Frailty, Outcomes, Recovery and Care Steps of Critically Ill Patients (FORECAST): a prospective, multi-centre, cohort study.

PURPOSE: Frailty is common in critically ill patients but the timing and optimal method of frailty ascertainment, trajectory and relationship with care processes remain uncertain. We sought to elucidate the trajectory and care processes of frailty in critically ill patients as measured by the Clinical Frailty Scale (CFS) and Frailty Index (FI). METHODS: This is a multi-centre prospective cohort study enrolling patients ≥ 50 years old receiving life support > 24 h. Frailty severity was assessed with a CFS, and a FI based on the elements of a comprehensive geriatric assessment (CGA) at intensive care unit (ICU) admission, hospital discharge and 6 months. For the primary outcome of frailty prevalence, it was a priori dichotomously defined as a CFS ≥ 5 or FI ≥ 0.2. Processes of care, adverse events were collected during ICU and ward stays while outcomes were determined for ICU, hospital, and 6 months. RESULTS: In 687 patients, whose age (mean ± standard deviation) was 68.8 ± 9.2 years, frailty prevalence was higher when measured with the FI (CFS, FI %): ICU admission (29.8, 44.8), hospital discharge (54.6, 67.9), 6 months (34.1, 42.6). Compared to ICU admission, aggregate frailty severity increased to hospital discharge but improved by 6 months; individually, CFS and FI were higher in 45.3% and 50.6% patients, respectively at 6 months. Compared to hospital discharge, 18.7% (CFS) and 20% (FI) were higher at 6 months. Mortality was higher in frail patients. Processes of care and adverse events were similar except for worse ICU/ward mobility and more frequent delirium in frail patients. CONCLUSIONS: Frailty severity was dynamic, can be measured during recovery from critical illness using the CFS and FI which were both associated with worse outcomes. Although the CFS is a global measure, a CGA FI based may have advantages of being able to measure frailty levels, identify deficits, and potential targets for intervention.

Administration and effects of beta blockers and oxandrolone in severely burned adults: a post hoc analysis of the RE-ENERGIZE trial.

Background: Prospective randomized trials in severely burned children have shown the positive effects of oxandrolone (OX), beta blockers (BB) and a combination of the two (BBOX) on hypermetabolism, catabolism and hyperinflammation short- and long-term post-burn. Although data on severely burned adults are lacking in comparison, BB, OX and BBOX appear to be commonly employed in this patient population. In this study, we perform a secondary analysis of an international prospective randomized trial dataset to provide descriptive evidence regarding the current utilization patterns and potential treatment effects of OX, BB and BBOX. Methods: The RE-ENERGIZE (RandomizEd Trial of ENtERal Glutamine to minimIZE Thermal Injury, NCT00985205) trial included 1200 adult patients with severe burns. We stratified patients according to their receipt of OX, BB, BBOX or none of these drugs (None) during acute hospitalization. Descriptive statistics describe the details of drug therapy and unadjusted analyses identify predisposing factors for drug use per group. Association between OX, BB and BBOX and clinical outcomes such as time to discharge alive and 6-month mortality were modeled using adjusted multivariable Cox regressions. Results: More than half of all patients in the trial received either OX (n = 138), BB (n = 293) or BBOX (n = 282), as opposed to None (n = 487, 40.6%). Per study site and geographical region, use of OX, BB and BBOX was highly variable. Predisposing factors for the use of OX, BB and BBOX included larger total body surface area (TBSA) burned, higher acute physiology and chronic health evaluation (APACHE) II scores on admission and younger patient age. After adjustment for multiple covariates, the use of OX was associated with a longer time to discharge alive [hazard ratio (HR) 0.62, confidence interval (CI) (0.47-0.82) per 100% increase, p = 0.001]. A higher proportion of days on BB was associated with lower in-hospital-mortality (HR: 0.5, CI 0.28-0.87, p = 0.015) and 6-month mortality (HR: 0.44, CI 0.24-0.82, p = 0.01). Conclusions: The use of OX, BB and BBOX is common within the adult burn patient population, with its use varying considerably across sites worldwide. Our findings found mixed associations between outcomes and the use of BB and OX in adult burn patients, with lower acute and 6-month-mortality with BB and longer times to discharge with OX. Further research into these pharmacological modulators of the pathophysiological response to severe burn injury is indicated.

Exploring the Diagnostic Spectrum of Children with Raised Faecal Calprotectin Levels.

