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1.
Br J Clin Pharmacol ; 90(6): 1376-1394, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38408767

RESUMO

AIMS: The aim of this study was to estimate the prevalence of potentially inappropriate prescriptions (PIPs) in patients starting their first noninsulin antidiabetic treatment (NIAD) using two explicit process measures of the appropriateness of prescribing in UK primary care, stratified by age and polypharmacy status. METHODS: A descriptive cohort study between 2016 and 2019 was conducted to assess PIPs in patients aged ≥45 years at the start of their first NIAD, stratified by age and polypharmacy status. The American Geriatrics Society Beers criteria 2015 was used for older (≥65 years) patients and the Prescribing Optimally in Middle-age People's Treatments criteria was used for middle-aged (45-64 years) patients. Prevalence of overall PIPs and individual PIPs criteria was reported using the IQVIA Medical Research Data incorporating THIN, a Cegedim Database of anonymized electronic health records in the UK. RESULTS: Among 28 604 patients initiating NIADs, 18 494 (64.7%) received polypharmacy. In older and middle-aged patients with polypharmacy, 39.6% and 22.7%, respectively, received ≥1 PIP. At the individual PIP level, long-term proton pump inhibitors (PPI) use was the most frequent PIP among older adults, and strong opioid without laxatives was the most frequent PIP in middle-aged patients with polypharmacy (11.1% and 4.1%, respectively). CONCLUSIONS: This study revealed that patients starting NIAD treatment receiving polypharmacy have the potential for pharmacotherapy optimization.


Assuntos
Diabetes Mellitus Tipo 2 , Hipoglicemiantes , Prescrição Inadequada , Polimedicação , Lista de Medicamentos Potencialmente Inapropriados , Atenção Primária à Saúde , Humanos , Pessoa de Meia-Idade , Diabetes Mellitus Tipo 2/tratamento farmacológico , Idoso , Atenção Primária à Saúde/estatística & dados numéricos , Reino Unido/epidemiologia , Feminino , Masculino , Prescrição Inadequada/estatística & dados numéricos , Hipoglicemiantes/uso terapêutico , Prevalência , Lista de Medicamentos Potencialmente Inapropriados/estatística & dados numéricos , Estudos de Coortes , Fatores Etários , Idoso de 80 Anos ou mais , Padrões de Prática Médica/estatística & dados numéricos , Padrões de Prática Médica/normas
2.
Eur J Clin Pharmacol ; 77(6): 913-919, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33341923

RESUMO

PURPOSE: In response to a large trial, the World Health Organization broadened their recommendation on tranexamic acid to be used for post-partum hemorrhage. A 2013 French periodic safety update report warned of an abnormally high rate of renal cortical necrosis associated with tranexamic acid and other drugs for severe post-partum hemorrhage. We aimed to identify the reporting incidence of adverse thrombo-embolic events among women in child-bearing age who received tranexamic acid, with a focus on renal vascular and ischemic conditions. METHODS: We analyzed individual case safety reports (ICSRs) on renal vascular and ischemic conditions, pulmonary thrombotic and embolic conditions, and peripheral embolism and thrombosis from the database of the World Health Organization - Uppsala Monitoring Centre (WHO-UMC). ICSRs were restricted to reports including tranexamic acid as a suspected drug, sex reported as female, and reported age between 18 and 44 years. Reporting odds ratios (RORs) and 95% confidence intervals (95% CIs) were calculated by comparing ICSRs on tranexamic acid to all other drugs in VigiBase. RESULTS: Within 2245 included ICSRs on tranexamic acid, we identified 29 reports of adverse renal vascular and ischemic conditions, 42 reports of pulmonary thrombotic and embolic conditions, and 41 reports of peripheral embolism and thrombosis. RORs were statistically significant by 32.6-fold (32.62, 95% CI: 22.50-47.29), 2.5-fold (2.52, 95% CI: 1.85-3.42), and 2.7-fold (2.67, 95% CI: 1.96-3.64), respectively, when compared to any other drug within VigiBase. CONCLUSION: Tranexamic acid might bear an increased risk for renal ischemic adverse drug events in women of child-bearing age.


