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1.
Lancet Reg Health West Pac ; 48: 101116, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38966601

RESUMO

Background: The Northern Territory (NT) has the highest prevalence of chronic hepatitis B (CHB) in Australia. The Hep B PAST program aims to improve health outcomes for people living with CHB. Methods: This mixed methods study involves First Nations peoples living in the NT. We used participatory action research principles across three steps: 1. Foundation step: establishing hepatitis B virus (HBV) status and linkage to care; 2. Capacity building: training the health workforce; 3. Supported transition to primary healthcare: implementation of the "Hub and Spoke" model and in-language resources. Analysis occurred at three time points: 1. Pre-Hep B PAST (2018); 2. Foundation step (2020); and 3. Completion of Hep B PAST (2023). Evaluation focuses on four key indicators, the number of people: 1) with documented HBV status; 2) diagnosed with CHB; 3) receiving care; and 4) receiving treatment. Findings: Hep B PAST (2018-23) reached 40,555 people. HBV status was documented in 11% (1192/10,853), 79.2% (26,075/32,915) and 90.8% (28,675/31,588) of people at pre-Hep B PAST, foundation step, and completion respectively. An estimated 99.9% (821/822) of people were diagnosed, 86.3% (709/822) engaged in care, and 24.1% (198/822) on antiviral treatment at completion. CHB prevalence in the study population is 2.6%, decreasing from 6.1% to 0.4% in the pre- and post-vaccination cohorts. Interpretation: Hep B PAST is an effective model of care. Partner health services are exceeding elimination targets. This model could enable other countries to enhance the cascade of care and work towards eliminating HBV. Funding: National Health and Medical Research Council.

2.
JAMA ; 2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38864155

RESUMO

Importance: Whether ß-lactam antibiotics administered by continuous compared with intermittent infusion reduces the risk of death in patients with sepsis is uncertain. Objective: To evaluate whether continuous vs intermittent infusion of a ß-lactam antibiotic (piperacillin-tazobactam or meropenem) results in decreased all-cause mortality at 90 days in critically ill patients with sepsis. Design, Setting, and Participants: An international, open-label, randomized clinical trial conducted in 104 intensive care units (ICUs) in Australia, Belgium, France, Malaysia, New Zealand, Sweden, and the United Kingdom. Recruitment occurred from March 26, 2018, to January 11, 2023, with follow-up completed on April 12, 2023. Participants were critically ill adults (≥18 years) treated with piperacillin-tazobactam or meropenem for sepsis. Intervention: Eligible patients were randomized to receive an equivalent 24-hour dose of a ß-lactam antibiotic by either continuous (n = 3498) or intermittent (n = 3533) infusion for a clinician-determined duration of treatment or until ICU discharge, whichever occurred first. Main Outcomes and Measures: The primary outcome was all-cause mortality within 90 days after randomization. Secondary outcomes were clinical cure up to 14 days after randomization; new acquisition, colonization, or infection with a multiresistant organism or Clostridioides difficile infection up to 14 days after randomization; ICU mortality; and in-hospital mortality. Results: Among 7202 randomized participants, 7031 (mean [SD] age, 59 [16] years; 2423 women [35%]) met consent requirements for inclusion in the primary analysis (97.6%). Within 90 days, 864 of 3474 patients (24.9%) assigned to receive continuous infusion had died compared with 939 of 3507 (26.8%) assigned intermittent infusion (absolute difference, -1.9% [95% CI, -4.9% to 1.1%]; odds ratio, 0.91 [95% CI, 0.81 to 1.01]; P = .08). Clinical cure was higher in the continuous vs intermittent infusion group (1930/3467 [55.7%] and 1744/3491 [50.0%], respectively; absolute difference, 5.7% [95% CI, 2.4% to 9.1%]). Other secondary outcomes were not statistically different. Conclusions and Relevance: The observed difference in 90-day mortality between continuous vs intermittent infusions of ß-lactam antibiotics did not meet statistical significance in the primary analysis. However, the confidence interval around the effect estimate includes the possibility of both no important effect and a clinically important benefit in the use of continuous infusions in this group of patients. Trial Registration: ClinicalTrials.gov Identifier: NCT03213990.

