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1.
Open Forum Infect Dis ; 11(8): ofae449, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39189033

RESUMO

Outcomes are presented for a multisite retrospective case series, describing a contemporary cohort of 22 immunocompromised patients with persistent coronavirus disease 2019 (COVID-19) polymerase chain reaction positivity who were retreated with antiviral therapy. For those with data available 14 and 30 days after commencement of antiviral therapy, 41% (9 of 22) and 68% (15 of 22), respectively, cleared COVID-19.

2.
J Hosp Infect ; 148: 39-50, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38490489

RESUMO

Patients with cancer experience higher rates of preventable harm from hospital-acquired bloodstream infections (haBSIs) and central-line-associated bloodstream infections (CLABSIs) compared with the general hospital population. The prevention of haBSIs and CLABSIs in patients with cancer is an urgent priority, and requires standardized surveillance and reporting efforts. The application of haBSI and CLABSI definitions, classification systems and surveillance strategies for patients with cancer is complex, and there is wide variation in clinical practice. Existing systems were not designed explicitly for patients with cancer, and have different strengths and weaknesses in the cancer setting. For these reasons, epidemiological estimates of haBSIs and CLABSIs in patients with cancer also require careful interpretation. This complexity can be a barrier to identifying appropriate targets for intervention and reducing preventable harm. This review provides an overview of key concepts and challenges in haBSI surveillance and prevention specific to patients with cancer. In addition, this review summarizes the strengths and weaknesses of commonly used surveillance definitions and denominators in the setting of cancer care; existing surveillance practice; epidemiology of haBSIs and CLABSIs; prevention strategies; and current knowledge gaps. A global collaborative effort to harmonize the surveillance of hospital-acquired infections in patients with cancer would be invaluable to improve the accuracy and utility of existing data, advance efforts to prevent hospital-acquired infections, and improve patient safety.


Assuntos
Infecções Relacionadas a Cateter , Infecção Hospitalar , Neoplasias , Humanos , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/prevenção & controle , Neoplasias/complicações , Neoplasias/epidemiologia , Infecções Relacionadas a Cateter/epidemiologia , Infecções Relacionadas a Cateter/prevenção & controle , Monitoramento Epidemiológico , Controle de Infecções/métodos , Sepse/epidemiologia , Sepse/etiologia , Bacteriemia/epidemiologia , Bacteriemia/prevenção & controle
4.
J Antimicrob Chemother ; 78(6): 1367-1377, 2023 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-37038993

RESUMO

BACKGROUND: The Antifungal National Antimicrobial Prescribing Survey (AF-NAPS) was developed to undertake streamlined quality audits of antifungal prescribing. The validity and reliability of such tools is not characterized. OBJECTIVES: To assess the validity and reliability of the AF-NAPS quality assessment tool. METHODS: Case vignettes describing antifungal prescribing were prepared. A steering group was assembled to determine gold-standard classifications for appropriateness and guideline compliance. Infectious diseases physicians, antimicrobial stewardship (AMS) and specialist pharmacists undertook a survey to classify appropriateness and guideline compliance of prescriptions utilizing the AF-NAPS tool. Validity was measured as accuracy, sensitivity and specificity compared with gold standard. Inter-rater reliability was measured using Fleiss' kappa statistics. Assessors' responses and comments were thematically analysed to determine reasons for incorrect classification. RESULTS: Twenty-eight clinicians assessed 59 antifungal prescriptions. Overall accuracy of appropriateness assessment was 77.0% (sensitivity 85.3%, specificity 68.0%). Highest accuracy was seen amongst specialist (81%) and AMS pharmacists (79%). Prescriptions with lowest accuracy were in the haematology setting (69%), use of echinocandins (73%), mould-active azoles (75%) and for prophylaxis (71%). Inter-rater reliability was fair overall (0.3906), with moderate reliability amongst specialist pharmacists (0.5304). Barriers to accurate classification were incorrect use of the appropriateness matrix, knowledge gaps and lack of guidelines for some indications. CONCLUSIONS: The AF-NAPS is a valid tool, assisting assessors to correctly classify appropriate prescriptions more accurately than inappropriate prescriptions. Specialist and AMS pharmacists had similar performance, providing confidence that both can undertake AF-NAPS audits to a high standard. Identified reasons for incorrect classification will be targeted in the online tool and educational materials.