Faecal calprotectin (FC) is a marker of gut inflammation. The cause and relevance of raised FC in children outside the context of established inflammatory bowel disease (IBD) have had minimal attention. This study aimed to address this by carrying out a retrospective study on children with abnormal FC tests aged 4-17 years without established IBD in the South Island, New Zealand. Abnormal FC results were stratified: 51-249 µg/g, 250-499 µg/g, and 500+ µg/g, and participants were categorised into diagnostic groups. Data were collected on symptoms and diagnostic tests. Three-hundred and ten children had abnormal index FC results, with a mean age of 12.9 years, and a 55% proportion of females. The median FC was 125 µg/g; 71% had levels 51-249 µg/g and 21% had levels 500+ µg/g. Of those with FC 500+ µg/g, 89% either had infectious diarrhoea or were diagnosed with IBD at the time of, or subsequent to, the index FC. Alarm symptoms did not delineate between groups with FC 500+ µg/g. Abnormalities in platelet levels, abdominal ultrasound, and colonoscopy were more frequent for children diagnosed with IBD. Repeat FC test levels were significantly reduced except for those subsequently diagnosed with IBD. Abnormal FC levels for the majority were below the level indicative of mucosal inflammation. Repeat FC testing could play an important role in distinguishing between diagnoses.

Nebulized Furosemide for Pulmonary Inflammation in Intubated Patients With COVID-19: A Phase 2 Randomized Controlled Double-Blind Study.

OBJECTIVES: Respiratory failure secondary to COVID-19 is associated with morbidity and mortality. Current anti-inflammatory therapies are effective but are given systemically and have significant side effects. Furosemide has anti-inflammatory properties, can be administered by inhalation, and is inexpensive. We investigated the efficacy of nebulized furosemide as an adjunctive therapy for COVID-19 respiratory failure. DESIGN: A double-blind, randomized, placebo-controlled trial. SETTING: Multicenter ICU study. PATIENTS: Adults requiring invasive mechanical ventilation secondary to COVID-19. INTERVENTION: Patients were randomized within 48 hours of intubation to receive inhaled furosemide or placebo until day 28, death, or liberation from mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: The study was stopped early due to waning incidence of COVID-19; 39 patients were available for analysis with mean ± sd age of 70.5 (10.8) years, Acute Physiology and Chronic Health Evaluation II 26.1 (7.8) and Fio2 60.0% (21.9). Baseline characteristics were similar between the groups. For the primary outcome of change in Pao2/Fio2 ratio between day 1 and day 6, it was +31.4 (83.5) in the furosemide arm versus +20.1 (92.8) in the control (p = 0.58). For secondary outcomes, furosemide versus control: 60-day mortality was 48% versus 71% (p = 0.20), hospital stay was 25.6 (21.9) versus 27.4 (25.0) days, p = 0.94 and VFD was 6.0 (9.1) versus 3.1 (7.1), p value of equals to 0.28. A post hoc analysis of the hierarchical composite outcome, alive and ventilator-free favored furosemide. There were no adverse events. CONCLUSIONS: In this trial of inhaled furosemide for COVID-19 respiratory failure, differences in Pao2/Fio2 ratio to day 6 and other clinical outcomes were not significantly different, although the trial was underpowered due to early termination. Given the favorable profile of inhaled furosemide, further study is warranted in disease states where acute pulmonary inflammation contributes to the underlying pathophysiology.

Patterns of vitamin D testing and supplementation for children with inflammatory bowel disease in Australasia.

Background and Aim: For children with inflammatory bowel disease (IBD), optimal levels of vitamin D are ascribed anti-inflammatory and essential immune system roles that are associated with reduced disease activity, lower postoperative recurrence, and higher quality of life. International guidelines for vitamin D testing and supplementation provide inconsistent recommendations. The aim of this study was to survey Australasian pediatric gastroenterologists to ascertain current practices of vitamin D testing and supplementation for children with IBD. Methods: Members of the Australian Society of Pediatric Gastroenterology, Hepatology and Nutrition were invited to complete an online survey. Respondents were asked to provide information on frequency of vitamin D testing and supplementation, adherence, and benefits of vitamin D to children with IBD. Results: Thirty-two (54%) pediatric gastroenterologists completed the survey: 27 (84%) from Australia and 5 (16%) from New Zealand. The majority (90%) tested vitamin D levels at diagnosis and follow up, although testing frequency varied (1-3 times/year) and only 8 (28%) tested seasonally. While 28 (88%) recommended supplementation based on serum levels, inconsistent cutoff values were used. Most respondents (n = 27) recommended Stoss (single dose) or vitamin D3 (daily for 8-12 weeks). The majority (84%) rated the overall benefit of optimal vitamin D levels at ≥6/10, although fewer (54%) rated the benefit to disease activity at ≥6/10. Conclusions: The results indicate that standardized guidelines for vitamin D testing and supplementation for clinicians caring for children with IBD throughout Australasia are required. Consensus statements may optimize the care of children with IBD in this diverse geographical region.

