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1.
BMC Oral Health ; 22(1): 519, 2022 11 20.
Artigo em Inglês | MEDLINE | ID: mdl-36404324

RESUMO

BACKGROUND: Broad spectrum antibiotics are often used for the prophylaxis of infectious endocarditis and treatment of odontogenic infections, but there are limited data related to antibiotic use and adherence to prescription guidelines.  METHODS: Data from patients with tooth extraction between 2014 and 2018 were selected from a database of a regional health insurance fund. We created three data sets, one based on all tooth extractions, one on multiple teeth extractions, and one including only single tooth extraction. After data collection, descriptive analysis was carried out. The differences in prescription pattern of antibiotic medicine were tested by χ2 test, Student´s t-test or ANOVA. RESULTS: From 43,863 patients with tooth extraction, 53% were female, and 3,983 patients (9.1%) filled a prescription for antibiotic medicine. From 43,863 patients, 157 patients (0.4%) had endocarditis risk, but only 8 patients of these (5.1%) filled an antibiotic prescription. In total, 9,234 patients had multiple and 34,437 patients had only one tooth extraction. Patients with more than one tooth extraction received more often antibiotic treatment (10.7%) compared to those with single tooth extractions (χ2 = 36; p < 0,001). Patients with more than one tooth extraction were older, however, younger patients received antibiotics more frequently (t = 28,774, p = 0.001). There was no relationship with endocarditis risk status. Clindamycin and amoxicillin/clavulanic acid were the most frequently prescribed antibiotic medicines. CONCLUSIONS: In this retrospective cohort study, dentists did not discriminate prophylactic antibiotic prescription with regard to endocarditis risk status. A factor influencing prescribing behaviour of antibiotic medicines was the number of extracted teeth.


Assuntos
Antibacterianos , Endocardite , Humanos , Adulto , Feminino , Masculino , Antibacterianos/uso terapêutico , Áustria , Estudos Retrospectivos , Extração Dentária/efeitos adversos , Prescrições de Medicamentos , Endocardite/tratamento farmacológico
2.
Pharmacoepidemiol Drug Saf ; 30(10): 1332-1338, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34021676

RESUMO

PURPOSE: Patients with stroke are at high risk of recurrence of vascular events. Non-vitamin K oral anticoagulant (NOAC) and vitamin K antagonists (VKA) are used as secondary prophylaxis. The aim of this study was to evaluate the utilization of NOAC and VKA, and their impact on re-stroke or death in Austria. METHODS: We analyzed retrospective data between 2012 and 2017 from medical services covered by the health insurance funds, which provides health care for all residents in Austria. Patients without anticoagulant medication 3 months preceding the index event were eligible. RESULTS: 76 354 patients were discharged with a hospital diagnosis of stroke. From these, 16 436 patients with a median age of 78 years received VKA or NOAC. After adjustment, the recurrence of stroke was less frequent in patients with NOAC compared to those with VKA (HR 0.87; 95%CI 0.77-0.97). However, there was no difference in mortality rate after adjustment for age, sex, and co-morbidities for patients with NOAC (HR 1.0; 95%CI 0.92-1.08). Diabetes (HR 1.25, 95%CI 1.08-1.45; HR 1.25, 95% CI 1.13-1.38) and cardiovascular disease (HR 1.43, 95%CI 1.24-1.65; HR 1.27, 95%CI 1.16-1.39) were significantly associated with re-stroke or death. Younger age (p = 0.0028; HR 0.99, 95%CI 0.99-0.99) was significantly associated with re-stroke, and advanced age (p < 0.0001; HR 1.09, 95%CI 1.08-1.09) with death. CONCLUSION: NOAC prescription is related with a reduced risk of re-stroke but increased mortality compared to patients with VKA. The event risk is associated with diabetes, cardiovascular disease and age.


Assuntos
Anticoagulantes , Acidente Vascular Cerebral , Idoso , Áustria , Estudos de Coortes , Humanos , Estudos Retrospectivos , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/prevenção & controle
3.
BMC Geriatr ; 21(1): 117, 2021 02 10.
Artigo em Inglês | MEDLINE | ID: mdl-33568102

