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1.
Br J Clin Pharmacol ; 90(4): 1173-1182, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38304967

RESUMO

AIMS: Amikacin requires therapeutic drug monitoring for optimum efficacy; however, the optimal model-informed precision dosing strategy for the area under the concentration-time curve (AUC) of amikacin is uncertain. This simulation study aimed to determine the efficient blood sampling points using the Bayesian forecasting approach for early achievement of the target AUC range for amikacin in critically ill patients. METHODS: We generated a virtual population of 3000 individuals using 2 validated population pharmacokinetic models identified using a systematic literature search. AUC for each blood sampling point was evaluated using the probability of achieving a ratio of estimated/reference AUC at steady state in the 0.8-1.2 range. RESULTS: On day 1, the 1-point samplings for population pharmacokinetic models showed a priori probabilities of 26.3 and 45.6%, which increased to 47.3 and 94.4% at 23 and 15 h, respectively. Using 2-point sampling at the peak (3 and 4 h) and trough (24 h) on day 1, these probabilities further increased to 72.3 and 99.5%, respectively. These probabilities were comparable on days 2 and 3, regardless of 3 and 6 sampling points or estimated glomerular filtration rate. These results indicated the higher predictive accuracy of 2-point sampling than 1-point sampling on day 1 for amikacin AUC estimation. Moreover, 2-point sampling was a more reasonable approach than rich sampling. CONCLUSIONS: This study contributes to the development of an efficient model-informed precision dosing strategy for early targeting of amikacin AUC in critically ill patients.


Assuntos
Amicacina , Estado Terminal , Humanos , Amicacina/farmacocinética , Amicacina/uso terapêutico , Teorema de Bayes , Estado Terminal/terapia , Simulação por Computador , Fatores de Tempo , Área Sob a Curva , Antibacterianos
2.
Clin Transl Sci ; 16(11): 2265-2275, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37718491

RESUMO

In this study, we aimed to evaluate limited sampling strategies for achieving the therapeutic ranges of the area under the concentration-time curve (AUC) of vancomycin on the first and second day (AUC0-24 , AUC24-48 , respectively) of therapy. A virtual population of 1000 individuals was created using a population pharmacokinetic (PopPK) model, which was validated and incorporated into our model-informed precision dosing tool. The results were evaluated using six additional PopPK models selected based on a study design of prospective or retrospective data collection with sufficient concentrations. Bayesian forecasting was performed to evaluate the probability of achieving the therapeutic range of AUC, defined as a ratio of estimated/reference AUC within 0.8-1.2. The Bayesian posterior probability of achieving the AUC24-48 range increased from 51.3% (a priori probability) to 77.5% after using two-point sampling at the trough and peak on the first day. Sampling on the first day also yielded a higher Bayesian posterior probability (86.1%) of achieving the AUC0-24 range compared to the a priori probability of 60.1%. The Bayesian posterior probability of achieving the AUC at steady-state (AUCSS ) range by sampling on the first or second day decreased with decreased kidney function. We demonstrated that second-day trough and peak sampling provided accurate AUC24-48 , and first-day sampling may assist in rapidly achieving therapeutic AUC24-48 , although the AUCSS should be re-estimated in patients with reduced kidney function owing to its unreliable predictive performance.


Assuntos
Antibacterianos , Vancomicina , Humanos , Teorema de Bayes , Estudos Retrospectivos , Estudos Prospectivos , Monitoramento de Medicamentos/métodos , Área Sob a Curva
3.
Toxicol In Vitro ; 90: 105606, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37146920

RESUMO

Flutamide is a non-steroidal anti-androgen agent, which is mainly used for the treatment of prostate cancer. Flutamide is known to cause severe adverse events, which includes idiosyncratic liver injury. However, details of the mechanism of these adverse reactions have not been elucidated. We investigated whether flutamide induces the release of damage-associated molecular patterns (DAMPs) that activate inflammasomes. We also tested bicalutamide, enzalutamide, apalutamide, and darolutamide for their ability to activate inflammasomes in differentiated THP-1 cells. The supernatant from the incubation of flutamide and bicalutamide with human hepatocarcinoma functional liver cell-4 (FLC-4) cells increased caspase-1 activity and production of IL-1ß by differentiated THP-1 cells. In the supernatant of FLC-4 cells with flutamide and bicalutamide, the heat shock protein (HSP) 40 or 60 was significantly increased. Addition of a carboxylesterase or a CYP inhibitor to the FLC-4 cells prevented release of HSPs from the FLC-4 cells. These results suggested that the reactive metabolites of flutamide and bicalutamide can cause the release of DAMPs from hepatocytes and activate inflammasomes. Inflammasome activation may be an important step in the activation of the immune system by flutamide or bicalutamide, which in some patients, can cause immune-related adverse events.


