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1.
Br J Clin Pharmacol ; 2024 Mar 07.
Artigo em Inglês | MEDLINE | ID: mdl-38450747

RESUMO

We report a poisoning with paliperidone palmitate, a once-monthly, long-acting injectable antipsychotic. The patient suffered from deep sedation and dystonia. She had been treated with extended release intramuscular paliperidone for several years and had received her last injection 8 days prior to admission. The plasma paliperidone was nearly five times higher than the upper reference range. Paliperidone is a substrate of p-glycoprotein and we therefore aimed to increase its elimination by inducing p-glycoprotein through treatment with St John's wort. This seemed to have a limited effect on paliperidone clearance. Plasma concentration levels decreased with time as did the dystonia. All antipsychotic treatment was discontinued after this unfortunate event, and the patient did specifically not receive any prescriptions of paliperidone or risperidone. However, the plasma paliperidone concentration was in the low end of the normal therapeutic range 2.5 years after the last dose of paliperidone was administered, and the patient still had some extrapyramidal symptoms.

2.
Am J Kidney Dis ; 82(6): 715-724, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37516299

RESUMO

RATIONALE & OBJECTIVE: Older adults represent nearly half of all hospitalized patients and are vulnerable to inappropriate dosing of medications eliminated through the kidneys. However, few studies in this population have evaluated the performance of equations for estimating the glomerular filtration rate (GFR)-particularly those that incorporate multiple filtration markers. STUDY DESIGN: Cross-sectional diagnostic test substudy of a randomized clinical trial. SETTING & PARTICIPANTS: Adults≥65 years of age presenting to the emergency department of Copenhagen University Hospital Amager and Hvidovre in Hvidovre, Denmark, between October 2018 and April 2021. TESTS COMPARED: Measured GFR (mGFR) determined using 99mTc-DTPA plasma clearance compared with estimated GFR (eGFR) calculated using 6 different equations based on creatinine; 3 based on creatinine and cystatin C combined; and 2 based on panels of markers including creatinine, cystatin C, ß-trace protein (BTP) and/or ß2-microglobulin (B2M). OUTCOME: The performance of each eGFR equation compared with mGFR with respect to bias, relative bias, inaccuracy (1-P30), and root mean squared error (RMSE). RESULTS: We assessed eGFR performance for 106 patients (58% female, median age 78.3 years, median mGFR 62.9mL/min/1.73m2). Among the creatinine-based equations, the 2009 CKD-EPIcr equation yielded the smallest relative bias (+4.2%). Among the creatinine-cystatin C combination equations, the 2021 CKD-EPIcomb equation yielded the smallest relative bias (-3.4%), inaccuracy (3.8%), and RMSE (0.139). Compared with the 2021 CKD-EPIcomb, the CKD-EPIpanel equation yielded a smaller RMSE (0.136) but larger relative bias (-4.0%) and inaccuracy (5.7%). LIMITATIONS: Only White patients were included; only a subset of patients from the original clinical trial underwent GFR measurement; and filtration marker concentration can be affected by subclinical changes in volume status. CONCLUSIONS: The 2009 CKD-EPIcr, 2021 CKD-EPIcomb, and CKD-EPIpanel equations performed best and notably outperformed their respective full-age spectrum equations. The addition of cystatin C to creatinine-based equations improved performance, while the addition of BTP and/or B2M yielded minimal improvement. FUNDING: Grants from public sector industry (Amgros I/S) and government (Capital Region of Denmark). TRIAL REGISTRATION: Registered at ClinicalTrials.gov with registration number NCT03741283. PLAIN-LANGUAGE SUMMARY: Inaccurate kidney function assessment can lead to medication errors, a common cause of hospitalization and early readmission among older adults. Several novel methods have been developed to estimate kidney function based on a panel of kidney function markers that can be measured from a single blood sample. We evaluated the accuracy of these new methods (relative to a gold standard method) among 106 hospitalized older adults. We found that kidney function estimates combining 2 markers (creatinine and cystatin C) were highly accurate and noticeably more accurate than estimates based on creatinine alone. Estimates incorporating additional markers such as ß-trace protein and ß2-microglobulin did not further improve accuracy.


