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2.
Clin Infect Dis ; 75(8): 1467-1480, 2022 10 12.
Artigo em Inglês | MEDLINE | ID: mdl-35438780

RESUMO

Cytomegalovirus (CMV) is the leading infectious cause of congenital neurological disabilities. Valacyclovir and CMV hyperimmune globulin (HIG) may reduce vertical transmission and sequelae in neonates. A systematic review on valacyclovir and CMV HIG in preventing vertical transmission or reducing sequelae in neonates was conducted to 3 September 2021. Valacyclovir as a preventive strategy was supported by a well-conducted randomized controlled trial. Evidence supporting valacyclovir as a treatment strategy was limited to observational studies at moderate risk of bias. CMV HIG was not supported as a preventive strategy in 2 randomized controlled trials, which contrasted with observational studies. Evidence favoring CMV HIG as a treatment strategy was limited to observational studies at moderate risk of bias. The role of valacyclovir and CMV HIG in CMV infection in pregnancy is still being defined. Valacyclovir to prevent vertical transmission has the highest quality evidence in favor of use.


Assuntos
Infecções por Citomegalovirus , Doenças Fetais , Globulinas , Complicações Infecciosas na Gravidez , Citomegalovirus , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/prevenção & controle , Feminino , Humanos , Imunoglobulinas Intravenosas , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Gravidez , Complicações Infecciosas na Gravidez/prevenção & controle , Ensaios Clínicos Controlados Aleatórios como Assunto , Valaciclovir/uso terapêutico
3.
JBI Evid Synth ; 19(12): 3209-3237, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34402489

RESUMO

OBJECTIVE: The objective of this review was to synthesize the best available evidence for the diagnostic test accuracy of serum procalcitonin compared with serum C-reactive protein for suspected osteomyelitis and septic arthritis in hospitalized children and adolescents. INTRODUCTION: Measurement of serum C-reactive protein remains a routine investigation for the diagnosis of osteoarticular infection in children and adolescents. Measurement of serum procalcitonin has been shown to outperform C-reactive protein in adults with osteomyelitis and septic arthritis. Before procalcitonin can be considered as a potential replacement or add-on test in children and adolescents, a systematic review and meta-analysis targeting this population should be conducted. INCLUSION CRITERIA: Original studies reporting the diagnostic accuracy of procalcitonin and/or C-reactive protein in children and adolescents between one month and 18 years of age admitted to hospital with suspected osteoarticular infection were included. Studies must have compared the index test to at least one reference test. Reference test was defined as positive culture or polymerase chain reaction confirmation of a pathogen from blood, bone biopsy, or joint fluid aspirate in combination with at least two of the following: i) purulent material from sterile site, ii) positive radiological findings consistent with osteoarticular infection, and ii) symptoms and signs consistent with osteomyelitis and/or septic arthritis. METHODS: The JBI methodology for systematic reviews of diagnostic test accuracy was followed. Information was sourced from four databases (MEDLINE, Embase, Cochrane Central Register of Controlled Trials, and Web of Science) and four gray literature sources (MedNar, OpenGrey, Google Scholar, and ProQuest Dissertations and Theses). Only studies published in English were considered. The methodological quality of selected studies was formally evaluated, sensitivity and specificity data were extracted, and 95% confidence intervals determined. Meta-analysis was performed to estimate summary points using a bivariate model and to generate a hierarchical summary receiver operating characteristic (HSROC) curve with global measures of test accuracy performance, such as likelihood ratio and diagnostic odds ratio. A narrative was provided where meta-analysis was not appropriate. RESULTS: Eight studies were included in the review. Four of these studies used a common C-reactive protein test threshold of 20 mg/L. At this threshold, the estimated pooled sensitivity of C-reactive protein was 0.86 (0.68-0.96) and the pooled specificity was 0.9 (0.83-0.94). Using a hierarchical summary receiver operating characteristic model from six studies, the diagnostic odds ratio for C-reactive protein was estimated to be 39.4 (14.8-104.9) with a positive likelihood ratio 5.3 (2.3-11.9) and a negative likelihood ratio 0.1 (0.07-0.2). There were insufficient studies from this review to statistically evaluate the diagnostic accuracy of procalcitonin. CONCLUSION: Clinicians should continue to measure serum C-reactive protein as the preferred inflammatory marker in hospitalized children and adolescents with suspected osteomyelitis or septic arthritis. More evidence is needed before incorporating procalcitonin routinely into clinicians' diagnostic test strategy. Improvements with the design, quality, and reporting of procalcitonin diagnostic test assays in children and adolescents with osteoarticular infection is needed. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42019140276.


