Giving adolescents with cystic fibrosis a voice: Predicting cystic fibrosis nutritional adherence from their decision-making involvement.

OBJECTIVE: Suboptimal nutritional adherence in adolescents with cystic fibrosis (awCF) has been associated with lower lung function. AwCF often have more independence in dietary decisions than younger children, yet little research has examined how adolescent decision-making relates to nutritional adherence. This study explored whether components of adolescent decision-making involvement facilitate enzyme and caloric adherence in awCF. METHODS: 37 families participated and completed study procedures. AwCF and caregivers completed electronic surveys, including the Decision-Making Involvement Scale (DMIS). The DMIS evaluated awCF behaviors during nutrition-related decision-making/discussions with caregivers using DMIS subscales: Child Seek (asking for help/advice from caregivers), Child Express (awCF stating opinions) and Joint/Options (awCF participating in joint decision-making or caregiver providing options). AwCF completed 2, 24-hr diet recalls via videoconferencing/phone to estimate adherence. Chart reviews collected medical information. DMIS subscales were regressed onto enzyme and caloric adherence. RESULTS: 43% of awCF met calorie recommendations; 48.6% took all enzymes as prescribed. Caloric adherence was positively correlated with adolescent- and parent-reported Child Seek (r = 0.53; r = 0.36) and adolescent-reported Joint/Options (r = 0.41). Per adolescent-report, the caloric adherence regression model was significant, with Child Seek contributing unique variance in caloric adherence (ß = .62, p = .03). Parent-reported adolescent-decision-making involvement significantly predicted caloric adherence, but none of the subscales contributed unique variance. No other regressions were significant. CONCLUSIONS: When awCF participated in nutrition-related discussions with a caregiver, especially with questions, caloric adherence was better. Future research should examine whether family factors influence these results. AwCF are encouraged to ask questions in nutrition discussions.

Population Pharmacokinetics and Safety of Solithromycin following Intravenous and Oral Administration in Infants, Children, and Adolescents.

Solithromycin is a novel fluoroketolide antibiotic which was under investigation for the treatment of community-acquired bacterial pneumonia (CABP). A phase 1 study was performed to characterize the pharmacokinetics (PK) and safety of solithromycin in children. Eighty-four subjects (median age, 6 years [age range, 4 days to 17 years]) were administered intravenous (i.v.) or oral (capsules or suspension) solithromycin (i.v., 6 to 8 mg/kg of body weight; capsules/suspension, 14 to 16 mg/kg on days 1 and 7 to 15 mg/kg on days 2 to 5). PK samples were collected after the first and multidose administration. Data from 83 subjects (662 samples) were combined with previously collected adolescent PK data (n = 13; median age, 16 years [age range, 12 to 17 years]) following capsule administration to perform a population PK analysis. A 2-compartment PK model characterized the data well, and postmenstrual age was the only significant covariate after accounting for body size differences. Dosing simulations suggested that 8 mg/kg i.v. daily and oral dosing of 20 mg/kg on day 1 (800-mg adult maximum) followed by 10 mg/kg on days 2 to 5 (400-mg adult maximum) would achieve a pediatric solithromycin exposure consistent with the exposures observed in adults. Seventy-six treatment-emergent adverse events (TEAEs) were reported in 40 subjects. Diarrhea (6 subjects) and infusion site pain or phlebitis (3 subjects) were the most frequently reported adverse events related to treatment. Two subjects experienced TEAEs of increased hepatic enzymes that were deemed not to be related to the study treatment. (The phase 1 pediatric studies discussed in this paper have been registered at ClinicalTrials.gov under identifiers NCT01966055 and NCT02268279.).

A Quality Improvement Initiative to Improve Patient Adherence to Vitamin Supplementation in Cystic Fibrosis.