Assuntos
Cistatina C , Insuficiência Renal Crônica , Humanos , Feminino , Idoso , Masculino , Taxa de Filtração Glomerular , Creatinina , Estudos Transversais , Insuficiência Renal Crônica/epidemiologia , Biomarcadores
3.
Br J Clin Pharmacol ; 89(11): 3421-3431, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37353311

RESUMO

AIMS: To investigate the pharmacokinetics and safety of prolonged paracetamol use (>72 h) for neonatal pain. METHODS: Neonates were included if they received paracetamol orally or intravenously for pain treatment. A total of 126 samples were collected. Alanine aminotransferase and bilirubin were measured as surrogate liver safety markers. Paracetamol and metabolites were measured in plasma. Pharmacokinetic parameters for the parent compound were estimated with a nonlinear mixed-effects model. RESULTS: Forty-eight neonates were enrolled (38 received paracetamol for >72 h). Median gestational age was 38 weeks (range 25-42), and bodyweight at inclusion was 2954 g (range 713-4750). Neonates received 16 doses (range 4-55) over 4.1 days (range 1-13.8). The median (range) dose was 10.1 mg/kg (2.9-20.3). The median oxidative metabolite concentration was 14.6 µmol/L (range 0.12-113.5) and measurable >30 h after dose. There was no significant difference (P > .05) between alanine aminotransferase and bilirubin measures at <72 h or >72 h of paracetamol treatment or the start and end of the study. Volume of distribution and paracetamol clearance for a 2.81-kg neonate were 2.99 L (% residual standard error = 8, 95% confidence interval 2.44-3.55) and 0.497 L/h (% residual standard error = 7, 95% confidence interval 0.425-0.570), respectively. Median steady-state concentration from the parent model was 50.3 µmol/L (range 30.6-92.5), and the half-life was 3.55 h (range 2.41-5.65). CONCLUSION: Our study did not provide evidence of paracetamol-induced liver injury nor changes in metabolism in prolonged paracetamol administration in neonates.


Assuntos
Acetaminofen , Analgésicos não Narcóticos , Recém-Nascido , Humanos , Lactente , Acetaminofen/efeitos adversos , Estudos de Coortes , Alanina Transaminase , Dor/tratamento farmacológico , Bilirrubina
4.
Ther Drug Monit ; 45(4): 487-493, 2023 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-36631415

RESUMO

BACKGROUND: Amiodarone is a class III antiarrhythmic drug used to prevent supraventricular and ventricular tachyarrhythmias. It has substantial toxicity; however, the use of therapeutic drug monitoring (TDM) seems unclear in the absence of a therapeutic range or an association between amiodarone blood concentration and effect. In this review, the authors examined the reported amiodarone blood concentration measurements in the last 10 years and subsequently noted the frequency by which TDM was used to optimize therapy. METHODS: In March 2022, the Embase and MEDLINE databases were searched for articles published in English in the previous 10 years using the keywords "amiodarone," "therapeutic drug monitoring," or "serum/plasma/blood". RESULTS: This study included 19 of the 478 articles identified. TDM has not been studied in conjunction with regular amiodarone maintenance therapy. One study used TDM during the initial treatment phase but the amiodarone dose was not changed. In 3 other case reports, TDM was used to guide amiodarone treatment through drug-drug interactions, and plasma levels of the active metabolite mono-N-desethyl-amiodarone (MDEA) verified 2 amiodarone toxicities. CONCLUSIONS: Because the antiarrhythmic effect of amiodarone is not correlated with blood concentrations and is easily detectable by electrocardiogram, the routine use of TDM in maintenance therapy is controversial, as evidenced by a scarcity of published literature in the recent decade. Furthermore, amiodarone toxicity is evident with normal/low amiodarone or MDEA levels; hence, TDM of amiodarone provides no therapeutic benefit to patients.