RESUMO

BACKGROUND: The use of potentially inappropriate medication (PIM) in population of older adults may result in adverse drug events (ADE) already after short term exposure, especially when it is prescribed to patients with chronic kidney disease (CKD). In order to limit ADE in the treatment of older adults PIM lists have been constructed as a source of information for healthcare professionals. The aim of this study was to estimate the utilization of PIM and incidence of ADE in older adults (≥70 years) with CKD. METHODS: We conducted a retrospective population-wide cohort study including patients from Lower Austria who were 70 years or older and diagnosed with CKD in the period from 2008 to 2011. Utilization of PIM was estimated from prescriptions filled by target population. We estimated risks of hospitalization due to ADE within 30 days after incident PIM prescription and compared them to a PIM-free control group by using marginal structural models (MSM). RESULTS: We identified 11,547 patients (women: 50.6%, median age in 2008: 78 years) who fulfilled the inclusion criteria. In total 24.7 and 8.1% of all prescriptions from that period contained a medication with a substance listed in the EU (7)-PIM and AT-PIM list, respectively. Proton pump inhibitors and Ginkgo biloba were the most often prescribed PIMs in this population. 94.6 and 79.3% patients filled at least one EU(7)-PIM and AT-PIM prescription, respectively. Despite the relatively high utilization of PIM there was only a low incidence of clinically relevant ADE. No event type exceeded the threshold level of 1% in the analysis of risks of ADE after filling a prescription for PIM. Nevertheless, MSM analysis showed an increased risk for 11 drugs and reduced risk for 4 drugs. CONCLUSIONS: PIM prescription was common among older adults with CKD, however, only a small number of these drugs eventually led to hospitalization due to ADE within 30 days after incident PIM was filled. In the absence of a clinically important PIM-related increase in risk, an assessment of potential ADE severity to a PIM list by using a warning score system seems prudent.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Insuficiência Renal Crônica , Minorias Sexuais e de Gênero , Idoso , Áustria , Estudos de Coortes , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/diagnóstico , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Feminino , Homossexualidade Masculina , Humanos , Prescrição Inadequada , Masculino , Lista de Medicamentos Potencialmente Inapropriados , Insuficiência Renal Crônica/induzido quimicamente , Insuficiência Renal Crônica/diagnóstico , Insuficiência Renal Crônica/tratamento farmacológico , Estudos Retrospectivos
4.
Br J Clin Pharmacol ; 86(8): 1610-1619, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32145041

RESUMO

AIMS: Oral opioid preparations combined with naloxone are intended to induce a transient acute withdrawal syndrome to avoid intravenous misuse. This trial aimed to establish an appropriate morphine-naloxone dose ratio for an abuse-deterrent oral opioid formulation. METHODS: In a randomized, double-blinded, 2 × 2 cross-over trial, 43 patients with opioid use disorder were challenged with intravenous morphine HCl Ph.Eur. (75 mg; [morphine mono]) or morphine HCl Ph.Eur. and naloxone HCl Ph.Eur. at ratios of 100:1 (75 mg: 0.75 mg; [morphine-naloxone 100:1]) or 200:1 (75 mg: 0.375 mg; [morphine-naloxone 200:1]). Acute naloxone-induced opioid withdrawal was evaluated using subjective (Short Opiate Withdrawal Scale-German [SOWS-G]) and observer-rated (Objective Opiate Withdrawal Scale [OOWS], Wang scale) questionnaires, and physiological parameters. For statistical analysis, the area under the curve between baseline and 20 minutes after drug administration of the outcome variables was calculated. RESULTS: Intravenous morphine-naloxone caused rapid withdrawal symptoms. Coadministration of naloxone dose-dependently (morphine-naloxone 100:1 > morphine-naloxone 200:1) increased SOWS-G, OOWS and Wang Scale area under the curve when compared to morphine mono, respectively (all P < .0001). A similar response was detectable for changes of pupil diameter. Blood pressure and respiratory rate changed heterogeneously, and heart rate was unaltered by morphine without or with naloxone. CONCLUSION: Morphine-naloxone 100:1 effectively suppresses the pleasurable effects of intravenous morphine and results in an aversive withdrawal reaction. A lower naloxone concentration as used in morphine-naloxone 200:1 does not appear to be appropriate to prevent intravenous morphine misuse.


Assuntos
Antagonistas de Entorpecentes/uso terapêutico , Transtornos Relacionados ao Uso de Opioides , Síndrome de Abstinência a Substâncias , Analgésicos Opioides/efeitos adversos , Animais , Feminino , Humanos , Masculino , Morfina/efeitos adversos , Naloxona/administração & dosagem , Naloxona/uso terapêutico , Antagonistas de Entorpecentes/administração & dosagem , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Síndrome de Abstinência a Substâncias/tratamento farmacológico , Suínos
5.
Eur J Clin Invest ; 49(1): e13041, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30365159

