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1.
Ther Drug Monit ; 46(5): 681-686, 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-38967524

RESUMO

BACKGROUND: This study was conducted to evaluate the cost-benefit indicators of a vancomycin monitoring protocol based on area under the curve estimation using commercial Bayesian software. METHODS: This quasi-experimental study included patients who were aged >18 years with a vancomycin prescription for >24 hours. Patients who were terminally ill or those with acute kidney injury (AKI) ≤24 hours were excluded. During the preintervention period, doses were adjusted based on the trough concentration target of 15-20 mg/L, whereas the postintervention period target was 400-500 mg × h/L for the area under the curve. The medical team was responsible for deciding to stop the antimicrobial prescription without influence from the therapeutic drug monitoring team. The main outcomes were the incidence of AKI and length of stay. Cost-benefit simulation was performed after statistical analysis. RESULTS: There were 96 patients in the preintervention group and 110 in the postintervention group. The AKI rate decreased from 20% (n = 19) to 6% (n = 6; P = 0.003), whereas the number of vancomycin serum samples decreased from 5 (interquartile range: 2-7) to 2 (interquartile range: 1-3) examinations per patient ( P < 0.001). The mean length of hospital stay for patients was 26.19 days after vancomycin prescription, compared with 17.13 days for those without AKI ( P = 0.003). At our institution, the decrease in AKI rate and reduced length of stay boosted yearly savings of up to US$ 369,000 for 300 patients receiving vancomycin therapy. CONCLUSIONS: Even in resource-limited settings, a commercial Bayesian forecasting-based protocol for vancomycin is important for determining cost-benefit outcomes.


Assuntos
Antibacterianos , Área Sob a Curva , Teorema de Bayes , Análise Custo-Benefício , Monitoramento de Medicamentos , Vancomicina , Humanos , Vancomicina/farmacocinética , Vancomicina/economia , Vancomicina/uso terapêutico , Vancomicina/sangue , Análise Custo-Benefício/métodos , Monitoramento de Medicamentos/métodos , Monitoramento de Medicamentos/economia , Masculino , Feminino , Antibacterianos/uso terapêutico , Antibacterianos/economia , Antibacterianos/farmacocinética , Antibacterianos/sangue , Pessoa de Meia-Idade , Idoso , Injúria Renal Aguda , Tempo de Internação , Adulto , Região de Recursos Limitados
2.
Artigo em Inglês | MEDLINE | ID: mdl-39078535

RESUMO

The efficacy and safety of direct oral anticoagulants (DOAC) in patients with embolic stroke of undetermined source (ESUS) remains unclear. We systematically searched PubMed, Embase, and Cochrane Library for randomized controlled trials (RCT) comparing DOACs versus aspirin in patients with ESUS. Risk ratios (RR) and 95% confidence intervals (CI) were computed for binary endpoints. Four RCTs comprising 13,970 patients were included. Compared with aspirin, DOACs showed no significant reduction of recurrent stroke (RR 0.95; 95% CI 0.84-1.09; p = 0.50; I2 = 0%), ischemic stroke or systemic embolism (RR 0.97; 95% CI 0.80-1.17; p = 0.72; I2 = 0%), ischemic stroke (RR 0.92; 95% CI 0.79-1.06; p = 0.23; I2 = 0%), and all-cause mortality (RR 1.11; 95% CI 0.87-1.42; p = 0.39; I2 = 0%). DOACs increased the risk of clinically relevant non-major bleeding (CRNB) (RR 1.52; 95% CI 1.20-1.93; p < 0.01; I2 = 7%) compared with aspirin, while no significant difference was observed in major bleeding between groups (RR 1.57; 95% CI 0.87-2.83; p = 0.14; I2 = 63%). In a subanalysis of patients with non-major risk factors for cardioembolism, there is no difference in recurrent stroke (RR 0.98; 95% CI 0.67-1.42; p = 0.90; I2 = 0%), all-cause mortality (RR 1.24; 95% CI 0.58-2.66; p = 0.57; I2 = 0%), and major bleeding (RR 1.00, 95% CI 0.32-3.08; p = 1.00; I2 = 0%) between groups. In patients with ESUS, DOACs did not reduce the risk of recurrent stroke, ischemic stroke or systemic embolism, or all-cause mortality. Although there was a significant increase in clinically relevant non-major bleeding, major bleeding was similar between DOACs and aspirin.