Assuntos
Doença Hepática Crônica Induzida por Substâncias e Drogas , Neoplasias da Próstata , Masculino , Humanos , Flutamida/toxicidade , Inflamassomos/metabolismo , Antagonistas de Androgênios/toxicidade , Anilidas/farmacologia , Nitrilas/toxicidade
4.
J Cardiothorac Surg ; 18(1): 103, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37024987

RESUMO

BACKGROUND: Postoperative atrial fibrillation (POAF) after open-heart surgery is a non-negligible complication. We aimed to describe the efficacy of a transdermal patch of bisoprolol for managing POAF and flutter in thoracic surgical procedures. METHODS: We analyzed the data of 384 patients who underwent open-heart surgery at our hospital and received oral bisoprolol to prevent POAF. Among them, 65 patients (16.9%) also received a 4-mg transdermal patch of bisoprolol to control the heart rate due to POAF. We applied the bisoprolol transdermal patch when the heart rate was > 80 bpm and removed it at ≤ 60 bpm; an additional patch was applied when the heart rate was > 140 bpm. Heparin calcium injections were administered twice daily for anticoagulation between 2 and 6 days postoperatively. RESULTS: The average number of prescriptions for transdermal patches of bisoprolol during hospitalization was 1.8 ± 1.1 (1-5). The median first prescription date was on postoperative day 2 (range: days 0-37). Sinus rhythm recovered within 24 h in 18 patients (27.7%). Eight patients (12.3%) were switched to continuous landiolol infusion because of persistent tachycardia. In three patients, the transdermal patch was removed owing to severe bradycardia. Fifteen patients experienced persistent atrial fibrillation and were treated with electrical cardioversion during hospitalization. We did not observe any serious complications that could be directly attributed to bisoprolol transdermal patch use. CONCLUSIONS: Single-use bisoprolol transdermal patch may help control the heart rate during the initial treatment of POAF after open-heart surgery.


Assuntos
Fibrilação Atrial , Procedimentos Cirúrgicos Cardíacos , Humanos , Bisoprolol/uso terapêutico , Bisoprolol/efeitos adversos , Fibrilação Atrial/etiologia , Fibrilação Atrial/prevenção & controle , Frequência Cardíaca , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Cardioversão Elétrica , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/induzido quimicamente
5.
Ann Thorac Surg ; 116(6): 1195-1203, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36739072

RESUMO

BACKGROUND: There is a paucity of data regarding shorter life expectancy after aortic valve replacement (AVR) in patients with severe aortic stenosis (AS). METHODS: Among 3815 patients with severe AS enrolled in the CURRENT AS (Contemporary outcomes after sURgery and medical tREatmeNT in patients with severe Aortic Stenosis) registry, there were 1469 patients (initial AVR: n = 647; conservative strategy: n = 822) with low surgical risk, 1642 patients (initial AVR: n = 433; conservative strategy: n = 1209) with intermediate surgical risk, and 704 patients (initial AVR: n = 117; conservative strategy: n = 587) with high surgical risk. Among 1163 patients who actually underwent surgical AVR as the initial strategy, patients were divided into 4 groups according to age <65 years (n = 185), 65 to 74 (n = 394), 75 to 80 (n = 345), and >80 (n = 239). The expected survival of the general Japanese population was obtained from the Statistics Bureau of Japan. The surgical risk was estimated using The Society of Thoracic Surgery (STS) score. RESULTS: The median follow-up was 3.7 years. The cumulative incidences of all-cause death were significantly lower in the initial AVR strategy than in the initial conservative strategy across the 3 STS groups. Shorter life expectancy after surgical AVR was seen especially in younger patients. The observed mortality in low-risk patients was comparable to the expected mortality across all the age-groups, while intermediate-risk patients aged <75 years, and high-risk patients across all age-groups had higher mortality compared with the expected mortality. CONCLUSIONS: The risk stratification according to age and STS score might be useful to estimate shorter life expectancy after AVR, and these findings have implications for decision making in the choice of surgical or transcatheter AVR.


