The optimal thresholds for the initiation of invasive ventilation in patients with hypoxemic respiratory failure are unknown. Using the saturation-to-inspired oxygen ratio (SF), we compared lower ...versus higher hypoxemia severity thresholds for initiating invasive ventilation.
This target trial emulation included patients from the Medical Information Mart for Intensive Care (MIMIC-IV, 2008-2019) and the Amsterdam University Medical Centers (AmsterdamUMCdb, 2003-2016) databases admitted to intensive care and receiving inspired oxygen fraction ≥ 0.4 via non-rebreather mask, noninvasive ventilation, or high-flow nasal cannula. We compared the effect of using invasive ventilation initiation thresholds of SF < 110, < 98, and < 88 on 28-day mortality. MIMIC-IV was used for the primary analysis and AmsterdamUMCdb for the secondary analysis. We obtained posterior means and 95% credible intervals (CrI) with nonparametric Bayesian G-computation.
We studied 3,357 patients in the primary analysis. For invasive ventilation initiation thresholds SF < 110, SF < 98, and SF < 88, the predicted 28-day probabilities of invasive ventilation were 72%, 47%, and 19%. Predicted 28-day mortality was lowest with threshold SF < 110 (22.2%, CrI 19.2 to 25.0), compared to SF < 98 (absolute risk increase 1.6%, CrI 0.6 to 2.6) or SF < 88 (absolute risk increase 3.5%, CrI 1.4 to 5.4). In the secondary analysis (1,279 patients), the predicted 28-day probability of invasive ventilation was 50% for initiation threshold SF < 110, 28% for SF < 98, and 19% for SF < 88. In contrast with the primary analysis, predicted mortality was highest with threshold SF < 110 (14.6%, CrI 7.7 to 22.3), compared to SF < 98 (absolute risk decrease 0.5%, CrI 0.0 to 0.9) or SF < 88 (absolute risk decrease 1.9%, CrI 0.9 to 2.8).
Initiating invasive ventilation at lower hypoxemia severity will increase the rate of invasive ventilation, but this can either increase or decrease the expected mortality, with the direction of effect likely depending on baseline mortality risk and clinical context.
The Symptom Screening in Pediatrics Tool (SSPedi) is valid for assessing symptoms in children aged 8-18 years receiving cancer treatments. The objective was to develop a new self-report symptom ...screening tool for children receiving cancer treatments who are 4-7 years of age (mini-SSPedi), based on SSPedi.
Respondents were children with cancer or pediatric hematopoietic stem cell transplantation (HSCT) recipients who were 4-7 years of age. We included the same 15 symptoms contained in SSPedi. Using cognitive interviewing, we developed mini-SSPedi in three phases and made decisions based upon respondent understanding. First, we developed questionnaire structure regarding recall period, concept of bother and response option format. Second, we determined wording of each symptom. Third, we evaluated the entire mini-SSPedi instrument for understanding and ease of completion.
We enrolled 100 participants in total and included 30, 40 and 30 in each of the three phases. Questionnaire structure was satisfactory with a recall period of "today" and a faces-based 3-point Likert scale. Bother was well-understood. Five symptoms required modification to achieve satisfactory understanding while the remaining 10 SSPedi symptoms did not require modification. Among the last 10 children enrolled, all understood each mini-SSPedi item and none thought mini-SSPedi was hard to complete.
We developed a symptom screening tool for children with cancer and pediatric HSCT recipients between 4 and 7 years of age that is understandable and easy to complete. Future work will evaluate the psychometric properties of mini-SSPedi and develop an electronic version of the instrument.
Benefits of prophylactic hematopoietic colony-stimulating factors (CSFs) in adults and children receiving cancer chemotherapy or undergoing stem-cell transplantation (SCT) are unclear.
To determine ...whether prophylactic CSFs decrease mortality, infections, and febrile neutropenia more than does placebo or no therapy in patients with cancer and in patients undergoing SCT.
Electronic searches of Ovid MEDLINE and EMBASE from inception until April 2007 and of the Cochrane Central Register of Controlled Trials until the second quarter of 2006.
We selected 148 trials that were reported in any language that randomly assigned patients to CSFs or to either placebo or no therapy. Prophylactic CSFs were given concurrently with or after initiation of chemotherapy.
Two reviewers independently extracted data onto standardized forms.
