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.
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.
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.
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.
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.
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.
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.
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.
Language , Social Media , Humans , Temperature , Educational Status , Research Personnel
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.
Brain , Cognition , Humans , Brain/physiology , Cognition/physiology , Electroencephalography/methods , Brain Mapping/methods , Sensation
BACKGROUND: Injecting drug use is a risk factor for severe bacterial infection, but there is limited high-quality evidence to guide clinicians providing care to people who inject drugs. Management can be complicated by mistrust, stigma, and competing patient priorities. OBJECTIVES: To review the management of severe infections in people who inject drugs, using an illustrative clinical scenario of complicated Staphylococcus aureus bloodstream infection. SOURCES: The discussion is based on recent literature searches of relevant topics. Very few randomized clinical trials have focussed specifically on the management of severe bacterial infections among people who inject drugs. Most recommendations are, therefore, based on observational studies, extrapolation from other patient groups, and the experience and opinions of the authors. CONTENT: We discuss evidence and options regarding the following management issues for severe bacterial infections among people who inject drugs: initial management of sepsis; indications for surgical management; assessment and management of substance dependence; approaches to antibiotic administration following clinical stability; opportunistic health promotion; and secondary prevention of bacterial infections. Throughout, we highlight the importance of harm reduction and strategies to optimize patient engagement in care through a patient-centred approach. IMPLICATIONS: We advocate for a multi-disciplinary trauma-informed approach to the management of severe bacterial infection among people who inject drugs. We emphasize the need for pragmatic trials to inform management guidelines, including those that are co-designed with the community. In particular, research is needed to establish the comparative effectiveness, safety, and cost-effectiveness of inpatient intravenous antibiotics vs. early oral antibiotic switch, outpatient parenteral therapy, and long-acting lipoglycopeptide antibiotics in this scenario.
BACKGROUND: Excision is routinely recommended for atypical ductal hyperplasia (ADH) found on core biopsy given cancer upstage rates of near 20%. Identifying a cohort at low-risk for upstage may avoid low-value surgery. Objectives were to elucidate factors predictive of upstage in ADH, specifically near-complete core sampling, to potentially define a group at low upstage risk. PATIENTS AND METHODS: This retrospective, cross-sectional, multi-institutional study from 2015 to 2019 of 221 ADH lesions in 216 patients who underwent excision or active observation (≥ 12 months imaging surveillance, mean follow-up 32.6 months) evaluated clinical, radiologic, pathologic, and procedural factors for association with upstage. Radiologists prospectively examined imaging for lesional size and sampling proportion. RESULTS: Upstage occurred in 37 (16.7%) lesions, 25 (67.6%) to ductal carcinoma in situ (DCIS) and 12 (32.4%) to invasive cancer. Factors independently predictive of upstage were lesion size ≥ 10 mm (OR 5.47, 95% CI 2.03-14.77, p < 0.001), pathologic suspicion for DCIS (OR 12.29, 95% CI 3.24-46.56, p < 0.001), and calcification distribution pattern (OR 8.08, 95% CI 2.04-32.00, p = 0.003, "regional"; OR 19.28, 95% CI 3.47-106.97, p < 0.001, "linear"). Near-complete sampling was not correlated with upstage (p = 0.64). All three significant predictors were absent in 65 (29.4%) cases, with a 1.5% upstage rate. CONCLUSIONS: The upstage rate among 221 ADH lesions was 16.7%, highest in lesions ≥ 10 mm, with pathologic suspicion of DCIS, and linear/regional calcifications on mammography. Conversely, 30% of the cohort exhibited all low-risk factors, with an upstage rate < 2%, suggesting that active surveillance may be permissible in lieu of surgery.
Breast Neoplasms , Calcinosis , Carcinoma, Ductal, Breast , Carcinoma, Intraductal, Noninfiltrating , Female , Humans , Biopsy, Large-Core Needle , Breast/pathology , Breast Neoplasms/diagnosis , Breast Neoplasms/surgery , Breast Neoplasms/pathology , Calcinosis/pathology , Carcinoma, Ductal, Breast/surgery , Carcinoma, Ductal, Breast/pathology , Carcinoma, Intraductal, Noninfiltrating/surgery , Carcinoma, Intraductal, Noninfiltrating/pathology , Cross-Sectional Studies , Hyperplasia/pathology , Mammography , Retrospective Studies , Watchful Waiting
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.