Assuntos
Artrite Infecciosa , Pró-Calcitonina , Adolescente , Adulto , Artrite Infecciosa/diagnóstico , Proteína C-Reativa , Criança , Testes Diagnósticos de Rotina , Humanos , Curva ROC
4.
Antibiotics (Basel) ; 9(11)2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33143280

RESUMO

This study aimed to compare and contrast the safety and efficacy of nurse- and self-administered paediatric outpatient parenteral antimicrobial therapy (OPAT) models of care and to identify clinical factors associated with documented adverse events (AEs). A total of 100 OPAT episodes among children aged between 1 month and 18 years who were discharged from hospital and who received continuous 24 h intravenous antimicrobial therapy at home via an elastomeric infusion device were included. All documented AEs from the case notes were reviewed by a paediatrician and classified as either major or minor. Multivariable logistic regression was used to determine associations between clinical factors and any AE. A total of 86 patients received 100 treatment OPAT episodes (49 self-administered, 51 nurse administered). The most commonly prescribed antimicrobial via continuous infusion was ceftazidime (25 episodes). Overall, an AE was recorded for 27 (27%) OPAT episodes. Major AEs was recorded for 15 episodes and minor AEs were reported in 14 episodes. The odds of an AE was increased in episodes with self-administration (adjusted odds ratio (aOR) 6.25, 95% confidence interval (CI) 1.44-27.15) and where the duration of vascular access was >14 days (aOR 1.08, 95%CI 1.01-1.15). Our findings suggest minor AEs may be more frequently reported when intravenous antimicrobials are self-administered via 24 h continuous infusions.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32397193

RESUMO

Infections are leading causes of hospitalizations from residential aged care services (RACS), which provide supported accommodation for people with care needs that can no longer be met at home. Preventing infections and early and effective management are important to avoid unnecessary hospital transfers, particularly in the Australian setting where new quality standards require RACS to minimize infection-related risks. The objective of this study was to examine root causes of infection-related hospitalizations from RACS and identify strategies to limit infections and avoid unnecessary hospitalizations. An aggregate root cause analysis (RCA) was undertaken using a structured local framework. A clinical nurse auditor and clinical pharmacist undertook a comprehensive review of 49 consecutive infection-related hospitalizations from 6 RACS. Data were collected from nursing progress notes, medical records, medication charts, hospital summaries, and incident reports using a purpose-built collection tool. The research team then utilized a structured classification system to guide the identification of root causes of hospital transfers. A multidisciplinary clinical panel assessed the root causes and formulated strategies to limit infections and hospitalizations. Overall, 59.2% of hospitalizations were for respiratory, 28.6% for urinary, and 10.2% for skin infections. Potential root causes of infections included medications that may increase infection risk and resident vaccination status. Potential contributors to hospital transfers included possible suboptimal selection of empirical antimicrobial therapy, inability of RACS staff to establish on-site intravenous access for antimicrobial administration, and the need to access subsidized medical services not provided in the RACS (e.g., radiology and pathology). Strategies identified by the panel included medication review, targeted bundles of care, additional antimicrobial stewardship initiatives, earlier identification of infection, and models of care that facilitate timely access to medical services. The RCA and clinical panel findings provide a roadmap to assist targeting services to prevent infection and limit unnecessary hospital transfers from RACS.


Assuntos
Instituição de Longa Permanência para Idosos , Hospitalização , Controle de Infecções , Preparações Farmacêuticas , Análise de Causa Fundamental , Austrália , Atenção à Saúde , Feminino , Humanos
6.
JBI Evid Synth ; 18(3): 564-570, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32197015