OBJECTIVES: Patients with cystic fibrosis (CF) and pancreatic insufficiency are prescribed fat-soluble vitamins, although compliance remains low. Our objective was to identify patient and caregiver knowledge deficits regarding vitamin supplementation, provide targeted education, and examine serum vitamin levels pre-and posteducation. METHODS: This prospective quality improvement study involved 118 patients. A vitamin knowledge survey was given to patients/caregivers during a clinic visit, education was provided targeting knowledge deficits, and the survey was re-administered at the next clinic visit. Serum vitamin levels were collected at pre- and postsurvey. RESULTS: Results showed significant pre-post increases for patient and caregiver knowledge scores, and significant decreases in self-reported nonadherence to vitamin use and number of reported barriers affecting adherence. A significant change in vitamin E level to therapeutic range post-education was demonstrated. CONCLUSIONS: Our brief, targeted educational interventions regarding vitamin supplementation showed utility in a routine clinic setting.

Phase I Study Assessing the Pharmacokinetic Profile, Safety, and Tolerability of a Single Dose of Ceftazidime-Avibactam in Hospitalized Pediatric Patients.

This study aimed to investigate the pharmacokinetics (PK), safety, and tolerability of a single dose of ceftazidime-avibactam in pediatric patients. A phase I, multicenter, open-label PK study was conducted in pediatric patients hospitalized with an infection and receiving systemic antibiotic therapy. Patients were enrolled into four age cohorts (cohort 1, ≥12 to <18 years; cohort 2, ≥6 to <12 years; cohort 3, ≥2 to <6 years; cohort 4, ≥3 months to <2 years). Patients received a single 2-h intravenous infusion of ceftazidime-avibactam (cohort 1, 2,000 to 500 mg; cohort 2, 2,000 to 500 mg [≥40 kg] or 50 to 12.5 mg/kg [<40 kg]; cohorts 3 and 4, 50 to 12.5 mg/kg). Blood samples were collected to describe individual PK characteristics for ceftazidime and avibactam. Population PK modeling was used to describe characteristics of ceftazidime and avibactam PK across all age groups. Safety and tolerability were assessed. Thirty-two patients received study drug. Mean plasma concentration-time curves, geometric mean maximum concentration (Cmax), and area under the concentration-time curve from time zero to infinity (AUC0-∞) were similar across all cohorts for both drugs. Six patients (18.8%) reported an adverse event, all mild or moderate in intensity. No deaths or serious adverse events occurred. The single-dose PK of ceftazidime and avibactam were comparable between each of the 4 age cohorts investigated and were broadly similar to those previously observed in adults. No new safety concerns were identified. (This study has been registered at ClinicalTrials.gov under registration no. NCT01893346.).

Increasing dental and medical students' understanding of race as a social construct.

PURPOSE: To improve health equity, dental and medical students must have a firm grasp of the proper use of race as a social construct. The purpose of this study was to determine the degree to which an innovative learning event affected students' understanding of race as a social construct. It also sought to examine the effects that personally experienced and/or witnessed racism and previous education had on students' responses to the learning event. METHODS: In 2022, all incoming first-year dental (N = 48) and medical (N = 114) students completed an online pre-matriculation assignment about the use of race in healthcare. Students initially completed an anonymous 14-item pre-survey and then read assigned publications, followed by answering questions about a real-life vignette concerning the topic of race as a social construct. Students finished the assignment by completing an anonymous seven-item post-survey. Data from the pre- and post-surveys were collected and analyzed to assess if differences existed among students and between the two surveys. RESULTS: Dental and medical students were significantly more likely to endorse race as a social construct after the learning experience (p < 0.001). Students who had experienced discrimination or obtained training were more likely to define race as a social construct before and after the learning event. CONCLUSION: Dental and medical schools can increase students' understanding of race as a social construct, rather than a biological construct, with educational interventions.

Discontinuation versus continuation of hypertonic saline or dornase alfa in modulator treated people with cystic fibrosis (SIMPLIFY): results from two parallel, multicentre, open-label, randomised, controlled, non-inferiority trials.