Assuntos
Antifibrinolíticos/efeitos adversos , Embolia/induzido quimicamente , Isquemia/induzido quimicamente , Nefropatias/induzido quimicamente , Trombose/induzido quimicamente , Ácido Tranexâmico/efeitos adversos , Adolescente , Adulto , Antifibrinolíticos/administração & dosagem , Bases de Dados Factuais , Feminino , Humanos , Farmacovigilância , Hemorragia Pós-Parto/prevenção & controle , Trombose/prevenção & controle , Ácido Tranexâmico/administração & dosagem , Organização Mundial da Saúde , Adulto Jovem
3.
Eur J Clin Pharmacol ; 77(6): 895-902, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33404754

RESUMO

PURPOSE: Tizanidine, an alpha-adrenergic substance with antinociceptive and antihypertensive effects, is extensively metabolized via cytochrome P450 (CYP) 1A2. Therefore, coadministration with potent CYP1A2 inhibitors, such as ciprofloxacin, is contraindicated. However, both drugs are broadly utilized in various countries. Their concomitant use bears an inherent high risk for clinically significant symptoms, especially in multimorbid patients experiencing polypharmacy. This study aims to investigate the impact of coadministration of tizanidine and ciprofloxacin using real-world pharmacovigilance data and to raise awareness of this potentially underestimated safety issue. METHODS: We conducted a retrospective study including Individual Case Safety Reports (ICSR) registered until March 1, 2017, in the World Health Organization (WHO) global database. Demographic data, drug administration information, the course of the adverse drug reaction (ADR), its severity, and outcomes were analyzed for cases reporting ciprofloxacin comedication. RESULTS: In 91 (2.0%) of the identified 4192 worldwide ICSR on tizanidine, coadministration of ciprofloxacin was reported. Most of the patients were female (n = 59, 64.8%) with a median age of 54 years (range 13-85 years). The countries contributing most reports were the USA (n = 54, 59.3%) and Switzerland (n = 16, 17.6%). ADRs reported most often affected the nervous system and the cardiac function, especially with large tizanidine doses or drugs with CNS and cardiovascular depressant effects. In two cases, a fatal outcome was reported. CONCLUSION: Despite the existing formal contraindication, the concomitant use of tizanidine and ciprofloxacin can be observed in real-world clinical practice. Reactions mainly affected the central nervous and the cardiovascular system resulting in potentially severe adverse effects. The concomitant use of tizanidine and ciprofloxacin should absolutely be avoided.


Assuntos
Agonistas de Receptores Adrenérgicos alfa 2/farmacocinética , Antibacterianos/farmacocinética , Ciprofloxacina/farmacocinética , Clonidina/análogos & derivados , Adolescente , Agonistas de Receptores Adrenérgicos alfa 2/efeitos adversos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/efeitos adversos , Área Sob a Curva , Ciprofloxacina/efeitos adversos , Clonidina/efeitos adversos , Clonidina/farmacocinética , Bases de Dados Factuais , Interações Medicamentosas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Farmacovigilância , Estudos Retrospectivos , Organização Mundial da Saúde , Adulto Jovem
4.
Eur Child Adolesc Psychiatry ; 30(7): 1047-1058, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32621088

RESUMO

For patients with attention deficit hyperactivity disorder and comorbid conduct-dissocial disorder, a combination therapy of the psychostimulant methylphenidate and the antipsychotic risperidone may be prescribed. Case reports describe the occurrence of movement disorders under this combination therapy, but clinical trials had limited power to detect these events. This study aimed (1) to summarise published case reports and (2) to analyse pharmacovigilance data consisting of adverse drug event reports to elucidate these reactions. PubMed, Embase, and APA PsycInfo were used to retrieve case reports. For the pharmacovigilance data, aggregated information on individual case safety reports (ICSRs) within the database of suspected adverse drug events by the WHO were analysed. ICSRs were assessed for disproportionality in reporting. Thirteen published case reports (62% male) on movement disorders were identified, with ages between 5 and 15 years. Seven reports (54%) described incidents when risperidone was tapered down or switched to methylphenidate. From the WHO, we identified 25,556 ICSRs (16,118 for methylphenidate, 8,614 for risperidone, and 824 for both). Of these, 953 (5.9%), 1356 (15.7%), and 159 (19.3%) ICSRs reported movement disorders in association with methylphenidate, risperidone or both, respectively. The analyses on disproportionality showed an increased number of ICSRs with movement disorders when the two drugs were coded in combination. The potential of movement disorders as adverse effects might be amplified when methylphenidate and risperidone are used in combination. The results from the literature underline the necessity of caution and patient monitoring when risperidone dosing is modified during methylphenidate therapy.