Assuntos
Anti-Infecciosos , Antifúngicos , Humanos , Antifúngicos/uso terapêutico , Reprodutibilidade dos Testes , Anti-Infecciosos/uso terapêutico , Prescrições , Inquéritos e Questionários , Prescrição Inadequada
5.
Sci Rep ; 11(1): 1390, 2021 01 14.
Artigo em Inglês | MEDLINE | ID: mdl-33446852

RESUMO

Post operative ventral hernias are common following Hartmann's procedure. There is a debate whether hernia repair is safe when performed concomitantly with colostomy closure. In this study we aimed to evaluate the outcomes of synchronous Hartmann reversal (HR) with a hernia repair, compared to a staged procedure. A retrospective multi-center study was conducted, including all patients who underwent Hartmann's procedure from January 2004 to July 2017 in 5 medical centers. Patient data included demographics, surgical data and post-operative outcome. Two hundred and seventy-four patients underwent colostomy reversal following Hartmann's procedure. In 107 patients (39%) a concomitant ventral hernia was reported during the Hartmann's reversal. Out of this cohort, 62 patients (58%) underwent hernia repair during follow-up. Thirty two patients (52%) underwent a synchronous hernia repair and 30 patients (48%) underwent hernia repair as a separate procedure. Post operative complication rate was significantly higher in the colostomy reversal with synchronous hernia repair group when compared to HR alone group (53% vs. 20%; p < 0.01; OR 4.5). In addition, severe complication rate (Clavien-Dindo score ≥ 3) was higher in the synchronous hernia repair group (25% vs. 7%). A tendency for higher hernia recurrence rate was noted in the synchronous group (56% vs. 40%). Median follow up time was 2.53 years (range 1-13.3 years). Synchronous colostomy closure and ventral hernia repair following Hartmann's procedure carries a significant risk for post operative complications, indicating that a staged procedure might be preferable.


Assuntos
Colostomia/efeitos adversos , Hérnia Ventral/cirurgia , Herniorrafia/efeitos adversos , Hérnia Incisional/cirurgia , Complicações Pós-Operatórias/epidemiologia , Idoso , Feminino , Seguimentos , Hérnia Ventral/epidemiologia , Humanos , Hérnia Incisional/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
6.
J Antimicrob Chemother ; 76(1): 253-262, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33057605

RESUMO

BACKGROUND: Guidance on assessment of the quantity and appropriateness of antifungal prescribing is required to assist hospitals to interpret data effectively and structure quality improvement programmes. OBJECTIVES: To achieve expert consensus on a core set of antifungal stewardship (AFS) metrics and to determine their feasibility for implementation. METHODS: A literature review was undertaken to develop a list of candidate metrics. International experts were invited to participate in sequential web-based surveys to evaluate the importance and feasibility of metrics in the area of AFS using Delphi methodology. Three surveys were completed. Consensus was predefined as ≥80% agreement on the importance of each metric. RESULTS: Eighty-two experts consented to participate from 17 different countries. Response rate for each survey was >80%. The panel included adult and paediatric physicians, microbiologists and pharmacists with diverse content expertise. Consensus was achieved for 38 metrics considered important to routinely include in AFS programmes, and related to antifungal consumption (n = 5), quality of antifungal prescribing and management of invasive fungal infection (IFI) (n = 24), and clinical outcomes (n = 9). Twenty-one consensus metrics were considered to have moderate to high feasibility for routine collection. CONCLUSIONS: The identified core AFS metrics will provide a framework to comprehensively assess the quantity and quality of antifungal prescribing within hospitals to develop quality improvement programmes aimed at improving IFI prevention, management and patient-centred outcomes. A standardized approach will support collaboration and benchmarking to monitor the efficacy of current prophylaxis and treatment guidelines, and will provide important feedback to guideline developers.