RESUMO

BACKGROUND: Increased asymmetrical dimethylarginine (ADMA) and NT pro-BNP concentrations have been associated with mortality in patients with cardiovascular (CV) disease and the general population. The use of these prognostic markers in an older population is not established yet. The aim of the present study was to investigate the prognostic value of age, sex, BMI, co-medication and CV laboratory risk markers in geriatric care patients. MATERIALS AND METHODS: In this prospective observational single-centre cohort study data of long-term geriatric care patients were collected. Blood samples were collected between 14.09.2009 and 16.12.2009, and mortality was recorded up to 90 months. ADMA, its symmetric isomer SDMA, L-arginine, NT pro-BNP and CRP were determined at study entry. Simple associations of risk factors for survival period were explored by Spearman correlation coefficient. Significant univariate predictors for survival period were used in the Cox proportional hazard model. RESULTS: A total of 481 patients were screened, and data from 449 patients were analysed. A total of 381 patients died during the observation period. Full data sets from 344 patients were used for Cox regression analysis. Male sex, older age, lower BMI, use of neuroleptic medicine, peripheral artery disease, and elevated plasma concentrations of ADMA, NT pro-BNP, and CRP were significant predictors of mortality. CONCLUSION: The concentration of ADMA and NT pro-BNP may be used as an early risk marker for overall mortality in geriatric care. Neuroleptic medicine is associated with increased mortality in this population.


Assuntos
Arginina/análogos & derivados , Doenças Cardiovasculares/mortalidade , Peptídeo Natriurético Encefálico/metabolismo , Fragmentos de Peptídeos/metabolismo , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Arginina/metabolismo , Áustria/epidemiologia , Biomarcadores/metabolismo , Índice de Massa Corporal , Doenças Cardiovasculares/sangue , Feminino , Serviços de Saúde para Idosos/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Estudos Prospectivos , Fatores de Risco , Distribuição por Sexo , Análise de Sobrevida
6.
Int J Geriatr Psychiatry ; 34(8): 1194-1199, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30968457

RESUMO

OBJECTIVES: Non-vitamin K oral anticoagulants (NOACs) or vitamin K antagonists (VKAs) are used for the prophylaxis and treatment of thromboembolic events. A potential drug-drug interaction and increased bleeding events have been reported with co-medication of selective serotonin receptor inhibitors (SSRIs) and VKA. The aim of this study was to investigate the bleeding risk of a coprescription of NOAC or VKA with SSRI. METHODS: Patients with prescription of NOAC or VKA and an antidepressant drug therapy (ADTx) were selected from the drug reimbursement database of 13 Austrian health insurance funds. For this cohort, hospital discharge diagnoses for gastrointestinal bleeding, cerebral haemorrhage, and bleeding anaemia between 2010 and 2015 were analysed. RESULTS: Data were available from 50 196 female and 31 308 male patients. Among these, 892 patients had 987 hospitalisations with bleeding events. The most frequent bleeding cases were gastrointestinal bleedings with 588 events (59.6%), followed by cerebral haemorrhage with 344 (34.8%), and bleeding anaemia with 55 events (5.6%), respectively. The risk of bleeding events was similar between SSRI and other ADTx, when combined with oral anticoagulants (p = 0.51). Concomitant treatment of patients with SSRI or other ADTx and NOAC was associated with an increased bleeding risk compared with cotreatment with VKA (1.21, 95% CI: 1.05-1.40; p = 0.0097). CONCLUSION: Co-medication of SSRI with VKA or NOAC has little if any impact on hospital discharge diagnoses for bleeding events compared with cotreatment of those anticoagulants with other antidepressant medications.


Assuntos
Anticoagulantes/efeitos adversos , Hemorragia/induzido quimicamente , Hospitalização/estatística & dados numéricos , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Tromboembolia/tratamento farmacológico , Vitamina K/antagonistas & inibidores , Administração Oral , Idoso , Áustria , Interações Medicamentosas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
7.
Horm Metab Res ; 50(6): 478-484, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29883974