Association between serum 25-hydroxyvitamin D level and myopia in children and adolescents: a cross-sectional study.

Background: Prior reports have indicated an inconsistent relationship between vitamin D levels and myopia in children and adolescents with limited sample size. This study was undertaken to further clarify this relationship with a repeated cross-section study. Methods: The National Health and Nutrition Examination Survey (NHANES) database with samples <19 years old was utilized. Data on rates of myopia (spherical equivalent less than or equal to -1.0 D), serum 25-hydroxyvitamin D [25(OH)D] level (high performance liquid chromatography), and other key variables were extracted and analyzed. Three models were utilized to evaluate the dose response of vitamin D levels using stepwise logistic regression. Logistic regressions for sex subgroups and other covariates were also performed, and Forest plots were drawn. Results: Data were available from 6,814 children (49.5% girls; mean age: 14.9±1.85 years). The myopia and non-myopia differed in serum 25(OH)D level, gender, race, poverty income ratio (PIR), and body mass index (BMI). Serum 25(OH)D levels were negatively correlated with myopia [odds ratio (OR) =0.98, 95% confidence interval (CI): 0.77-0.99, P<0.05] regardless of sex. Although the relationship did not appear to be linear, there was a dose effect with higher serum 25(OH)D levels linked with lower rates of myopia. In addition, rates of myopia were increased in females compared with males (OR =1.12, 95% CI: 1.01-1.24, P=0.03), those with a high PIR (OR =1.08, 95% CI: 1.04-1.11, P<0.001), and those with high BMI (OR =1.19, 95% CI: 1.11-1.27, P<0.001). White ethnicity (OR =0.78, 95% CI: 0.68-0.90, P<0.001) and leisure-time exercise (OR =0.94, 95% CI: 0.92-0.97, P=0.02) were associated with lower rates of myopia. Conclusions: These findings indicate that higher serum 25(OH)D levels and increased amounts of leisure-time exercise are associated with lower rates of myopia in this group of children and adolescents. Meanwhile, female gender, high PIR level, and high BMI were associated with greater rates of myopia. The findings indicated that children and adolescents needed leisure-time exercise to lower the risk of myopia.

The Association Between Malnutrition and High Protein Treatment on Outcomes in Critically Ill Patients: A Post Hoc Analysis of the EFFORT Protein Randomized Trial.

BACKGROUND: Preexisting malnutrition in critically ill patients is associated with adverse clinical outcomes. Malnutrition can be diagnosed with the Global Leadership Initiative on Malnutrition using parameters such as weight loss, muscle wasting, and BMI. International critical care nutrition guidelines recommend high protein treatment to improve clinical outcomes in critically ill patients diagnosed with preexisting malnutrition. However, this recommendation is based on expert opinion. RESEARCH QUESTION: In critically ill patients, what is the association between preexisting malnutrition and time to discharge alive (TTDA), and does high protein treatment modify this association? STUDY DESIGN AND METHODS: This multicenter randomized controlled trial involving 16 countries was designed to investigate the effects of high vs usual protein treatment in 1,301 critically ill patients. The primary outcome was TTDA. Multivariable regression was used to identify if preexisting malnutrition was associated with TTDA and if protein delivery modified their association. RESULTS: The prevalence of preexisting malnutrition was 43.8%, and the cumulative incidence of live hospital discharge by day 60 was 41.2% vs 52.9% in the groups with and without preexisting malnutrition, respectively. The average protein delivery in the high vs usual treatment groups was 1.6 g/kg per day vs 0.9 g/kg per day. Preexisting malnutrition was independently associated with slower TTDA (adjusted hazard ratio, 0.81; 95% CI, 0.67-0.98). However, high protein treatment in patients with and without preexisting malnutrition was not associated with TTDA (adjusted hazard ratios of 0.84 [95% CI, 0.63-1.11] and 0.97 [95% CI, 0.77-1.21]). Furthermore, no effect modification was observed (ratio of adjusted hazard ratio, 0.84; 95% CI, 0.58-1.20). INTERPRETATION: Malnutrition was associated with slower TTDA, but high protein treatment did not modify the association. These findings challenge current international critical care nutrition guidelines. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT03160547; URL: www. CLINICALTRIALS: gov.