BACKGROUND: Synthetic serine protease inhibitors block the cellular enzyme transmembrane protease serine 2, thus preventing SARS-CoV-2 cell entry. There are two relevant drugs in this class, namely, nafamostat (intravenous formulation) and camostat (oral formulation). OBJECTIVE: To determine whether transmembrane protease serine 2 inhibition with nafamostat or camostat is associated with a reduced risk of 30-day all-cause mortality in adults with COVID-19. DATA SOURCES: Scientific databases and clinical trial registry platforms. STUDY ELIGIBILITY CRITERIA, INTERVENTIONS, AND PARTICIPANTS: Preprints or published randomized clinical trials (RCTs) of nafamostat or camostat vs. usual care or placebo in adults requiring treatment for COVID-19. METHODS OF DATA SYNTHESIS AND RISK-OF-BIAS ASSESSMENT: The primary outcome of the meta-analysis was 30-day all-cause mortality. Secondary outcomes included time to recovery, adverse events, and serious adverse events. Risk of bias (RoB) was assessed using the revised Cochrane RoB 2 tool for individually randomized trials. Meta-analysis was conducted in the R package meta (v7.0-0) using inverse variance and random effects. Protocol registration number was INPLASY202320120. RESULTS: Twelve RCTs were included. Overall, the number of available patients was small (nafamostat = 387; camostat = 1061), the number of enrolled patients meeting the primary outcome was low (nafamostat = 12; camostat = 13), and heterogeneity was high. In hospitalized adults, we did not identify differences in 30-day all-cause mortality (risk ratio [95% CI]: 0.58 [0.19, 1.80], p 0.34; I2 = 0%; n = 6) and time to recovery (mean difference [95% CI]: 0.08 days [-0.74, 0.89], p 0.86; n = 2) between nafamostat vs. usual care; and for 30-day all-cause mortality (risk ratio [95% CI]: 0.99 [0.31, 3.18], p 0.99; n = 2) between camostat vs. placebo. CONCLUSION: The RCT evidence is inconclusive to determine whether there is a mortality reduction and safety with either nafamostat or camostat for the treatment of adults with COVID-19. There were high RoB, small sample size, and high heterogeneity between RCTs.
INTRODUCTION: Informed consent forms (ICFs) for randomised clinical trials (RCTs) can be onerous and lengthy. The process has the potential to overwhelm patients with information, leading them to miss elements of the study that are critical for an informed decision. Specifically, overly long and complicated ICFs have the potential to increase barriers to trial participation for patients with mild cognitive impairment, those who do not speak English as a first language or among those with lower medical literacy. In turn, this can influence trial recruitment, completion and external validity. METHODS AND ANALYSIS: SIMPLY-SNAP is a pragmatic, multicentre, open-label, two-arm parallel-group superiority RCT, nested within a larger trial, the Staphylococcus aureus Network Adaptive Platform (SNAP) trial. We will randomise potentially eligible participants of the SNAP trial 1:1 to a full-length ICF or a SIMPlified LaYered (SIMPLY) consent process where basic information is summarised with embedded hyperlinks to supplemental information and videos. The primary outcome is recruitment into the SNAP trial. Secondary outcomes include patient understanding of the clinical trial, patient and research staff satisfaction with the consent process, and time taken for consent. As an exploratory outcome, we will also compare measures of diversity (eg, gender, ethnicity), according to the consent process randomised to. The planned sample size will be 346 participants. ETHICS AND DISSEMINATION: The study has been approved by the ethics review board (Sunnybrook Health Sciences Research Ethics Board) at sites in Ontario. We will disseminate study results via the SNAP trial group and other collaborating clinical trial networks. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Registry (NCT06168474; www. CLINICALTRIALS: gov).
COVID-19 , Staphylococcal Infections , Humans , SARS-CoV-2 , Informed Consent , Ontario , Treatment Outcome , Randomized Controlled Trials as Topic , Multicenter Studies as Topic
BACKGROUND: Chronic hepatitis B (CHB) is endemic in the Aboriginal and Torres Strait Islander population of Australia's Northern Territory. Progression to liver disease can be prevented if holistic care is provided. Low health literacy amongst health professionals is a known barrier to caring for people living with CHB. We co-designed and delivered a culturally safe "Managing hepatitis B" training course for the Aboriginal health workforce. Here, we present an evaluation of the course. OBJECTIVES: 1. To improve course participants CHB-related knowledge, attitudes, and clinical practice. 2. To evaluate the "Managing hepatitis B" training course. 3. To enable participants to have the skills and confidence to be part of the care team. METHODS: We used participatory action research and culturally safe principles. We used purpose-built quantitative and qualitative evaluation tools to evaluate our "Managing hepatitis B" training course. We integrated the two forms of data, deductively analysing codes, grouped into categories, and assessed pedagogical outcomes against Kirkpatrick's training evaluation framework. RESULTS: Eight courses were delivered between 2019 and 2023, with 130 participants from 32 communities. Pre- and post-course questionnaires demonstrated statistically significant improvements in all domains, p<0.001 on 93 matched pairs. Thematic network analysis demonstrated high levels of course acceptability and significant knowledge acquisition. Other themes identified include cultural safety, shame, previous misinformation, and misconceptions about transmission. Observations demonstrate improvements in post-course engagement, a deep understanding of CHB as well as increased participation in clinical care teams. CONCLUSIONS: The "Managing hepatitis B" training course led to a sustained improvement in the knowledge and attitudes of the Aboriginal health workforce, resulting in improved care and treatment uptake for people living with CHB. Important non-clinical outcomes included strengthening teaching and leadership skills, and empowerment.