RESUMO

Increased free fatty acids stimulate sympathetic nervous system activity, impair endothelium-dependent vasodilation, and increase regional blood flow. The aim of this study was to assess if fatty acids acutely elevated by infusion of intralipid/heparin affect cardiovascular reactivity employing two stressors eliciting either a cardiac (Stroop test) or vascular (Cold Face test) dominated pressor response. Two stress tasks were performed in 20 healthy subjects (10 women, 10 men) before and during a 180-min intralipid/heparin or saline infusion as placebo on alternate trial days in a randomized crossover study design. Blood pressure, heart rate, cardiac index, and total peripheral resistance index were measured. At baseline, the Stroop test did not affect hemodynamic parameters, and the Cold Face test had an impact on hemodynamic parameters except for heart rate. Plasma fatty acids concentrations increased to 810% (t=11.0, p<0.001) of baseline and C-peptide increased by 17% (t=4.66, p<0.001) during intralipid/heparin infusion. This was paralleled by increased cardiac index (F=9.98; p<0.005 vs. saline) and reduced total peripheral resistance index (F=4.46; p<0.05 vs saline). There was no effect of intralipid/heparin or saline infusion on Stroop test or Cold Face test reactivity of hemodynamic parameters. An acute increase in free fatty acids does not affect the magnitude or pattern of stress response in healthy volunteers, but primarily alter the underlying cardiovascular tone by decreasing total peripheral resistance index and increasing cardiac index to maintain a constant blood pressure.


Assuntos
Doenças Cardiovasculares/etiologia , Ácidos Graxos não Esterificados/administração & dosagem , Estresse Psicológico/complicações , Adolescente , Adulto , Doenças Cardiovasculares/sangue , Estudos Cross-Over , Método Duplo-Cego , Feminino , Frequência Cardíaca , Humanos , Masculino , Estresse Psicológico/sangue , Análise e Desempenho de Tarefas , Adulto Jovem
8.
Artigo em Inglês | MEDLINE | ID: mdl-26290038

RESUMO

OBJECTIVES: The aim of the trial was to assess the effect of self-evaluation and sexual diary keeping on female sexual function and depressive symptoms in women diagnosed with sexual dysfunction. METHODS: A single-arm non-randomised trial included 30 women (53 ± 7 years of age) with female sexual dysfunction (Female Sexual Function Index [FSFI] < 27) and a stable partnership duration of 5-40 years. Female sexual function was assessed by sexual, psychological and gynaecological history taking and validated questionnaires including the FSFI, Female Sexual Distress Scale (FSDS) and Hamilton Depression Scale (HDS), before and after 4 weeks of sexual diary keeping. RESULTS: A subjective improvement in communication of sexual problems was reported by 60% of participants; no participants reported any worsening of communication. FSFI and FSDS scores were, respectively, 18.0 ± 7.7 and 22.0 ± 10.0 at baseline and 20.2 ± 7.2 and 20.6 ± 11.5 after 4 weeks. HDS score decreased from 6.0 ± 4.0 at baseline to 4.4 ± 2.7 after 4 weeks (p = 0.042). CONCLUSIONS: Self-evaluation and sexual diary keeping may improve aspects of sexual life, such as couple communication, without a direct effect on variables measured with validated questionnaires on different domains of sexual function.


Assuntos
Comunicação , Depressão/psicologia , Características da Família , Qualidade de Vida , Saúde Reprodutiva , Disfunções Sexuais Psicogênicas/terapia , Autoavaliação Diagnóstica , Feminino , Humanos , Prontuários Médicos , Pessoa de Meia-Idade , Projetos Piloto , Disfunções Sexuais Psicogênicas/psicologia , Inquéritos e Questionários
9.
Brain Commun ; 5(6): fcad325, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38107502

RESUMO

In multiple sclerosis, lesions are formed in various areas of the CNS, which are characterized by reactive gliosis, immune cell infiltration, extracellular matrix changes and demyelination. CAQK peptide (peptide sequence: cysteine-alanine-glutamine-lysine) was previously introduced as a targeting peptide for the injured site of the brain. In the present study, we aimed to develop a multifunctional system using nanoparticles coated by CAQK peptide, to target the demyelinated lesions in animal model of multiple sclerosis. We investigated the binding of fluorescein amidite-labelled CAQK and fluorescein amidite-labelled CGGK (as control) on mouse brain sections. Then, the porous silicon nanoparticles were synthesized and coupled with fluorescein amidite-labelled CAQK. Five days after lysolecithin-induced demyelination, male mice were intravenously injected with methylprednisolone-loaded porous silicon nanoparticles conjugated to CAQK or the same amount of free methylprednisolone. Our results showed that fluorescein amidite-labelled CAQK recognizes demyelinated lesions in brain sections of animal brains injected with lysolecithin. In addition, intravenous application of methylprednisolone-loaded nanoparticle porous silicon conjugated to CAQK at a single dose of 0.24 mg reduced the levels of microglial activation and astrocyte reactivation in the lesions of mouse corpus callosum after 24 and 48 h. No significant effect was observed following the injection of the same dose of free methylprednisolone. CAQK seems a potential targeting peptide for delivering drugs or other biologically active chemicals/reagents to the CNS of patients with multiple sclerosis. Low-dose methylprednisolone in this targeted drug delivery system showed significant beneficial effect.