Selection of ethanol tolerant strains of Candida albicans by repeated ethanol exposure results in strains with reduced susceptibility to fluconazole.

Candida albicans is a commensal yeast that has important impacts on host metabolism and immune function, and can establish life-threatening infections in immunocompromised individuals. Previously, C. albicans colonization has been shown to contribute to the progression and severity of alcoholic liver disease. However, relatively little is known about how C. albicans responds to changing environmental conditions in the GI tract of individuals with alcohol use disorder, namely repeated exposure to ethanol. In this study, we repeatedly exposed C. albicans to high concentrations (10% vol/vol) of ethanol-a concentration that can be observed in the upper GI tract of humans following consumption of alcohol. Following this repeated exposure protocol, ethanol small colony (Esc) variants of C. albicans isolated from these populations exhibited increased ethanol tolerance, altered transcriptional responses to ethanol, and cross-resistance/tolerance to the frontline antifungal fluconazole. These Esc strains exhibited chromosomal copy number variations and carried polymorphisms in genes previously associated with the acquisition of fluconazole resistance during human infection. This study identifies a selective pressure that can result in evolution of fluconazole tolerance and resistance without previous exposure to the drug.

Ceragenin-coated endotracheal tubes for the reduction of ventilator-associated pneumonia: a prospective, longitudinal, cross-over, interrupted time, implementation study protocol (CEASE VAP study).

BACKGROUND: Critically ill patients are at high risk of acquiring ventilator-associated pneumonia (VAP), which occurs in approximately 20% of mechanically ventilated patients. VAP results either from aspiration of pathogen-contaminated oropharyngeal secretions or contaminated biofilms that form on endotracheal tubes (ETTs) after intubation. VAP results in increased duration of mechanical ventilation, increased intensive care unit and hospital length of stay, increased risk of death and increased healthcare costs. Because of its impact on patient outcomes and the healthcare system, VAP is regarded as an important patient safety issue and there is an urgent need for better evidence on the efficacy of prevention strategies. Modified ETTs that reduce aspiration of oropharyngeal secretions with subglottic secretion drainage or reduce the occurrence of biofilm with a coating of ceragenins (CSAs) are available for clinical use in Canada. In this implementation study, we will evaluate the efficacy of these two types of Health Canada-licensed ETTs on the occurrence of VAP, and impact on patient-centred outcomes. METHODS: In this ongoing, pragmatic, prospective, longitudinal, interrupted time, cross-over implementation study, we will compare the efficacy of a CSA-coated ETT (CeraShield N8 Pharma) with an ETT with subglottic secretion drainage (Taper Guard, Covidien). The study periods consist of four alternating time periods of 11 or 12 weeks or a total of 23 weeks for each ETT. All patients intubated with the study ETT in each time period will be included in an intention-to-treat analysis. Outcomes will include VAP incidence, mortality and health services utilisation including antibiotic use and length of stay. ETHICS AND DISSEMINATION: This study has been approved by the Health Sciences Research Ethics Board at Queen's University. The results of this study will be actively disseminated through manuscript publication and conference presentations. TRIAL REGISTRATION NUMBER: NCT05761613.

Association between urea trajectory and protein dose in critically ill adults: a secondary exploratory analysis of the effort protein trial (RE-EFFORT).

