Excessive androgen exposure and risk of malignancies: A cohort study.

BACKGROUND: A link between androgen use and the risk of cancers, especially prostate and breast cancer, has been suggested. The knowledge about a possible association is limited. OBJECTIVE: The study aimed to investigate cancer incidence rates, particularly those related to prostate and breast cancer, in male androgen users and compare them to a control group. METHODS: We included male androgen users identified through a nationwide anti-doping testing program in Danish fitness centers from 2006 to 2018. We paired each case with 50 male controls of the same age, selected randomly. The cohort was followed from baseline and until 2023. The outcome was the incidence of prostate cancer, breast cancer, or any cancer excluding non-melanoma skin cancer. RESULTS: The study included 1,189 androgen users and 59,450 controls, with a mean age of 27 years at enrolment. During the follow-up period with a mean length of 11 years, 13 androgen users, and 612 controls were diagnosed with cancer. This resulted in an incidence rate ratio of 1.05 (95% CI: 0.55-1.81). None of the androgen users were diagnosed with prostate or breast cancer. DISCUSSION AND CONCLUSION: Male androgen users did not face an increased short-term risk of cancer, neither overall nor related to prostate or breast cancer. Our study indicates that the absolute risk of malignancies in androgen users is comparable to that in the background population. However, we cannot exclude androgens as a cancer risk factor due to the limited sample size, relatively short follow-up period, and subject age.

Extensive androgen exposure and meningioma risk - A matched cohort study.

INTRODUCTION: Meningiomas frequently occur within the field of neuro-oncology, but it is unclear whether exogenous or imbalanced endogenous hormones are involved in the pathophysiology. A previous case-control study found an almost 20-fold increase in the risk of developing meningioma among users of androgenic anabolic steroids. We, therefore, investigated this hypothesis. METHODS: We compared the incidence rate of meningioma in a cohort of males sanctioned for the use of androgenic anabolic steroids with age- and sex-matched controls with an identical enrollment date. RESULTS: We followed 1189 males sanctioned for using androgenic anabolic steroids for a total of 13,305 person-years and found 0 cases of meningioma. The control cohort of 59,450 males was followed for a total of 654,938 person-years, and 16 were diagnosed with meningioma. Thus, the incidence rate ratio was 0 (95% CI: 0-12.8). CONCLUSION: We did not find any evidence supporting the hypothesis of an increased risk of meningioma development with the use of androgenic anabolic steroids. Due to the limited sample size, we cannot exclude androgenic anabolic steroids as a potential risk factor for meningioma development, despite the lack of apparent evidence in this study.

Using soluble urokinase plasminogen activator receptor to stratify patients for medication review in the emergency department.

AIMS: To investigate whether the association between levels of medication use (including polypharmacy and potentially inappropriate medications [PIMs]) and health outcomes such as readmission and mortality is dependent on baseline soluble urokinase plasminogen activator receptor (suPAR). METHODS: This registry-based cohort study included medical patients admitted to the emergency department at Copenhagen University Hospital Hvidovre, Denmark. Patients were grouped according to their admission suPAR levels: low (0-3 ng/mL), intermediate (3-6 ng/mL), or high (>6 ng/mL). Hyper-polypharmacy was defined as ≥10 prescribed medications. PIMs were identified based on the EU(7)-PIM list, and data on admissions and mortality were obtained from national registries. Risk of 90-day readmission and mortality was assessed by Cox regression analysis adjusted for sex, age and Charlson comorbidity index. Results were reported as hazard ratios within 90 days of index discharge. RESULTS: In total, 26 291 patients (median age 57.3 y; 52.7% female) were included. Risk of 90-day readmission and mortality increased significantly for patients with higher suPAR or higher number of medications. Among patients with low suPAR, patients with ≥10 prescribed medications had a hazard ratio of 2.41 (95% confidence interval = 2.09-2.78) for 90-day readmission and 8.46 (95% confidence interval = 2.53-28.28) for 90-day mortality compared to patients with 0 medications. Patients with high suPAR generally had high risk of readmission and mortality, and the impact of medication use was less pronounced in this group. Similar, but weaker, association patterns were observed between suPAR and PIMs. CONCLUSION: The association between levels of medication use and health outcomes is dependent on baseline suPAR.