3.
Neurol Sci ; 45(5): 2119-2125, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38044393

RESUMO

BACKGROUND: Swallowing is a complex function that can be disrupted after stroke. Transcranial Direct Current Stimulation (tDCS) is a non-invasive brain stimulation therapy that recently has been tested to treat stroke-related dysphagia. METHODS: The authors performed a search in the literature to review the described evidence of the use of tDCS in dysphagia after stroke. Three electronic databases were searched. The risk of bias evaluation was carried out through the RoB-2 tool. The Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) framework was also implemented. RESULTS: Of 265 articles, only nine studies were included in this review. The most common location of the tDCS stimulation was the unaffected hemisphere (44%). Regarding the outcome measure, the Dysphagia Outcome and Severity Scale (DOSS) was the most commonly used (55%). However, due to the high heterogeneity of the protocols, and considering the differences between the types of stroke, the authors opted not to perform a metanalysis. Instead, a systematic review with a thorough analysis of each individual study and the impact of the differences to the outcomes was preferred. CONCLUSIONS: The final considerations are that even though the majority of studies described benefits from tDCS in post-stroke dysphagia, as they present too many methodological differences, it is not possible to compare them. In addition, many articles included patients with less than 6 months after stroke, which is an important bias as the swallowing function can be recovered spontaneously within this period, turning the certainty of the evidence really low.


Assuntos
Transtornos de Deglutição , Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Estimulação Transcraniana por Corrente Contínua , Humanos , Estimulação Transcraniana por Corrente Contínua/métodos , Transtornos de Deglutição/etiologia , Transtornos de Deglutição/terapia , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Nível de Saúde
4.
Neurol Sci ; 45(10): 4679-4686, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-38763935

RESUMO

Recent randomized controlled trials (RCTs) have shown a benefit of brexpiprazole in managing agitation in patients with Alzheimer's disease (AD). However, its efficacy and safety remain unclear. We systematically searched PubMed, Embase, and Cochrane Library for RCTs comparing brexpiprazole with placebo in patients with agitation and AD. Three studies comprising 1,048 patients were included. In patients with agitation and AD, brexpiprazole significantly improved the Cohen-Mansfield Agitation Inventory total score (CMAI) at any dose (MD -3.05; 95% CI -5.12, -0.98; p < 0.01; I2 = 19%) and at 2 mg (MD -4.36; 95% CI -7.02, -1.70; p < 0.01; I2 = 0%) over 12 weeks. Brexpiprazole at any dose and 2 mg also showed benefit in the Clinical Global Impression - Severity of illness (CGI-S) score as related to agitation over 12 weeks (MD -0.20; 95% CI -0.36, -0.05; p < 0.01; I2 = 35%). There is no significant difference between the groups in the incidence of at least one treatment-emergent adverse events (TEAEs; RR 1.14; 95% CI 0.95, 1.37; p = 0.16; I2 = 45%) and all-cause mortality (RR 1.99; 95% CI 0.37, 10.84; p = 0.42; I2 = 0%). Brexpiprazole at any dose significantly increased the Simpson-Angus Scale (SAS; MD 0.47; 95% CI 0.28, 0.66; p < 0.01). Our results suggest that brexpiprazole is more efficacious than placebo in the treatment of agitation in AD patients. Further studies are still necessary to confirm long-term effects of brexpiprazole.Prospero registry: CRD42023486694.


Assuntos
Doença de Alzheimer , Agitação Psicomotora , Quinolonas , Ensaios Clínicos Controlados Aleatórios como Assunto , Tiofenos , Humanos , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/complicações , Quinolonas/uso terapêutico , Quinolonas/efeitos adversos , Agitação Psicomotora/tratamento farmacológico , Agitação Psicomotora/etiologia , Tiofenos/uso terapêutico , Tiofenos/efeitos adversos , Antipsicóticos/efeitos adversos , Antipsicóticos/uso terapêutico , Resultado do Tratamento
5.
Neurol Sci ; 45(8): 3879-3886, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38494461

RESUMO

BACKGROUND: This study sought to determine whether intensive blood pressure (BP) control for patients with successful reperfusion following acute ischemic stroke (AIS) is beneficial, compared to conventional BP management. METHODS: PubMed, Embase, and Cochrane databases were systematically searched for randomized controlled trials (RCTs) on the subject. The studied outcomes included dependency or death at 90 days (modified Rankin Scale [mRS] 3-6); severe disability at 90 days (mRS 3-5); mortality at 90 days; and symptomatic intracranial hemorrhage. Odds ratios (OR) with 95% confidence intervals were used to compare the treatment effects for categorical outcomes. We employed a fixed-effect model for analyses with low heterogeneity (I2 < 25%) and a random-effects model for analyses with higher heterogeneity. RESULTS: A total of 1519 patients were included, with 50% (n = 760) receiving intensive BP control (systolic BP < 140 mmHg). Functional disability or death at 90 days was significantly higher in the intensive group (54.9%) compared to the conventional treatment group (44.1%) (OR = 1.51; 95% Confidence Interval [CI]: 1.15-1.96; p = 0.003; I2 = 29%). Severe functional disability (mRS 3-5) was significantly higher in the intensive group (30.6% vs. 43.5%, OR = 1.75; 95%CI = 1.36-2.25; p < 0.0001; I2 = 0%). There was no difference in symptomatic intracranial hemorrhage (OR = 1.13; 95%CI = 0.76-1.67) or mortality (OR = 1.22; 95%CI = 0.9-1.64). CONCLUSIONS: Intensive BP control is harmful in patients who underwent EVT for AIS and achieved successful reperfusion. It yields higher rates of functional dependence, with no differences in mortality or symptomatic intracranial hemorrhage.