3.
Antimicrob Agents Chemother ; 68(7): e0021824, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38837393

RESUMO

NaHCO3 responsiveness is a novel phenotype where some methicillin-resistant Staphylococcus aureus (MRSA) isolates exhibit significantly lower minimal inhibitory concentrations (MIC) to oxacillin and/or cefazolin in the presence of NaHCO3. NaHCO3 responsiveness correlated with treatment response to ß-lactams in an endocarditis animal model. We investigated whether treatment of NaHCO3-responsive strains with ß-lactams was associated with faster clearance of bacteremia. The CAMERA2 trial (Combination Antibiotics for Methicillin-Resistant Staphylococcus aureus) randomly assigned participants with MRSA bloodstream infections to standard therapy, or to standard therapy plus an anti-staphylococcal ß-lactam (combination therapy). For 117 CAMERA2 MRSA isolates, we determined by broth microdilution the MIC of cefazolin and oxacillin, with and without 44 mM of NaHCO3. Isolates exhibiting ≥4-fold decrease in the MIC to cefazolin or oxacillin in the presence of NaHCO3 were considered "NaHCO3-responsive" to that agent. We compared the rate of persistent bacteremia among participants who had infections caused by NaHCO3-responsive and non-responsive strains, and that were assigned to combination treatment with a ß-lactam. Thirty-one percent (36/117) and 25% (21/85) of MRSA isolates were NaHCO3-responsive to cefazolin and oxacillin, respectively. The NaHCO3-responsive phenotype was significantly associated with sequence type 93, SCCmec type IVa, and mecA alleles with substitutions in positions -7 and -38 in the regulatory region. Among participants treated with a ß-lactam, there was no association between the NaHCO3-responsive phenotype and persistent bacteremia (cefazolin, P = 0.82; oxacillin, P = 0.81). In patients from a randomized clinical trial with MRSA bloodstream infection, isolates with an in vitro ß-lactam-NaHCO3-responsive phenotype were associated with distinctive genetic signatures, but not with a shorter duration of bacteremia among those treated with a ß-lactam.


Assuntos
Antibacterianos , Cefazolina , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Oxacilina , Infecções Estafilocócicas , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/genética , Humanos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Cefazolina/farmacologia , Cefazolina/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Oxacilina/farmacologia , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Fenótipo , beta-Lactamas/farmacologia , beta-Lactamas/uso terapêutico , Masculino , Bicarbonato de Sódio/farmacologia , Feminino , Pessoa de Meia-Idade
4.
J Environ Manage ; 365: 121365, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38897080

RESUMO

Effective engagement is crucial for enhancing environmental decision-making processes, fostering more sustainable and equitable outcomes. However, the success of engagement is highly variable and context-dependent. While theoretical frameworks have been developed to explain outcome variance in engagement in environmental decision-making, they have not yet been tested in digital contexts, leaving their applicability to digital engagement processes unclear. More broadly, there are unanswered questions about the effectiveness of digital tools in achieving the goals of engagement, which have become increasingly pertinent amidst growing concerns about the potential of digital technologies for exacerbating exclusions, ethical issues, and systematically undermining democratic progress. This paper addresses this evidence gap by presenting findings from interviews with practitioners in UK public, private, and third sector organisations. Our results provide empirical insights into the technical, ethical, and inclusivity debates surrounding digital tools and their effectiveness in promoting accessible engagement, high-quality social interaction, place-based decision-making, and more trustworthy and credible outcomes. Our findings indicate that while current engagement theories are applicable to digital environments, the key explanatory factors acquire new dimensions in digital compared to in-person contexts. Drawing on the findings, this study contributes novel insights to expand current theory for explaining "what works" in engagement in environmental decisions, enhancing its relevance and applicability in the digital age. The paper concludes with evidence-led recommendations for environmental practitioners to improve engagement processes in digital and remote settings.