Assuntos
Metilfenidato/efeitos adversos , Transtornos dos Movimentos/epidemiologia , Risperidona/efeitos adversos , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Terapia Combinada/efeitos adversos , Comorbidade , Transtorno da Conduta/tratamento farmacológico , Bases de Dados Factuais , Humanos , Metilfenidato/uso terapêutico , Farmacovigilância , Risperidona/uso terapêutico , Organização Mundial da Saúde
5.
Eur J Clin Pharmacol ; 75(3): 409-416, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30430215

RESUMO

PURPOSE: Statins represent an effective treatment for hyperlipidaemia. Immune-mediated necrotising myopathy (IMNM), a form of statin myopathy, has recently been described, and is characterized by elevated creatine kinase, presence of antibodies against HMG-CoA and no improvement after drug discontinuation, even with immunosuppressive treatment. Information on IMNM is mainly from case reports and small case series. Therefore, all reported cases of IMNM in VigiBase, the WHO global database of individual case safety reports (ICSRs) including the underlying reporting patterns, were analysed to characterize more detailed this adverse drug reaction. METHODS: ICSRs of IMNM up to October 1, 2016 were extracted from VigiBase. Corresponding case narratives were requested from responsible national authorities to maximize the available data. The reports were analysed in terms of reporting criteria, co-reported terms, patient demographics, clinical data, administered medication, latency time, seriousness of the reaction and outcome. RESULTS: One hundred one deduplicated ICSRs of IMNM were reported from 17 countries until October 2016. Approximately two thirds of the cases were from the year 2016. Slightly more males than females were affected (52 [57%] males vs 39 [42%] females). Median reported patient age was 68 years (range 16 - 87 years). Ninety-one cases (99%) were classified as serious. Median latency time was 26 months (range 1 - 288 months). Median creatine kinase value was 6860 U/L (range 576 - 35,000 U/L). In total, eight patients (9%) had recovered from IMNM. Atorvastatin was the most frequently reported statin in 80% of cases. CONCLUSIONS: The number of IMNM reports has increased in recent years. IMNM associated with statin treatment seems to occur worldwide. Most IMNM cases were reported with atorvastatin. No dose dependency of statin-associated IMNM pathogenesis was identified.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos/estatística & dados numéricos , Atorvastatina/efeitos adversos , Doenças Autoimunes/induzido quimicamente , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Doenças Musculares/induzido quimicamente , Autoanticorpos/sangue , Doenças Autoimunes/epidemiologia , Doenças Autoimunes/patologia , Creatina Quinase/metabolismo , Bases de Dados Factuais , Feminino , Humanos , Hidroximetilglutaril-CoA Redutases/imunologia , Masculino , Doenças Musculares/epidemiologia , Doenças Musculares/patologia , Necrose
6.
Int J Clin Pharmacol Ther ; 57(5): 240-248, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30900982

RESUMO

OBJECTIVE: Kounis syndrome (KS) is an acute coronary syndrome with coronary spasm, acute myocardial infarction and stent thrombosis that can be associated with a variety of drugs as an adverse drug reaction (ADR). To characterize this rare phenomenon, we analyzed all cases of KS in the WHO database for pharmacovigilance. MATERIALS AND METHODS: All cases of KS worldwide until December 31, 2017, were included and analyzed in terms of age, sex, country, year of ADR, seriousness, clinical outcome, suspected drugs, administration, reported reaction, and -MedDRA terms. Time to onset of the ADR was calculated, and a subgroup analysis of KS associated with analgesics was performed. IC025 values were calculated for the most frequently reported pain medication to indicate the strength of relation between ADR and the suspected analgesics. RESULTS: A total of 403 cases of KS reported from 17 countries were included, of which 121 cases were associated with analgesics (subgroup). Males were more frequently affected overall (267 (66%) males vs. 123 (31%) females), whereas in the subgroup, males and females were equally affected (58 (48%) males vs. 56 (46%) females). Median reported patient age was 57 years (range 2 - 99) overall vs. 48 years (range 20 - 85) in the subgroup. Nearly all cases were classified as serious (370 (92%) overall vs. 119 (98%) subgroup). The most frequently suspected substance was amoxicillin/clavulanic acid (n = 50, 9.3%) overall and ibuprofen (n = 33, 6.2%) in the subgroup, respectively. Most drugs were administered orally (21% overall vs. 21% subgroup) and intravenously (18.7% overall vs. 8% subgroup) in either group. A high proportion of patients with "life threatening" reactions received intravenous administration (37%) of the suspected drug. CONCLUSION: Antibiotics and analgesics are the drug classes most often associated with KS. The way of administration might have an influence on the seriousness of the reaction.
.