RESUMO

OBJECTIVE: The objective of this review is to synthesize the best available evidence for the diagnostic test accuracy of procalcitonin (PCT) compared to C-reactive protein (CRP) in diagnosing osteomyelitis (OM) and septic arthritis in hospitalized children and adolescents. INTRODUCTION: Serum measurement of PCT has been shown to outperform CRP in diagnosing adult osteoarticular infections. Before PCT can be considered as a potential diagnostic test in children and adolescents, a systematic review is required. INCLUSION CRITERIA: This review will consider studies with children and adolescents aged one month to 18 years, admitted to hospital with suspected acute osteoarticular infection. This review will consider original studies measuring the diagnostic accuracy of PCT and/or CRP in the diagnosis of acute OM or septic arthritis, defined as: positive culture or polymerase chain reaction (PCR) confirmation of an accepted pathogen from blood, bone biopsy or joint fluid aspirate and/or at least two of the following: i) purulent material from biopsy or aspirate specimen, ii) positive radiological findings of osteoarticular infection, and iii) symptoms and signs consistent with OM/septic arthritis. METHODS: JBI methodology for systematic reviews of diagnostic test accuracy will be utilized. A three-step search strategy will be undertaken to find relevant studies that will be assessed and reviewed using JBI SUMARI. A standardized critical appraisal tool will be used to assess methodological quality of studies. The main outcome will be pooled sensitivity and specificity measures with 95% confidence intervals for PCT and CRP in OM or septic arthritis. Results will be presented using paired forest plots, receiver operator characteristic curves, and narrative synthesis, and will include a Summary of Findings. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42019140276.


Assuntos
Artrite Infecciosa , Proteína C-Reativa/análise , Pró-Calcitonina/sangue , Adolescente , Artrite Infecciosa/diagnóstico , Biomarcadores/sangue , Criança , Testes Diagnósticos de Rotina , Humanos , Projetos de Pesquisa , Revisões Sistemáticas como Assunto
7.
J Patient Saf ; 16(2): 123-129, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32084091

RESUMO

OBJECTIVES: The aim of the study was to evaluate clinical outcomes and adverse events (AEs) experienced by patients treated within the Hospital in the Home (HITH) service of a major metropolitan hospital in South Australia. METHODS: A retrospective case note audit of 100 HITH episodes among adults who received continuous intravenous antimicrobial therapy via an elastomeric or electronic infusion device was undertaken. Age- and sex-adjusted binomial logistic regression analyses were undertaken to identify factors associated with major and minor AEs. RESULTS: Of the 100 patients included, 71 were male and the mean (SD) patient age was 62.8 (17.19) years. Elastomeric infusion devices were used for 98 patients. The mean (SD) HITH treatment duration was 20.1 (11.9) days. Overall, 130 AEs were documented for 72 patients (72%), of whom 12 patients experienced a major AE and 68 patients experienced a minor AE. There were 45 occasions among 23 patients where an infusion administered through an elastomeric device did not run to completion. Fifteen patients were readmitted to hospital. Minor AEs were more likely among people with more vascular line days (adjusted odds ratio [aOR] = 1.05; 95% confidence interval (CI) = 1.01-1.10 per day increase) and females (aOR = 4.43; 95% CI = 1.14-17.17). An increased number of vascular line days was associated with an increased likelihood of an incomplete infusion (aOR = 1.05; 95% CI = 1.01-1.09). Hospital readmission was more likely with increasing age (aOR = 1.06; 95% CI = 1.01-1.11 per year increase). CONCLUSIONS: Adverse events need to be monitored carefully when HITH treatment is provided for extended periods.


Assuntos
Serviços de Assistência Domiciliar/normas , Segurança do Paciente/normas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
8.
Expert Rev Med Devices ; 16(8): 735-742, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31192697

RESUMO

Background: Elastomeric infusion pumps are widely used in the delivery of parenteral medications in the home, but real-life conditions may not match calibration or standardised testing conditions. This study investigated the impact of changes in infusion pump height and/or back pressure on infusion pump function. Methods: Volume delivered after one day, infusion duration, average and peak flow rates and time spent within stated accuracy were determined for four elastomeric and one electronic pump using gravimetric technique. Experiments were repeated after altering the height of the pump relative to the output (±40cm, ±20cm) and/or adding a back pressure (10-30mmHg) to the output of an attached catheter. Results: Under ideal operating conditions, the flow rate deviated from that specified by the manufacturer and between 88.5% and 99% of the total infusion volume was delivered. Varying the height or applying back pressure led to further changes in average flow rates and the volume of infusion solution delivered by the elastomeric pumps, but had little effect on the electronic pump. Conclusions: Clinicians should consider potential impact on drug delivery, safety and therapeutic effect for home infusion patients given variations in infusion pump performance observed in this study.