Assuntos
Pressão Sanguínea , AVC Isquêmico , Ensaios Clínicos Controlados Aleatórios como Assunto , Reperfusão , Humanos , AVC Isquêmico/terapia , AVC Isquêmico/cirurgia , Pressão Sanguínea/fisiologia , Reperfusão/métodos , Trombectomia/métodos
6.
Neurol Sci ; 45(7): 3051-3059, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38353849

RESUMO

Monitoring intracranial pressure (ICP) is pivotal in the management of severe traumatic brain injury (TBI), but secondary brain injuries can arise despite normal ICP levels. Cerebral tissue oxygenation monitoring (PbtO2) may detect neuronal tissue infarction thresholds, enhancing neuroprotection. We performed a systematic review and meta-analysis to evaluate the effects of combined cerebral tissue oxygenation (PbtO2) and ICP compared to isolated ICP monitoring in patients with TBI. PubMed, Embase, Cochrane, and Web of Sciences databases were searched for trials published up to June 2023. A total of 16 studies comprising 37,820 patients were included. ICP monitoring was universal, with additional placement of PbtO2 in 2222 individuals (5.8%). The meta-analysis revealed a reduction in mortality (OR 0.57, 95% CI 0.37-0.89, p = 0.01), a greater likelihood of favorable outcomes (OR 2.28, 95% CI 1.66-3.14, p < 0.01), and a lower chance of poor outcomes (OR 0.51, 95% CI 0.34-0.79, p < 0.01) at 6 months for the PbtO2 plus ICP group. However, these patients experienced a longer length of hospital stay (MD 2.35, 95% CI 0.50-4.20, p = 0.01). No significant difference was found in hospital mortality rates (OR 0.81, 95% CI 0.61-1.08, p = 0.16) or intensive care unit length of stay (MD 2.46, 95% CI - 0.11-5.04, p = 0.06). The integration of PbtO2 to ICP monitoring improved mortality outcomes and functional recovery at 6 months in patients with TBI. PROSPERO (International Prospective Register of Systematic Reviews) CRD42022383937; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=383937.


Assuntos
Lesões Encefálicas Traumáticas , Pressão Intracraniana , Humanos , Lesões Encefálicas Traumáticas/terapia , Lesões Encefálicas Traumáticas/mortalidade , Lesões Encefálicas Traumáticas/fisiopatologia , Pressão Intracraniana/fisiologia , Monitorização Neurofisiológica/métodos , Oxigênio/metabolismo , Oxigênio/sangue , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Monitorização Fisiológica/métodos
7.
Neurosurg Rev ; 47(1): 196, 2024 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-38676753

RESUMO

Ruptured anterior communicating artery (ACoA) aneurysms are frequently associated with neuropsychological deficits. This review aims to compare neuropsychological outcomes between surgical and endovascular approaches to ACoA. We systematically searched PubMed, Embase, and Web of Science for studies comparing the endovascular and surgical approaches to ruptured ACoA aneurysms. Outcomes of interest were the cognitive function, covered by memory, attention, intelligence, executive, and language domains, as well as motor and visual functions. Nine studies, comprising 524 patients were included. Endovascularly-treated patients showed better memory than those treated surgically (Standardized Mean Difference (SMD) = -2; 95% CI: -3.40 to -0.61; p < 0.01). Surgically clipped patients had poorer motor ability than those with coiling embolization (p = 0.01). Executive function (SMD = -0.20; 95% CI: -0.47 to 0.88; p = 0.55), language (SMD = -0.33; 95% CI: -0.95 to 0.30; p = 0.30), visuospatial function (SMD = -1.12; 95% CI: -2.79 to 0.56; p = 0.19), attention (SMD = -0.94; 95% CI: -2.79to 0.91; p = 0.32), intelligence (SMD = -0.25; 95% CI: -0.73 to 0.22; p = 0.30), and self-reported cognitive status (SMD = -0.51; 95% CI: -1.38 to 0.35; p = 0.25) revealed parity between groups. Patients with ACoA treated endovascularly had superior memory and motor abilities. Other cognitive domains, including executive function, language, visuospatial function, attention, intelligence and self-reported cognitive status revealed no statistically significant differences between the two approaches. Trial Registration PROSPERO (International Prospective Register of Systematic Reviews) CRD42023461283; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=461283.