10.
Minerva Med ; 114(3): 307-315, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36255709

RESUMO

BACKGROUND: We aimed to investigate predictors for long-term survival of in-hospital patients with medical emergency team (MET) consultation with or without in-hospital cardiac arrest (IHCA) in Austria's largest medical center. METHODS: Data of patients, who needed an intervention of a MET between 01/2014 and 03/2020 were reviewed for this retrospective analysis. RESULTS: In total, 708 MET calls were analyzed. The minimum follow-up was 7 months, the maximum 6.2 years. The main MET indications were circulatory failure (63%) followed by respiratory failure (27.1%), and bleeding events (3.5%). IHCA with subsequent cardiopulmonary resuscitation (CPR) was experienced by 425 (60%) patients. Of those, 274 (64%) reached return of spontaneous circulation (ROSC), and 221 (52%) survived the first 24-hours (median survival: 146 days) and 22.1% the first year. After adjustment for potential confounders, age (P<0.001), time to ROSC (P<0.001), a non-shockable rhythm (P=0.041), chronic kidney disease (CKD, P=0.041), peak lactate levels (P<0.001), and C-reactive protein (P=0.001) were associated with long-term all-cause mortality in IHCA patients in Cox regression analysis. The 283 MET calls (40%) which were due to other reasons than IHCA were associated with a much better 24-hours (93%) and 1-year survival (61.8%). Beside age (P<0.001), the main risk factors associated with mortality in MET patients without IHCA were comorbidities such as chronic obstructive pulmonary disease (COPD, P=0.008), CKD (P=0.001), pulmonary hypertension/chronic thromboembolic pulmonary hypertension (PH/CTEPH, P=0.024), and cancer (P=0.040). CONCLUSIONS: Patients triggering MET calls have an increased mortality, especially those with IHCA. Predictors of mortality comprise age, comorbidities, and cardiac arrest-related parameters. A better characterization of MET call populations and their outcome might help to improve clinical decision making.


Assuntos
Parada Cardíaca , Equipe de Respostas Rápidas de Hospitais , Hipertensão Pulmonar , Doença Pulmonar Obstrutiva Crônica , Humanos , Estudos Retrospectivos , Áustria , Hospitais , Medição de Risco
11.
Front Med (Lausanne) ; 9: 830580, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35833107

RESUMO

Aims: To evaluate the performance of the ABC (Age, Biomarkers, Clinical history) and CHA2DS2-VASc stroke scores under real-world conditions in an emergency setting. Methods and Results: The performance of the biomarker-based ABC-stroke score and the clinical variable-based CHA2DS2-VASc score for stroke risk assessment were prospectively evaluated in a consecutive series of 2,108 patients with acute symptomatic atrial fibrillation at a tertiary care emergency department. Performance was assessed according to methods for the development and validation of clinical prediction models by Steyerberg et al. and the Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis. During a cumulative observation period of 3,686 person-years, the stroke incidence rate was 1.66 per 100 person-years. Overall, the ABC-stroke and CHA2DS2-VASc scores revealed respective c-indices of 0.64 and 0.55 for stroke prediction. Risk-class hazard ratios comparing moderate to low and high to low were 3.51 and 2.56 for the ABC-stroke score and 1.10 and 1.62 for the CHA2DS2-VASc score. The ABC-stroke score also provided improved risk stratification in patients with moderate stroke risk according to the CHA2DS2-VASc score, who lack clear recommendations regarding anticoagulation therapy (HR: 4.35, P = 0.001). Decision curve analysis indicated a superior net clinical benefit of using the ABC-stroke score. Conclusion: In a large, real-world cohort of patients with acute atrial fibrillation in the emergency department, the ABC-stroke score was superior to the guideline-recommended CHA2DS2-VASc score at predicting stroke risk and refined risk stratification of patients labeled moderate risk by the CHA2DS2-VASc score, potentially easing treatment decision-making.