Assuntos
Estenose da Valva Aórtica , Implante de Prótese de Valva Cardíaca , Humanos , Resultado do Tratamento , Implante de Prótese de Valva Cardíaca/efeitos adversos , Fatores de Risco , Valva Aórtica/cirurgia , Expectativa de Vida , Índice de Gravidade de Doença
6.
Clin Transl Sci ; 16(4): 704-713, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36748688

RESUMO

Teicoplanin, a glycopeptide antimicrobial, is recommended for therapeutic drug monitoring, but it remains unclear how to target the area under the concentration-time curve (AUC). This simulation study purposed to demonstrate the potential of the Bayesian forecasting approach for the rapid achievement of the target AUC for teicoplanin. We generated concordant and discordant virtual populations against a Japanese population pharmacokinetic model. The predictive performance of the Bayesian posterior AUC in limited sampling on the first day against the reference AUC was evaluated as an acceptable target AUC ratio within the range of 0.8-1.2. In the concordant population, the probability for the maximum a priori or Bayesian posterior AUC on the first day (AUC0-24 ) was 61.3% or more than 77.0%, respectively. The Bayesian posterior AUC on the second day (AUC24-48 ) was more than 75.1%. In the discordant population, the probability for the maximum a priori or Bayesian posterior AUC0-24 was 15.5% or 11.7-80.7%, respectively. The probability for the maximum a priori or Bayesian posterior AUC24-48 was 23.4%, 30.2-82.1%. The AUC at steady-state (AUCSS ) was correlated with trough concentration at steady-state, with a coefficient of determination of 0.930; the coefficients on days 7 and 4 were 0.442 and 0.125, respectively. In conclusion, this study demonstrated that early sampling could improve the probability of AUC0-24 and AUC24-48 but did not adequately predict AUCSS . Further studies are necessary to apply early sampling-based model-informed precision dosing in the clinical settings.


Assuntos
Antibacterianos , Teicoplanina , Humanos , Teorema de Bayes , Previsões , Probabilidade
7.
Int J Clin Pharm ; 45(2): 442-450, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36609809

RESUMO

BACKGROUND: Although acetaminophen is recommended for the treatment of mild-to-moderate cancer pain, acetaminophen-induced hepatic disorders pose an important clinical challenge. Concomitant prescription of immune checkpoint inhibitors (ICIs) may further increase the risk of hepatic disorders in patients taking acetaminophen; however, there are few clinical studies that confirm this. AIM: To evaluate the risk of hepatic disorders in patients taking concomitant acetaminophen and ICIs using a disproportionality analysis from the Japanese Adverse Drug Event Report database. METHOD: Acetaminophen users aged ≥ 20 years were included; factors that can affect the risk of acetaminophen-induced hepatic disorders were collated. Similar data on the widely used analgesic, loxoprofen, were used for comparison. RESULTS: Among 233,594 patients surveyed, 10,403 were prescribed acetaminophen, and among them, 1,245 patients developed hepatic disorders. The disproportionality of hepatic disorders was observed in acetaminophen users regardless of concomitant ICI use (without ICI: reporting odds ratio [ROR], 1.18; 95% confidence intervals [CI], 1.10-1.26; with ICI: ROR 1.87, 95%CI 1.59-2.20); it was even higher in concomitant acetaminophen and ICI users (ROR 1.94, 95%CI 1.65-2.29). However, increased disproportionality of hepatic disorders was not observed in patients taking concomitant loxoprofen and ICI. Multivariable logistic regression showed that the risk of hepatic disorders in acetaminophen users was associated with concomitant use of ICI (ROR, 1.91; 95% CI, 1.49-2.45); (P < 0.01). CONCLUSION: Our findings suggest that the risk of hepatic disorders is greater with concomitant acetaminophen and ICI treatment than with acetaminophen alone.