Assuntos
Amiodarona , Humanos , Amiodarona/efeitos adversos , Monitoramento de Medicamentos , Antiarrítmicos/uso terapêutico
5.
Pharmacogenet Genomics ; 32(2): 72-78, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-34750329

RESUMO

Chemotherapy-induced nausea and vomiting (CINV) remains a common adverse effect for children with cancer. In children, chemotherapy emetogenicity and patient factors such as susceptibility to motion sickness and age group determine a patient's risk of CINV. Besides known risk factors, genetic factors may play a role in interindividual variation in the occurrence of CINV. We investigated the influence of candidate gene polymorphisms on the efficacy of antiemetics and on the background sensitivity to CINV in children. This prospective study included 100 children with cancer (median age 6.4 years, range 0.8-17.9) who received moderately to highly emetogenic chemotherapy. Participants registered nausea and vomiting episodes in a mobile app. Genotypes were determined by whole-genome sequencing (n = 79) or Sanger sequencing (n = 21) for 71 genetic polymorphisms involved in motion sickness and antiemetic pathways. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to estimate associations between acute CINV and genotypes adjusting for susceptibility to motion sickness and age group. Rs3782025 in the 5-hydroxytryptamine type 3 (5-HT3) receptor gene (HTR3B) [minor allele frequency (MAF): 0.48] affected response to 5-HT3 receptor antagonists; acute CINV occurred in 76% of patients with GA/AA genotypes and in 41% of patients with GG genotype (OR 5.59; 95% CI 1.74-17.9, dominant genetic model). Rs2975226 in the dopamine transporter gene (SLC6A3) (MAF: 0.54) was associated with acute CINV (OR 5.79; 95% CI 1.09-30.67, recessive genetic model). Polymorphisms in HTR3B and SLC6A3 may contribute to the variability in response to antiemetic prophylaxis for CINV in children.


Assuntos
Antieméticos , Antineoplásicos , Neoplasias , Adolescente , Antieméticos/uso terapêutico , Antineoplásicos/efeitos adversos , Criança , Pré-Escolar , Proteínas da Membrana Plasmática de Transporte de Dopamina , Estudos de Associação Genética , Humanos , Lactente , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Náusea/genética , Neoplasias/tratamento farmacológico , Neoplasias/genética , Estudos Prospectivos , Vômito/induzido quimicamente , Vômito/tratamento farmacológico , Vômito/genética
6.
Br J Clin Pharmacol ; 88(4): 1679-1690, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34242432

RESUMO

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.


Assuntos
Revisão de Medicamentos , Receptores de Ativador de Plasminogênio Tipo Uroquinase , Biomarcadores , Estudos de Coortes , Serviço Hospitalar de Emergência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
7.
Depress Anxiety ; 39(12): 805-812, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36281632

RESUMO

OBJECTIVE: The purpose of this study was to investigate the psychiatric morbidity among men with abuse of anabolic steroids. METHODS: The design is a retrospectively matched cohort study. Five hundred and fourty-five males, who tested positive for anabolic steroids in Danish fitness centers during the period January 3, 2006 to March 1, 2018, were matched with 5450 randomly chosen male controls. Data was cross-referenced with seven national registers pertaining to information about education, employment status, and psychiatric comorbidity. Main outcomes and measures were prescription of psychopharmacological treatment. RESULTS: The incidence of treatment with anxiolytics (HR: 2.34, 95% CI: 1.62-3.38) and antipsychotics (HR: 2.69, 95% CI: 1.99-3.63) displayed a remarkable increase in the years following doping sanction, compared to the control group. The prevalence of antidepressant use was already markedly elevated several years before doping sanction, but also displayed a higher incidence in the years following sanction (HR: 1.65, 95% CI: 1.28-2.13). The associations remained highly significant after controlling for socioeconomic factors. CONCLUSION: Anabolic steroids use is strongly associated with psychiatric morbidity.