Assuntos
Aneurisma Roto , Procedimentos Endovasculares , Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/cirurgia , Aneurisma Intracraniano/complicações , Aneurisma Roto/cirurgia , Aneurisma Roto/complicações , Procedimentos Endovasculares/métodos , Resultado do Tratamento , Embolização Terapêutica/métodos , Procedimentos Neurocirúrgicos/métodos , Testes Neuropsicológicos
8.
Neurosurg Rev ; 47(1): 300, 2024 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-38951288

RESUMO

The diagnosis of Moyamoya disease (MMD) relies heavily on imaging, which could benefit from standardized machine learning tools. This study aims to evaluate the diagnostic efficacy of deep learning (DL) algorithms for MMD by analyzing sensitivity, specificity, and the area under the curve (AUC) compared to expert consensus. We conducted a systematic search of PubMed, Embase, and Web of Science for articles published from inception to February 2024. Eligible studies were required to report diagnostic accuracy metrics such as sensitivity, specificity, and AUC, excluding those not in English or using traditional machine learning methods. Seven studies were included, comprising a sample of 4,416 patients, of whom 1,358 had MMD. The pooled sensitivity for common and random effects models was 0.89 (95% CI: 0.85 to 0.92) and 0.92 (95% CI: 0.85 to 0.96), respectively. The pooled specificity was 0.89 (95% CI: 0.86 to 0.91) in the common effects model and 0.91 (95% CI: 0.75 to 0.97) in the random effects model. Two studies reported the AUC alongside their confidence intervals. A meta-analysis synthesizing these findings aggregated a mean AUC of 0.94 (95% CI: 0.92 to 0.96) for common effects and 0.89 (95% CI: 0.76 to 1.02) for random effects models. Deep learning models significantly enhance the diagnosis of MMD by efficiently extracting and identifying complex image patterns with high sensitivity and specificity. Trial registration: CRD42024524998 https://www.crd.york.ac.uk/prospero/displayrecord.php?RecordID=524998.


Assuntos
Aprendizado Profundo , Doença de Moyamoya , Doença de Moyamoya/diagnóstico , Humanos , Algoritmos , Sensibilidade e Especificidade
9.
Neurosurg Rev ; 47(1): 255, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38833192

RESUMO

Neuroendoscopy (NE) surgery emerged as a promising technique for the treatment of spontaneous intracerebral hemorrhage (ICH). A previous meta-analysis of randomized controlled trials (RCTs) analyzed the efficacy and safety of NE compared to craniotomy, but NE did not present a significant improvement in functional outcomes. However, a new study provided an opportunity to update the current knowledge. We searched PubMed, Embase, and Cochrane Central Register of Controlled Trials for RCTs reporting NE evacuation of spontaneous supratentorial ICH compared to craniotomy. The efficacy outcomes of interest were favorable functional outcome, functional disability, hematoma evacuation rate, and residual hematoma volume. The safety outcomes of interest were rebleeding, infection, and mortality. Seven RCTs were included containing 879 patients. The NE approach presented a significantly higher rate of favorable functional outcome compared with craniotomy (RR: 1.42; 95% CI 1.17, 1.73; p < 0.001). The evacuation rate was higher in patients who underwent the NE approach (MD: -8.36; 95% CI -12.66, -4.07; p < 0.001). NE did not show a benefit in improving the mortality rate (RR: 0.81, 95% CI 0.54, 1.22; p = 0.32). NE was associated with more favorable functional outcomes and lower rates of functional disabilities compared to craniotomy. Also, NE was superior regarding evacuation rate, while presenting a reduction in residual hematoma volume. NE might be associated with lower infection rates. Mortality was not improved by NE surgery. Larger, higher-quality randomized studies are needed to adequately evaluate the efficacy and safety of NE compared to craniotomy.


Assuntos
Hemorragia Cerebral , Craniotomia , Neuroendoscopia , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Neuroendoscopia/métodos , Craniotomia/métodos , Craniotomia/efeitos adversos , Hemorragia Cerebral/cirurgia , Resultado do Tratamento
10.
Neurocrit Care ; 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886326