BACKGROUND: Reducing treatment burden is a priority for people with cystic fibrosis, whose health has benefited from using new modulators that substantially increase CFTR protein function. The SIMPLIFY study aimed to assess the effects of discontinuing nebulised hypertonic saline or dornase alfa in individuals using the CFTR modulator elexacaftor plus tezacaftor plus ivacaftor (ETI). METHODS: The SIMPLIFY study included two parallel, multicentre, open-label, randomised, controlled, non-inferiority trials at 80 participating clinics across the USA in the Cystic Fibrosis Therapeutics Development Network. We included individuals with cystic fibrosis aged 12-17 years with percent predicted FEV1 (ppFEV1) of 70% or more, or those aged 18 years or older with ppFEV1 of 60% or more, if they had been taking ETI and either (or both) mucoactive therapies (≥3% hypertonic saline or dornase alfa) for at least 90 days before screening. Participants on both hypertonic saline and dornase alfa were randomly assigned to one of the two trials, and those on a single therapy were assigned to the applicable trial. All participants were then randomly assigned 1:1 to continue or discontinue therapy for 6 weeks using permuted blocks of varying size, stratified by baseline ppFEV1 (week 0; ≥90% or <90%), single or concurrent use of hypertonic saline and dornase alfa, previous SIMPLIFY study participation (yes or no), and age (≥18 or <18 years). For participants randomly assigned to continue their therapy during a given trial, this therapy was instructed to be taken at least once daily according to each participant's pre-existing, clinically prescribed regimen. Hypertonic saline concentration was required to be at least 3%. The primary objective for each trial was to determine whether discontinuing was non-inferior to continuing, measured by the 6-week change in ppFEV1 in the per-protocol population. We established a non-inferiority margin of -3% for the difference between groups in the 6-week change in ppFEV1. Safety outcomes were analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, NCT04378153. FINDINGS: From Aug 25, 2020, to May 25, 2022, a total of 672 unique participants were screened for eligibility for one or both trials, resulting in 847 total random assignments across both trials with 594 unique participants. 370 participants were randomly assigned in the hypertonic saline trial and 477 in the dornase alfa trial. Participants across both trials had an average ppFEV1 of 96·9%. Discontinuing treatment was non-inferior to continuing treatment with respect to the absolute 6-week change in ppFEV1 in both the hypertonic saline trial (-0·19% [95% CI -0·85 to 0·48] in the discontinuation group [n=133] vs 0·14% [-0·51 to 0·78] in the continuation group [n=140]; between-group difference -0·32% [-1·25 to 0·60]) and dornase alfa trial (0·18% [-0·38 to 0·74] in the discontinuation group [n=199] vs -0·16% [-0·73 to 0·41] in the continuation group [n=193]; between-group difference 0·35% [-0·45 to 1·14]), with consistent results in the intention-to-treat populations. In the hypertonic saline trial, 64 (35%) of 184 in the discontinuation group versus 44 (24%) of 186 participants in the continuation group and, in the dornase alfa trial, 89 (37%) of 240 in the discontinuation group versus 55 (23%) of 237 in the continuation group had at least one adverse event. INTERPRETATION: In individuals with cystic fibrosis on ETI with relatively well preserved pulmonary function, discontinuing daily hypertonic saline or dornase alfa for 6 weeks did not result in clinically meaningful differences in pulmonary function when compared with continuing treatment.

Teaching Diagnostic Reasoning to Faculty Using an Assessment for Learning Tool: Training the Trainer.

Introduction: There is a need for a standardized approach to understand and assess clinical reasoning in medical learners. The Assessment of Reasoning Tool was developed based on prevalent theories and frameworks using a multidisciplinary expert panel. As the tool provides a standardized rubric for assessing clinical reasoning, we designed an interactive train-the-trainer workshop for clinical educators and education leaders interested in improving their teaching skills and/or introducing curricula surrounding diagnostic reasoning. Methods: In this workshop, participants were exposed to the major domains of diagnostic reasoning and how to apply it to the assessment of a learner's skills. Kolb's experiential learning was the underlying model, which we showcased by using multiple interactive techniques, including small-group discussion, peer sharing, and case practice. We presented the workshop at a national conference of pediatric educators and as a faculty development workshop at a single institution. Participants were asked to complete a survey after the workshop to gauge their reactions and look for areas of improvement. Results: A total of 34 participants attended the two workshops. Participants rated the workshop favorably, with most planning to make a change to their practice. Comments were largely positive, emphasizing the benefits of the interactive approach. Discussion: The workshop and teaching materials represent an important early step in the workplace-based assessment of diagnostic reasoning in medical learners. Grounded in the clinical reasoning literature, the workshop offers one approach to assessing these skills in learners with or without direct observation of clinical skills.