Assuntos
Elastômeros/química , Eletrônica Médica/instrumentação , Terapia por Infusões no Domicílio/instrumentação , Bombas de Infusão , Pressão , Reologia , Análise de Variância , Calibragem , Humanos
9.
BMJ Open ; 7(7): e016763, 2017 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-28760798

RESUMO

INTRODUCTION: Previous studies comparing satisfaction with electronic and elastomeric infusion pumps are limited, and improvements in size and usability of electronic pumps have since occurred. The Comparing Home Infusion Devices (CHID) study plans to assess patient and nurse satisfaction with an elastomeric and electronic pump for delivering intravenous antibiotic treatment in the home. Secondary objectives are to determine pump-related complications and actual antibiotic dose administered, evaluate temperature variation and compare pump operating costs. METHODS AND ANALYSIS: The CHID study will be a randomised, crossover trial. A trained research nurse will recruit patients with infectious disease aged ≥18 years and prescribed ≥8 days of continuous intravenous antibiotic therapy from the Royal Adelaide Hospital (RAH) (Adelaide, Australia). Patients will be randomised to receive treatment at home via an elastomeric (Baxter Infusor) or an electronic (ambIT Continuous) infusion pump for 4-7 days, followed by the other for a further 4-7 days. Patient satisfaction will be assessed by a 10-item survey to be completed at the end of each arm. Nurse satisfaction will be assessed by a single 24-item survey. Patient logbooks and case notes from clinic visits will be screened to identify complications. Pumps/infusion bags will be weighed to estimate the volume of solution delivered. Temperature sensors will record skin and ambient temperatures during storage and use of the pumps throughout the infusion period. Costs relating to pumps, consumables, antibiotics and servicing will be determined. Descriptive statistics will summarise study data. ETHICS AND DISSEMINATION: This study has been approved by the RAH Human Research Ethics Committee (HREC/16/RAH/133 R20160420, version 6.0, 5 September 2016). Study results will be disseminated through peer-reviewed publications and conference presentations. The CHID study will provide key insights into patient and provider satisfaction with elastomeric and electronic infusion pumps and inform future device selection. TRIAL REGISTRATION NUMBER: ACTRN12617000251325; Pre-results.


Assuntos
Antibacterianos/administração & dosagem , Atitude do Pessoal de Saúde , Bombas de Infusão/normas , Dor Pós-Operatória/tratamento farmacológico , Satisfação do Paciente , Autoadministração/instrumentação , Adulto , Estudos Cross-Over , Elastômeros , Feminino , Humanos , Infusões Intravenosas/métodos , Masculino , Pessoa de Meia-Idade , Polímeros , Estudos Prospectivos , Adulto Jovem
10.
Asia Pac J Clin Nutr ; 22(3): 449-56, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23945416

RESUMO

Childhood malnutrition remains a public health issue in Indonesia with a national prevalence of wasting of 13% and stunting of 36%. In rural areas nutritional status depends on local agriculture and may fluctuate in relation to harvest time. The aim of this study was to characterise seasonal variations in nutritional status in two resettlement villages in the Oesao district, Nusa Tenggara Timur. A cross sectional study was conducted in a convenience sample of children after the wet season (March). Children aged 6 to 60 months were assessed for nutritional status using anthropometric and biochemical measures. A subset of these children was re-assessed for anthropometry after the dry season (November). Weight-for-height z scores improved significantly from mean±SD of -1.7± 0.9 in March to -1.3±0.9 in November (p<0.001). There was no significant change in height between seasons. Prevalence of wasting, (weight-for-height z score <-2), was 42% in March and 19% in November (p<0.001). However, stunting rates increased significantly from 42% in March to 45% in November (p<0.001). Thirty six per cent of children were anaemic (Hb level <11 mg/100 mL), 68% were vitamin A deficient (plasma vitamin A level <0.8 µmol/L) and 50% were zinc deficient (plasma zinc <9.94 µmol/L). All children except one were positive for intestinal parasites. These data indicate seasonal changes in anthropometry with inconsistent effects depending on the anthropometric index measured. Wasting and stunting were higher than the national average, alongside high rates of anaemia, zinc and vitamin A deficiencies.


Assuntos
Estado Nutricional , Estações do Ano , Anemia/epidemiologia , Antropometria , Estatura , Peso Corporal , Pré-Escolar , Estudos Transversais , Dieta , Feminino , Transtornos do Crescimento/epidemiologia , Hemoglobinas/análise , Humanos , Indonésia/epidemiologia , Lactente , Enteropatias Parasitárias/epidemiologia , Masculino , Deficiência de Vitamina A/epidemiologia , Zinco/deficiência
11.
Antimicrob Agents Chemother ; 56(12): 6154-9, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22985886