Short-term all-cause mortality appeared to be similar between the prophylactic CSF and the control groups (7.6% vs. 8.0%; relative risk, 0.95 95% CI, 0.84 to 1.08; absolute risk reduction, 0.4% CI, -0.5% to 1.4%). Risks for infection-related death with CSFs and placebo or no therapy were 3.1% and 3.8%, respectively (relative risk, 0.82 CI, 0.66 to 1.02; absolute risk reduction, 0.8% CI, 0.0% to 1.5%). Use of CSFs reduced the following more than did placebo or no therapy: documented infections (median rate, 38.9% vs. 43.1%; rate ratio, 0.85 CI, 0.79 to 0.92), microbiologically documented infections (median rate, 23.5% vs. 28.6%; rate ratio, 0.86 CI, 0.77 to 0.96), and episodes of febrile neutropenia (median rate, 25.3% vs. 44.2%; rate ratio, 0.71 CI, 0.63 to 0.80).
Trial designs, including assessments of infections, and participants were heterogeneous. Estimates of mortality effects were imprecise.
Prophylactic CSFs may have little or no effect on mortality but do decrease rates of infection in patients receiving cancer chemotherapy or those undergoing SCT.
The objectives of the study were to describe quality of life (QoL), identify predictors of worse QoL and examine QoL during different phases of active therapy for acute lymphoblastic leukemia (ALL). ...A multiinstitutional cross‐sectional study was performed in children with ALL. We included children at least 2 months from diagnosis who were receiving treatment in first remission. Parents described QoL using the PedsQL 4.0 Generic Core Scales and the PedsQL 3.0 Acute Cancer Module. The 206 children on treatment for ALL had overall median 62.5, 95% confidence interval (CI) 34.8–94.4, physical (median 62.5, 95% CI 18.8–100.0) and psychosocial (median 65.4, 95% CI 38.3–94.2) summary scores that were one to two standard deviations lower than population norms. In high‐risk ALL, girls and older children had worse QoL. In standard‐risk ALL, those with lower household incomes and unmarried parents had worse QoL. QoL scores were generally constant across phases of ALL therapy. Children on therapy for ALL have lower QoL compared to healthy children. Age and gender predicted QoL in high‐risk ALL, whereas socioeconomics predicted QoL in standard‐risk ALL. Future efforts should focus on longitudinal studies that describe QoL over time within individual patients.
Summary Treatment-related mortality is an important outcome in paediatric cancer clinical trials. An international group of experts in supportive care in paediatric cancer developed a consensus-based ...definition of treatment-related mortality and a cause-of-death attribution system. The reliability and validity of the system was tested in 30 deaths, which were independently assessed by two clinical research associates and two paediatric oncologists. We defined treatment-related mortality as death occurring in the absence of progressive cancer. Of the 30 reviewed deaths, the reliability of classification for treatment-related mortality was noted as excellent by clinical research associates (κ=0·83, 95% CI 0·60–1·00) and paediatric oncologists (0·84, 0·63–1·00). Criterion validity was established because agreement between the consensus classifications by clinical research associates and paediatric oncologists was almost perfect (0·92, 0·78–1·00). Our approach should allow comparison of treatment-related mortality across trials and across time.
To develop a summary format of clinical practice guideline (CPG) recommendations to improve understandability among health care professionals.
We developed a summary format based on current research ...and used the "Think Aloud" technique in one-on-one cognitive interviews to iteratively improve it. Interviews of health care professionals from Children's Oncology Group-member, National Cancer Institute Community Oncology Research Program sites were conducted. After every five interviews (a round), responses were reviewed, and changes made to the format until it was well understood and no new, substantive suggestions for revision were raised. We took a directed (deductive) approach to content analysis of the interview notes to identify concerns related to recommendation summary usability, understandability, validity, applicability and visual appeal.
During seven rounds of interviews with 33 health care professionals, we identified important factors that influenced understandability. Participants found understanding weak recommendations more challenging than strong recommendations. Understanding was improved when the term 'conditional' recommendation was used instead of 'weak' recommendation. Participants found a Rationale section to be very helpful but desired more information when a recommendation entailed a practice change. In the final format, the recommendation strength is clearly indicated in the title, highlighted, and defined within a text box. The rationale for the recommendation is in a column on the left, with supporting evidence on the right. In a bulleted list, the Rationale section describes the benefits and harms and additional factors, such as implementation, that were considered by the CPG developers. Each bullet under the supporting evidence section indicates the level of evidence with an explanation and the supporting studies with hyperlinks when applicable.
A summary format to present strong and conditional recommendations was created through an iterative interview process. The format is straightforward, making it easy for organizations and CPG developers to use it to communicate recommendations clearly to intended users.