Assuntos
Acetaminofen , Inibidores de Checkpoint Imunológico , Humanos , Inibidores de Checkpoint Imunológico/efeitos adversos , Acetaminofen/efeitos adversos , Farmacovigilância , Estudos Retrospectivos
9.
J Int Med Res ; 50(10): 3000605221127518, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36217268

RESUMO

OBJECTIVE: Using a prospective observational design, we assessed adverse events (AEs) after COVID-19 vaccination in Japanese patients. METHODS: Two doses of the mRNA-1273 (SPIKEVAX®) or BNT162b2 (COMIRNATY®) vaccine were administered to participants aged 12 to 18 years, and AEs after each dose were recorded for 14 days. Data on the duration and nature (local vs. systemic) of AEs were collected using a questionnaire. Sex-based differences in AE frequency were also analyzed. RESULTS: After the first and second doses, 152 and 135 vaccinees were enrolled, respectively. After the first dose, fever (>37.1°C) occurred in 38.9% of males and 50.0% of females, whereas local pain occurred in 89.8% and 97.7% of males and females, respectively (only SPIKEVAX® was used as the first dose). After the second dose, fever (>37.1°C) occurred in 77.8% and 82.6% of males vaccinated with COMIRNATY® and SPIKEVAX®, respectively, and 82.6% of females (all received SPIKEVAX®). The local pain rates in these groups were 80.6%, 76.3%, and 100%, respectively. After the second dose, local pain, fever (>38.1°C) and headache were significantly more common in female participants, and the median symptom duration was 3 days. CONCLUSIONS: AEs were more frequent after the second dose and in females.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Feminino , Febre/epidemiologia , Febre/etiologia , Humanos , Japão/epidemiologia , Masculino , Dor/etiologia , RNA Mensageiro , Vacinas de mRNA
10.
Adv Mater ; 34(44): e2203250, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36086880

RESUMO

The diverse series of transition metal dichalcogenide (TMDC) materials has been employed in various optoelectronic applications, such as photodetectors, light-emitting diodes, and lasers. Typically, the detection or emission range of optoelectronic devices is unique to the bandgap of the active material. Therefore, to improve the capability of these devices, extensive efforts have been devoted to tune the bandgap, such as gating, strain, and dielectric engineering. However, the controllability of these methods is severely limited (typically ≈0.1 eV). In contrast, alloying TMDCs is an effective approach that yields a composition-dependent bandgap and enables light emissions over a wide range. In this study, a color-tunable light-emitting device using compositionally graded TMDC alloys is fabricated. The monolayer WS2 /WSe2 alloy grown by chemical vapor deposition shows a spatial gradient in the light-emission energy, which varies from 2.1 to 1.7 eV. This alloy is incorporated in an electrolyte-based light-emitting device structure that can tune the recombination zone laterally. Thus, a continuous and reversible color-tunable light-emitting device is successfully fabricated by controlling the light-emitting positions. The results provide a new approach for exploring monolayer semiconductor-based broadband optical applications.

11.
Gen Thorac Cardiovasc Surg ; 70(10): 916-919, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35932352

RESUMO

Massive pulmonary artery aneurysms, while extremely rare, might require surgical intervention. Most previous cases have been repaired either by pulmonary artery plication or synthetic graft replacement. We report a case of massive pulmonary artery aneurysm that was successfully repaired using an 'overlapping-plasty' technique with the help of 3D image simulation. This specially designed procedure might be useful as a surgical option for pulmonary artery aneurysms.


Assuntos
Aneurisma , Artéria Pulmonar , Aneurisma/diagnóstico por imagem , Aneurisma/cirurgia , Humanos , Imageamento Tridimensional , Pulmão , Artéria Pulmonar/diagnóstico por imagem , Artéria Pulmonar/cirurgia
12.
Wounds ; 34(4): 99-105, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35452407

RESUMO

INTRODUCTION: Venous ulcers are often intractable. OBJECTIVE: The aim of this study was to retrospectively analyze the effectiveness of endovenous ablation, compression therapy, moist wound healing, and skin care in the management of venous ulcers. MATERIALS AND METHODS: Twenty-eight consecutive patients (10 male, 18 female; mean age, 70.1 years) with Clinical-Etiology-Anatomy-Pathophysiology (CEAP) class C6 venous ulcer underwent endovenous ablation between December 2014 and August 2020. The main treatment strategies were radiofrequency ablation and varicectomy (including stab avulsion of incompetent perforating veins), use of compression therapy until complete healing was achieved, moist wound healing (washing the ulcer site and covering it with dressings twice daily), and skin care, taking into consideration the balance of the microbiome. RESULTS: Active venous leg ulcers (CEAP class C6) were diagnosed in 36 patients at the first visit. In 7 of these patients, compression therapy and use of strategies to promote moist wound healing resulted in ulcer healing by the day of the planned surgery. One patient was unable to quit smoking and, therefore, could not undergo surgery. After excluding these 8 patients, the authors analyzed the data from 28 patients who underwent endovenous ablation. The mean surgical time was 38.9 minutes, and the mean number of stab avulsion incision sites was 9.7. All ulcers healed within a median of 55.5 days (range, 13-365 days). Ulcer healing was achieved by 1 year in all 28 patients (100%). No ulceration recurred as of the final follow-up (median, 24.5 months [range, 3-66 months]). CONCLUSIONS: Endovenous ablation, adequate varicectomy (stab avulsion [maximum number of sites in 1 patient, 43]), compression therapy, moist wound healing, and skin care are effective in treating and preventing recurrence of venous ulcers.