RESUMO

Three clinical Pseudomonas aeruginosa isolates (WCH2677, WCH2813, and WCH2837) isolated from the Women's and Children's Hospital, Adelaide, Australia, produced a metallo-ß-lactamase (MBL)-positive Etest result. All isolates were PCR negative for known MBL genes. A gene bank was created, and an MBL gene, designated bla(AIM-1), was cloned and fully characterized. The encoded enzyme, AIM-1, is a group B3 MBL that has the highest level of identity to THIN-B and L1. It is chromosomal and flanked by two copies (one intact and one truncated) of an ISCR element, ISCR15. Southern hybridization studies indicated the movement of both ISCR15 and bla(AIM-1) within the three different clinical isolates. AIM-1 hydrolyzes most ß-lactams, with the exception of aztreonam and, to a lesser extent, ceftazidime; however, it possesses significantly higher k(cat) values for cefepime and carbapenems than most other MBLs. AIM-1 was the first mobile group B3 enzyme detected and signals further problems for already beleaguered antimicrobial regimes to treat serious P. aeruginosa and other Gram-negative infections.


Assuntos
Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Infecções por Pseudomonas/microbiologia , Pseudomonas aeruginosa/efeitos dos fármacos , beta-Lactamases/genética , beta-Lactamases/metabolismo , Adolescente , Sequência de Aminoácidos , Austrália , DNA Bacteriano/genética , Diabetes Mellitus Tipo 2/complicações , Eletroforese em Gel de Campo Pulsado , Endocardite Bacteriana/complicações , Endocardite Bacteriana/microbiologia , Feminino , Genes Bacterianos , Humanos , Hibridização Genética , Falência Renal Crônica/complicações , Cinética , Leucemia Mieloide/complicações , Masculino , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Infecções por Pseudomonas/complicações , Infecções Estafilocócicas/complicações , Infecções Estafilocócicas/microbiologia , Streptococcus bovis
12.
Gastroenterology ; 142(4): 790-5, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22248659

RESUMO

BACKGROUND & AIMS: Although interleukin 28B (interferon, lambda 3) (IL28B) genotype affects the response of patients with chronic hepatitis C to peginterferon and ribavirin, little is known regarding its effect on response to direct-acting antivirals in interferon-free combinations. We analyzed the effects of IL28B genotype on the viral kinetic (VK) response to an interferon-free combination of the nucleoside polymerase inhibitor mericitabine (RG7128) and the hepatitis C virus (HCV) protease inhibitor danoprevir. METHODS: We performed a double-blind, dose-escalation study of patients with chronic HCV genotype 1 infection who were interferon treatment naive or had not responded to previous therapy with peginterferon and ribavirin. Patients were sequentially assigned to 1 of 7 cohorts then randomly assigned to groups that received up to 13 days of treatment with mericitabine (500 or 1000 mg, twice daily) plus danoprevir (100 or 200 mg, every 8 hours, or 600 or 900 mg, twice daily) or placebo. Eighty-three of 87 patients were genotyped for the IL28B single-nucleotide polymorphism rs12979860. VKs were analyzed only in patients who received 13 days of treatment, at optimal doses, using a biphasic model to describe first- and second-phase slopes of viral decay during therapy. RESULTS: At day 14 (the end of interferon-free treatment), the mean reduction in the serum level of HCV RNA was slightly greater in patients with the CC polymorphism (5.01 log(10) IU/mL) than those without (4.59 log(10) IU/mL). Modeling revealed that patients with the CC polymorphism had slightly better early VKs, most apparent in the ß-phase of viral decay. A mixed effect on the α-phase was observed, which was reduced in magnitude but prolonged in patients with CC, who also had better on-treatment response to peginterferon and ribavirin during follow up. CONCLUSIONS: IL28B genotype appears to affect early VKs in patients with chronic hepatitis C receiving interferon-free treatment.


Assuntos
Antivirais/uso terapêutico , Desoxicitidina/análogos & derivados , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Interleucinas/genética , Lactamas/uso terapêutico , Polimorfismo de Nucleotídeo Único , Sulfonamidas/uso terapêutico , Austrália , Ciclopropanos , Desoxicitidina/uso terapêutico , Método Duplo-Cego , Quimioterapia Combinada , Genótipo , Hepacivirus/genética , Hepacivirus/crescimento & desenvolvimento , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/genética , Hepatite C Crônica/imunologia , Humanos , Interferons , Isoindóis , Cinética , Lactamas Macrocíclicas , Modelos Biológicos , Modelos Estatísticos , Nova Zelândia , Fenótipo , Prolina/análogos & derivados , RNA Viral/sangue , Resultado do Tratamento , Carga Viral , Replicação Viral/efeitos dos fármacos
13.
Lancet ; 376(9751): 1467-75, 2010 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-20951424