RESUMO

BACKGROUND: Head elevation is recommended as a tier zero measure to decrease high intracranial pressure (ICP) in neurocritical patients. However, its quantitative effects on cerebral perfusion pressure (CPP), jugular bulb oxygen saturation (SjvO2), brain tissue partial pressure of oxygen (PbtO2), and arteriovenous difference of oxygen (AVDO2) are uncertain. Our objective was to evaluate the effects of head elevation on ICP, CPP, SjvO2, PbtO2, and AVDO2 among patients with acute brain injury. METHODS: We conducted a systematic review and meta-analysis on PubMed, Scopus, and Cochrane Library of studies comparing the effects of different degrees of head elevation on ICP, CPP, SjvO2, PbtO2, and AVDO2. RESULTS: A total of 25 articles were included in the systematic review. Of these, 16 provided quantitative data regarding outcomes of interest and underwent meta-analyses. The mean ICP of patients with acute brain injury was lower in group with 30° of head elevation than in the supine position group (mean difference [MD] - 5.58 mm Hg; 95% confidence interval [CI] - 6.74 to - 4.41 mm Hg; p < 0.00001). The only comparison in which a greater degree of head elevation did not significantly reduce the ICP was 45° vs. 30°. The mean CPP remained similar between 30° of head elevation and supine position (MD - 2.48 mm Hg; 95% CI - 5.69 to 0.73 mm Hg; p = 0.13). Similar findings were observed in all other comparisons. The mean SjvO2 was similar between the 30° of head elevation and supine position groups (MD 0.32%; 95% CI - 1.67% to 2.32%; p = 0.75), as was the mean PbtO2 (MD - 1.50 mm Hg; 95% CI - 4.62 to 1.62 mm Hg; p = 0.36), and the mean AVDO2 (MD 0.06 µmol/L; 95% CI - 0.20 to 0.32 µmol/L; p = 0.65).The mean ICP of patients with traumatic brain injury was also lower with 30° of head elevation when compared to the supine position. There was no difference in the mean values of mean arterial pressure, CPP, SjvO2, and PbtO2 between these groups. CONCLUSIONS: Increasing degrees of head elevation were associated, in general, with a lower ICP, whereas CPP and brain oxygenation parameters remained unchanged. The severe traumatic brain injury subanalysis found similar results.

11.
Liver Transpl ; 29(1): 91-102, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-35643926

RESUMO

The liver plays a major role in drug metabolism. Liver transplantation impacts the intrinsic metabolic capability and extrahepatic mechanisms of drug disposition and elimination. Different levels of inflammation and oxidative stress during transplantation, the process of liver regeneration, and the characteristics of the graft alter the amount of functional hepatocytes and activity of liver enzymes. Binding of drugs to plasma proteins is affected by the hyperbilirubinemia status and abnormal synthesis of albumin and alpha-1-acid glycoproteins. Postoperative intensive care complications such as biliary, circulatory, and cardiac also impact drug distribution. Renally eliminated antimicrobials commonly present reduced clearance due to hepatorenal syndrome and the use of nephrotoxic immunosuppressants. In addition, liver transplantation recipients are particularly susceptible to multidrug-resistant infections due to frequent manipulation, multiple hospitalizations, invasive devices, and frequent use of empiric broad-spectrum therapy. The selection of appropriate anti-infective therapy must consider the pathophysiological changes after transplantation that impact the pharmacokinetics and pharmacodynamics of antibiotics and antifungal drugs.


Assuntos
Antifúngicos , Transplante de Fígado , Humanos , Antifúngicos/uso terapêutico , Antifúngicos/farmacocinética , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Transplante de Fígado/efeitos adversos , Fígado
12.
Ther Drug Monit ; 45(2): 200-208, 2023 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-36622029

RESUMO

PURPOSE: Antimicrobial stewardship programs are important for reducing antimicrobial resistance because they can readjust antibiotic prescriptions to local guidelines, switch intravenous to oral administration, and reduce hospitalization times. Pharmacokinetics-pharmacodynamics (PK-PD) empirically based prescriptions and therapeutic drug monitoring (TDM) programs are essential for antimicrobial stewardship, but there is a need to fit protocols according to cost benefits. The cost benefits can be demonstrated by reducing toxicity and hospital stay, decreasing the amount of drug used per day, and preventing relapses in infection. Our aim was to review the data available on whether PK-PD empirically based prescriptions and TDM could improve the cost benefits of an antimicrobial stewardship program to decrease global hospital expenditures. METHODS: A narrative review based on PubMed search with the relevant studies of vancomycin, aminoglycosides, beta-lactams, and voriconazole. RESULTS: TDM protocols demonstrated important cost benefit for patients treated with vancomycin, aminoglycosides, and voriconazole mainly due to reduce toxicities and decreasing the hospital length of stay. In addition, PK-PD strategies that used infusion modifications to meropenem, piperacillin-tazobactam, ceftazidime, and cefepime, such as extended or continuous infusion, demonstrated important cost benefits, mainly due to reducing daily drug needs and lengths of hospital stays. CONCLUSIONS: TDM protocols and PK-PD empirically based prescriptions improve the cost-benefits and decrease the global hospital expenditures.