Assuntos
Úlcera Varicosa , Idoso , Feminino , Humanos , Masculino , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Úlcera , Úlcera Varicosa/prevenção & controle , Úlcera Varicosa/cirurgia , Cicatrização
13.
Int J Clin Pharm ; 44(4): 1067-1071, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35449346

RESUMO

BACKGROUND: The profile of ceftriaxone-induced encephalopathy is not well understood. AIM: To identify risk factors associated with ceftriaxone-induced encephalopathy. METHOD: In this observational study, anonymised patient data were retrieved from the open-access Japanese Adverse Drug Event Report database for ceftriaxone users aged 20 years or higher. RESULTS: Data of 256,788 individuals and 12,160 cases of encephalopathy were extracted, and 2,939 ceftriaxone users, of whom 193 had encephalopathy, were identified. A disproportionate prevalence of encephalopathy was observed among the ceftriaxone users (reported odds ratio = 1.42; 95% confidence interval [CI] = 1.23-1.65; p < 0.001). Multivariate logistic regression analysis of 2,057 ceftriaxone users showed encephalopathy was associated with female sex (odds ratio [OR] = 1.52; 95% CI, 1.05-2.19; p = 0.027), chronic kidney disease (OR = 2.32; 95% CI, 1.47-3.67; p < 0.001), a ceftriaxone dosage of > 2 g/day (OR = 2.66; 95% CI, 1.66-4.26; p < 0.001), and a treatment duration of > 14 days (OR = 1.94; 95% CI, 1.21-3.11; p = 0.006). CONCLUSION: Patients with chronic kidney disease, receiving ceftriaxone at a dosage of > 2 g/day, being treated for over 14 days, and/or females may be at an increased risk of ceftriaxone-induced encephalopathy.


Assuntos
Encefalopatias , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Insuficiência Renal Crônica , Antibacterianos , Encefalopatias/induzido quimicamente , Encefalopatias/tratamento farmacológico , Encefalopatias/epidemiologia , Ceftriaxona , Feminino , Humanos , Japão/epidemiologia , Insuficiência Renal Crônica/tratamento farmacológico
14.
Clin Cancer Res ; 28(12): 2623-2632, 2022 06 13.
Artigo em Inglês | MEDLINE | ID: mdl-35363302

RESUMO

PURPOSE: Rapid decision-making is essential in precision medicine for initiating molecular targeted therapy for patients with cancer. This study aimed to extract pathomorphologic features that enable the accurate prediction of genetic abnormalities in cancer from hematoxylin and eosin images using deep learning (DL). EXPERIMENTAL DESIGN: A total of 1,657 images (one representative image per patient) of thin formalin-fixed, paraffin-embedded tissue sections from either primary or metastatic tumors with next-generation sequencing-confirmed genetic abnormalities-including BRAFV600E and KRAS mutations, and microsatellite instability high (MSI-H)-that are directly relevant to therapeutic strategies for advanced colorectal cancer were obtained from the nationwide SCRUM-Japan GI-SCREEN project. The images were divided into three groups of 986, 248, and 423 images to create one training and two validation cohorts, respectively. Pathomorphologic feature-prediction DL models were first developed on the basis of pathomorphologic features. Subsequently, gene-prediction DL models were constructed for all possible combinations of pathomorphologic features that enabled the prediction of gene abnormalities based on images filtered by the combination of pathomorphologic feature-prediction models. RESULTS: High accuracies were achieved, with AUCs > 0.90 and 0.80 for 12 and 27, respectively, of 33 analyzed pathomorphologic features, with high AUCs being yielded for both BRAFV600E (0.851 and 0.859) and MSI-H (0.923 and 0.862). CONCLUSIONS: These findings show that novel next-generation pathology methods can predict genetic abnormalities without the need for standard-of-care gene tests, and this novel next-generation pathology method can be applied for colorectal cancer treatment planning in the near future.