Assuntos
Antifúngicos , Infecções Fúngicas Invasivas , Adulto , Antifúngicos/uso terapêutico , Benchmarking , Criança , Hospitais , Humanos , Infecções Fúngicas Invasivas/tratamento farmacológico , Melhoria de Qualidade
7.
Clin Microbiol Infect ; 26(6): 784.e1-784.e5, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31972317

RESUMO

OBJECTIVES: Lomentospora prolificans is an emerging cause of serious invasive fungal infections. Optimal treatment of these infections is unknown, although voriconazole-containing treatment regimens are considered the treatment of choice. The objective of this study was to evaluate the role of combination antifungal therapy for L. prolificans infections. METHODS: We performed a retrospective review of medical records of patients with invasive L. prolificans infection diagnosed between 1 January 2008 and 9 September 2019 that were documented in the FungiScope® registry of rare invasive fungal infections. We compared clinical outcomes between antifungal treatment strategies. RESULTS: Over the study period, 41 individuals with invasive L. prolificans infection from eight different countries were documented in the FungiScope® registry. Overall, 17/40 (43%) had treatment response/stable disease and 21/40 (53%) had a fatal outcome attributed to invasive fungal infection. Combination antifungal therapy was associated with increased 28-day survival (15/24 survived versus 4/16 receiving monotherapy; p 0.027) and the combination voriconazole plus terbinafine trended to be associated with higher rates of treatment success (10/16, 63%, 95% CI 35%-85%) compared with other antifungal treatment regimens (7/24, 29%, 95% CI 13%-51%, p 0.053). In Kaplan-Meier survival analysis there was a higher survival probability in individuals receiving the voriconazole/terbinafine combination compared with other antifungal regimens (median survival 150 days versus 17 days). CONCLUSIONS: While overall mortality was high, combination antifungal treatment, and in particular combination therapy with voriconazole plus terbinafine may be associated with improved treatment outcomes compared with other antifungal regimens for the treatment of invasive L. prolificans infections.


Assuntos
Antifúngicos/uso terapêutico , Infecções Fúngicas Invasivas/tratamento farmacológico , Terbinafina/uso terapêutico , Voriconazol/uso terapêutico , Adulto , Idoso , Quimioterapia Combinada , Feminino , Humanos , Infecções Fúngicas Invasivas/sangue , Masculino , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Sistema de Registros , Estudos Retrospectivos , Scedosporium/efeitos dos fármacos , Resultado do Tratamento
9.
Support Care Cancer ; 28(6): 2745-2752, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31712951

RESUMO

BACKGROUND: CRS-HIPEC is associated with improved cancer survival but an increased risk of infection. METHODS: Consecutive patients undergoing CRS-HIPEC between January 2016 and May 2018 were retrospectively reviewed. Malignancy type, comorbidities, perioperative risk factors and infectious complications were captured, using standardised definitions. Association between risk factors and infection outcomes was evaluated by logistic regression modelling. RESULTS: One-hundred patients underwent CRS-HIPEC, predominantly for colorectal cancer and pseudomyxoma peritonei. Overall, 43 (43.0%) experienced an infectious complication, including infections at surgical site (27), respiratory tract (9), urinary tract (11), Clostridium difficile (2) and post-operative sepsis (15). In most, infection onset was within 7 days post-operatively. Median length of hospitalisation was 19 days for patients with infection, compared to 8 days for those without (p = 0.000). There were no deaths at 60 days. Of variables potentially associated with surgical site infection, small bowel resection (OR 4.01, 95% confidence interval [CI] 1.53-10.83; p = 0.005) and number of resected viscera (OR 1.41, 95% CI 1.00-1.98; p = 0.048) were significantly associated with infection. CONCLUSIONS: We demonstrate a significant burden of early infective complications in patients undergoing CRS-HIPEC. Higher-risk subgroups, including those with small bowel resection and increased number of resected viscera, may benefit from enhanced monitoring.