Assuntos
Sistemas de Notificação de Reações Adversas a Medicamentos , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Síndrome de Kounis/epidemiologia , Farmacovigilância , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Bases de Dados Factuais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
7.
N Engl J Med ; 383(6): 599-600, 2020 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-32757536
8.
BMC Nephrol ; 18(1): 360, 2017 Dec 12.
Artigo em Inglês | MEDLINE | ID: mdl-29233098

RESUMO

BACKGROUND: Mycophenolic acid (MPA), either given as an ester pro-drug or as an enteric-coated sodium salt, is the most commonly prescribed anti-proliferative immunosuppressive agent used following organ transplantation and widely applied in immune-mediated diseases. Clinicians are well aware of common adverse reactions related to MPA treatment, in particular diarrhea, leukopenia and infections. Here we report a case of severe, persistent ascites associated with MPA treatment. The otherwise unexplained and intractable ascites, requiring repeated paracenteses for more than 8 months, rapidly ceased with stopping the MPA treatment. To our knowledge this is the first case of severe ascites associated with MPA treatment reported in the scientific literature. CASE PRESENTATION: A 45-year old female with type 1 diabetes mellitus received a simultaneous kidney-pancreas transplant. The surgery was uneventful. However, post-operatively she developed severe transudative ascites requiring in total more than 40 paracenteses treatments draining in the average 2.8 l of ascites fluid. The ascites formation persisted despite exclusion of a surgical complication, fully functioning kidney and pancreas allografts, lack of any significant proteinuria, normalization of circulating albumin levels, intensive use of diuretics and deliberate attempts to increase the intervals between the paracentesis treatments. Various differential diagnoses, including infectious, hepatic, vascular and cardiac causes were ruled out. Nine months after surgery enteric-coated mycophenolate sodium was switched to azathioprine after which ascites completely resolved. When mycophenolate was recommenced abdominal fullness and weight gain reoccurred. The patient had to be switched to long-term azathioprine treatment. More than 1 year post-conversion the patient remains free of ascites. CONCLUSION: MPA is the most widely used antimetabolite immunosuppressive agent. We suggest to consider MPA treatment in the differential diagnosis of severe and unexplained ascites in transplant and non-transplant patients.


Assuntos
Ascite , Transplante de Rim , Ácido Micofenólico , Transplante de Pâncreas , Complicações Pós-Operatórias , Ascite/induzido quimicamente , Ascite/diagnóstico , Ascite/fisiopatologia , Ascite/terapia , Diabetes Mellitus Tipo 1/complicações , Diagnóstico Diferencial , Insuficiência Pancreática Exócrina/etiologia , Insuficiência Pancreática Exócrina/cirurgia , Feminino , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/efeitos adversos , Falência Renal Crônica/etiologia , Falência Renal Crônica/cirurgia , Transplante de Rim/efeitos adversos , Transplante de Rim/métodos , Pessoa de Meia-Idade , Ácido Micofenólico/administração & dosagem , Ácido Micofenólico/efeitos adversos , Transplante de Pâncreas/efeitos adversos , Transplante de Pâncreas/métodos , Paracentese/métodos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/fisiopatologia , Complicações Pós-Operatórias/terapia , Resultado do Tratamento , Suspensão de Tratamento
10.
Strahlenther Onkol ; 192(5): 342-8, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26907093