Assuntos
Tomada de Decisões , Humanos , Tecnologia Digital , Conservação dos Recursos Naturais/métodos
5.
BMC Health Serv Res ; 24(1): 710, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38849881

RESUMO

BACKGROUND: Hepatitis B is endemic amongst the Australian Aboriginal population in the Northern Territory. A participatory action research project identified the lack of culturally appropriate education tools and led to the development of the "Hep B Story" app in the Aboriginal language Yolŋu Matha. This paper describes a formal evaluation of the app's first version, which informed improvements and translation into a further ten Aboriginal languages. METHODS: The evaluation employed Participatory Action Research (PAR) principles to work within Indigenous research methodologies and prioritise Indigenous knowledge to improve the app iteratively. Semi-structured interviews and focus groups were conducted across the Northern Territory with 11 different language groups. Local Community Based Researchers and Aboriginal Research team members coordinated sessions. The recorded, translated conversations were transcribed verbatim and thematically analysed using an inductive and deductive approach. RESULTS: Between November 2018 and September 2020, 94 individuals from 11 language groups participated in 25 semi-structured interviews and 10 focus groups. All participants identified as Aboriginal. Most participants felt the app would be culturally appropriate for Aboriginal communities in the Northern Territory and improve knowledge surrounding hepatitis B. The information gathered from these interviews allowed for identifying five main themes: support for app, relationships, concept versus language, shame, and perceptions of images, along with errors that required modification. CONCLUSIONS: A "real-life" evaluation of the app was comprehensively completed using a PAR approach blended with Indigenous research methods. This evaluation allowed us to develop an updated and enhanced version of the app before creating the additional ten language versions. An iterative approach alongside strong community engagement was pivotal in ensuring the app's cultural safety and appropriateness. We recommend avoiding the use of knowledge-based evaluations in an Aboriginal setting to ensure relevant and culturally appropriate feedback is obtained.


Assuntos
Pesquisa Participativa Baseada na Comunidade , Grupos Focais , Hepatite B , Aplicativos Móveis , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Competência Cultural , Hepatite B/etnologia , Hepatite B/prevenção & controle , Entrevistas como Assunto , Northern Territory , Povos Aborígenes Australianos e Ilhéus do Estreito de Torres
6.
J Bone Joint Surg Am ; 106(13): 1197-1204, 2024 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-38723046

RESUMO

BACKGROUND: The role of patient-reported outcome measures (PROMs) as tools for monitoring the impact and outcomes of periprosthetic joint infection (PJI) is not well described. This study analyzed the Oxford Hip Score (OHS) or Oxford Knee Score (OKS) in a prospective observational cohort of patients with hip or knee PJI. METHODS: The PIANO (Prosthetic joint Infection in Australia and New Zealand, Observational study) cohort prospectively enrolled patients with newly diagnosed PJI from multiple centers. The OHS and OKS were evaluated at PJI diagnosis (baseline) and at 3, 12, and 24 months. Scores and score changes were examined according to PJI type, patient characteristics, and management. A successful functional outcome at 12 months was defined as an OHS of >38 or OHS of >36 and/or an improvement from baseline of >12 or >9, respectively. RESULTS: Of the 741 participants, PROMs were available at 12 months for 233 with hip and 342 with knee PJI. Significant improvements (p < 0.0001) were seen at 12 months for both the OHS (24.5 to 36) and OKS (25 to 34), with no further improvement at 24 months. Patients with late-acute PJI had a higher median baseline OHS (35; interquartile range [22 to 46]) and OKS (30 [18 to 41]) than those with early PJI (OHS: 19 [15 to 29]; OKS: 22 [16 to 29.5]) or chronic PJI (OHS: 23 [14 to 34]; OKS 22 [14 to 28]). Logistic regression showed that a clinical cure (adjusted odds ratio [aOR] = 1.88, 95% confidence interval [CI] = 1.28 to 2.76, p = 0.001) and early PJI (aOR = 2.56, 95% CI = 1.64 to 4.07, p < 0.0001) independently predicted a successful functional outcome. Chronic renal impairment (aOR = 0.31, 95% CI = 0.13 to 0.71, p = 0.007), congestive cardiac failure (aOR = 0.41, 95% CI = 0.17 to 0.95, p = 0.04), and clinical signs of inflammation (aOR = 0.53, 95% CI = 0.33 to 0.85, p = 0.009) at diagnosis independently predicted failure to achieve a successful functional outcome. CONCLUSIONS: The OHS and OKS varied significantly at baseline and 12 months according to PJI type, emphasizing the need to consider the PJI type when evaluating treatment success. This study highlights superior functional outcomes associated with early PJI and with achievement of a clinical cure. LEVEL OF EVIDENCE: Therapeutic Level II . See Instructions for Authors for a complete description of levels of evidence.