12.
J Clin Med ; 9(11)2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33114045

RESUMO

BACKGROUND: Dual antiplatelet therapy improves patient outcome after acute coronary syndrome (ACS), but prescription differences of P2Y12 inhibitor treatments exist. The aim of the present investigation was to study the long-term utilization and patient outcomes of clopidogrel, prasugrel, and ticagrelor in patients with ACS from 2015 to 2017 in Austria. METHODS: Data from 13 Austrian health insurance funds of patients with a hospital discharge diagnosis of ACS for the years 2015 to 2017 were analyzed. The primary end point was to investigate the recurrence of ACS or death. RESULTS: Of 49,124 P2Y12 inhibitor-naive patients with a hospital discharge diagnosis of ACS, 25,147 subjects filled a P2Y12 inhibitor prescription within 30 days after the index event. Of these patients, 10,626 (42.9%) subjects had a prescription for clopidogrel, 4788 (19.3%) for prasugrel, and 9383 (37.8%) for ticagrelor. Ticagrelor was the most frequently prescribed P2Y12 inhibitor among patients below 70 years old, and clopidogrel in those aged ≥70 years. Occurrence of an endpoint was highest in elderly patients. After adjustment for age, sex, and pre-existing medication as proxy for comorbidity, the hazard ratio for ACS or death for prasugrel vs. clopidogrel of 0.70 (95% CI: 0.61; 0.79) was similar to that of ticagrelor vs. clopidogrel (0.70; 95% CI: 0.64; 0.77). CONCLUSION: Prescription of ticagrelor or prasugrel after ACS were associated with a lower risk of ACS recurrence or death compared to clopidogrel.

13.
Int J Biol Macromol ; 146: 162-170, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31899243

RESUMO

Removal of chondroitin sulfate proteoglycans (CSPGs) with chondroitinase ABC I (ChABC) facilitates axonal plasticity, axonal regeneration and remyelination, following injury to the central nervous system (CNS). However, the ChABC rapidly undergoes thermal inactivity and needs to be injected repeatedly. Here this limitation was overcame by immobilizing the ChABC on porous silicon (PSi) nanoparticles (ChABC@PSi). The efficacy of immobilized ChABC on CSPGs level and the demyelination insult was assessed in mice corpora callosa demyelinated by 6 weeks cuprizone (CPZ) feeding. ChABC@PSi was able to reduce the amount of CSPGs two weeks after animals treatment. CSPGs digestion by ChABC@PSi reduced the extent of demyelinated area as well as the astrogliosis. Furthermore, ChABC@PSi treatment increased the number of newly generated oligodendrocyte lineage cells which imply for enhanced myelin repair. Our results showed that effective CSPGs digestion by ChABC@PSi enhanced remyelination in CPZ model. Accordingly, ChABC@PSi may have a great potential to be used for treatment of diseases like multiple sclerosis and spinal cord injury by promoting the regeneration of damaged nerves.


Assuntos
Condroitina ABC Liase/química , Enzimas Imobilizadas/química , Esclerose Múltipla/metabolismo , Bainha de Mielina/metabolismo , Nanopartículas/química , Silício/química , Animais , Modelos Animais de Doenças , Humanos , Masculino , Camundongos , Esclerose Múltipla/patologia , Esclerose Múltipla/terapia
14.
Int J Pharm ; 571: 118694, 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31525444

RESUMO

Important aspects in the development of new dermal drug delivery systems are the formulations' physicochemical properties and stability. Moreover, their influence on skin physiology and their penetration performance in vivo are of crucial interest. We have recently developed novel concentrated water-in-oil emulsions based on a non-ionic silicone surfactant; the present study deals with the effect of these formulations on physiological skin parameters of healthy volunteers after repeated application. Variations in skin condition and barrier integrity were investigated using classical biophysical and spectroscopic techniques. After four weeks of continuous treatment, no signs of skin irritation could be observed. Both tested emulsions had a positive effect on skin properties despite their relatively high water content and low lipid content. In vivo tape stripping studies revealed penetrated amounts of the incorporated model drug fluorescein sodium of almost 50% of the applied dose, with a superior performance of emulsions with isopropyl myristate when compared to liquid paraffin. In summary, our study confirmed the suitability of the developed W/O emulsions for pharmaceutic and cosmetic applications.


Assuntos
Sistemas de Liberação de Medicamentos/métodos , Óleos/química , Pele/metabolismo , Água/química , Administração Cutânea , Adulto , Emulsificantes/química , Emulsões , Fluoresceína/administração & dosagem , Fluoresceína/farmacocinética , Corantes Fluorescentes/administração & dosagem , Corantes Fluorescentes/farmacocinética , Voluntários Saudáveis , Humanos , Permeabilidade , Projetos Piloto , Silicones/química , Pele/efeitos dos fármacos , Perda Insensível de Água/efeitos dos fármacos , Adulto Jovem
15.
Clin Respir J ; 12(12): 2627-2634, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30276967