BACKGROUND: Delivering higher doses of protein to mechanically ventilated critically ill patients did not improve patient outcomes and may have caused harm. Longitudinal urea measurements could provide additional information about the treatment effect of higher protein doses. We hypothesised that higher urea values over time could explain the potential harmful treatment effects of higher doses of protein. METHODS: We conducted a reanalysis of a randomised controlled trial of higher protein doses in critical illness (EFFORT Protein). We applied Bayesian joint models to estimate the strength of association of urea with 30-day survival and understand the treatment effect of higher protein doses. RESULTS: Of the 1301 patients included in EFFORT Protein, 1277 were included in this analysis. There were 344 deaths at 30 days post-randomisation. By day 6, median urea was 2.1 mmol/L higher in the high protein group (95% CI 1.1-3.2), increasing to 3.0 mmol/L (95% CI 1.3-4.7) by day 12. A twofold rise in urea was associated with an increased risk of death at 30 days (hazard ratio 1.34, 95% credible interval 1.21-1.48), following adjustment of baseline characteristics including age, illness severity, renal replacement therapy, and presence of AKI. This association persisted over the duration of 30-day follow-up and in models adjusting for evolution of organ failure over time. CONCLUSIONS: The increased risk of death in patients randomised to a higher protein dose in the EFFORT Protein trial was estimated to be mediated by increased urea cycle activity, of which serum urea is a biological signature. Serum urea should be taken into consideration when initiating and continuing protein delivery in critically ill patients. CLINICALTRIALS: gov Identifier: NCT03160547 (2017-05-17).

Physiological Characterization of Preserved Ratio Impaired Spirometry in the CanCOLD Study: Implications for Exertional Dyspnea and Exercise Intolerance.

RATIONALE: It is increasingly recognized that adults with preserved ratio impaired spirometry (PRISm) are prone to increased morbidity. However, the underlying pathophysiological mechanisms are unknown. OBJECTIVES: Evaluate the mechanisms of increased dyspnea and reduced exercise capacity in PRISm. METHODS: We completed a cross-sectional analysis of the CanCOLD population-based study. We compared physiological responses in 59 participants meeting PRISm spirometric criteria (post-bronchodilator FEV1<80% predicted and FEV1/FVC≥0.7), 264 controls, and 170 ever-smokers with chronic obstructive pulmonary disease (COPD), at rest and during cardiopulmonary exercise testing (CPET). MEASUREMENTS AND MAIN RESULTS: PRISm had lower total lung, vital and inspiratory capacities than controls (all p<0.05), and minimal small airway, pulmonary gas-exchange, and radiographic parenchymal lung abnormalities. Compared with control, PRISm had higher dyspnea/oxygen uptake [V̇O2] ratio at peak exercise (4.0±2.2vs2.9±1.9, Borg units/L/min, p<0.001) and lower V̇O2peak (74±22vs96±25% predicted, p<0.001). At standardized submaximal work rates, PRISm had greater tidal volume/inspiratory capacity (VT%IC, p<0.001), reflecting inspiratory mechanical constraint. In contrast to PRISm, COPD had characteristic small airways dysfunction, dynamic hyperinflation, and pulmonary gas-exchange abnormalities. Despite these physiological differences between the 3 groups, the relationship between increasing dyspnea and VT%IC during CPET was similar. Resting IC significantly correlated with V̇O2peak (r=0.65, p<0.001) in the entire sample, even after adjusting for airflow limitation, gas-trapping and diffusing capacity. CONCLUSION: In PRISm, lower exercise capacity and higher exertional dyspnea than healthy controls were mainly explained by lower resting lung volumes and earlier onset of dynamic inspiratory mechanical constraints at relatively low work rates.

Transitional care of adolescents with inflammatory bowel disease to adult services varies widely across Australia and New Zealand.

Background and Aim: Children and adolescents account for approximately 14% of inflammatory bowel disease (IBD) diagnoses. At an appropriate age and level of development adolescents with IBD have their care transferred from the pediatric to adult clinical team during a process termed "transition". The study aim was to survey pediatric gastroenterologists throughout Australasia to identify commonality in the transition process to contribute to standardized guideline development. Methods: A descriptive survey captured key variables: transition clinic format, process and infrastructure, transition assessments, and guidelines. The survey was distributed electronically to 59 Pediatric Gastroenterologists throughout Australasia in January 2023. Results: Seventeen (29%) clinicians completed the survey: Australia 13 (76%). New Zealand 4 (24%). Thirteen (76%) respondents had access to a dedicated IBD transition clinic. Adolescents attended transition clinics 1-7 times, and the main processes transferred were: prescription provision, biologic appointments, and adult team contacts. Transition was first discussed age 13-15 years (53%), or 16-18 years (47%), with the main discussion topics including: continuing adherence (88%), smoking (59%), alcohol use (59%), recreational drug use (59%). Transition readiness assessments were done infrequently (24%). The minority (24%) used formal guidelines to inform the transition process, but 15 (88%) considered the development of a standardized Australasian guideline as beneficial/extremely beneficial. Conclusions: This survey highlighted that transition care for adolescents with IBD is variable across Australasia. Australasian guideline development may optimize the transition process for adolescents with IBD and improve their longitudinal outcomes.

