to occur on weeks 6, 7.5, 8, 8, 10, 10, 10.5, and 12 after treatment initiation, respectively, with no significant difference between treatment groups. Despite that, hepatitis and AKI tended to occur earlier with atezolizumab (week 2, p = 0.084) and pembrolizumab (week 2, p = 0.062), respectively, compared to their comparators. The female gender and a history of hepatitis were found to increase the odds of hepatic complication with anti-PD1 or anti-PD-L1 use [OR = 2.71; 95% CI 1.07–6.85, OR = 11.14; 95% CI 3.46–35.88, respectively]. Previous exposure to cancer therapy only was found to increase the odds of developing pneumonia among the treated patients [OR = 3.08; 95% CI 1.12–8.85]. Having hematological malignancy influenced the odds of hematological complications positively (either neutropenia or thrombocytopenia) compared to solid malignancies when patients were treated with anti-PD1 or anti-PD-L1 [OR = 17.18; 95% CI 4.06–72.71]. Finally, the female gender was found to positively associate with the odds of nausea/vomiting and fatigue secondary to anti-PD1 or anti-PD-L1 administration [OR = 2.08; 95% CI 1.34–3.21, OR = 1.65; 95% CI 1.09–2.51, respectively]. On the other hand, previous exposure to cancer therapy was found to reduce the risk of having arthralgia with anti-PD1 or anti-PD-L1 administration [OR = 0.344; 95% CI 0.121–0.974]. Conclusions: Treatment with anti-PD1 or anti-PD-L1 was associated with a spectrum of complications and side effects. Several risk factors have been identified to impact their occurrence. ICI toxicities and risk factors influencing their odds should be recognized and considered in clinical practice, as this could help in individualizing therapeutics regimens and avoiding treatment interruption. [ABSTRACT FROM AUTHOR]

Background: In the context of modern cancer therapy, the management of adverse effects of systemic therapies can lead to the avoidance of underdosing and withdrawal and increases in the quality of the therapeutic act and the quality of life. This review offers an overview of the skin-related toxicities associated with Cabozantinib, a multikinase inhibitor (MKI) that is approved for treating advanced kidney cancer, hepatocellular carcinoma, and medullary thyroid cancer. It covers the most common dermatological side effects, such as palmar–plantar erythrodysesthesia, stomatitis, hair alterations, xerosis, scrotal erythema, and subungual splinter hemorrhages. Additionally, this review includes suggested preventive strategies and management approaches based on the severity of these adverse effects. [ABSTRACT FROM AUTHOR]