RESUMO

INTRODUCTION: Beta-blockers are indicated for secondary prevention of coronary artery disease (CAD). However, in patients with co-morbidity of chronic obstructive pulmonary disease (COPD) an underuse of beta-blocker has been reported. MATERIALS AND METHODS: Prescription and demographic data and information on hospital discharge diagnoses from 13 Austrian health insurance funds for the years 2006-2007 were analyzed. The primary end point was all-cause mortality of patients with CAD with or without COPD and its association with use of beta-blockers. RESULTS: In 2006 and 2007, 65717 patients (37% female, 63% male) were discharged with a diagnosis of CAD. Among these patients, 46% had a co-diagnosis of COPD, 24% had diabetes, and 75% received beta-blockers. Use of beta-blockers was comparable in CAD patients with COPD and without COPD with 77% and 74%, respectively. Thousand eight hundred seventy-two (8.1%) and 1473 (5.6%) patients with and without COPD, who used beta-blockers died within months in 2006 and 2007. Thousand five hundred fifty-three (22.0%) and 1862 (22.2%) of patients with and without COPD and without beta-blockers died during the corresponding time period. DISCUSSION: Use of beta-blockers was similar in patients with CAD with or without co-diagnosis of COPD. However, mortality of beta-blocker users was markedly lower than that of nonusers in patients with CAD with or without COPD.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Uso de Medicamentos/estatística & dados numéricos , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Adolescente , Antagonistas Adrenérgicos beta/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Áustria/epidemiologia , Comorbidade , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/prevenção & controle , Uso de Medicamentos/tendências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/mortalidade , Estudos Retrospectivos , Fatores de Risco , Prevenção Secundária , Análise de Sobrevida , Adulto Jovem
16.
Int J Cardiol ; 235: 61-66, 2017 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-28262344

RESUMO

BACKGROUND: The beneficial use of dual antiplatelet therapy (DAPT) with acetylsalicylic acid (ASA) and P2Y12 õinhibitors has been established for patients after acute coronary syndrome (ACS). However, the optimal duration of DAPT is under debate. The aim of the present study was to investigate the long-term utilization and clinical outcome of clopidogrel, prasugrel, and ticagrelor in patients with ACS from 2009 to 2014 in Austria. METHODS: We analysed data from 13 Austrian health insurance funds for the years 2009 to 2014, on 72,676 patients with a hospital discharge diagnosis of ACS. The primary end point was recurrence of ACS or death >30days after the index event. RESULTS: 32,830 subjects received a prescription of a P2Y12 inhibitor within 30days after the index ACS. 18,640 (56.8%) subjects were discharged with clopidogrel, 6683 (20.4%) with prasugrel, and 7507 (22.9%) with ticagrelor, respectively. Data from 32,174 patients with 4975 events during a median follow-up period of 24.9months were available for survival analysis. The cumulative incidence for recurrence of ACS or death at two years was 18.7% in patients receiving clopidogrel, and 8.7% and 12.0% in those receiving prasugrel or ticagrelor, respectively. CONCLUSION: Utilization of P2Y12 inhibitors in patients with ACS was consistent with guideline recommendations. Prasugrel and ticagrelor are increasingly used in ACS patients and associated with a lower number of recurrence of ACS or death compared to clopidogrel. However, clopidogrel was predominantly used in older patients with more co-morbidities.


Assuntos
Síndrome Coronariana Aguda , Adenosina/análogos & derivados , Aspirina/uso terapêutico , Cloridrato de Prasugrel/uso terapêutico , Ticlopidina/análogos & derivados , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/tratamento farmacológico , Síndrome Coronariana Aguda/epidemiologia , Adenosina/uso terapêutico , Idoso , Áustria/epidemiologia , Clopidogrel , Quimioterapia Combinada/métodos , Quimioterapia Combinada/estatística & dados numéricos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Masculino , Conduta do Tratamento Medicamentoso/organização & administração , Conduta do Tratamento Medicamentoso/estatística & dados numéricos , Alta do Paciente/estatística & dados numéricos , Inibidores da Agregação Plaquetária/uso terapêutico , Recidiva , Análise de Sobrevida , Ticagrelor , Ticlopidina/uso terapêutico
17.
Fertil Steril ; 107(3): 781-787.e3, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28189292