Knowledge Levels About Inflammatory Bowel Disease Vary Between Healthcare Professional Groups.

BACKGROUND: Inflammatory Bowel Disease (IBD) is one of the most serious chronic diseases affecting the global population. Clinical team members involved in the care of individuals with IBD should have sufficient knowledge about IBD. AIMS: The study aim was to assess IBD knowledge among four health care professional groups in New Zealand: nurses, medical students, dietitians, and pharmacists. METHODS: All four groups completed surveys on demographics, work experience, and contact with patients with IBD. All completed a validated IBD knowledge assessment questionnaire (IBD-KID2), and percentage scores with standard deviation (SD) for each group calculated and compared. RESULTS: Participants included 200 nurses, 196 medical students, 45 dietitians, and 28 pharmacists. Mean IBD-KID2 percentage scores were nurses 69.7% (SD 14.7), medical students 77.6% (SD 14.5), dietitians 87.4% (SD 8.3), and pharmacists 83.4% (SD 10.1). Nurses scored lower than other HCP (P < 0.001). Independent variables were associated (P < 0.05) with higher scores for nurses having first degree relative with IBD, access to IBD guidelines, worked with children with IBD; medical students in their clinical years of study; and dietitians with IBD-specific education. Specific items scored poorly: growth, food triggers, heritability of IBD, and nutrient absorption. CONCLUSIONS: Knowledge gaps exist among HCP that may be addressed with targeted education. Improvements in the knowledge of those caring for people with IBD may optimize patient outcomes.

Comparison of Predictive Models for Prevention of Missed Endoscopy Appointments- failure of a Predictive Model to Outperform Overbooking Model.

BACKGROUND: Patient late cancelation and nonattendance for endoscopy appointments is an ongoing problem affecting the productivity and wait times of endoscopy units. Previous research evaluated a model for predictive overbooking and had promising results. STUDY: All endoscopy visits at an outpatient endoscopy unit during 4 nonconsecutive months were included in the data analysis. Patients who did not attend their appointment, or canceled with 48 hours of their appointment were considered nonattendees. Demographic, health, and prior visit behavior data was collected and the groups compared. RESULTS: 1780 patients attended 2331 visits in the study period. Comparing the attendee versus non-attendees, there were significant differences in mean age, prior absenteeism, prior cancelations, and total number of hospital visits. No significant differences were seen between groups in winter versus non-winter months, the day of the week, sex distribution, type of procedure booked, or whether the referral was from specialist clinic or direct to procedure. The visit cancelation proportion (calculated excluding current visit) was substantially higher in the absentee group ( P <0.0001). A predictive model was developed and compared to current booking as well as a straight overbooking of 7%. Both overbooking models performed better than the current practice, but the predictive overbooking model did not outperform straight overbooking. CONCLUSIONS: Developing an endoscopy unit specific predictive model may not be more beneficial than straight overbooking as calculated by missed appointment percentage.

Profile of Helicobacter pylori infections among children in the South Island of New Zealand (2010-2021).

BACKGROUND: Helicobacter pylori is a gram-negative gut bacterium most often acquired during childhood. International guidelines state that children with suspected H. pylori infection should be referred to a gastroenterologist for investigation via gastroscopy and biopsy. Eradication therapy should be prescribed for children with peptic ulcer disease or following a treatment risk/benefit discussion for those with an incidental gastroscopy finding. Guidelines state that for children a "test-and-treat" approach is not warranted, contrasting recommendations for adults. The aim of this study was to profile pediatric H. pylori infections in the South Island of New Zealand (NZ) to determine diagnostic and management strategies, and adherence to international guidelines. MATERIALS AND METHODS: Retrospective data for positive H. pylori tests between 2010 and 2021 were retrieved from hospitals and regional testing laboratories throughout the South Island (NZ) for children ≤18 years. Outcome data were retrieved from tertiary care hospital records; sociodemographic, testing methods, eradication therapy, and symptoms. RESULTS: Two-hundred and forty children were identified: 105 (44%) male, mean age 13.2 years (SD 4.3). Participants of Pasifika, Asian, and Middle Eastern/Latin American/African heritage were overrepresented compared to the NZ census data. Overall, 138 (58%) children were diagnosed via stool antigen tests, 78 (32%) serum, and only 24 (10%) adhered to international guidelines in being confirmed via gastroscopy. Only 59 (25%) had a record of eradication therapy, and 39/59 (66%) were retested to determine eradication success, with 32 (82%) negative tests and seven (18%) remaining positive. Of the 181 (75%) that had eradication status unknown, 66 (28%) had a retest result available with 48 (73%) testing negative and 18 (27%) positive, suggesting a substantial proportion had received eradication therapy without adhering to international guidelines. CONCLUSIONS: International guidelines were not adhered to for most children in the study cohort. Implications of this include cost, unnecessary venipuncture, and unjustified antibiotic exposure.