Smartphone App to Self-Monitor Nausea During Pediatric Chemotherapy Treatment: User-Centered Design Process.

BACKGROUND: Nausea and vomiting are common and distressing side effects for children receiving chemotherapy. Limited evidence is available to guide antiemetic recommendations; therefore, prospective and reliable evaluation of antiemetic efficacy is needed. Smartphone apps can be used to effortlessly and precisely collect patient-reported outcomes in real time. OBJECTIVE: Our objective was to develop a smartphone app to monitor nausea and vomiting episodes in pediatric cancer patients aged 0 to 18 years and to test its usability and adherence to its use. METHODS: We used a user-centered design process and the evolutionary prototype model to develop and evaluate the app. Multidisciplinary group discussions and several rounds of patient feedback and modification were conducted. We translated the validated Pediatric Nausea Assessment Tool to assess nausea severity in children aged 4 to 18 years. The child's own term for nausea was interactively incorporated in the nausea severity question, with response options expressed as 4 illustrative faces. Parent-reported outcomes were used for children aged 0 to 3 years. Reminders were sent using push notifications in order to ensure high response rates. Children aged 0 to 18 years who were undergoing chemotherapy were recruited from the Department of Pediatric Oncology at Copenhagen University Hospital Rigshospitalet to evaluate the app. RESULTS: The app's most important function was to record nausea severity in children. After assistance from a researcher, children aged 4 to 18 years were able to report their symptoms in the app, and parents were able to report symptoms for their children aged 0 to 3 years. Children (n=20, aged 2.0-17.5 years) and their parents evaluated the app prospectively during a collective total of 60 chemotherapy cycles. They expressed that the app was user-friendly, intuitive, and that the time spent on data entry was fair. The response rates were on average 92%, 93%, and 80% for the day before, the first day of, and the next 3 days after chemotherapy, respectively. Researchers and clinicians were able to obtain an overview of the patient's chemotherapy dates and responses through a secure and encrypted web-based administrative portal. Data could be downloaded for further analysis. CONCLUSIONS: The user-friendly app could be used to facilitate future pediatric antiemetic trials and to refine antiemetic treatment during chemotherapy.

Two-bag intravenous N-acetylcysteine, antihistamine pretreatment and high plasma paracetamol levels are associated with a lower incidence of anaphylactoid reactions to N-acetylcysteine.

Context:N-acetylcysteine (NAC) is used worldwide to prevent liver injury after paracetamol overdoses. Anaphylactoid reactions to NAC occur frequently and often lead to treatment interruptions or discontinuations. In Denmark in 2013, the NAC treatment regimen was simplified from a three-bag to a two-bag NAC regimen. Factors of importance for the development of anaphylactoid reaction to this new regimen are poorly explored. Previous studies have suggested a protective effect of high plasma levels of paracetamol on the development of anaphylactoid reactions. Likewise, exposure to antihistamines prior to NAC treatment may protect against these reactions.Methods: This is a retrospective cohort study of patients treated with NAC and with at least one plasma paracetamol sample performed in the Capital Region of Denmark from 2010 to 2017. The primary outcome was the incidence of anaphylactoid reactions to NAC requiring intravenous treatment with antihistamines and/or glucocorticoids. Logistic regression analyses were carried out to identify the risk of developing an anaphylactoid reaction to NAC affected by influencing factors.Results: Of 4315 admissions included in the study, 259 (6.0%) developed an anaphylactoid reaction to NAC. The two-bag regimen (adjusted OR 0.44 [95%CI: 0.32-0.60]), increasing age (adjusted OR 0.84 [95%CI: 0.78-0.90] per 10-year increase) or children <10 years (adjusted OR 0.14 [95%CI: 0.04-0.36]) and antihistamine co-ingestion in overdose (adjusted OR 0.17 [95%CI: 0.02-0.64]) were associated with significantly fewer anaphylactoid reactions. High plasma paracetamol concentrations protected against development of anaphylactoid reactions during the two-bag regimen (adjusted OR 0.59 [95%CI: 0.47-0.71] and three-bag regimen 0.82 [95%CI: 0.72-0.94] per doubling of paracetamol concentration). The effect differed between the two regimens (p = .004 for interaction).Conclusion: In this retrospective cohort, a high peak plasma paracetamol concentration, age, antihistamine co-ingestion and use of the two-bag NAC regimen were associated with fewer anaphylactoid reactions to NAC.