Assuntos
Anabolizantes , Masculino , Humanos , Anabolizantes/efeitos adversos , Estudos de Coortes , Estudos Retrospectivos , Congêneres da Testosterona/efeitos adversos , Incidência
8.
Acta Paediatr ; 111(3): 667-674, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34773285

RESUMO

AIM: To evaluate the prevalence of potentially hepatoxic paracetamol ingestion and associated N-acetylcysteine treatment in young children suspected of paracetamol poisoning. METHODS: A retrospective cohort study of children aged 0-6 years suspected of paracetamol poisoning with a related plasma-paracetamol measurement in the Capital Region of Denmark in the period 2010-2017. Data from the clinical laboratory system were linked to data from electronic patient records via the unique identification number given to all Danish residents. RESULTS: Of 297 children included, suspected single paracetamol overdoses were present in 281 (95%). Sixty-nine per cent were treated with N-acetylcysteine, and the mean treatment period was 20.3 h (SD 20.8). A maximum of 6 (2%) of the children suspected of single overdose had plasma-paracetamol concentrations that exceeded the recommended treatment thresholds. No cases of severe hepatotoxicity were registered. Adverse events to N-acetylcysteine-treatment were registered in 3 (2%) children including one anaphylactoid reaction (0.5%). CONCLUSION: This study shows that initiating N-acetylcysteine as a 'one size fit all' treatment regimen in all children aged 0-6 years with a suspected single paracetamol overdose leads to substantial overtreatment. The data support that it is feasible to initiate N-acetylcysteine within 10 h based on an early plasma-paracetamol test.


Assuntos
Acetaminofen , Analgésicos não Narcóticos , Acetilcisteína/uso terapêutico , Antídotos/uso terapêutico , Criança , Pré-Escolar , Dinamarca/epidemiologia , Humanos , Lactente , Recém-Nascido , Estudos Retrospectivos
11.
Clin Chem Lab Med ; 56(12): 2047-2057, 2018 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-30004900

RESUMO

Background Intravenous lipid emulsion (ILE) is used to treat drug poisonings. The resultant hyperlipemia may affect laboratory tests but the consequences are poorly characterized. In a clinical trial we therefore investigated the effects of ILE on laboratory tests analyzed on common analytical platforms (Roche® cobas 8000 and SYSMEX® flow-cytometry). Methods Ten healthy participants each completed 4 trial days (two with ILE and two with placebo). ILE (5.25 mL/kg) was administered from 12.5 to 30 min from baseline. At 0, 30 and 60 min, blood samples were drawn for measurement of 20 analytes. We investigated the effects of ILE on analyte levels and frequencies of exceedance of predefined analyzer hemolysis (H) or lipemia (L)-index cut-offs and test-specific reference change values (RCVs) on ILE-days. If the results were blocked due to exceedance of index values, we manually extracted the results. Results Sixteen out of 20 tests were blocked because H- or L-index cut-offs were exceeded on ILE-days. Differences in analyte levels between ILE- and placebo-days above the RCV were observed for aspartate aminotransferase, total calcium, lactate dehydrogenase (LDH), sodium and neutrophils. Mean values outside the normal range after ILE were observed for LDH (219 U/L), sodium (135.3 mmol/L) and total calcium (2.1 mmol/L). Conclusions ILE-infusion caused report failure of nearly all laboratory tests performed on a cobas 8000-platform, but it was possible to manually retrieve the results. For most test results - particularly alkaline phosphatase, bilirubin, phosphate and carbamide - the consequences of ILE were marginal, and the effects of ILE were reduced at the 60-min timepoint.