A Comparison of High and Usual Protein Dosing in Critically Ill Patients With Obesity: A Post Hoc Analysis of an International, Pragmatic, Single-Blinded, Randomized Clinical Trial.

OBJECTIVES: Across guidelines, protein dosing for critically ill patients with obesity varies considerably. The objective of this analysis was to evaluate whether this population would benefit from higher doses of protein. DESIGN: A post hoc subgroup analysis of the effect of higher protein dosing in critically ill patients with high nutritional risk (EFFORT Protein): an international, multicenter, pragmatic, registry-based randomized trial. SETTING: Eighty-five adult ICUs across 16 countries. PATIENTS: Patients with obesity defined as a body mass index (BMI) greater than or equal to 30 kg/m 2 ( n = 425). INTERVENTIONS: In the primary study, patients were randomized into a high-dose (≥ 2.2 g/kg/d) or usual-dose protein group (≤ 1.2 g/kg/d). MEASUREMENTS AND MAIN RESULTS: Protein intake was monitored for up to 28 days, and outcomes (time to discharge alive [TTDA], 60-d mortality, days of mechanical ventilation [MV], hospital, and ICU length of stay [LOS]) were recorded until 60 days post-randomization. Of the 1301 patients in the primary study, 425 had a BMI greater than or equal to 30 kg/m 2 . After adjusting for sites and covariates, we observed a nonsignificant slower rate of TTDA with higher protein that ruled out a clinically important benefit (hazard ratio, 0.78; 95% CI, 0.58-1.05; p = 0.10). We found no evidence of difference in TTDA between protein groups when subgroups with different classes of obesity or patients with and without various nutritional and frailty risk variables were examined, even after the removal of patients with baseline acute kidney injury. Overall, 60-day mortality rates were 31.5% and 28.2% in the high protein and usual protein groups, respectively (risk difference, 3.3%; 95% CI, -5.4 to 12.1; p = 0.46). Duration of MV and LOS in hospital and ICU were not significantly different between groups. CONCLUSIONS: In critically ill patients with obesity, higher protein doses did not improve clinical outcomes, including those with higher nutritional and frailty risk.

Relevance of Protein Intake for Weaning in the Mechanically Ventilated Critically Ill: Analysis of a Large International Database.

OBJECTIVES: The association between protein intake and the need for mechanical ventilation (MV) is controversial. We aimed to investigate the associations between protein intake and outcomes in ventilated critically ill patients. DESIGN: Analysis of a subset of a large international point prevalence survey of nutritional practice in ICUs. SETTING: A total of 785 international ICUs. PATIENTS: A total of 12,930 patients had been in the ICU for at least 96 hours and required MV by the fourth day after ICU admission at the latest. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We modeled associations between the adjusted hazard rate (aHR) of death in patients requiring MV and successful weaning (competing risks), and three categories of protein intake (low: < 0.8 g/kg/d, standard: 0.8-1.2 g/kg/d, high: > 1.2 g/kg/d). We compared five different hypothetical protein diets (an exclusively low protein intake, a standard protein intake given early (days 1-4) or late (days 5-11) after ICU admission, and an early or late high protein intake). There was no evidence that the level of protein intake was associated with time to weaning. However, compared with an exclusively low protein intake, a standard protein intake was associated with a lower hazard of death in MV: minimum aHR 0.60 (95% CI, 0.45-0.80). With an early high intake, there was a trend to a higher risk of death in patients requiring MV: maximum aHR 1.35 (95% CI, 0.99-1.85) compared with a standard diet. CONCLUSIONS: The duration of MV does not appear to depend on protein intake, whereas mortality in patients requiring MV may be improved by a standard protein intake. Adverse effects of a high protein intake cannot be excluded.