RESUMO

BACKGROUND: Radiation recall dermatitis (RRD) is an acute inflammatory reaction confined to previously irradiated skin, mainly subsequent to the administration of certain chemotherapeutics. Here we present a rare case of RRD induced by the oral multikinase inhibitor sorafenib. CASE REPORT: A 77-year-old male with hepatocellular carcinoma was irradiated at ten different sites for bone metastases with 20-36 Gray in 5-12 fractions from January to March 2015. Sorafenib 400 mg was administered twice daily from mid-March. One week later the patient presented with fever and erythematous lesions on the right upper arm, mandible, and trunk. All skin symptoms were confined to previously irradiated areas. After RRD was diagnosed by exclusion of other causes and skin biopsy, sorafenib was paused. With the administration of topical corticosteroids and oral antihistamines, the skin reaction subsided within several days. Sorafenib was readministered after 3 weeks, which did not lead to recurrence of RRD but did cause fluctuating fever. DISCUSSION: Only four other such cases have been reported in the literature and WHO pharmacovigilance database on individual case safety reports. The current report is the first to show a potential relationship between the severity of sorafenib-induced RRD and radiation dose, histopathological features, and simultaneous acute radiation dermatitis and mucositis. CONCLUSION: RRD induced by sorafenib is a rare phenomenon, but should be considered in patients showing erythematous skin lesions 1-2 weeks after initiation of the drug, predominantly in areas where skin has been irradiated with an equivalent dose ≥ 30 Gy. Discontinuation of sorafenib with possible readministration should be evaluated with respect to the clinical situation and severity of reaction.


Assuntos
Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/secundário , Niacinamida/análogos & derivados , Compostos de Fenilureia/efeitos adversos , Radiodermite/induzido quimicamente , Radiodermite/prevenção & controle , Radioterapia Conformacional/efeitos adversos , Idoso , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Neoplasias Ósseas/complicações , Humanos , Masculino , Niacinamida/administração & dosagem , Niacinamida/efeitos adversos , Compostos de Fenilureia/administração & dosagem , Inibidores de Proteínas Quinases/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Sorafenibe , Resultado do Tratamento
11.
Ther Umsch ; 72(11-12): 737-41, 2015 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-26654818

RESUMO

Rare cases of high anion gap metabolic acidosis during long-term paracetamol administration in therapeutic doses with causative 5-oxoproline (pyroglutamic acid} accumulation have been reported. Other concomitant risk factors such as malnutrition, alcohol abuse, renal or hepatic dysfunction, comedication with flue/oxacillin, vigabatrin, netilmicin or sepsis have been described. The etiology seems to be a drug-induced reversible inhibition of glutathione synthetase or 5-oxoprolinase leading to elevated serum and urine levels of 5-oxoproline. Other more frequent differential diagnoses, such as intoxications, ketoacidosis or lactic acidosis should be excluded. Causative substances should be stopped. 5-oxoproline concentrations in urine can be quantified to establish the diagnosis. Adverse drug reactions, which are not listed or insufficiently described in the respective Swiss product information, should be reported to the regional pharmacovigilance centres for early signal detection. 5-0 xoproline acidosis will be integrated as a potential adverse drug reaction in the Swiss product information for paracetamol.


Assuntos
Acetaminofen/efeitos adversos , Acidose/induzido quimicamente , Acidose/diagnóstico , Erros de Medicação/prevenção & controle , Ácido Pirrolidonocarboxílico/urina , Acidose/urina , Analgésicos não Narcóticos/efeitos adversos , Biomarcadores/urina , Diagnóstico Diferencial , Humanos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade
13.
BMC Health Serv Res ; 14: 306, 2014 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-25027581