Assuntos
Gestão de Antimicrobianos , Vancomicina , Humanos , Aminoglicosídeos , Antibacterianos/uso terapêutico , Ceftazidima , Análise Custo-Benefício , Monitoramento de Medicamentos , Vancomicina/uso terapêutico , Voriconazol
13.
Eur J Clin Pharmacol ; 79(7): 1003-1012, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37256410

RESUMO

PURPOSE: The aim of this work was to integrate the Therapeutic Drug Monitoring (TDM) with the model-informed precision dosing (MIPD) approach, using Physiologically-based Pharmacokinetic/Pharmacodynamic (PBPK/PD) modelling and simulation, to explore the relationship between amikacin exposure and estimated glomerular filtration rate (GFR) in critically ill patients with cancer. METHODS: In the TDM study, samples from 51 critically-ill patients with cancer treated with amikacin were analysed. Patients were stratified according to renal function based on GFR status. A full-body PBPK model with 12 organs model was developed using Simcyp V. 21, including steady-state volume of distribution of 0.21 L/kg and renal clearance of 6.9 L/h in healthy adults. PK parameters evaluated were within the 2-fold error range. RESULTS: During the validation step, predicted vs observed amikacin clearance values after single infusion dose in patients with normal renal function, mild and moderate renal impairment were 7.6 vs 8.1 L/h (7.5 mg/kg dose); 3.8 vs 4.5 L/h (1500 mg dose) and 2.2 vs 3.1 L/h (25 mg/kg dose), respectively. However, predicted vs observed amikacin clearance after a single dose infusion of 1400 mg in critically-ill patients with cancer were 1.46 vs 1.63 (P = 0.6406) L/h (severe), 2.83 vs 1.08 (P < 0.05) L/h (moderate), 4.23 vs 2.49 (P = 0.0625) L/h (mild) and 7.41 vs 3.36 (P < 0.05) L/h (normal renal function). CONCLUSION: This study demonstrated that estimated GFR did not predict amikacin elimination in critically-ill patients with cancer. Further studies are necessary to find amikacin PK covariates to optimize the pharmacotherapy in this population. Therefore, TDM of amikacin is imperative in cancer patients.


Assuntos
Amicacina , Neoplasias , Adulto , Humanos , Amicacina/uso terapêutico , Estado Terminal/terapia , Taxa de Filtração Glomerular , Monitoramento de Medicamentos , Neoplasias/tratamento farmacológico , Antibacterianos/uso terapêutico
14.
Gerontology ; 69(1): 65-72, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-35584617

RESUMO

INTRODUCTION: Radiological indicators in head computed tomography (CT) scan have emerged as tools to evaluate sarcopenia using the sectional area and thickness of the temporal muscle. They can be obtained by standardized measurements in preoperative image assessment of patients with brain aneurysms. We aimed to evaluate the association between functional outcomes after interventions for intracranial aneurysms (IAs) and temporal muscle thickness (TMT) and area (TMA), as surrogates of sarcopenia. METHODS: This is a prospective observational cohort study in patients who underwent microsurgery or embolization for ruptured or unruptured IA between January 2018 and December 2019, with a 6-month follow-up. Preoperative CT scans were analyzed to measure TMT and TMA. The functional outcome was assessed by the modified Rankin Scale (mRS). The main outcome was the relationship between sarcopenia and the postoperative functional outcome. RESULTS: A total of 361 patients were included, of whom 199 (55.1%) had ruptured and 162 (44.9%) had unruptured lesions. Larger TMA significantly predicted better functional outcomes at discharge. TMT was associated with functional outcomes at both discharge and 6 months, adjusted for rupture and hypertension. Maximizing the sum sensitivity-specificity, an optimal TMT cutoff of 6.25 mm can predict unfavorable outcomes. Maximizing the positive predictive value × negative predictive value of a product, the cutpoint was 3.55 mm. CONCLUSIONS: Sarcopenia, represented by TMT and TMA, is associated with poorer functional results at discharge and 6-month follow-up in IA surgery. TMT below 6.25 mm was associated with unfavorable functional outcomes. These easily obtainable measurements may improve the decision-making process for patients with IAs.


Assuntos
Aneurisma Intracraniano , Sarcopenia , Humanos , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Estudos de Coortes , Sarcopenia/diagnóstico , Sarcopenia/diagnóstico por imagem , Estudos Retrospectivos , Valor Preditivo dos Testes , Resultado do Tratamento
15.
Childs Nerv Syst ; 39(3): 743-750, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36689000

RESUMO

PURPOSE: Neurocysticercosis (NCC) is considered a neglected infectious disease, but the most common parasitic disease of the central nervous system (CNS). Due to oral tendencies in childhood, it is hypothesized that individuals are infected around this age and develop symptoms as lately as during young adulthood. Although it is considered a benign disease, it may cause great impact in the patient's quality of life due to epilepsy, visual symptoms, and hydrocephalus, which eventually requires frequent hospitalizations. The treatment of hydrocephalus is the main challenge for neurosurgeons. METHODS: We performed a concise review on neurocysticercosis in children and the main presentations of NCC in the neurosurgery practice and a systematic review on hydrocephalus secondary to extraparenchymal NCC. RESULTS: Our review showed a rate of complete resolution of hydrocephalus secondary to NCC of around 80% with the first attempt of surgical treatment combined with medication therapy. Endoscopic removal of the intraventricular cysts with third ventriculostomy was the most common treatment modality. Patients previously managed with ventricular shunts are likely to have worse outcomes and complications. CONCLUSION: Endoscopic approach is the gold standard surgical treatment for hydrocephalus secondary to neurocysticercosis.