RESUMO

BACKGROUND: Present interferon-based standard of care treatment for chronic hepatitis C virus (HCV) infection is limited by both efficacy and tolerability. We assessed the safety, tolerability, and antiviral activity of an all-oral combination treatment with two experimental anti-HCV drugs-RG7128, a nucleoside polymerase inhibitor; and danoprevir, an NS3/4A protease inhibitor-in patients with chronic HCV infection. METHODS: Patients from six centres in New Zealand and Australia who were chronically infected with HCV genotype 1 received up to 13 days oral combination treatment with RG7128 (500 mg or 1000 mg twice daily) and danoprevir (100 mg or 200 mg every 8 h or 600 mg or 900 mg twice daily) or placebo. Eligible patients were sequentially enrolled into one of seven treatment cohorts and were randomly assigned by interactive voice or web response system to either active treatment or placebo. Patients were separately randomly assigned within each cohort with a block size that reflected the number of patients in the cohort and the ratio of treatment to placebo. The random allocation schedule was computer generated. Dose escalation was started in HCV treatment-naive patients; standard of care treatment-experienced patients, including previous null responders, were enrolled in higher-dose danoprevir cohorts. Investigators, personnel at the study centre, and patients were masked to treatment allocation. However, the pharmacist who prepared the doses, personnel involved in pharmacokinetic sample analyses, statisticians who prepared data summaries, and the clinical pharmacologists who reviewed the data before deciding to initiate dosing in the next cohort were not masked to treatment allocation. The primary outcome was change in HCV RNA concentration from baseline to day 14 in patients who received 13 days of combination treatment. All patients who completed treatment with the study drugs were included in the analyses. This study is registered with ClinicalTrials.gov, NCT00801255. FINDINGS: 88 patients were randomly assigned to a study drug treatment regimen (n=74 over seven treatment groups; 73 received at least one dose of study drug) or to placebo (n=14, all of whom received at least one dose). The median change in HCV RNA concentration from baseline to day 14 ranged from -3·7 to -5·2 log(10) IU/mL in the cohorts that received 13 days of combination treatment. At the highest combination doses tested (1000 mg RG7128 and 900 mg danoprevir twice daily), the median change in HCV RNA concentration from baseline to day 14 was -5·1 log(10) IU/mL (IQR -5·6 to -4·7) in treatment-naive patients and -4·9 log(10) IU/mL in previous standard of care null responders (-5·2 to -4·5) compared with an increase of 0·1 log(10) IU/mL in the placebo group. The combination of RG7128 and danoprevir was well tolerated with no treatment-related serious or severe adverse events, no grade 3 or 4 changes in laboratory parameters, and no safety-related treatment discontinuations. INTERPRETATION: This oral combination of a nucleoside analogue polymerase inhibitor and protease inhibitor holds promise as an interferon-free treatment for chronic HCV. FUNDING: Roche Palo Alto.


Assuntos
Antivirais/administração & dosagem , Desoxicitidina/análogos & derivados , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Lactamas/administração & dosagem , Sulfonamidas/administração & dosagem , Proteínas não Estruturais Virais/antagonistas & inibidores , Administração Oral , Adulto , Antivirais/efeitos adversos , Ciclopropanos , Desoxicitidina/administração & dosagem , Desoxicitidina/efeitos adversos , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Hepatite C Crônica/virologia , Humanos , Interferon alfa-2 , Interferon-alfa/administração & dosagem , Isoindóis , Lactamas/efeitos adversos , Lactamas Macrocíclicas , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , Prolina/análogos & derivados , RNA Viral/sangue , Proteínas Recombinantes , Sulfonamidas/efeitos adversos
14.
J Pediatr Gastroenterol Nutr ; 50(6): 619-24, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20400916