RESUMO

BACKGROUND: Assessment of the proportion of patients with well controlled cardiovascular risk factors underestimates the proportion of patients receiving high quality of care. Evaluating whether physicians respond appropriately to poor risk factor control gives a different picture of quality of care. We assessed physician response to control cardiovascular risk factors, as well as markers of potential overtreatment in Switzerland, a country with universal healthcare coverage but without systematic quality monitoring, annual report cards on quality of care or financial incentives to improve quality. METHODS: We performed a retrospective cohort study of 1002 randomly selected patients aged 50-80 years from four university primary care settings in Switzerland. For hypertension, dyslipidemia and diabetes mellitus, we first measured proportions in control, then assessed therapy modifications among those in poor control. "Appropriate clinical action" was defined as a therapy modification or return to control without therapy modification within 12 months among patients with baseline poor control. Potential overtreatment of these conditions was defined as intensive treatment among low-risk patients with optimal target values. RESULTS: 20% of patients with hypertension, 41% with dyslipidemia and 36% with diabetes mellitus were in control at baseline. When appropriate clinical action in response to poor control was integrated into measuring quality of care, 52 to 55% had appropriate quality of care. Over 12 months, therapy of 61% of patients with baseline poor control was modified for hypertension, 33% for dyslipidemia, and 85% for diabetes mellitus. Increases in number of drug classes (28-51%) and in drug doses (10-61%) were the most common therapy modifications. Patients with target organ damage and higher baseline values were more likely to have appropriate clinical action. We found low rates of potential overtreatment with 2% for hypertension, 3% for diabetes mellitus and 3-6% for dyslipidemia. CONCLUSIONS: In primary care, evaluating whether physicians respond appropriately to poor risk factor control, in addition to assessing proportions in control, provide a broader view of the quality of care than relying solely on measures of proportions in control. Such measures could be more clinically relevant and acceptable to physicians than simply reporting levels of control.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Atenção Primária à Saúde/normas , Indicadores de Qualidade em Assistência à Saúde , Idoso , Idoso de 80 Anos ou mais , Doenças Cardiovasculares/epidemiologia , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Suíça/epidemiologia
14.
Antimicrob Agents Chemother ; 57(8): 4053-7, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23733471

RESUMO

Caspofungin pharmacokinetics was assessed in 27 critically ill patients, including 7 on continuous venovenous hemofiltration (CVVH), 8 on continuous venovenous hemodialysis (CVVHD), and 13 not requiring continuous renal replacement therapy (CRRT). Caspofungin exposure during CRRT was very similar to that of the control group and comparable to that in healthy volunteers. Caspofungin clearance by CRRT was very low. Therefore, the standard dosage of caspofungin is probably adequate for critically ill patients undergoing CVVH or CVVHD.


Assuntos
Equinocandinas/farmacocinética , Diálise Renal/métodos , Terapia de Substituição Renal/métodos , Estudos de Casos e Controles , Caspofungina , Estado Terminal , Avaliação de Medicamentos/métodos , Equinocandinas/administração & dosagem , Feminino , Humanos , Lipopeptídeos , Masculino , Taxa de Depuração Metabólica , Pessoa de Meia-Idade
15.
Clin Toxicol (Phila) ; 61(2): 104-109, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36594830

RESUMO

OBJECTIVE: Presentations of Taxus baccata (yew) poisoning can range between asymptomatic cases and life-threatening cardiotoxicity - depending on the amount ingested. This study aimed to describe emergency department (ED) presentations after yew exposure, and covers their clinical presentation, diagnostic and specific treatment, to contribute to optimising intreatment and prophylaxis. METHODS: Retrospective observational study of cases (≥ 16 years of age) presenting at the ED of the University Hospital of Bern, Switzerland, from 1 May 2012 to 31 May 2020 following reported yew exposure. Cases were retrieved from the electronic patient database using full-text terms. RESULTS: During the study period, 55 presentations (11 patients) of the 350,381 ED attendances were included. All patients were female and the median age on first presentation was 22 years (range 16-48). All 10 patients with intentional intake had previous diagnoses of psychiatric disorders. Commonly reported symptoms on presentation were gastrointestinal disturbances (31 presentations, 56%), neurological (six presentations, 11%) and subjective cardiovascular symptoms (five presentations, 9%). The most frequent clinical findings on presentation were tachycardia (15 presentations, 27%) and hypotension (11 presentations, 20%). In 52 presentations (95%), gastroscopic extraction of the leaves was performed, activated charcoal was administered in 25 cases (45%), and there were no fatalities. In the majority of the cases (40, 73%), the patient was admitted to psychiatric care and in 10 (18%) the patient was discharged home. CONCLUSION: ED presentations after yew exposure appear to be rare, but potentially life-threatening and commonly observed in this study in young female patients with underlying psychiatric diseases. In this case series, gastroscopic extraction and activated charcoal application were commonly performed and there were no fatalities.