RESUMO

OBJECTIVE: To study sexual function, quality of life, and depression in men, whose female partners are undergoing double-blind placebo-controlled randomized treatment for hypoactive sexual desire disorder (HSDD). DESIGN: Open prospective cohort study of 22 weeks. SETTING: Academic medical center. PATIENT(S): Male partners of 30 premenopausal and postmenopausal women with HSDD. INTERVENTION(S): Baseline, 3-month, and 5-month assessment (for 8 weeks each) of male response to female partner's use of oxytocin nasal spray (32 IE) and placebo within 50 minutes before sexual intercourse. MAIN OUTCOME MEASURE(S): Primary outcome parameters were Sexual Life Quality Questionnaire-Male, Sexual Activity Record, Partner Performance Questionnaire, and Hamilton Depression Scale. RESULT(S): Male Sexual Life Quality questionnaire improved significantly from -7.4 ± 9.9 at baseline to 8.2 ± 12 with female partners' treatment with oxytocin nasal spray and to 10.8 ± 13.8 with placebo. Frequency of intercourse improved slightly but not significantly from 6.3 ± 3.9 at baseline to 7.3 ± 4 with female oxytocin therapy, but not with placebo. Male desire and arousal remained stable throughout the study period. Evaluation of female partners' performance by men improved significantly from 8.9 ± 2.8 at baseline to 10.6 ± 2.2 with oxytocin and to 11.2 ± 2.6 with placebo. CONCLUSION(S): Female treatment with either oxytocin or placebo for HSDD significantly improves male sexual quality of life and evaluation of female partner's sexual performance with no difference between oxytocin and placebo on any outcome parameters. A nonsignificant improvement was seen in the frequency of intercourse, male arousal, desire, satisfaction, and Hamilton depression scale. CLINICAL TRIAL REGISTRATION NUMBER: NCT02229721.


Assuntos
Ocitocina/administração & dosagem , Comportamento Sexual/efeitos dos fármacos , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Parceiros Sexuais/psicologia , Centros Médicos Acadêmicos , Administração por Inalação , Áustria , Estudos Cross-Over , Depressão/diagnóstico , Depressão/psicologia , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ocitocina/efeitos adversos , Estudos Prospectivos , Escalas de Graduação Psiquiátrica , Qualidade de Vida , Disfunções Sexuais Psicogênicas/diagnóstico , Disfunções Sexuais Psicogênicas/psicologia , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento
18.
Fertil Steril ; 104(3): 715-23.e4, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26151620

RESUMO

OBJECTIVE: To assess the effect of on-demand intranasal oxytocin administration on female sexual function and activity. DESIGN: Randomized, prospective, double-blind, placebo-controlled, crossover trial with duration of 22 weeks. SETTING: Academic medical center. PATIENT(S): Thirty pre-and postmenopausal women with sexual dysfunction. INTERVENTION(S): Over 8 weeks, intranasal oxytocin (32 IU) or placebo self-administered by women within 50 minutes before sexual intercourse; after a washout period of 2 weeks, crossover with patients switched to the alternate group for another 8 weeks. MAIN OUTCOME MEASURE(S): Primary outcome parameter: Female Sexual Function Index (FSFI); secondary outcome parameters: Female Sexual Distress Scale (FSDS), Sexual Quality of Life-Female (SQOL-F), Sexual Interest and Desire Inventory-Female (SIDI-F), and Hamilton depression scale (HDS). RESULT(S): After oxytocin and placebo, the FSFI score increased by 26% and 31%, SQOL-F score by 144% and 125%, and SIDI-F score by 29% and 23%, respectively (repeated measures analysis of variance between groups). After oxytocin and placebo, the FSDS score decreased by 36% and 45%, respectively (repeated measures analysis of variance between groups). There was no statistically significant treatment, sequence (placebo first/second), or interaction effect. CONCLUSION(S): Long-term intranasal oxytocin and placebo administration both improved sexual function and symptoms of depression in women over time with no treatment, sequence (placebo first/second), or interaction effect. CLINICAL TRIAL REGISTRATION NUMBER: NCT02229721.


Assuntos
Ocitocina/administração & dosagem , Pós-Menopausa , Pré-Menopausa , Comportamento Sexual/efeitos dos fármacos , Disfunções Sexuais Fisiológicas/tratamento farmacológico , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Administração Intranasal , Adulto , Idoso , Áustria , Estudos Cross-Over , Depressão/diagnóstico , Depressão/tratamento farmacológico , Depressão/psicologia , Método Duplo-Cego , Esquema de Medicação , Feminino , Humanos , Pessoa de Meia-Idade , Ocitocina/efeitos adversos , Estudos Prospectivos , Qualidade de Vida , Disfunções Sexuais Fisiológicas/diagnóstico , Disfunções Sexuais Fisiológicas/fisiopatologia , Disfunções Sexuais Fisiológicas/psicologia , Disfunções Sexuais Psicogênicas/diagnóstico , Disfunções Sexuais Psicogênicas/fisiopatologia , Disfunções Sexuais Psicogênicas/psicologia , Inquéritos e Questionários , Fatores de Tempo , Resultado do Tratamento
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