Assuntos
Neoplasias Colorretais , Instabilidade de Microssatélites , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Detecção Precoce de Câncer , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Mutação
15.
Phlebology ; 37(5): 393-399, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35318865

RESUMO

OBJECTIVES: Whether incompetent perforator veins (IPVs) require treatment remains controversial. We retrospectively evaluated the feasibility of IPV excision performed using the stab avulsion technique without ligation and sutures in patients undergoing endovenous ablation (EA). METHODS: This was a single-center, retrospective, observational cohort study. EA was performed in 1503 consecutive patients, including 33 patients with ulcers, between December 2014 and May 2021. Varicectomy was performed using the stab avulsion technique; IPV cases were included. RESULTS: Stab avulsion was performed at a mean number of 11.4 ± 7.8 sites. No deep vein thromboses or pulmonary emboli were noted. The incidence of nerve injury was 0.3%. All 33 (100%) patients with ulcers achieved healing by 1 year (median: 55.5 days; range: 13-365 days). CONCLUSIONS: IPV excision via stab avulsion may be a viable option for treating varicose veins and ulcers. This technique offers multiple advantages, including simplicity, safety, and reduced healthcare costs.


Assuntos
Varizes , Insuficiência Venosa , Estudos de Viabilidade , Humanos , Estudos Retrospectivos , Veia Safena/cirurgia , Resultado do Tratamento , Úlcera , Varizes/cirurgia , Insuficiência Venosa/cirurgia
16.
Diagn Microbiol Infect Dis ; 103(1): 115662, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35321800

RESUMO

Although early transition from intravenous to oral antimicrobials can reduce hospitalization duration, susceptibility breakpoints have not been established for many oral antimicrobials against Escherichia coli and Klebsiella pneumoniae bacteremia. Thus, we used population pharmacokinetic models, pharmacokinetic/pharmacodynamic indices, and Monte Carlo simulations to evaluate the probability of target attainment (PTA) for common oral antimicrobial dosages against E. coli and K. pneumoniae. The oral antimicrobial agents evaluated included cephalexin, cefaclor, cefditoren, amoxicillin/clavulanic acid, faropenem, and levofloxacin. For E. coli, the percentage of isolates with minimum inhibitory concentrations for which a PTA >90% was achieved was 53% and less than 20% for levofloxacin and the ß-lactams, respectively. For K. pneumoniae, the percentages of isolates for which a PTA >90% was achieved were comparatively higher (cephalexin, 73%; amoxicillin/clavulanic acid, 83%; levofloxacin, 96%). Our results suggest clinicians should check if pharmacokinetic/pharmacodynamic indices are achieved in individual patients before transitioning to oral antimicrobial therapy.


Assuntos
Anti-Infecciosos , Infecções por Escherichia coli , Amoxicilina , Antibacterianos/uso terapêutico , Cefalexina , Ácido Clavulânico , Escherichia coli , Infecções por Escherichia coli/tratamento farmacológico , Humanos , Klebsiella pneumoniae , Levofloxacino/farmacologia , Testes de Sensibilidade Microbiana , Método de Monte Carlo , Probabilidade
17.
Am J Infect Control ; 50(7): 772-776, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34863897

RESUMO

BACKGROUND: Inappropriate blood collection subjected to blood culture (BC) causes BC contamination and may complicate the diagnose is of infectious diseases. Therefore, we developed a bundle based on the guideline recommendations for appropriate blood collection and examined the effects of bundle introduction. METHODS: We performed a retrospective analysis of BC samples to determine the contamination rates before and after introducing the BC bundle. We also analyzed the correlation between the compliance rate of the bundle and contamination rate, and between each bundle element and contamination. RESULTS: After the introduction of the bundle, the contamination rate was significantly reduced from 5.4% ± 0.9% to 1.7± 0.7% (P < .01). The compliance rate of the bundle was significantly associated with a lower contamination rate (P < .01). Multivariable logistic regression showed that collection from superficial veins of the cubital fossa (odds ratio [OR], 0.25; 95% confidence interval [CI], 0.13-0.51, P < .01) and disinfection of the skin at the blood collection site with 1% chlorhexidine alcohol swab (OR, 0.41; 95% CI, 0.25-0.68, P < .01) were significantly associated with lower contamination. CONCLUSIONS: This study suggests that the introduction of the BC bundle significantly reduced the contamination rate, and bundle compliance was associated with a lower contamination rate.