Assuntos
Transtornos Mentais , Taxus , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Masculino , Carvão Vegetal , Serviço Hospitalar de Emergência , Ingestão de Alimentos
16.
Antimicrob Agents Chemother ; 56(10): 5414-8, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22850517

RESUMO

The pharmacokinetics of lipid-bound and liberated amphotericin B (AMB) was assessed in 11 critically ill patients with cholestatic liver disease (CSLD) and in 9 subjects with normal liver function treated with AMB colloidal dispersion (ABCD). Exposure to lipid-bound AMB was higher in patients with CSLD. Levels of liberated AMB were elevated by CSLD only after the first dose, whereas its pharmacokinetics was unaffected at steady state. The standard dosage of ABCD is probably adequate for patients with CSLD.


Assuntos
Anfotericina B/farmacocinética , Antifúngicos/farmacocinética , Estado Terminal , Hepatopatias/sangue , Adolescente , Adulto , Idoso , Anfotericina B/sangue , Antifúngicos/sangue , Criança , Coloides , Feminino , Humanos , Hepatopatias/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Adulto Jovem
17.
Swiss Med Wkly ; 152: w30117, 2022 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-35072413

RESUMO

OBJECTIVE: The private keeping of exotic venomous snakes is legally permitted in Switzerland. The aim of the present study was to characterise the epidemiological and clinical features of bites by exotic venomous snakes over a period of 22 years in Switzerland. METHODS: We included all calls related to exotic snakebites recorded at the Swiss National Poisons Information Centre (Tox Info Suisse) from 1997 to 2018. Exclusion criteria comprised indigenous snakes, non-venomous exotic snakes such boas or pythons, clinical courses incompatible with a snakebite or calls from abroad. Follow-up information was graded according to the Poisoning Severity Score. RESULTS: Within the study period, 1,364 calls related to snakebites were recorded at Tox Info Suisse; 148 (11%) cases were attributed to exotic venomous snakes and fulfilled the study criteria. A total of 112 (98%) of 114 patients with medical follow-up information exhibited sufficient causality between exposure and clinical effects. Only adult patients were affected. The median age was 40 years (range 16-71) and the male gender was predominant (n = 136, 92%). Viperidae were involved in 87 (78%) and Elapidae in 25 (22%) patients. Overall, the main affected body part was the hand (89 patients, 79%). In the majority of the patients the clinical course was mild (46, 41%) or moderate (40, 36%), in a lower proportion asymptomatic (6, 5%) or with severe symptoms (20, 18%). No fatalities were reported in the study period. Severe symptoms were observed after elapid bites in six patients (24%) and after viper bites in 14 patients (16%). Besides local effects, neurological disorders after elapid bites and haematological disorders after viper bites were most frequently reported. Antivenom was administered in 24% (27 patients: 18 Viperidae, 21% and 9 Elapidae, 36%; 5 patients (4%) required multiple doses), overall, with good resolution of symptoms. CONCLUSION: Exotic snakebite is a rare occurrence in Switzerland but has led to medically relevant morbidity, sometimes requiring antivenom treatment. Over half of the envenomed patients required symptomatic or specific treatment. No fatalities or bites in children were reported.


Assuntos
Venenos , Mordeduras de Serpentes , Antivenenos/uso terapêutico , Humanos , Centros de Informação , Masculino , Mordeduras de Serpentes/tratamento farmacológico , Mordeduras de Serpentes/epidemiologia , Suíça/epidemiologia
18.
J Glob Antimicrob Resist ; 29: 520-526, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34896339

RESUMO

OBJECTIVES: In this study, we examined the toxicities, including poisoning and overdoses, with polyene, azole, flucytosine and echinocandin antifungals reported to the Swiss National Poison Centre. METHODS: An observational cross-sectional study on antifungals was performed based on reports between 1995 and 2016 to Tox Info Suisse. Patient demographic and clinical characteristics were summarised among all reported calls, stratified by age group. In secondary analyses, we evaluated cases with clinical follow-up information. RESULTS: In total, 149 cases were reported to the National Poison Centre during the study period, of which 49 (32.9%) were male and 91 (61.1%) were female, and 95 (63.8%) were adults and 54 (36.2%) were children (age ≤16 years). The most frequently reported drug class was azoles (136; 91.3%). In 31 cases (20.8%) reported by treating physicians, further clinical follow-up information was available. Nearly one-half of these patients were asymptomatic (15/31; 48.4%). In 11 patients (35.5%) among those with symptoms, the symptoms of toxicity were categorised with a strong causality to the respective antifungal. Clinical findings caused by triazoles were effects in the gastrointestinal tract, hallucinations and predelirium state. Clinical findings caused by polyenes were mostly minor symptoms with infusion-related effects or hypokalaemia. The severity was categorised as minor in 6 (54.5%) of 11 cases and as moderate in 5 cases (45.5%). CONCLUSION: Despite high administered doses, no severe or fatal cases occurred within the study period. Although various toxicities can occur with antifungal administration and overdoses, they showed a favourable safety profile.