Assuntos
Procedimentos Cirúrgicos de Citorredução/efeitos adversos , Procedimentos Cirúrgicos do Sistema Digestório/efeitos adversos , Hipertermia Induzida/efeitos adversos , Infecção da Ferida Cirúrgica/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Terapia Combinada , Procedimentos Cirúrgicos de Citorredução/métodos , Feminino , Humanos , Hipertermia Induzida/métodos , Masculino , Pessoa de Meia-Idade , Neoplasias Peritoneais/cirurgia , Pseudomixoma Peritoneal/cirurgia , Estudos Retrospectivos , Infecção da Ferida Cirúrgica/microbiologia , Adulto Jovem
10.
J Psychoactive Drugs ; 51(5): 405-412, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31319769

RESUMO

Up to 35% of adults in the United States suffer from sleep disturbances, which covary with a host of negative mental and physical health outcomes. Previous research suggests that cannabis' sedative effects may be associated with improved sleep. The present study examined the self-reported effect of cannabis use on individual's sleep-related problems. Participants included 311 individuals recruited online, who reported both sleep-related problems and cannabis use. Analyses revealed that participants expected cannabis to decrease the incidence of sleep-related problems, including allowing participants to have an earlier bedtime, to fall asleep more quickly, and to have a longer night's sleep. Moreover, expectancies about the influence of cannabis on sleep negatively covaried with cannabis-related problems. These findings suggest that individuals believe using cannabis might positively influence their sleep quality and believing so may be protective against cannabis problems. Randomized control trials of cannabis for insomnia appear justified.


Assuntos
Cannabis , Conhecimentos, Atitudes e Prática em Saúde , Abuso de Maconha , Maconha Medicinal/uso terapêutico , Transtornos do Sono-Vigília/tratamento farmacológico , Adulto , Comorbidade , Humanos , Abuso de Maconha/epidemiologia , Transtornos do Sono-Vigília/epidemiologia
11.
BMC Infect Dis ; 19(1): 445, 2019 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-31113382

RESUMO

BACKGROUND: Candidaemia is associated with high mortality. Variables associated with mortality have been published previously, but not developed into a risk predictive model for mortality. We sought to describe the current epidemiology of candidaemia in Australia, analyse predictors of 30-day all-cause mortality, and develop and validate a mortality risk predictive model. METHODS: Adults with candidaemia were studied prospectively over 12 months at eight institutions. Clinical and laboratory variables at time of blood culture-positivity were subject to multivariate analysis for association with 30-day all-cause mortality. A predictive score for mortality was examined by area under receiver operator characteristic curves and a historical data set was used for validation. RESULTS: The median age of 133 patients with candidaemia was 62 years; 76 (57%) were male and 57 (43%) were female. Co-morbidities included underlying haematologic malignancy (n = 20; 15%), and solid organ malignancy in (n = 25; 19%); 55 (41%) were in an intensive care unit (ICU). Non-albicans Candida spp. accounted for 61% of cases (81/133). All-cause 30-day mortality was 31%. A gastrointestinal or unknown source was associated with higher overall mortality than an intravascular or urologic source (p < 0.01). A risk predictive score based on age > 65 years, ICU admission, chronic organ dysfunction, preceding surgery within 30 days, haematological malignancy, source of candidaemia and antibiotic therapy for ≥10 days stratified patients into < 20% or ≥ 20% predicted mortality. The model retained accuracy when validated against a historical dataset (n = 741). CONCLUSIONS: Mortality in patients with candidaemia remains high. A simple mortality risk predictive score stratifying patients with candidaemia into < 20% and ≥ 20% 30-day mortality is presented. This model uses information available at time of candidaemia diagnosis is easy to incorporate into decision support systems. Further validation of this model is warranted.


Assuntos
Candidemia/mortalidade , Idoso , Antifúngicos/uso terapêutico , Austrália/epidemiologia , Candida/classificação , Candida/genética , Candida/isolamento & purificação , Candidemia/tratamento farmacológico , Candidemia/epidemiologia , Candidemia/microbiologia , Feminino , Neoplasias Hematológicas/complicações , Hospitalização/estatística & dados numéricos , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Valor Preditivo dos Testes , Estudos Prospectivos , Curva ROC , Fatores de Risco
12.
Clin Microbiol Infect ; 25(1): 26-34, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30036666