Assuntos
Anti-Infecciosos Locais , Hemocultura , Coleta de Amostras Sanguíneas , Clorexidina , Humanos , Estudos Retrospectivos
18.
J Hepatobiliary Pancreat Sci ; 29(3): e10-e11, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34637609

RESUMO

Highlight A 51-year-old man was referred for further evaluation of a hepatic anomaly detected on abdominal ultrasonography. Contrast-enhanced computed tomography showed an extremely rare portal venous anomaly, almost like a 'portal circle'. Ataka and colleagues present the first report of this type of anomaly and describe it from an embryological perspective.


Assuntos
Veia Porta , Tomografia Computadorizada por Raios X , Humanos , Masculino , Pessoa de Meia-Idade , Veia Porta/anormalidades , Veia Porta/diagnóstico por imagem , Ultrassonografia
19.
J Clin Pharmacol ; 62(6): 756-761, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34817883

RESUMO

Pregabalin is a first-line treatment option for neuropathic pain. Recently, some cases of pregabalin-induced hypoglycemia have been reported, which can complicate the treatment of neuropathic pain and worsen patient outcomes. Therefore, a better understanding of the clinical condition of patients with pregabalin-induced hypoglycemia is desirable. In this study, we evaluated the risk of hypoglycemia in patients administered pregabalin, using the Japanese Adverse Drug Event Report database. All patients on pregabalin not taking any antidiabetic agents were screened from April 2004 to July 2020, and data on adverse events related to hypoglycemia, sex, age, weight, and the presence of chronic kidney disease were collected. Gabapentin and duloxetine, which are usually indicated for neuropathic pain, were used for comparison. Among 242 275 patients, 4287 were administered pregabalin, which included 37 patients who reported hypoglycemic incidents. Disproportionality of hypoglycemia was observed in patients administered pregabalin (reporting odds ratio, 2.25; 95%CI, 1.16-3.13; P < .01), whereas this was not the case in patients taking gabapentin and duloxetine. Multivariate logistic regression showed that hypoglycemia in patients on pregabalin was associated with age ≥70 years (odds ratio, 2.76; 95%CI, 1.29-5.91; P < 0.01) and weight <40 kg (odds ratio, 2.97; 95%CI, 1.32-6.71; P < 0.01). These findings suggest that pregabalin may be associated with a higher risk of hypoglycemia, especially in elderly individuals with low body weight. Health care providers may need to be aware of pregabalin-induced hypoglycemia in patients with these risk factors during therapy.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Hipoglicemia , Neuralgia , Idoso , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/complicações , Cloridrato de Duloxetina/efeitos adversos , Gabapentina/uso terapêutico , Humanos , Hipoglicemia/induzido quimicamente , Hipoglicemia/epidemiologia , Japão , Neuralgia/tratamento farmacológico , Pregabalina/efeitos adversos
20.
Cureus ; 14(12): e32617, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36654604

RESUMO

Community-acquired pneumonia (CAP) caused by Pseudomonas aeruginosa in healthy adults can rapidly lead to severe outcomes. We treated a case of P. aeruginosa-induced CAP and concurrent severe coronavirus disease (COVID-19) in a healthy 39-year-old man without other serious risk factors for severe illness except smoking. Immediately after admission, the patient developed sepsis and received intensive broad-spectrum antibacterial therapy with meropenem and vancomycin, veno-arterial extracorporeal membrane oxygenation (VAECMO), and catecholamine supplementation. Despite receiving multidisciplinary treatment, the patient died within 24 hours. P. aeruginosa with normal antimicrobial susceptibility was identified in blood and sputum cultures of samples taken at admission. Gram staining of the bacteria detected in blood cultures was suspicious for non-glucose-fermenting Gram-negative rods, including P. aeruginosa, and the antimicrobial regimen that was initiated following admission was considered effective. The patient was a plumber and a smoker, which are risk factors for P. aeruginosa-induced CAP, and the clinical course matched those in previous reports of P. aeruginosa-induced CAP, including necrotizing pneumonia with cavities and rapid progression of sepsis. Although COVID-19 can be the sole cause of septic shock, the combination of P. aeruginosa bacteremia and COVID-19 was possibly the cause of septic shock in this case. Even during an infectious disease pandemic, reviewing the patient's occupational history and comorbidities and performing blood and sputum culture tests, including Gram staining, are important for the provision of appropriate treatment.

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