Assuntos
Técnicas de Laboratório Clínico , Lipídeos/administração & dosagem , Lipídeos/sangue , Adulto , Estudos Cross-Over , Método Duplo-Cego , Emulsões/administração & dosagem , Emulsões/análise , Voluntários Saudáveis , Hemólise , Humanos , Injeções Intravenosas , Masculino , Placebos , Adulto Jovem
12.
Br J Clin Pharmacol ; 83(7): 1506-1514, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28087982

RESUMO

AIMS: This study investigated the influence of CES1 variations, including the single nucleotide polymorphism (SNP) rs71647871 (G143E) and variation in copy number, on the pharmacokinetics of a single oral dose of 10 mg methylphenidate. METHODS: CES1 genotype was obtained from 200 healthy Danish Caucasian volunteers. Based on the genotype, 44 (19 males and 25 females) were invited to participate in an open, prospective trial involving six predefined genotypes: three groups with two, three and four CES1 copies, respectively; a group of carriers of the CES1 143E allele; a group of individuals homozygous for CES1A1c (CES1VAR); and a group having three CES1 copies, in which the duplication, CES1A2, had increased transcriptional activity. Plasma concentrations of methylphenidate and its primary metabolites were determined at scheduled time points. RESULTS: Median AUC of d-methylphenidate was significantly larger in the group carrying the 143E allele (53.3 ng ml-1  h-1 , range 38.6-93.9) than in the control group (21.4 ng ml-1  h-1 , range 15.7-34.9) (P < 0.0001). Median AUC of d-methylphenidate was significantly larger in the group with four CES1 copies (34.5 ng ml-1  h-1 , range 21.3-62.8) than in the control group (P = 0.01) and the group with three CES1 copies (23.8 ng ml-1  h-1 , range 15.3-32.0, P = 0.03). There was no difference between the groups with two and three copies of CES1. CONCLUSIONS: The 143E allele resulted in an increased AUC, suggesting a significantly decreased CES1 enzyme activity. Surprisingly, this was also the case in subjects with homozygous duplication of CES1, perhaps reflecting an undiscovered mutation affecting the activity of the enzyme.


Assuntos
Hidrolases de Éster Carboxílico/genética , Estimulantes do Sistema Nervoso Central/farmacocinética , Metilfenidato/farmacocinética , Administração Oral , Adulto , Alelos , Estimulantes do Sistema Nervoso Central/administração & dosagem , Estudos Cross-Over , Variações do Número de Cópias de DNA , Dinamarca , Feminino , Duplicação Gênica , Genótipo , Voluntários Saudáveis , Heterozigoto , Humanos , Masculino , Metilfenidato/administração & dosagem , Mutação , Polimorfismo de Nucleotídeo Único , Estudos Prospectivos , Adulto Jovem
13.
Scand J Public Health ; 45(8): 773-781, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28825523

RESUMO

AIMS: This study investigated the long-term mortality following poisoning by amphetamine or substituted amphetamines. Furthermore, we examined the social problems and somatic and psychiatric co-morbidity related to amphetamine poisoning, and their impact on the long-term survival. METHODS: We identified amphetamine poisoned patients from the Danish Poison Information Centre database and correlated their personal identification numbers with seven Danish national registries related to different social and health aspects. For each case, we sampled 100 age and gender matched controls from the background population. RESULTS: From August 2006 to December 2013 we identified 1444 patients (70% males) who experienced amphetamine poisoning; 52% of the cases were classified as mixed poisonings and the average age at first contact was 24.8 years (SD 8.6). The prevalence of psychiatric disorders, HIV, viral hepatitis, and previous prison incarceration was approximately 10 times higher than among healthy controls. After seven years 11% were deceased as opposed to 0.6% in the control group, and 64% of the patients died from unnatural causes. Male gender (HR 2.29, 95% CI (1.07-4.90)), age (HR 1.06, 95% CI (1.03-1.09)), opioid dependence (HR 2.88, 95% CI (1.42-5.85)), schizophrenia (HR 3.09,95% CI (1.63-5.86)), affective disorders (HR 2.65, 95% CI (1.44-4.90)) and HIV (HR 5.45, 95% CI (1.19-24.90)) were associated with a high mortality. Furthermore, a significant proportion of these patients experienced social and health related deterioration in the years following poisoning. CONCLUSIONS: Amphetamine poisoning is associated with a poor long-term prognosis and is complicated by additional social and health related issues.