RESUMO

BACKGROUND: The epidemiology of mucormycosis in the era of modern diagnostics is relatively under-explored. OBJECTIVES: To examine the contemporary epidemiology, clinical manifestations, diagnosis and causative pathogens of mucormycosis. DATA SOURCES: Ovid MEDLINE and Ovid EMBASE from January 2000 to January 2017. STUDY ELIGIBILITY CRITERIA: Published case reports/series of proven/probable mucormycosis. PARTICIPANTS: Patients ≥18 years old. METHODS: Patient characteristics, disease manifestations and causative pathogens were summarized descriptively. Categorical variables were assessed by chi-square test or Fischer's exact test, and continuous variables by the Wilcoxon-Mann-Whitney or Kruskal-Wallis test. Risk factors for the different clinical manifestations of mucormycosis were identified using multivariate logistic regression. RESULTS: Initial database searches identified 3619 articles of which 600 (851 individual patient cases) were included in the final analysis. Diabetes mellitus was the commonest underlying condition (340/851, 40%) and was an independent risk for rhino-orbital-cerebral mucormycosis (odds ratio (OR) 2.49; 95% CI 1.77-3.54; p < 0.001). Underlying haematological malignancy was associated with disseminated infection (OR 3.86; 95% CI 1.78-8.37; p 0.001), whereas previous solid organ transplantation was associated with pulmonary (OR 3.19; 95% CI 1.50-6.82; p 0.003), gastrointestinal (OR 4.47; 95% CI 1.69-11.80; p 0.003), or disseminated (OR 4.20; 95% CI 1.68-10.46; p 0.002) mucormycosis. Eight genera (24 species) of Mucorales organisms were identified in 447/851 (53%) cases, of which Rhizopus spp. (213/447, 48%) was the most common. Compared with other genera, Rhizopus spp. was predominantly observed in patients with rhino-orbital-cerebral mucormycosis (75/213, 35% versus 34/234, 15%; p < 0.001). Death was reported in 389/851 (46%) patients. Mortality associated with Cunninghamella infections was significantly higher than those caused by other Mucorales (23/30, 71% versus 185/417, 44%; p < 0.001). However, Cunninghamella spp. were isolated primarily in patients with pulmonary (17/30, 57%) or disseminated disease (10/30, 33%). CONCLUSIONS: Findings from the current review have helped ascertain the association between various manifestations of mucormycosis, their respective predisposing factors and causative organisms.


Assuntos
Mucormicose/epidemiologia , Diabetes Mellitus/epidemiologia , Neoplasias Hematológicas/complicações , Neoplasias Hematológicas/epidemiologia , Humanos , Mucorales , Mucormicose/complicações , Mucormicose/mortalidade , Rhizopus , Fatores de Risco
13.
Eur J Nucl Med Mol Imaging ; 46(1): 166-173, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29882160

RESUMO

PURPOSE: Invasive fungal infections (IFIs) are common in immunocompromised patients. While early diagnosis can reduce otherwise high morbidity and mortality, conventional CT has suboptimal sensitivity and specificity. Small studies have suggested that the use of FDG PET/CT may improve the ability to detect IFI. The objective of this study was to describe the proven and probable IFIs detected on FDG PET/CT at our centre and compare the performance with that of CT for localization of infection, dissemination and response to therapy. METHODS: FDG PET/CT reports for adults investigated at Peter MacCallum Cancer Centre were searched using keywords suggestive of fungal infection. Chart review was performed to describe the risk factors, type and location of IFIs, indication for FDG PET/CT, and comparison with CT for the detection of infection, and its dissemination and response to treatment. RESULTS: Between 2007 and 2017, 45 patients had 48 proven/probable IFIs diagnosed prior to or following FDG PET/CT. Overall 96% had a known malignancy with 78% being haematological. FDG PET/CT located clinically occult infection or dissemination to another organ in 40% and 38% of IFI patients, respectively. Of 40 patients who had both FDG PET/CT and CT, sites of IFI dissemination were detected in 35% and 5%, respectively (p < 0.001). Of 18 patents who had both FDG PET/CT and CT follow-up imaging, there were discordant findings between the two imaging modalities in 11 (61%), in whom normalization of FDG avidity of a lesion suggested resolution of active infection despite a residual lesion on CT. CONCLUSION: FDG PET/CT was able to localize clinically occult infection and dissemination and was particularly helpful in demonstrating response to antifungal therapy.