Assuntos
Artroplastia de Quadril , Medidas de Resultados Relatados pelo Paciente , Infecções Relacionadas à Prótese , Humanos , Infecções Relacionadas à Prótese/etiologia , Infecções Relacionadas à Prótese/terapia , Infecções Relacionadas à Prótese/diagnóstico , Masculino , Feminino , Estudos Prospectivos , Idoso , Pessoa de Meia-Idade , Estudos Longitudinais , Artroplastia de Quadril/efeitos adversos , Artroplastia do Joelho/efeitos adversos , Prótese de Quadril/efeitos adversos , Austrália , Prótese do Joelho/efeitos adversos , Resultado do Tratamento , Nova Zelândia , Idoso de 80 Anos ou mais
7.
J Surg Oncol ; 130(1): 93-101, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38712939

RESUMO

BACKGROUND AND OBJECTIVES: Deep learning models (DLMs) are applied across domains of health sciences to generate meaningful predictions. DLMs make use of neural networks to generate predictions from discrete data inputs. This study employs DLM on prechemotherapy cross-sectional imaging to predict patients' response to neoadjuvant chemotherapy. METHODS: Adult patients with colorectal liver metastasis who underwent surgery after neoadjuvant chemotherapy were included. A DLM was trained on computed tomography images using attention-based multiple-instance learning. A logistic regression model incorporating clinical parameters of the Fong clinical risk score was used for comparison. Both model performances were benchmarked against the Response Evaluation Criteria in Solid Tumors criteria. A receiver operating curve was created and resulting area under the curve (AUC) was determined. RESULTS: Ninety-five patients were included, with 33,619 images available for study inclusion. Ninety-five percent of patients underwent 5-fluorouracil-based chemotherapy with oxaliplatin and/or irinotecan. Sixty percent of the patients were categorized as chemotherapy responders (30% reduction in tumor diameter). The DLM had an AUC of 0.77. The AUC for the clinical model was 0.41. CONCLUSIONS: Image-based DLM for prediction of response to neoadjuvant chemotherapy in patients with colorectal cancer liver metastases was superior to a clinical-based model. These results demonstrate potential to identify nonresponders to chemotherapy and guide select patients toward earlier curative resection.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Colorretais , Aprendizado Profundo , Neoplasias Hepáticas , Terapia Neoadjuvante , Humanos , Neoplasias Colorretais/patologia , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Tomografia Computadorizada por Raios X , Fluoruracila/administração & dosagem , Fluoruracila/uso terapêutico , Quimioterapia Adjuvante , Oxaliplatina/administração & dosagem , Oxaliplatina/uso terapêutico , Adulto , Seguimentos , Estudos Retrospectivos
10.
Clin Infect Dis ; 2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38801783

RESUMO

INTRODUCTION: The use of adjunctive antibiotics directed against exotoxin production in Staphylococcus aureus bacteremia (SAB) is widespread, and is recommended in many guidelines, but there is limited evidence underpinning this. Existing guidelines are based on the theoretical premise of toxin suppression, as many strains of S. aureus produce toxins such as leucocidins (e.g., Panton-Valentine Leucocidin (PVL), toxic shock syndrome toxin 1 (TSST-1), exfoliative toxins, and various enterotoxins). Many clinicians therefore believe that limiting exotoxin production release by S. aureus could reduce its virulence and improve clinical outcomes. Clindamycin, a protein synthesis inhibitor antibiotic, is commonly used for this purpose. We report the domain-specific protocol, embedded in a large adaptive, platform trial, seeking to definitively answer this question. METHODS AND ANALYSIS: The Staphylococcus aureus Network Adaptive Platform (SNAP) trial is a pragmatic, randomized, multi-center adaptive platform trial that aims to compare different SAB therapies, simultaneously, for 90-day mortality. The adjunctive treatment domain aims to test the effectiveness of adjunctive antibiotics, initially comparing clindamycin to no adjunctive antibiotic, but future adaptations may include other agents. Individuals will be randomized to receive either five days of adjunctive clindamycin (or lincomycin) or no adjunctive antibiotic therapy alongside standard of care antibiotics. Most participants with SAB (within 72hr of index blood culture and not contraindicated) will be eligible to participate in this domain. Prespecified analyses are defined in the statistical appendix to the core protocol and domain-specific secondary analyses will be adjusted for resistance to clindamycin, disease phenotype (complicated or uncomplicated SAB) and PVL-positive isolate.