RESUMO

OBJECTIVE: The effectiveness of probiotic therapy for acute rotavirus infectious diarrhoea in an indigenous setting with bacterial/parasitic diarrhoea is unclear. In the present study, we assessed the efficacy of probiotics in Australian Aboriginal children in the Northern Territory admitted to hospital with diarrhoeal disease. PATIENTS AND METHODS: A randomised double-blind placebo-controlled study was conducted in Aboriginal children (ages 4 months-2 years), admitted to hospital with acute diarrhoeal disease (>3 loose stools per day). Children received either oral Lactobacillus GG (5 x 10(9) colony-forming units 3 times per day for 3 days; n = 33) or placebo (n = 31). Small intestinal functional capacity was assessed by the noninvasive 13C-sucrose breath test on days 1 and 4. RESULTS: Both groups showed mean improvement in the sucrose breath test after 4 days; however, there was no difference (mean, 95% confidence interval) between probiotic (2.9 [cumulative percentage of dose recovered at 90 minutes]; 1.7-4.2) and placebo (3.7; 2.3-5.2) groups. Probiotics did not change the duration of diarrhoea, total diarrhoea stools, or diarrhoea score compared with placebo. There was a significant (P < 0.05) difference in diarrhoea frequency on day 2 between probiotics (3.3 [loose stools]; 2.5-4.3) and placebo (4.7; 3.8-5.7) groups. CONCLUSIONS: Lactobacillus GG did not appear to enhance short-term recovery following acute diarrhoeal illness in this setting.


Assuntos
Antidiarreicos/uso terapêutico , Diarreia/etnologia , Intestino Delgado/efeitos dos fármacos , Lactobacillus , Havaiano Nativo ou Outro Ilhéu do Pacífico , Probióticos/uso terapêutico , Doença Aguda , Testes Respiratórios , Defecação/efeitos dos fármacos , Diarreia/tratamento farmacológico , Diarreia/virologia , Método Duplo-Cego , Feminino , Humanos , Lactente , Intestino Delgado/virologia , Masculino , Probióticos/farmacologia , Estudos Prospectivos , Rotavirus
15.
Pediatrics ; 124(2): 620-6, 2009 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-19581263

RESUMO

OBJECTIVE: Environmental enteropathy syndrome may compromise growth and predispose to infectious diseases in children in the developing world, including Australian Aboriginal children from remote communities of the Northern Territory. In this study, we described the use of a biomarker (13)C-sucrose breath test (SBT) to measure enterocyte sucrase activity as a marker of small intestinal villus integrity and function. METHODS: This was a hospital-based prospective case-control study of Aboriginal and non-Aboriginal children with and without acute diarrheal disease. Using the SBT, we compared 36 Aboriginal case subjects admitted to a hospital (18 diarrheal and 18 nondiarrheal disease), with 7 healthy non-Aboriginal control subjects. Intestinal permeability using the lactulose/rhamnose (L/R) ratio on a timed 90-minute blood test was performed simultaneously with the SBT. The SBT results are expressed as a cumulative percentage of the dose recovered at 90 minutes. RESULTS: Aboriginal children with acute diarrheal disease have a significantly decreased absorptive capacity, as determined by the SBT, with a mean of 1.9% compared with either Aboriginal children without diarrhea (4.1%) or non-Aboriginal (6.1%) control subjects. The mean L/R ratio in the diarrhea group was 31.8 compared with 11.4 in Aboriginal children without diarrhea. There was a significant inverse correlation between the SBT and the L/R ratio. CONCLUSIONS: The SBT was able to discriminate among Aboriginal children with diarrhea, asymptomatic Aboriginal children with an underlying environmental enteropathy, and healthy non-Aboriginal controls. This test provides a noninvasive, easy-to-use, integrated marker of the absorptive capacity and integrity of the small intestine and could be a valuable tool in evaluating the efficacy of interventions aimed at improving gut health.


Assuntos
Testes Respiratórios/métodos , Radioisótopos de Carbono , Permeabilidade da Membrana Celular/fisiologia , Diarreia Infantil/etiologia , Doença Ambiental/diagnóstico , Absorção Intestinal/fisiologia , Havaiano Nativo ou Outro Ilhéu do Pacífico , Espru Tropical/diagnóstico , Sacarose , Pré-Escolar , Desidratação/diagnóstico , Desidratação/fisiopatologia , Diagnóstico Diferencial , Diarreia Infantil/fisiopatologia , Doença Ambiental/fisiopatologia , Feminino , Humanos , Lactente , Mucosa Intestinal/fisiopatologia , Intestino Delgado/fisiopatologia , Lactulose/sangue , Masculino , Northern Territory , Valor Preditivo dos Testes , Valores de Referência , Ramnose/sangue , Austrália do Sul , Espru Tropical/fisiopatologia
16.
Pediatr Infect Dis J ; 28(4): 287-9, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19258925