Assuntos
Fluordesoxiglucose F18 , Infecções Fúngicas Invasivas/diagnóstico por imagem , Infecções Fúngicas Invasivas/tratamento farmacológico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Adulto , Idoso , Antifúngicos/uso terapêutico , Feminino , Humanos , Infecções Fúngicas Invasivas/mortalidade , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
14.
Vaccine ; 36(14): 1804-1807, 2018 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-29503114

RESUMO

Healthcare workers (HCWs) at an Australian cancer centre were evaluated using a voluntary declination form program to determine factors contributing to declination of annual influenza vaccination. Overall, 1835/2041 HCWs (89.9%) completed a consent or declination form; 1783 were vaccinated and 52 declined. Staff roles with minimal patient contact were significantly associated with lower vaccine uptake (adjusted odds ratio 0.48, 95% confidence interval 0.23-0.99). Reasons for vaccine refusal included personal choice (41%), previous side-effect/s (23.1%), and medical reasons (23.1%). Of these, a large proportion may not be amenable to intervention, and this must be considered in setting threshold targets for future campaigns.


Assuntos
Atitude do Pessoal de Saúde , Pessoal de Saúde , Vacinas contra Influenza , Influenza Humana/prevenção & controle , Serviço Hospitalar de Oncologia , Vacinação , Adulto , Austrália/epidemiologia , Feminino , Humanos , Vacinas contra Influenza/administração & dosagem , Vacinas contra Influenza/efeitos adversos , Vacinas contra Influenza/imunologia , Masculino , Pessoa de Meia-Idade , Vigilância em Saúde Pública , Vacinação/efeitos adversos
15.
Clin Otolaryngol ; 43(2): 456-462, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28950046

RESUMO

OBJECTIVES: Intravenous opioid drug abuse (IVDA) was previously correlated with laryngeal cancer. However, discrimination of this correlation by anatomical subsites has not yet been described. In this study, we aim to further establish the association between IVDA and laryngeal squamous cell carcinoma (SCC) and to indicate the laryngeal subsites that are predisposed for this correlation. DESIGN: A retrospective matched case-control study. SETTING AND PARTICIPANTS: Patients diagnosed with supraglottic SCC (SG-SCC) between 1996 and 2016 treated in a tertiary academic referral centre were enrolled to the case group. The control group comprised of matched patients diagnosed with glottis SCC (G-SCC). Matching was based on gender, age and socio-economic rank. MAIN OUTCOME MEASURES: Variables studies as risk factors included the following: smoking, alcohol consumption, history of IVDA and infectious diseases. The variables were tested for association with the 2 groups and with each other. RESULTS: Forty-eight patients with SG-SCC were matched with 48 patients with G-SCC. IVDA rates significantly increased among patients with SG-SCC. Of the SG-SCC group, 18.8% had a positive history for IVDA compared with 2.1% of the G-SCC (P = .008). A history of IVDA was found to be a risk factor for SG-SCC, independent of smoking, excessive alcohol and socio-economic status. The odds ratio for patients with an IVDA history to have SG-SCC relatively to G-SCC was 10.846 (95% CI: 1.3-89.4). CONCLUSIONS: Intravenous opioid drug abuse represents an independent risk factor for SG-SCC. The pathogenesis should be investigated not just as a risk factor, as opioids are commonly used for pain management in oncologic patients.