11.
Open Forum Infect Dis ; 11(5): ofae181, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38698894

RESUMO

Background: Desirability of outcome ranking (DOOR) is an emerging approach to clinical trial outcome measurement using an ordinal scale to incorporate efficacy and safety endpoints. Methods: We applied a previously validated DOOR endpoint to a cohort of CAMERA2 trial participants with methicillin-resistant Staphylococcus aureus bacteremia (MRSAB). Participants were randomly assigned to standard therapy, or to standard therapy plus an antistaphylococcal ß-lactam (combination therapy). Each participant was assigned a DOOR category, within which they were further ranked according to their hospital length of stay (LOS) and duration of intravenous antibiotic treatment. We calculated the probability and the generalized odds ratio of participants receiving combination therapy having worse outcomes than those receiving standard therapy. Results: Participants assigned combination therapy had a 54.5% (95% confidence interval [CI], 48.9%-60.1%; P = .11) probability and a 1.2-fold odds (95% CI, .95-1.50; P = .12) of having a worse outcome than participants on standard therapy. When further ranked according to LOS and duration of antibiotic treatment, participants in the combination group had a 55.6% (95% CI, 49.5%-61.7%) and 55.3% (95% CI, 49.2%-61.4%) probability of having a worse outcome than participants in the standard treatment group, respectively. Conclusions: When considering both efficacy and safety, treatment of MRSAB with a combination of standard therapy and a ß-lactam likely results in a worse clinical outcome than standard therapy. However, a small benefit of combination therapy cannot be excluded. Most likely the toxicity of combination therapy outweighed any benefit from faster clearance of bacteremia.

12.
Ann Am Thorac Soc ; 21(7): 993-997, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38669620

RESUMO

Hemorrhagic shock results in acute respiratory failure due to respiratory muscle fatigue and inadequate pulmonary blood flow. Because positive pressure ventilation can reduce venous return and cardiac output, clinicians should use the minimum possible mean airway pressure during assisted or mechanical ventilation, particularly during episodes of severe hypovolemia. Hypoperfusion also worsens dead space fraction. Therefore, clinicians should monitor capnography during mechanical ventilation and recognize that hypercapnia may be treated with fluid resuscitation rather than increasing minute ventilation.


Assuntos
Respiração Artificial , Insuficiência Respiratória , Choque Hemorrágico , Humanos , Capnografia , Hidratação/métodos , Respiração com Pressão Positiva/métodos , Respiração Artificial/métodos , Insuficiência Respiratória/terapia , Insuficiência Respiratória/etiologia , Choque Hemorrágico/complicações , Choque Hemorrágico/terapia
13.
Artigo em Inglês | MEDLINE | ID: mdl-38566264

RESUMO

ISSUE ADDRESSED: In 2014 the 'Hep B Story App', the first hepatitis B educational app in an Aboriginal language was released. Subsequently, in 2018, it was assessed and adapted before translation into an additional 10 Aboriginal languages. The translation process developed iteratively into a model that may be applied when creating any health resource in Aboriginal languages. METHODS: The adaptation and translation of the 'Hep B Story' followed a tailored participatory action research (PAR) process involving crucial steps such as extensive community consultation, adaptation of the original material, forward and back translation of the script, content accuracy verification, voiceover recording, and thorough review before the publication of the new version. RESULTS: Iterative PAR cycles shaped the translation process, leading to a refined model applicable to creating health resources in any Aboriginal language. The community-wide consultation yielded widespread chronic hepatitis B education, prompting participants to share the story within their families, advocating for hepatitis B check-ups. The project offered numerous insights and lessons, such as the significance of allocating sufficient time and resources to undertake the process. Additionally, it highlighted the importance of implementing flexible work arrangements and eliminating barriers to work for the translators. CONCLUSIONS: Through our extensive work across the Northern Territory, we produced an educational tool for Aboriginal people in their preferred languages and developed a translation model to create resources for different cultural and linguistic groups. SO WHAT?: This translation model provides a rigorous, transferable method for creating accurate health resources for culturally and linguistically diverse populations.