Assuntos
Hidrocefalia , Neurocisticercose , Neurocirurgia , Humanos , Criança , Adulto Jovem , Adulto , Neurocisticercose/complicações , Neurocisticercose/cirurgia , Neurocisticercose/diagnóstico , Qualidade de Vida , Ventriculostomia/efeitos adversos , Hidrocefalia/etiologia , Hidrocefalia/cirurgia , Hidrocefalia/diagnóstico
16.
Neurosurg Rev ; 46(1): 143, 2023 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-37340151

RESUMO

Glioblastoma (GBM) is the most common and aggressive glioma histological subtype, associated with high disability and poor survival. The etiology of this condition is still mostly unknown, and evidence about risk factors is elusive. The aim of this study is to identify modifiable risk factors for GBM. Electronic search was performed by two reviewers independently using the keywords and MeSH terms 'glioblastoma' OR 'glioma' OR 'brain tumor' AND 'risk factor'. The inclusion criteria were (1) observational studies or experimental studies on humans, (2) studies assessing the association between glioblastoma and exposure to modifiable conditions, and (3) studies published in English or Portuguese. Studies on the pediatric population or about exposure to ionizing radiation were excluded. A total of 12 studies were included. Seven were case-control studies, and five were cohort studies. The risk factors assessed included body mass index, alcohol consumption, exposure to magnetic fields, diabetes mellitus type 2 (DM2), and use of non-steroidal anti-inflammatory drugs (NSAID). No significant link was found between GBM incidence and DM2 or magnetic field exposure. On the other hand, higher BMI, alcohol consumption, and NSAID use demonstrated a protective effect on GMB risk. However, given the limited number of studies, it is not possible to obtain a behavioral recommendation; instead, these findings are relevant to guide future basic scientific studies on GBM oncogenesis.


Assuntos
Neoplasias Encefálicas , Diabetes Mellitus Tipo 2 , Glioblastoma , Glioma , Humanos , Criança , Fatores de Risco , Neoplasias Encefálicas/epidemiologia , Anti-Inflamatórios não Esteroides/uso terapêutico
17.
Neurosurg Rev ; 46(1): 165, 2023 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-37405510

RESUMO

Bibliometric analyses are a well-established strategy for understanding the dynamics of publications. Aneurysmal subarachnoid hemorrhage (aSAH) is a hot topic in neurology and neurosurgery research. To perform a bibliometric analysis of recent publications within aSAH. Articles addressing aSAH published between 2017 and 2021 were included and had their information extracted from Scopus. A total of 2177 articles were included. The mean number of citations was 6.18 (95%CI = 5.77-6.59). 2021 and 2020 were the most prolific years. World Neurosurgery (N = 389/2,177 articles; 17,87%) was the leading publisher, and American Journal of Neuroradiology had the highest number of citations per article (14.82) among journals with ≥ 10 publications. Primary research (N = 1624/2177) predominated, followed by case reports (N = 434/2,177). Among secondary studies, systematic reviews (N = 78/119) surpassed narrative reviews (N = 41/119). USA led the number of publications (N = 548/2,177 articles; 25.17%), followed by China (N = 358/2,177 articles; 16.44%). High-income countries had a higher number of publications (N = 1624/2177) and more citations per article (6.84) than middle-income countries (N = 553/2177 and 4.25, respectively). There were zero articles from low-income countries. European and North American institutions had the greatest research impact. There was an increase in the number of published articles in the last few years (2020 and 2021). Many studies had a low level of evidence, whereas interventional studies were uncommon.


Assuntos
Neurocirurgia , Hemorragia Subaracnóidea , Estados Unidos , Humanos , Hemorragia Subaracnóidea/cirurgia , Bibliometria , Publicações , Procedimentos Neurocirúrgicos
18.
Neurocrit Care ; 2023 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-37667079

RESUMO

Delayed cerebral ischemia (DCI) is a common and severe complication after subarachnoid hemorrhage (SAH). Logistic regression (LR) is the primary method to predict DCI, but it has low accuracy. This study assessed whether other machine learning (ML) models can predict DCI after SAH more accurately than conventional LR. PubMed, Embase, and Web of Science were systematically searched for studies directly comparing LR and other ML algorithms to forecast DCI in patients with SAH. Our main outcome was the accuracy measurement, represented by sensitivity, specificity, and area under the receiver operating characteristic. In the six studies included, comprising 1828 patients, about 28% (519) developed DCI. For LR models, the pooled sensitivity was 0.71 (95% confidence interval [CI] 0.57-0.84; p < 0.01) and the pooled specificity was 0.63 (95% CI 0.42-0.85; p < 0.01). For ML models, the pooled sensitivity was 0.74 (95% CI 0.61-0.86; p < 0.01) and the pooled specificity was 0.78 (95% CI 0.71-0.86; p = 0.02). Our results suggest that ML algorithms performed better than conventional LR at predicting DCI.Trial Registration: PROSPERO (International Prospective Register of Systematic Reviews) CRD42023441586; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=441586.