Assuntos
Analgésicos Opioides/administração & dosagem , Carcinoma de Células Escamosas/epidemiologia , Neoplasias Laríngeas/epidemiologia , Abuso de Substâncias por Via Intravenosa/complicações , Adulto , Consumo de Bebidas Alcoólicas , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fumar , Fatores Socioeconômicos
17.
Clin Microbiol Infect ; 23(9): 676.e7-676.e10, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28344162

RESUMO

OBJECTIVES: Multi-antifungal drug resistance in Candida glabrata is increasing. We examined the feasibility of next-generation sequencing (NGS) to investigate the presence of antifungal drug resistance markers in C. glabrata. METHODS: The antifungal susceptibility of 12 clinical isolates and one ATCC strain of C. glabrata was determined using the Sensititre YeastOne® YO10 assay. These included three isolate pairs where the second isolate of each pair had developed a rise in drug MICs. Single nucleotide polymorphisms (SNPs) in genes known to be linked to echinocandin, azole and 5-fluorocytosine resistance were analysed in all isolates through NGS. RESULTS: High-quality non-synonymous SNPs in antifungal resistance genes such as FKS1, FKS2, CgCDR1, CgPDR1 and FCY2 were identified. For two of three isolate pairs, there was a >60-fold rise in MICs to all echinocandins in the second isolate from each pair; one echinocandin-resistant isolate harboured a mutation in FKS1 (S629P) and the other in FKS2 (S663P). Of the third pair, both the 5-fluorocytosine-susceptible, and resistant isolates had a mutation in FCY2 (A237T). SNPs in CgPDR1 were found in pan-azole-resistant isolates. SNPs in other genes linked to azole resistance (CgCDR1, ERG9 and CgFLR1) were present in both azole-susceptible and azole-resistant isolates. SNPs were also identified in Candida adhesin genes EPA1, EPA6, PWP2 and PWP5 but their presence was not associated with higher drug MICs. CONCLUSIONS: Genome-wide analysis of antifungal resistance markers was feasible and simultaneously revealed mutation patterns of genes implicated in resistance to different antifungal drug classes.


Assuntos
Antifúngicos/farmacologia , Azóis/farmacologia , Candida glabrata , Farmacorresistência Fúngica/genética , Equinocandinas/farmacologia , Flucitosina/farmacologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Candida glabrata/efeitos dos fármacos , Candida glabrata/genética , Candidíase/microbiologia , Estudos de Viabilidade , Marcadores Genéticos/genética , Humanos , Técnicas Microbiológicas , Polimorfismo de Nucleotídeo Único/genética
18.
Arch Toxicol ; 91(4): 1613-1621, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28180946

RESUMO

The echinocandins-caspofungin, anidulafungin and micafungin-are semi-synthetic cyclic hexapeptide antimicrobial agents with modified N-linked acyl lipid side chains which anchor the compounds to the phospholipid bilayer of the fungal cell membrane, thereby inhibiting synthesis of fungal cell wall glucan. Over the last 10 years, echinocandins have become the first-line antifungal treatment of candidaemia and other forms of invasive candidiasis (IC). Echinocandins are generally well tolerated, but their use is limited by their requirement for daily intravenous dosing, lack of oral formulation and limited spectrum. In critically ill patients, it is also recognised that achievement of their pharmacokinetic/pharmacodynamic targets shows large inter-individual variability. As a drug class, they are safe to use and are associated with few adverse reactions and few drug-drug interactions of significance. Recent discovery of their ability to prevent and treat Candida biofilm formation particularly in the presence of invasive medical devices and also their ability to penetrate into mucosal surfaces such as vulvovaginal candidiasis has opened up new opportunities for research into their drug delivery. New dosing intervals are being explored to allow less frequent intravenous dosing in the ambulatory setting, and a new long-acting echinocandin, CD101, is being developed for weekly and topical administration.


Assuntos
Antifúngicos/administração & dosagem , Candidíase/tratamento farmacológico , Equinocandinas/administração & dosagem , Lipopeptídeos/administração & dosagem , Administração Intravenosa , Anidulafungina , Animais , Antifúngicos/efeitos adversos , Antifúngicos/uso terapêutico , Biofilmes/efeitos dos fármacos , Caspofungina , Esquema de Medicação , Interações Medicamentosas , Equinocandinas/efeitos adversos , Equinocandinas/uso terapêutico , Humanos , Lipopeptídeos/efeitos adversos , Lipopeptídeos/uso terapêutico , Micafungina
19.
Med Mycol ; 55(7): 705-712, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28131991

