The Sunshine Coast University Hospital is a hospital on the Sunshine Coast, Queensland, affiliated with the University of the Sunshine Coast and Griffith University.
BACKGROUND:Approximately 10% of hospitalized patients globally report a penicillin allergy, leading to inappropriate antibiotic prescribing and inferior healthcare outcomes. Evidence supporting the effectiveness and widespread implementation of inpatient penicillin direct oral challenge (DOC) is limited. METHODS:A prospective, multicenter, international type 2 hybrid effectiveness-implementation study was conducted in 40 hospitals across 8 countries between November 2022 and May 2025. Adult inpatients with a penicillin allergy underwent assessment using a digital penicillin allergy toolkit (National Antibiotic Allergy Network [NAAN] App). According to site clinical practice, participants received penicillin DOC (effectiveness intervention) or assessment only. Participating sites received bimonthly audit and feedback at least 3 months after site activation (implementation strategy). Observational data were used to emulate a target trial to examine secondary effectiveness outcomes, including antibiotic prescribing at 90 days in DOC versus non-DOC participants. The primary implementation outcome was adoption of the NAAN App within 6 months of site activation. RESULTS:Among 5121 participants assessed, 1573 (30.7%) underwent DOC, of which 1502 (95.5%) were delabeled. Of 71 (4.5%) participants with a positive DOC, 6 (0.4%) had a serious adverse event. Of 1852 inpatients in the target trial analysis, 892 underwent DOC and 960 underwent assessment only. Participants who underwent DOC were more likely to be prescribed penicillin (risk ratio [RR], 13.25 [95% confidence interval {CI}, 7.82-22.46]), and less likely to be prescribed World Health Organization (WHO) "Watch" or "Reserve" antibiotics (RR, 0.73 [95% CI, .60-.89]) at 90 days post evaluation. Within 6 months of site activation, 77 clinicians adopted the NAAN App. CONCLUSIONS:Multidisciplinary adoption of inpatient penicillin DOC was safe and significantly improved penicillin prescribing and reduced use of WHO restricted antibiotics.
Earlier detection of colorectal cancer (CRC) can improve survival rates. A simple, effective blood test may help improve screening participation. The multi-target blood protein (MTBP; ColoSTAT®) test and algorithm uses concentrations of five protein biomarkers of CRC and patient’s sex and age to generate a CRC likelihood score. We compared the performance of the MTBP test in detecting CRC to colonoscopy, the ‘gold standard’. This cross-sectional, multicenter study enrolled participants into two cohorts: participants recently colonoscopically diagnosed with CRC and progressing to surgery or neoadjuvant treatment (Cohort 1), and participants with no CRC history who were scheduled for colonoscopy (Cohort 2). Due to COVID-19 pandemic-related recruitment delays, Cohort 1 was supplemented with bio-banked blood samples (BBS) from patients with clinically confirmed CRC. Performance goals for sensitivity and specificity of the MTBP test compared to colonoscopy were ≥ 73
Nontuberculous mycobacterial (NTM) infections are difficult to treat and are associated with significant morbidity and mortality. Reported success rates with guideline-based therapy vary depending on NTM species and up to 70
BACKGROUND:Blood-pressure reduction is the only proven treatment to prevent stroke. Whether a single pill that combines three antihypertensive drugs at low doses, in addition to standard antihypertensive treatment, can lower blood pressure more than standard care alone and reduce the risk of recurrent stroke after intracerebral hemorrhage is uncertain. METHODS:We conducted a multinational, double-blind, randomized, placebo-controlled trial involving patients with a history of intracerebral hemorrhage. Patients were eligible for the trial if they had a systolic blood pressure of 130 to 160 mm Hg at baseline and were in clinically stable condition. After a 2-week active run-in phase during which all the patients received a once-daily pill containing three antihypertensive agents at low doses (telmisartan at 20 mg, amlodipine at 2.5 mg, and indapamide at 1.25 mg; the triple pill), the patients were randomly assigned to continue receiving the triple pill or to receive matching placebo. The primary outcome was the first recurrent stroke. Secondary outcomes included blood-pressure control, major cardiovascular events, death from cardiovascular causes, and safety. RESULTS:Of 1670 patients who underwent randomization, 833 were assigned to receive the triple pill and 837 to receive placebo. The mean age of the patients was 58 years. At a median follow-up of 2.5 years, recurrent stroke had occurred in 38 patients (4.6%) in the triple-pill group and 62 (7.4%) in the placebo group (hazard ratio, 0.61; 95% confidence interval [CI], 0.41 to 0.92; P = 0.02). The mean systolic blood pressure during follow-up was 127 mm Hg and 138 mm Hg, respectively. The incidence of major cardiovascular events was lower with the triple pill than with placebo (6.6% vs. 9.8%; P = 0.04). Serious adverse events occurred in 23.2% of the patients in the triple-pill group and 26.0% of those in the placebo group. Early discontinuation of the trial regimen due to an adverse event occurred in 13.6% and 6.0%, respectively. The most common adverse event leading to discontinuation was an increase of 20% or more in the serum creatinine level. CONCLUSIONS:Among patients with intracerebral hemorrhage, treatment with a combination of three low-dose antihypertensive agents in a single pill, in addition to standard care, was associated with a lower incidence of recurrent stroke and major cardiovascular events than placebo. (Funded by the National Health and Medical Research Council of Australia and the Brazilian Ministry of Health; TRIDENT ClinicalTrials.gov number, NCT02699645; Australian New Zealand Clinical Trials Registry number, ACTRN12616000327482.).
PURPOSE:An abnormally high exercise systolic blood pressure (SBP) is associated with adverse left ventricular (LV) remodelling, a hallmark of hypertensive-heart disease. Fitness may modify this relationship through its effects on BP and cardiac structure, influencing the interpretation of exercise test results. This study explored the influence of fitness on the exercise SBP-cardiac structure relationship in individuals undergoing exercise stress echocardiography. METHODS:Cardiovascular structure and function (LV mass indexed to body surface area (LVMIBSA), relative wall thickness (RWT), cardiac output (CO) and total peripheral resistance (TPR)) were assessed by echocardiography in 5,087 individuals (aged 59.7±12.7 years, 53.1% male). BP was measured at peak exercise workload. Fitness was estimated by maximal oxygen consumption (VO2max) and categorised into three groups (low, moderate and high) based on age- and sex-predicted VO2max values. Regression analysis examined interactions of fitness on the exercise SBP-LV structure relationship, adjusting for age, sex, pre-exercise SBP, and history of cardiovascular disease. RESULTS:Peak SBP was positively associated with LVM, LVMIBSA and RWT (all p<0.005). Fitness modified these relationships; SBP was associated with LVM and LVMIBSA in moderate and high fitness (all p<0.05), but not in the low fitness group (p>0.40). RWT increased with SBP across all groups (all p<0.05), with highest values observed in the low fitness group (p<0.001). CO was lower and TPR higher in the low fitness (8.7±3.0L/min and 12.6±4.6mmHg·min/L) compared to high fitness (10.1±3.2L/min and 10.2±3.4mmHg·min/L) (all p<0.001). CONCLUSIONS:Fitness modifies the relationship between exercise SBP and cardiac structure, with low fitness exhibiting more adverse cardiovascular adaptations despite similar peak exercise SBP. Incorporating fitness into interpretation of peak exercise SBP is relevant for clinical decision-making.