Assuntos
Anfetaminas/intoxicação , Adolescente , Adulto , Dinamarca/epidemiologia , Feminino , Humanos , Masculino , Intoxicação/mortalidade , Prognóstico , Sistema de Registros , Fatores de Risco , Adulto Jovem
15.
Eur J Clin Pharmacol ; 71(11): 1375-9, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26257248

RESUMO

AIMS: We have looked for medication errors involving the use of low-dose methotrexate, by extracting information from Danish sources other than traditional pharmacovigilance databases. We used the data to establish the relative frequencies of different types of errors. METHODS: We searched four databases for cases involving low-dose methotrexate between 1999 and 2011: the Danish Patient Safety Databases (DPSD), controlled by the Danish National Agency for Patients' Rights and Complaints, the Patient Compensation Association (PCA), the Danish Poison and Information Centre (DPIC), and the online database of the Department for Patient Complaints (DPC). We categorized the place where the error occurred, the processes and types of error involved, the person responsible, and the clinical outcome. RESULTS: We identified 173 errors. In 109 (63%), either harm resulted or could not be excluded; of these, 26 (15%) resulted in serious harm, including nine deaths (5%); 53 (31%) involved incorrect daily administration; and 107 (62%) involved a dosing error. Sixteen events (9.2%) concerned insufficient or faulty monitoring, with four serious outcomes and two deaths. Prescription errors involving daily rather than weekly administration, by hospital physicians, were most likely to result in serious outcomes, including deaths. The error mechanism was evaluated in 129 events. Action-based errors comprised 50 % and knowledge-based errors 34 %. Action-based errors were more likely to result in completed errors, whereas knowledge-based errors more often resulted in near misses. CONCLUSIONS: The medication errors in this survey were most often action-based (50%) and knowledge-based (34%), suggesting that greater attention should be paid to education and surveillance of medical personnel who prescribe and monitor methotrexate, particularly physicians, who accounted for 40% of the errors.


Assuntos
Antirreumáticos/efeitos adversos , Fármacos Dermatológicos/efeitos adversos , Erros de Medicação/estatística & dados numéricos , Metotrexato/efeitos adversos , Antirreumáticos/uso terapêutico , Bases de Dados Factuais/estatística & dados numéricos , Dinamarca , Fármacos Dermatológicos/uso terapêutico , Humanos , Metotrexato/uso terapêutico
17.
Clin Neurol Neurosurg ; 239: 108217, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-38452714

RESUMO

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.


Assuntos
Anabolizantes , Neoplasias Meníngeas , Meningioma , Masculino , Humanos , Androgênios/efeitos adversos , Estudos de Coortes , Meningioma/induzido quimicamente , Meningioma/epidemiologia , Esteróides Androgênicos Anabolizantes , Anabolizantes/efeitos adversos , Neoplasias Meníngeas/induzido quimicamente , Neoplasias Meníngeas/epidemiologia
18.
Andrology ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38602128

RESUMO

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.