Hemodynamic Effects of Intravenous, High-Dose Lipid Emulsion With and Without Metoprolol Infusion in Healthy Volunteers: A Randomized Clinical Trial.

In a double-blinded, randomized, crossover trial, we investigated the hemodynamic effects of high-dose intravenous lipid emulsion (ILE) with/without metoprolol. Ten healthy volunteers each completed 4 trial days (placebo + ILE; metoprolol + placebo; metoprolol + ILE; placebo + placebo) in random order. Metoprolol was administered as an initial bolus (10 mg), followed by an infusion (50 mg) from 5 to 30 minutes. ILE was administered as a bolus at 12.5 minutes (2.5 mL/kg), followed by a 15-minute infusion (0.25 mL/kg per minute). On metoprolol + ILE days (compared with metoprolol + placebo) after 120 minutes, mean heart rates were significantly higher (difference, 5.5 beats per minute (bpm); 95% confidence interval (CI), 3.0-8.1 bpm; P < 0.001), and average relative cardiac output was higher (difference, 10 percentage points; 95% CI, 5-15 percentage points; P < 0.001). The hemodynamic effect of ILE developed gradually. ILE had no effect on plasma metoprolol or major adverse events. In conclusion, high-dose ILE has relatively marginal and delayed hemodynamic effects that may have limited clinical relevance in the short-term clinical toxicological setting.

[Insufficient evidence in prophylactic therapy of chemotherapy-induced nausea and vomiting in children and adolescents].

Nausea and vomiting are burdensome side effects of chemotherapy. Vomiting is observed in up to 60% of treated children. An appropriate and effective antiemetic regimen has the potential to eradicate or reduce the symptoms. Differences in local guidelines characterise the antiemetic treatment across the four Danish paediatric oncology departments because the overall knowledge of the most effective antiemetics is incomplete. There is an unmet need for research, which can promote evidence-based guidelines. The impact of host genome polymorphisms should be included in the research.

Clinical Implications of P-Glycoprotein Modulation in Drug-Drug Interactions.

Drug-drug interactions (DDIs) occur commonly and may lead to severe adverse drug reactions if not handled appropriately. Considerable information to support clinical decision making regarding potential DDIs is available in the literature and through various systems providing electronic decision support for healthcare providers. The challenge for the prescribing physician lies in sorting out the evidence and identifying those drugs for which potential interactions are likely to become clinically manifest. P-glycoprotein (P-gp) is a drug transporting protein that is found in the plasma membranes in cells of barrier and elimination organs, and plays a role in drug absorption and excretion. Increasingly, P-gp has been acknowledged as an important player in potential DDIs and a growing body of information on the role of this transporter in DDIs has become available from research and from the drug approval process. This has led to a clear need for a comprehensive review of P-gp-mediated DDIs with a focus on highlighting the drugs that are likely to lead to clinically relevant DDIs. The objective of this review is to provide information for identifying and interpreting evidence of P-gp-mediated DDIs and to suggest a classification for individual drugs based on both in vitro and in vivo evidence (substrates, inhibitors and inducers). Further, various ways of handling potential DDIs in clinical practice are described and exemplified in relation to drugs interfering with P-gp.