A token economy for exercise adherence in pediatric cystic fibrosis: a single-subject analysis.

OBJECTIVE: In cystic fibrosis (CF), adherence to airway clearance techniques (e.g., chest physiotherapy and exercise) is poor. Exercise is important because pulmonary difficulties are associated with the highest mortality rate. Despite this, very little research has focused on exercise adherence in CF. This study examined a token economy for increasing exercise in children with CF. METHODS: An ABAB single-subject design evaluated a token economy for increasing and maintaining exercise in three children with CF. Patient report, parent report, and physiological measures were used to assess treatment integrity, medical stability, and changes in exercise. RESULTS: Measures suggested that treatment integrity was strong. Results indicated strong treatment effects for all participants without negative medical side effects. Follow-up of 1 and 3 months supported continued exercise for all participants. CONCLUSIONS: A token economy effectively increased exercise in children with CF, and the single-subject design highlighted some of the intricacies of individualized treatment of adherence. Implications and recommendations for further research are discussed.

Time out based discipline strategy for children's non-compliance with cystic fibrosis treatment.

PURPOSE: To evaluate a time out based discipline strategy designed to decrease treatment avoidance in children with cystic fibrosis (CF) who displayed non-compliant behaviour to their parents' treatment requests. METHOD: A single-subject reversal design was used to compare baseline compliance when a time out based discipline strategy was in effect. Outcome measures included observational assessments of compliance, parent ratings of child treatment-related behaviour problems and parent reported preference for the time out strategy. RESULTS: Greater compliance was demonstrated when the time out strategy was in place. Parents reported fewer treatment-related behaviour problems and desired less professional help for these problems upon completion of the study and reported preferring the time out discipline strategy to their typical child management strategy. CONCLUSIONS: This discipline strategy represents a practical and appealing brief intervention that is shown to help parents maximise their children's participation in life-extending treatments. This intervention minimises the need for parent-therapist interaction, which may be of particular importance to families of patients with CF who already devote significant time to medical appointments and interventions. The preliminary nature of this data and lack of reversal for one of the participants emphasise the need for additional research to replicate the findings.

Leuconostoc spp sepsis in an extremely low birth weight infant: a case report and review of the literature.

A three week old extremely low birth weight (ELBW) infant infected by vancomycin-resistant Leuconostoc spp is presented. Treatment with appropriate antibiotics was successful after the percutaneous inserted central catheter (PICC) was removed. The infection with Leuconostoc spp is rare but should be suspected when vancomycin-resistant organisms resembling streptococci are isolated. Previous pediatric case reports are also summarized and reviewed.

Bilateral maculopathy in a patient with ataxia telangiectasia.

We report a case of toxoplasmosis with bilateral maculopathy in a 7-year-old boy diagnosed with ataxia telangiectasia (AT) at age 6. AT manifests as ataxia, apraxia, telangiectasia, and dysarthria. Common ophthalmologic findings in AT include fine conjunctival telangiectasia. Patients also suffer from recurrent sinopulmonary infections; however, serious opportunistic infection is rarely diagnosed. At 8 years of age he developed disseminated Toxoplasma gondii (toxoplasmosis) infection and meningoencephalitis. This ophthalmologic finding and the subsequent toxoplasmosis meningoencephalitis have not been previously reported in AT.

Congenital Herpes Simplex Virus in the Newborn: A Diagnostic Dilemma.

Although congenital herpes simplex virus (HSV) infection is rare, it is associated with severe morbidity. We report a 36-week gestational age infant who presented with atypical skin lesions, presumably mitigated by exposure to maternal antiviral suppressive therapy. The initial absence of typical herpetic vesicles and lack of viral detection in skin lesions delayed the correct diagnosis, highlighting the importance of differentiating HSV from other neonatal rashes.