14.
J Arthroplasty ; 2024 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-38599531

RESUMO

BACKGROUND: Periprosthetic joint infection (PJI) is a devastating complication in hip and knee joint arthroplasty. The "Joint-Specific Bone Involvement, Antimicrobial Options, Coverage of the Soft Tissues, and Host Status (JS-BACH)" classification system was developed in 2021 to stratify the complexity of PJI, and more importantly, to act as a tool to guide referrals to specialist centers. The "JS-BACH" classification has not been validated in an external cohort. This study aimed to do so using a large prospective cohort from Australia and New Zealand. METHODS: We applied the JS-BACH classification to the Prosthetic Joint Infection in Australia and New Zealand Observational (PIANO) cohort. This prospective study of newly diagnosed PJI collected 2-year outcome data from 653 participants enrolled in 27 hospitals. The definition of PJI treatment failure at 24 months was any of the following: death, clinical or microbiological signs of infection, destination prosthesis removed, or ongoing antibiotic use. Individual cases were classified as per JS-BACH into "1: uncomplicated" (n = 268), "2: complex" (n = 330), and "3: limited options" (n = 55). This cohort was similar to the original JS-BACH population in terms of baseline characteristics. However, there was a difference in complexity, with more debridement, antibiotics, and implant retention procedures, fewer revision procedures, and a higher proportion of uncomplicated patients in the PIANO cohort. RESULTS: The risk of treatment failure correlated strongly with the JS-BACH category, with odds ratios (95% confidence interval) for category 2 versus 1 of 1.75 (1.24 to 2.47) and for category 3 versus 1 of 7.12 (3.42 to 16.02). CONCLUSIONS: Despite the PIANO study population being less complicated than the original derivation cohort, the JS-BACH classification showed a clear association with treatment failure in this large external cohort.

15.
Open Forum Infect Dis ; 11(4): ofae155, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38651137

RESUMO

Background: Hepatitis C virus (HCV) infection can now be cured with well-tolerated direct-acting antiviral (DAA) therapy. However, a potential barrier to HCV elimination is the emergence of resistance-associated substitutions (RASs) that reduce the efficacy of antiviral drugs, but real-world studies assessing the clinical impact of RASs are limited. Here, an analysis of the impact of RASs on retreatment outcomes for different salvage regimens in patients nationally who failed first-line DAA therapy is reported. Methods: We collected data from 363 Australian patients who failed first-line DAA therapy, including: age, sex, fibrosis stage, HCV genotype, NS3/NS5A/NS5B RASs, details of failed first-line regimen, subsequent salvage regimens, and treatment outcome. Results: Of 240 patients who were initially retreated as per protocol, 210 (87.5%) achieved sustained virologic response (SVR) and 30 (12.5%) relapsed or did not respond. The SVR rate for salvage regimens that included sofosbuvir/velpatasvir/voxilaprevir was 94.3% (n = 140), sofosbuvir/velpatasvir 75.0% (n = 52), elbasvir/grazoprevir 81.6% (n = 38), and glecaprevir/pibrentasvir 84.6% (n = 13). NS5A RASs were present in 71.0% (n = 210) of patients who achieved SVR and in 66.7% (n = 30) of patients who subsequently relapsed. NS3 RASs were detected in 20 patients (20%) in the SVR group and 1 patient in the relapse group. NS5B RASs were observed in only 3 patients. Cirrhosis was a predictor of relapse after retreatment, as was previous treatment with sofosbuvir/velpatasvir. Conclusions: In our cohort, the SVR rate for sofosbuvir/velpatasvir/voxilaprevir was higher than with other salvage regimens. The presence of NS5A, NS5B, or NS3 RASs did not appear to negatively influence retreatment outcomes.