Assuntos
Antifúngicos , Adolescente , Adulto , Antifúngicos/toxicidade , Azóis/toxicidade , Criança , Estudos Transversais , Equinocandinas/toxicidade , Feminino , Humanos , Masculino , Polienos/toxicidade
19.
Sci Rep ; 12(1): 20653, 2022 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-36450743

RESUMO

Type 2 diabetes mellitus (T2DM) is associated with the development of chronic comorbidities, which can lead to high drug utilization and adverse events. We aimed to identify common comorbidity clusters and explore the progression over time in newly treated T2DM patients. The IQVIA Medical Research Data incorporating data from THIN, a Cegedim database of anonymized electronic health records, was used to identify all patients with a first-ever prescription for a non-insulin antidiabetic drug (NIAD) between January 2006 and December 2019. We selected 58 chronic comorbidities of interest and used Bayesian nonparametric models to identify disease clusters and model their progression over time. Among the 175,383 eligible T2DM patients, we identified the 20 most frequent comorbidity clusters, which were comprised of 14 latent features (LFs). Each LF was associated with a primary disease (e.g., 98% of patients in cluster 2, characterized by LF2, had congestive heart failure [CHF]). The presence of certain LFs increased the probability of having another LF active. For example, LF2 (CHF) frequently appeared with LFs related to chronic kidney disease (CKD). Over time, the clusters associated with cardiovascular diseases, such as CHF, progressed rapidly. Moreover, the onset of certain diseases led to further complications. Our models identified established T2DM complications and previously unknown connections, thus, highlighting the potential for Bayesian nonparametric models to characterize complex comorbidity patterns.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Doença Enxerto-Hospedeiro , Insuficiência Cardíaca , Humanos , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/epidemiologia , Teorema de Bayes , Comorbidade , Hipoglicemiantes
20.
Lancet Reg Health Eur ; 20: 100437, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36090669

RESUMO

Background: To examine time trends and characteristics of calls related to opioid poisonings reported to the National Poison Centre and opioid sales in Switzerland. Methods: We used population-level data from the Swiss National Poisons Information Centre on reported opioid-related poisonings and data provided by the Swiss Pharmacists' Association (pharmaSuisse) based on IQVIA data to identify sold opioid packages. The rate of opioid-related poisoning calls and dispensed opioid packages per 100,000 Swiss inhabitants between 2000 and 2019 were plotted by year and annual trends were assessed. All analyses were stratified by individual opioid and potency (strong vs weak). Findings: There was a significant 177% increase in the rate of calls for opioid-related poisonings (1·4 to 3·9 per 100,000 inhabitants, p<0·001) and a 91·3% increase in opioid sales (from 14,364·0 to 27,477·6 per 100,000 inhabitants, p<0.001). The increase associated with strong opioids was higher when compared to weak opioids, in both poison centre calls and sales. In 2019, tramadol was the most frequently reported opioid in the poison centre data (35·7%, n=133) and sales (37·5%, n=8,863,377), followed by oxycodone calls (24·4%, n=91) and sales 23·4%, n= 552,751). Poisoning calls and sales related to oxycodone increased substantially between 2009 and 2016, as did the rate of poison centre calls requiring medical care. Interpretation: Calls to the Swiss National poison centre and sales for opioid have increased substantially in Switzerland in the last two-decades. Increases were primarily driven by oxycodone and tramadol; however, sales have attenuated since 2016. Our findings mirror other European countries and stress the importance of surveillance and monitoring. Funding: The research did not receive external funding. Translation of the abstract in German, French and Italian are available in the Supplementary section.

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