Diagnostic codes are commonly used as inputs for clinical prediction models, to create labels for prediction tasks, and to identify cohorts for multicenter network studies. However, the coverage ...rates of diagnostic codes and their variability across institutions are underexplored. The primary objective was to describe lab- and diagnosis-based labels for 7 selected outcomes at three institutions. Secondary objectives were to describe agreement, sensitivity, and specificity of diagnosis-based labels against lab-based labels.
This study included three cohorts: SickKids from The Hospital for Sick Children, and StanfordPeds and StanfordAdults from Stanford Medicine. We included seven clinical outcomes with lab-based definitions: acute kidney injury, hyperkalemia, hypoglycemia, hyponatremia, anemia, neutropenia and thrombocytopenia. For each outcome, we created four lab-based labels (abnormal, mild, moderate and severe) based on test result and one diagnosis-based label. Proportion of admissions with a positive label were presented for each outcome stratified by cohort. Using lab-based labels as the gold standard, agreement using Cohen's Kappa, sensitivity and specificity were calculated for each lab-based severity level.
The number of admissions included were: SickKids (n = 59,298), StanfordPeds (n = 24,639) and StanfordAdults (n = 159,985). The proportion of admissions with a positive diagnosis-based label was significantly higher for StanfordPeds compared to SickKids across all outcomes, with odds ratio (99.9% confidence interval) for abnormal diagnosis-based label ranging from 2.2 (1.7-2.7) for neutropenia to 18.4 (10.1-33.4) for hyperkalemia. Lab-based labels were more similar by institution. When using lab-based labels as the gold standard, Cohen's Kappa and sensitivity were lower at SickKids for all severity levels compared to StanfordPeds.
Across multiple outcomes, diagnosis codes were consistently different between the two pediatric institutions. This difference was not explained by differences in test results. These results may have implications for machine learning model development and deployment.
BACKGROUND:Candida species are the third most common cause of pediatric health care–associated bloodstream infection in the United States and Europe. To our knowledge, this report from the ...International Pediatric Fungal Network is the largest prospective, multicenter observational study dedicated to pediatric and neonatal invasive candidiasis.
METHODS:From 2007 to 2011, we enrolled 196 pediatric and 25 neonatal patients with invasive candidiasis.
RESULTS:Non-albicans Candida species predominated in pediatric (56%) and neonatal (52%) age groups, yet Candida albicans was the most common species in both groups. Successful treatment responses were observed in pediatric (76%) and neonatal patients (92%). Infection with Candida parapsilosis led to successful responses in pediatric (92%) and neonatal (100%) patients, whereas infection with Candida glabrata was associated with a lower successful outcome in pediatric patients (55%). The most commonly used primary antifungal therapies for pediatric invasive candidiasis were fluconazole (21%), liposomal amphotericin B (20%) and micafungin (18%). Outcome of pediatric invasive candidiasis was similar in response to polyenes (73%), triazoles (67%) and echinocandins (73%). The most commonly used primary antifungal therapies for neonatal invasive candidiasis were fluconazole (32%), caspofungin (24%) and liposomal amphotericin B (16%) and micafungin (8%). Outcomes of neonatal candidiasis by antifungal class again revealed similar response rates among the classes.
CONCLUSIONS:We found a predominance of non-albicans Candida infection in children and similar outcomes based on antifungal class used. This international collaborative study sets the foundation for large epidemiologic studies focusing on the unique features of neonatal and pediatric candidiasis and comparative studies of therapeutic interventions in these populations.
The study purpose is to describe trajectories of financial distress for parents of children (ages 1-14.9 years) with newly diagnosed acute lymphoblastic leukemia (ALL). The secondary aim is to ...identify multilevel factors (child, parent, household, treating institution) that influence change in financial distress over time.
The study uses a prospective cohort design, repeated measurements, and mixed methods. The settings are Children's Oncology Group (COG) institutions participating in the National Cancer Institute Community Oncology Research Program (NCORP). Eligible participants are English- and/or Spanish-speaking parents or legal guardians (hereafter "parents") of index children. Parents are asked to complete a survey during their child's induction (T1) and maintenance therapy (T2), and near treatment completion (T3). Study surveys include items about (a) the child's cancer and clinical course, (b) parental socio-economic status, financial distress and financial coping behaviors, and (c) household material hardships. At least 15 parents will be invited to participate in an optional semi-structured interview. NCORP institutions that enroll at least one parent must complete an annual survey about institution resources that could influence parental financial distress.
The results will inform future interventions to mitigate financial distress for parents of children diagnosed with ALL and could be instructive beyond this disease group.
This trial was initially registered with the NCI Clinical Trial Reporting Program ID: NCI-2021-03,567 on June 16, 2021. The study can be found on clinicaltrials.gov, Identifier NCT04928599 .
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