16.
Sensors (Basel) ; 24(5)2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38475141

RESUMO

It is of great interest to develop advanced sensory technologies allowing non-invasive monitoring of neural correlates of cognitive processing in people performing everyday tasks. A lot of progress has been reported in recent years in this research area using scalp EEG arrays, but the high level of noise in the electrode signals poses a lot of challenges. This study presents results of detailed statistical analysis of experimental data on the cycle of creation of knowledge and meaning in human brains under multiple cognitive modalities. We measure brain dynamics using a HydroCel Geodesic Sensor Net, 128-electrode dense-array electroencephalography (EEG). We compute a pragmatic information (PI) index derived from analytic amplitude and phase, by Hilbert transforming the EEG signals of 20 participants in six modalities, which combine various audiovisual stimuli, leading to different mental states, including relaxed and cognitively engaged conditions. We derive several relevant measures to classify different brain states based on the PI indices. We demonstrate significant differences between engaged brain states that require sensory information processing to create meaning and knowledge for intentional action, and relaxed-meditative brain states with less demand on psychophysiological resources. We also point out that different kinds of meanings may lead to different brain dynamics and behavioral responses.


Assuntos
Encéfalo , Cognição , Humanos , Encéfalo/fisiologia , Cognição/fisiologia , Eletroencefalografia/métodos , Mapeamento Encefálico/métodos , Sensação
18.
JMIR Hum Factors ; 11: e53559, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38457221

RESUMO

More clinicians and researchers are exploring uses for large language model chatbots, such as ChatGPT, for research, dissemination, and educational purposes. Therefore, it becomes increasingly relevant to consider the full potential of this tool, including the special features that are currently available through the application programming interface. One of these features is a variable called temperature, which changes the degree to which randomness is involved in the model's generated output. This is of particular interest to clinicians and researchers. By lowering this variable, one can generate more consistent outputs; by increasing it, one can receive more creative responses. For clinicians and researchers who are exploring these tools for a variety of tasks, the ability to tailor outputs to be less creative may be beneficial for work that demands consistency. Additionally, access to more creative text generation may enable scientific authors to describe their research in more general language and potentially connect with a broader public through social media. In this viewpoint, we present the temperature feature, discuss potential uses, and provide some examples.


Assuntos
Idioma , Mídias Sociais , Humanos , Temperatura , Escolaridade , Pesquisadores
20.
J Arthroplasty ; 39(7): 1888-1893, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38309636

RESUMO

BACKGROUND: Despite increasing adoption of the direct anterior (DA) approach in total hip arthroplasty (THA), uncertainty persists regarding its outcomes beyond the 1-year mark in comparison to other approaches. We used the reverse fragility index (RFI) to evaluate the robustness of reported findings in the literature. METHODS: We conducted a systematic review of randomized controlled trials (RCTs) comparing implant revision rates between DA and other approaches in THA, defined as all those different from DA. Our primary outcome was the RFI, which gauges the number of events needed for a nonsignificant result to become significant, in the revision rate between DA and other approaches. We also calculated the reverse fragility quotient by dividing the RFI by each study's sample size. Median values and interquartile ranges (IQRs) were displayed. RESULTS: A total of 10 RCTs with a total of 971 patients were included. The median RFI was 5 (IQR, 4 to 5), indicating the study's results would be statistically significant if the outcomes of 5 patients in 1 treatment arm were reversed. The median reverse fragility quotient was 0.049 (IQR, 0.04 to 0.057), indicating that a change of outcome in 4.9% of patients would render the revision rate significant. The median number of patients lost to follow-up was 4 (IQR, 0 to 7). Of the 10 RCTs, 6 had more patients lost to follow-up than their respective RFI values. CONCLUSIONS: Notable fragility was evidenced in most studies comparing DA to other approaches for THA. Surgeons should not solely rely on the P value to determine clinical significance and instead use multiple metrics. LEVEL OF EVIDENCE: II.


Assuntos
Artroplastia de Quadril , Prótese de Quadril , Ensaios Clínicos Controlados Aleatórios como Assunto , Reoperação , Artroplastia de Quadril/métodos , Humanos , Reoperação/estatística & dados numéricos , Falha de Prótese , Resultado do Tratamento
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