19.
J Antimicrob Chemother ; 77(6): 1676-1684, 2022 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-35368079

RESUMO

BACKGROUND: During the COVID-19 pandemic, the burden of nosocomial infections caused by MDR pathogens has caused a shortage of polymyxins. Thus, we evaluated the in vitro synergism and antibiofilm activity of antimicrobial combinations and propose a test kit for synergism against carbapenem-resistant Acinetobacter baumannii (CRAB). METHODS: Fifty-six CRAB isolates were tested for synergy between meropenem, gentamicin and ampicillin/sulbactam. MICs were determined by broth microdilution. Synergism was tested using chequerboard analysis, followed by a time-kill curve. Additionally, minimum biofilm eradication concentration was determined and the antibiofilm activity of the combinations was evaluated by MTT assay and biomass reduction. A test kit was developed for routine laboratory testing to detect synergism. RESULTS: All CRAB isolates were resistant to gentamicin and ampicillin/sulbactam. Chequerboard synergism occurred against 75% of the isolates. Meropenem + ampicillin/sulbactam was the most frequent combination with synergism (69%), followed by ampicillin/sulbactam + gentamicin (64%) and meropenem + gentamicin (51%). All combinations presented only bacteriostatic activity and no bactericidal or antibiofilm effects. The routine laboratory test showed 100% accuracy compared with other in vitro assays. CONCLUSIONS: Our study demonstrates the potential role of antibiotic combinations against planktonic bacteria. In vitro synergism is possible and can be an alternative treatment for patients with CRAB infection during a polymyxin shortage.


Assuntos
Infecções por Acinetobacter , Acinetobacter baumannii , COVID-19 , Infecções por Acinetobacter/microbiologia , Ampicilina , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Biofilmes , Farmacorresistência Bacteriana Múltipla , Sinergismo Farmacológico , Gentamicinas/farmacologia , Humanos , Meropeném/farmacologia , Testes de Sensibilidade Microbiana , Pandemias , Polimixinas , Sulbactam/farmacologia
20.
Neurol Sci ; 43(8): 4909-4915, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35359214

RESUMO

INTRODUCTION: Previous meta-analyses comparing microsurgery and coiling that include BRAT may be inaccurate to compare the outcomes of ruptured saccular aneurysms. This study aims to evaluate 10-year efficiency, safety, and advantages of coiling compared with clipping in patients with spontaneous saccular aneurismal SAH as a primary outcome. Also analyzed secondary outcomes: no-occlusion, mortality, rebleeding, and retreatment. METHODS: A systematic search of the literature on microsurgical clipping versus coiling was done to identify RCTs with at least 10 years of follow-up published between 2000 and 2021. The primary outcome was favorable functional outcome, defined as a modified Rankin scale (mRS) score ≤ 2. Secondary outcomes were no-occlusion, mortality, rebleeding, and retreatment. Quality of the included trials was analyzed using the Risk of Bias 2.0 (RoB 2.0) tool. A random-effects meta-analysis was performed. RESULTS: Two studies reported 10-year follow-up results, and the meta-analysis did not demonstrate significant differences between groups (OR 0.9, 95%CI 0.66-1.24, I2 = 21%). No differences were observed compared clipping and coiling regarding occlusion rates (OR 5.3, 95%CI 0.8-36.3, I2 = 89%). Mortality rates did not show significant differences between treatment modalities (OR 0.97, 95%CI 0.77-1.21, I2 = 0%). Rebleeding rates were also similar between groups (OR 1.63, 95%CI 0.25-10.7, I2 = 37%); however, significantly higher retreatment rates were associated with coiling (OR 10.6, 95%CI 2.1-52.5, I2 = 80%). Overall, risk of bias was low. CONCLUSION: There are no long-term differences regarding no-occlusion, mortality, and rebleeding rates between coiling and clipping. Higher retreatment rates were associated with coiling.


Assuntos
Aneurisma Roto , Embolização Terapêutica , Procedimentos Endovasculares , Aneurisma Intracraniano , Aneurisma Roto/cirurgia , Embolização Terapêutica/métodos , Procedimentos Endovasculares/métodos , Humanos , Aneurisma Intracraniano/cirurgia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
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