RESUMO

BACKGROUND: : The prevalence of Helicobacter pylori infection among Aboriginal Australians children is unclear. The aims of the present study are to determine the prevalence of H. pylori infection among young Aboriginal children recovering from acute diarrheal disease in hospital and to evaluate the H. pylori stool antigen test as a noninvasive diagnostic test in this setting. METHODS: : This was a prospective comparative study using the C-Urea Breath Test as reference standard. Fifty-two children between 4 months and 2 years of age were consecutively enrolled. These children comprised a representative sample of Australian Aboriginal children admitted to hospital with acute diarrheal disease from remote and rural communities across Northern Territory of Australia. RESULTS: : The overall prevalence of H. pylori was 44.2%. The stool antigen test had a sensitivity of 0.55 (95% confidence interval [CI]: 0.35-0.73) with a positive predictive value of 0.65 (95% CI: 0.42-0.82). The specificity was 0.68 (95% CI: 0.46-0.84) with a negative predictive value of 0.58 (95% CI: 0.39-0.75). Analysis of receiver operator characteristic curve yielded an overall accuracy of the stool antigen test of 61% (48%-75%). CONCLUSIONS: : The prevalence of H. pylori infection among very young Aboriginal children from remote and rural communities was high and consistent with early acquisition. The diagnostic accuracy of the stool antigen test to diagnose H. pylori in this setting was poor.


Assuntos
Antígenos de Bactérias/análise , Fezes/microbiologia , Infecções por Helicobacter/diagnóstico , Infecções por Helicobacter/etnologia , Helicobacter pylori/isolamento & purificação , Havaiano Nativo ou Outro Ilhéu do Pacífico , Austrália , Testes Respiratórios , Isótopos de Carbono/análise , Interpretação Estatística de Dados , Erros de Diagnóstico , Diarreia/microbiologia , Fezes/química , Feminino , Helicobacter pylori/imunologia , Humanos , Lactente , Masculino , Curva ROC
17.
Prehosp Disaster Med ; 21(1): s20-5, 2006.
Artigo em Inglês | MEDLINE | ID: mdl-16602269

RESUMO

The 26 December 2004 Tsunami resulted in a death toll of >270,000 persons, making it the most lethal tsunami in recorded history. This article presents performance data observations and the lessons learned by a civilian team dispatched by the Australian government to "provide clinical and surgical functions and to make public health assessments". The team, prepared and equipped for deployment four days after the event, arrived at its destination 13 days after the Tsunami. Aspiration pneumonia, tetanus, and extensive soft tissue wounds of the lower extremities were the prominent injuries encountered. Surgical techniques had to be adapted to work in the austere environment. The lessons learned included: (1) the importance of team member selection; (2) strategies for self-sufficiency; (3) personnel readiness and health considerations; (4) face-to-face handover; (5) coordination and liaison; (6) the characteristics of injuries; (7) the importance of protocols for patient discharge and hospital staffing; and (8) requirements for interpreter services. Whereas disaster medical relief teams will be required in the future, the composition and equipment needs will differ according to the nature of the disaster. National teams should be on standby for international response.


Assuntos
Planejamento em Desastres/organização & administração , Desastres , Eficiência Organizacional , Serviços Médicos de Emergência/organização & administração , Trabalho de Resgate/organização & administração , Austrália/etnologia , Humanos , Indonésia , Cooperação Internacional , Equipe de Assistência ao Paciente , Tradução , Ferimentos e Lesões/classificação , Ferimentos e Lesões/epidemiologia
18.
Prehosp Disaster Med ; 21 Suppl 1: S20-5, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26829831

RESUMO

The 26 December 2004 Tsunami resulted in a death toll of >270,000 persons, making it the most lethal tsunami in recorded history. This article presents performance data observations and the lessons learned by a civilian team dispatched by the Australian government to "provide clinical and surgical functions and to make public health assessments". The team, prepared and equipped for deployment four days after the event, arrived at its destination 13 days after the Tsunami. Aspiration pneumonia, tetanus, and extensive soft tissue wounds of the lower extremities were the prominent injuries encountered. Surgical techniques had to be adapted to work in the austere environment. The lessons learned included: (1) the importance of team member selection; (2) strategies for self-sufficiency; (3) personnel readiness and health considerations; (4) race-to-face handover; (5) coordination and liaison; (6) the characteristics of injuries; (7) the importance of protocols for patient discharge and hospital staffing; and (8) requirements for interpreter services. Whereas disaster medical relief teams will be required in the future, the composition and equipment needs will differ according to the nature of the disaster. National teams should be on standby for international response.


Assuntos
Desastres , Tsunamis , Austrália , Humanos , Socorro em Desastres
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