The impact of cystic fibrosis on recovery from orthopedic trauma: a case study.

Cystic Fibrosis has effects on many body systems, including the skeletal system. In this case, we describe the impact of respiratory and endocrine disease on bone healing following orthopedic trauma in a 22-year-old woman. Limitations to mobility resulting from trauma complicated her respiratory condition. Disease-related effects on bone health and healing delayed her recovery from the trauma. It is important to recognize the multisystemic nature of CF, even when managing acute orthopedic injuries.

Pediatric infectious disease: unusual head and neck infections.

Infections in children in the head and neck regions are common, leading to frequent use and overuse of antibiotics. This review includes common as well as diverse and unusual infectious diseases, such as PFAPA (Periodic Fever Aphthous stomatitis, Pharyngitis, Adenitis) syndrome, Lemierre Syndrome, Arcanobacterium infection, and tuberculous and nontuberculous adenitis, which occur in infants, children, and adolescents. In addition, the first pediatric vaccines available with the potential to prevent oropharyngeal cancers are reviewed.

Impact of a Multimodal Antimicrobial Stewardship Program on Pseudomonas aeruginosa Susceptibility and Antimicrobial Use in the Intensive Care Unit Setting.

Objective. To study the impact of our multimodal antibiotic stewardship program on Pseudomonas aeruginosa susceptibility and antibiotic use in the intensive care unit (ICU) setting. Methods. Our stewardship program employed the key tenants of published antimicrobial stewardship guidelines. These included prospective audits with intervention and feedback, formulary restriction with preauthorization, educational conferences, guidelines for use, antimicrobial cycling, and de-escalation of therapy. ICU antibiotic use was measured and expressed as defined daily doses (DDD) per 1,000 patient-days. Results. Certain temporal relationships between antibiotic use and ICU resistance patterns appeared to be affected by our antibiotic stewardship program. In particular, the ICU use of intravenous ciprofloxacin and ceftazidime declined from 148 and 62.5 DDD/1,000 patient-days to 40.0 and 24.5, respectively, during 2004 to 2007. An increase in the use of these agents and resistance to these agents was witnessed during 2008-2010. Despite variability in antibiotic usage from the stewardship efforts, we were overall unable to show statistical relationships with P. aeruginosa resistance rate. Conclusion. Antibiotic resistance in the ICU setting is complex. Multimodal stewardship efforts attempt to prevent resistance, but such programs clearly have their limits.

Efficacy and Safety of a New Formulation of Pancrelipase (Ultrase MT20) in the Treatment of Malabsorption in Exocrine Pancreatic Insufficiency in Cystic Fibrosis.

Background. Pancreatic enzyme replacement therapy is the standard of care for treatment of malabsorption in patients with cystic fibrosis (CF) and exocrine pancreatic insufficiency (PI). Aim. To evaluate efficacy and safety of a new formulation of pancrelipase (Ultrase MT20) in patients with CF and PI. Coefficients of fat absorption (CFA%) and nitrogen absorption (CNA%) were the main efficacy parameters. Safety was evaluated by monitoring laboratory analyses, adverse events (AEs), and overall signs and symptoms. Methods. Patients (n = 31) were randomized in a crossover design comparing this pancrelipase with placebo during 2 inpatient evaluation periods (6-7 days each). Fat and protein/nitrogen ingestion and excretion were measured from food diaries and 72-hour stool collections. CFA% and CNA% were calculated for each period and compared. Results. Twenty-four patients provided analyzable data. This pancrelipase increased mean CFA% and CNA% (+34.7% and +25.7%, resp., P < .0001 for both), reduced stool frequency, and improved stool consistency compared with placebo. Placebo-treated patients reported more AEs, with gastrointestinal symptoms being the most frequently reported AE. Conclusions. This pancrelipase is a safe and effective treatment for malabsorption associated with exocrine PI in patients with CF.