Education, Medical, Continuing , Health Services, Indigenous , Hepatitis B, Chronic , Humans , Health Workforce , Northern Territory , Australian Aboriginal and Torres Strait Islander Peoples
BACKGROUND AND PURPOSE: Vancomycin is one of the most common clinical antibiotics, yet acute kidney injury is a major limiting factor. Common combinations of antibiotics with vancomycin have been reported to worsen and improve vancomycin-induced kidney injury. We aimed to study the impact of flucloxacillin and imipenem-cilastatin on kidney injury when combined with vancomycin in our translational rat model. EXPERIMENTAL APPROACH: Male Sprague-Dawley rats received allometrically scaled (1) vancomycin, (2) flucloxacillin, (3) vancomycin + flucloxacillin, (4) vancomycin + imipenem-cilastatin or (5) saline for 4 days. Kidney injury was evaluated via drug accumulation and urinary biomarkers including urinary output, kidney injury molecule-1 (KIM-1), clusterin and osteopontin. Relationships between vancomycin accumulation in the kidney and urinary kidney injury biomarkers were explored. KEY RESULTS: Urinary output increased every study day for vancomycin + flucloxacillin, but after the first dose only in the vancomycin group. In the vancomycin + flucloxacillin group, urinary KIM-1 increased on all days compared with vancomycin. In the vancomycin + imipenem-cilastatin group, urinary KIM-1 was decreased on Days 1 and 2 compared with vancomycin. Similar trends were observed for clusterin. More vancomycin accumulated in the kidney with vancomycin + flucloxacillin compared with vancomycin and vancomycin + imipenem-cilastatin. The accumulation of vancomycin in the kidney tissue correlated with increasing urinary KIM-1. CONCLUSIONS AND IMPLICATIONS: Vancomycin + flucloxacillin caused more kidney injury compared with vancomycin alone and vancomycin + imipenem-cilastatin in a translational rat model. The combination of vancomycin + imipenem-cilastatin was nephroprotective.
Floxacillin , Vancomycin , Rats , Male , Animals , Cilastatin, Imipenem Drug Combination , Vancomycin/pharmacology , Clusterin , Rats, Sprague-Dawley , Anti-Bacterial Agents , Kidney , Biomarkers , Drug Combinations
BACKGROUND: The prevalence of chronic hepatitis B (CHB) in Aboriginal and Torres Strait Islander Australians in Far North Queensland (FNQ) is greater than twice that of the general Australian population. CHB is common in Torres Strait Islanders diagnosed with hepatocellular carcinoma (HCC) - and in Aboriginals with HCC living in the Northern Territory - however, Aboriginals diagnosed with HCC in FNQ very rarely have CHB. The explanation for this apparent disparity is uncertain. AIMS: To determine the HBV genotypes in the FNQ Aboriginal and Torres Strait Islander population and their correlation with clinical phenotype. METHODS: We determined the HBV genotype of Aboriginal and Torres Strait Islander Australians living with CHB in FNQ and correlated this with demographic and clinical findings. RESULTS: 134/197 (68%) enrolled individuals had a sufficient viral load for genotyping. All 40 people with HBV/D genotype had Aboriginal heritage, whereas 85/93 (91%) with HBV/C had Torres Strait Islander heritage (P < 0.0001). Individuals with HBV/D were younger than those with HBV/C (median (interquartile range) age: 43 (39-48) vs 53 (42-66) years, P = 0.0002). However, they were less likely to be HBeAg positive (1/40 (3%) vs 23/93 (25%), P = 0.001). All three HCCs developed in Torres Strait Islanders; two-thirds were infected with HBV/C14; genotyping was not possible in the other individual. All 10 diagnoses of cirrhosis occurred in Torres Strait Islanders, 6/10 were infected with HBV/C14, genotyping was not possible in the other four individuals. CONCLUSIONS: HBV genotypes in Aboriginal and Torres Strait Islander Australians in FNQ differ markedly, which could explain the significant differences in the clinical phenotype in the two populations and might be used to inform cost-effective CHB care in the region.
