Early oral stepdown antibiotic therapy versus continuing intravenous therapy for uncomplicated Gram-negative bacteraemia (the INVEST trial): study protocol for a multicentre, randomised controlled, open-label, phase III, non-inferiority trial.

BACKGROUND: The incidence of Gram-negative bacteraemia is rising globally and remains a major cause of morbidity and mortality. The majority of patients with Gram-negative bacteraemia initially receive intravenous (IV) antibiotic therapy. However, it remains unclear whether patients can step down to oral antibiotics after appropriate clinical response has been observed without compromising outcomes. Compared with IV therapy, oral therapy eliminates the risk of catheter-associated adverse events, enhances patient quality of life and reduces healthcare costs. As current management of Gram-negative bacteraemia entails a duration of IV therapy with limited evidence to guide oral conversion, we aim to evaluate the clinical efficacy and economic impact of early stepdown to oral antibiotics. METHODS: This is an international, multicentre, randomised controlled, open-label, phase III, non-inferiority trial. To be eligible, adult participants must be clinically stable / non-critically ill inpatients with uncomplicated Gram-negative bacteraemia. Randomisation to the intervention or standard arms will be performed with 1:1 allocation ratio. Participants randomised to the intervention arm (within 72 h from index blood culture collection) will be immediately switched to an oral fluoroquinolone or trimethoprim-sulfamethoxazole. Participants randomised to the standard arm will continue to receive IV therapy for at least 24 h post-randomisation before clinical re-assessment and decision-making by the treating doctor. The recommended treatment duration is 7 days of active antibiotics (including empiric therapy), although treatment regimen may be longer than 7 days if clinically indicated. Primary outcome is 30-day all-cause mortality, and the key secondary outcome is health economic evaluation, including estimation of total healthcare cost as well as assessment of patient quality of life and number of quality-adjusted life years saved. Assuming a 30-day mortality of 8% in the standard and intervention arms, with 6% non-inferiority margin, the target sample size is 720 participants which provides 80% power with a one-sided 0.025 α-level after adjustment for 5% drop-out. DISCUSSION: A finding of non-inferiority in efficacy of oral fluoroquinolones or trimethoprim-sulfamethoxazole versus IV standard of care antibiotics may hypothetically translate to wider adoption of a more cost-effective treatment strategy with better quality of life outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT05199324 . Registered 20 January 2022.

Trends in inpatient urinary incontinence surgery in the USA, 1998-2007.

INTRODUCTION AND HYPOTHESIS: This study was conducted to assess national rates in stress urinary incontinence (SUI) surgery in the USA from 1998 to 2007. METHODS: We utilized the 1998-2007 Nationwide Inpatient Sample and assessed women aged 20 years and older who underwent SUI surgery based on the International Classification of Diseases, 9th Revision (ICD-9) procedure and diagnosis codes. RESULTS: The total number of SUI surgeries performed during this 10-year period was 759,821. The annual number of procedures increased from 37,953 in 1998 to 94,910 in 2007. The type of SUI surgery performed also changed (p < 0.001). In 1998, retropubic suspensions represented 52.3%, decreasing to 13.8% in 2007. "Other repair of SUI" (ICD-9 59.79) comprised 22.4% in 1998, increasing to 75.2% in 2007, likely representing midurethral slings. CONCLUSIONS: The total number and incidence rates of SUI surgeries have increased from 1998 to 2007. The type of SUI surgery performed has also changed significantly, likely secondary to adoption of midurethral slings.

External validation of the CRASH and IMPACT prognostic models in severe traumatic brain injury.

An accurate prognostic model is extremely important in severe traumatic brain injury (TBI) for both patient management and research. Clinical prediction models must be validated both internally and externally before they are considered widely applicable. Our aim is to independently externally validate two prediction models, one developed by the Corticosteroid Randomization After Significant Head injury (CRASH) trial investigators, and the other from the International Mission for Prognosis and Analysis of Clinical Trials in Traumatic Brain Injury (IMPACT) group. We used a cohort of 300 patients with severe TBI (Glasgow Coma Score [GCS] ≤8) consecutively admitted to the National Neuroscience Institute (NNI), Singapore, between February 2006 and December 2009. The CRASH models (base and CT) predict 14 day mortality and 6 month unfavorable outcome. The IMPACT models (core, extended, and laboratory) estimate 6 month mortality and unfavorable outcome. Validation was based on measures of discrimination and calibration. Discrimination was assessed using the area under the receiving operating characteristic curve (AUC), and calibration was assessed using the Hosmer-Lemeshow (H-L) goodness-of-fit test and Cox calibration regression analysis. In the NNI database, the overall observed 14 day mortality was 47.7%, and the observed 6 month unfavorable outcome was 71.0%. The CRASH base model and all three IMPACT models gave an underestimate of the observed values in our cohort when used to predict outcome. Using the CRASH CT model, the predicted 14 day mortality of 46.6% approximated the observed outcome, whereas the predicted 6 month unfavorable outcome was an overestimate at 74.8%. Overall, both the CRASH and IMPACT models showed good discrimination, with AUCs ranging from 0.80 to 0.89, and good overall calibration. We conclude that both the CRASH and IMPACT models satisfactorily predicted outcome in our patients with severe TBI.

Shifts in national rates of inpatient prolapse surgery emphasize current coding inadequacies.

OBJECTIVE: : This study aimed to assess national rates, types, and routes of inpatient surgery for pelvic organ prolapse in the United States in 1998 compared to those in 2007. METHODS: : We used the 1998 and 2007 Nationwide Inpatient Sample, which represents a stratified, random sample of discharge data from US hospitals. We included women 20 years and older who underwent surgery for prolapse based on diagnosis and procedure codes of the International Classification of Disease, 9th Revision, Clinical Modification. We calculated the number of women undergoing surgery each year and incidence rates. RESULTS: : The total number of women undergoing prolapse surgeries was 92,503 in 1998 versus 113,646 in 2007. The incidence rate of surgery increased slightly, from 90.8 to 100.9 per 100,000 women, respectively. The most common procedure was hysterectomy, representing approximately half of prolapse surgeries in 1998 and 2007. Suspension procedures accounted for 18.8% of procedures in 2007, an increase from 6.1% in 1998. Surgeries performed via a minimally invasive route increased from 4.8% in 1998 to 9.4% in 2007. However, it was difficult to determine the route for many procedures based on current ICD-9 codes. There were also no codes that specifically designated mesh kit procedures or minimally invasive sacrocolpopexies. CONCLUSIONS: : During the last decade, the rate of inpatient prolapse surgery has slightly increased. The proportion of suspension procedures has increased; however, it is difficult to determine the route of these procedures based on current ICD-9 codes. These findings emphasize that ICD-9 procedure codes have not kept up with changes in clinical practice.