19.
Expert Rev Clin Pharmacol ; 17(3): 225-234, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38345044

RESUMO

INTRODUCTION: Tyrosine kinase inhibitors (TKIs) have revolutionized survival rates of chronic myeloid leukemia (CML) and Philadelphia chromosome positive (Ph+) acute lymphoblastic leukemia (ALL) and replaced hematopoietic stem cell transplantation (hSCT) as the key treatment option for these patients. More recently, the so-called Philadelphia chromosome-like (Ph-like) ALL has similarly benefitted from TKIs. However, many patients shift from the first generation TKI, imatinib, due to treatment-related toxicities or lack of treatment efficacy. A more personalized approach to TKI treatment could counteract these challenges and potentially be more cost-effective. Therapeutic drug monitoring (TDM) has led to higher response rates and less treatment-related toxicity in adult CML but is rarely used in ALL or in childhood CML. AREAS COVERED: This review summarizes different antileukemic treatment indications for TKIs with focus on imatinib and its pharmacokinetic/-dynamic properties as well as opportunities and pitfalls of TDM for imatinib treatment in relation to pharmacogenetics and co-medication for pediatric and adult Ph+/Ph-like leukemias. EXPERT OPINION: TDM of imatinib adds value to standard monitoring of ABL-class leukemia by uncovering non-adherence and potentially mitigating adverse effects. Clinically implementable pharmacokinetic/-dynamic models adjusted for relevant pharmacogenetics could improve individual dosing. Prospective trials of TDM-based treatments, including both children and adults, are needed.


Assuntos
Leucemia Mielogênica Crônica BCR-ABL Positiva , Cromossomo Filadélfia , Adulto , Humanos , Criança , Mesilato de Imatinib/efeitos adversos , Monitoramento de Medicamentos , Estudos Prospectivos , Inibidores de Proteínas Quinases/efeitos adversos , Leucemia Mielogênica Crônica BCR-ABL Positiva/tratamento farmacológico , Resistencia a Medicamentos Antineoplásicos/genética
20.
Clin Toxicol (Phila) ; 61(5): 392-399, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37171194

RESUMO

OBJECTIVE: Poisonings contribute significantly to morbidity and mortality of patients. Some patients have numerous contacts to a poison information center, indicating repeated poisoning exposures. Information on the involved substances is necessary to explore methods to prevent self-harm and reduce mortality. The objective of this study was to characterize the patient population with repeated poison exposures in Denmark and identify the substances involved. METHODS: This study was a retrospective cohort study of enquiries to the nationwide Danish Poison Information Centre and the Danish National Patient Registry. The databases were used to identify patients with more than five individual poisoning episodes within a 12-month-period between 1 January 2013, and 31 December 2017. RESULTS: One hundred and thirty-seven patients and 995 patients met the inclusion criteria in the Danish Poison Information Centre and the Danish National Patient Registry, respectively. The majority were women (82.5% and 66.3% for the Danish Poison Information Centre and the Danish National Patient Registry cohorts, respectively). The mean age was 24.7 and 29.5 years. Psychiatric comorbidities were frequent with 74.5% and 67.0% suffering from personality disorders and 70.1% and 54.5% from affective disorders in the Danish Poison Information Centre and the Danish National Patient Registry cohorts, respectively. One thousand seven hundred and fifty-two poisoning episodes were identified in the Danish Poison Information Centre database, and the most common types of substance were 'pharmaceuticals' (1,420 episodes). The most common medications ingested were quetiapine, paracetamol and cyclizine. Median number of contacts to the Danish Poison Information Centre was 10. Patients with one or more poisoning episodes involving cyclizine had on average 11.4 poisoning episodes involving cyclizine. In the Danish National Patient Registry cohort 80.9% were alive after 10 years compared to 97.7% in the background population. CONCLUSION AND IMPLICATIONS: Most poisonings were intentional and occurred among younger women. Psychiatric comorbidity was frequent. Most often, pharmaceuticals were the toxic substance, mainly quetiapine, paracetamol and cyclizine. Changing the status of cyclizine from over the counter to prescription only medication, and implementing stricter rules for prescribing quetiapine, could limit future poisoning incidences.


Assuntos
Intoxicação , Venenos , Medicamentos sob Prescrição , Humanos , Masculino , Feminino , Adulto Jovem , Adulto , Ciclizina , Fumarato de Quetiapina , Acetaminofen , Estudos Retrospectivos , Centros de Controle de Intoxicações , Dinamarca/epidemiologia , Intoxicação/epidemiologia , Intoxicação/etiologia
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