RESUMO

Empirical antifungal therapy is frequently used in hematology patients at high risk of invasive aspergillosis (IA), with substantial cost and toxicity. Biomarkers for IA aim for earlier and more accurate diagnosis and targeted treatment. However, data on the cost-effectiveness of a biomarker-based diagnostic strategy (BDS) are limited. We evaluated the cost effectiveness of BDS using results from a randomized controlled trial (RCT) and individual patient costing data. Data inputs derived from a published RCT were used to construct a decision-analytic model to compare BDS (Aspergillus galactomannan and PCR on blood) with standard diagnostic strategy (SDS) of culture and histology in terms of total costs, length of stay, IA incidence, mortality, and years of life saved. Costs were estimated for each patient using hospital costing data to day 180 and follow-up for survival was modeled to five years using a Gompertz survival model. Treatment costs were determined for 137 adults undergoing allogeneic hematopoietic stem cell transplant or receiving chemotherapy for acute leukemia in four Australian centers (2005-2009). Median total costs at 180 days were similar between groups (US$78,774 for SDS [IQR US$50,808-123,476] and US$81,279 for BDS [IQR US$59,221-123,242], P = .49). All-cause mortality was 14.7% (10/68) for SDS and 10.1% (7/69) for BDS, (P = .573). The costs per life-year saved were US$325,448, US$81,966, and US$3,670 at 180 days, one year and five years, respectively. BDS is not cost-sparing but is cost-effective if a survival benefit is maintained over several years. An individualized institutional approach to diagnostic strategies may maximize utility and cost-effectiveness.


Assuntos
Biomarcadores/análise , Análise Custo-Benefício , Testes Diagnósticos de Rotina/economia , Testes Diagnósticos de Rotina/métodos , Aspergilose Pulmonar Invasiva/diagnóstico , Adulto , Feminino , Neoplasias Hematológicas/complicações , Humanos , Masculino , Pessoa de Meia-Idade
20.
Spinal Cord ; 54(12): 1183-1187, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27184917

RESUMO

STUDY DESIGN: Multi-center cross-sectional cohort study. OBJECTIVES: The objectives of this study were to develop and validate short forms (SFs) of participation for child- and parent-reported outcomes following spinal cord injury (SCI). SETTING: Three pediatric orthopedic hospitals in the United States. METHODS: The expert panel used calibration data from the pediatric computerized adaptive test (CAT) development study (convenience sample of 381 children and adolescents with SCI and 322 parents or caregivers) to select SF items. The panel selected items for two domains (participation self-relevant to what I want to do; participation friends-relevant to what my friends do), with parent and child versions for each domain. Psychometric analyses included group reliability, Cronbach's alpha, agreement (SFs and item banks), percent of sample with highest (ceiling) and lowest (floor) scores by level of lesion (paraplegia/tetraplegia), and test information function. RESULTS: Group reliability and Cronbach's alpha values are acceptable (0.74-0.92) and agreement (intraclass correlation coefficients for SFs and total item banks) is strong (0.89-0.95). Floor effects were minimal for people with tetraplegia and paraplegia (0-1.19%). Ceiling effects were minimal for people with tetraplegia (0-3.13%) and slightly higher, but acceptable, for people with paraplegia (8.06-14.02%). Test information function for the SFs was sufficiently high over the range of scores for the majority of the sample. CONCLUSION: Pediatric Measure of Participation (PMoP) SFs are acceptable for use when CATs are not feasible. SPONSORSHIP: The study was funded by the Shriners Hospitals for Children Research Grant 79142 (Mulcahey, PI) and the Boston ROC Grant 5R24HD065688-05 (Jette, PI).


Assuntos
Participação do Paciente/métodos , Traumatismos da Medula Espinal/terapia , Adolescente , Calibragem , Estudos Transversais , Estudos de Viabilidade , Feminino , Amigos , Hospitais Pediátricos , Humanos , Masculino , Paralisia/complicações , Paralisia/diagnóstico , Paralisia/psicologia , Paralisia/terapia , Pais , Psicometria , Autorrelato , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/diagnóstico , Traumatismos da Medula Espinal/psicologia , Resultado do Tratamento , Estados Unidos
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