Xylitol for the prevention of acute otitis media episodes in children aged 1-5 years: a randomised controlled trial.

OBJECTIVE: To investigate the regular use of xylitol, compared with sorbitol, to prevent acute otitis media (AOM), upper respiratory tract infections (URTIs) and dental caries. DESIGN: Blinded randomised controlled trial with a 6-month study period. SETTING: Enrolment took place at 11 primary care practices in Ontario, Canada. PATIENTS: Children aged 1-5 years who did not use xylitol or sorbitol at enrolment. INTERVENTIONS: Children were randomly assigned to use a placebo syrup with sorbitol or xylitol syrup two times per day for 6 months. MAIN OUTCOME MEASURES: Primary outcome was the number of clinician-diagnosed AOM episodes over 6 months. Secondary outcomes were caregiver-reported URTIs and dental caries. RESULTS: Among the 250 randomised children, the mean (SD) age was 38±14 months and there were 124 girls (50%). There were three clinician-diagnosed AOM episodes in the 125 placebo group participants and six in the 125 xylitol group participants (OR 2.04; 95% CI 0.43, 12.92; p=0.50). There was no difference in number of caregiver-reported URTI episodes (rate ratio (RR) 0.88; 95% CI 0.70, 1.11) between the placebo (4.2 per participant over 6 months; 95% CI 3.6, 5.0) and xylitol (3.7; 95% CI 3.2, 4.4) groups. Dental caries were reported for four participants in the placebo group and two in the xylitol group (OR 0.42; 95% CI 0.04, 3.05; p=0.42). In a post-hoc analysis of URTIs during the COVID-19 pandemic, the rate among the 59 participants receiving placebo was 2.3 per participant over 6 months (95% CI 1.8, 3.0) and for the 55 receiving xylitol, 1.3 over 6 months (95% CI 0.92, 1.82; RR 0.56; 95% CI 0.36, 0.87). The most common adverse event was diarrhoea (28% with placebo; 34% with xylitol). CONCLUSIONS: Regular use of xylitol did not prevent AOM, URTIs or dental caries in a trial with limited statistical power. A post-hoc analysis indicated that URTIs were less common with xylitol exposure during the COVID-19 pandemic, but this finding could be spurious. TRIAL REGISTRATION NUMBER: NCT03055091.

"I don't need any more unknowns hanging over my head": Views of patients with cancer on variants of uncertain significance and low/moderate risk results from genomic sequencing.

PURPOSE: We sought to explore patient-reported utility of all types of cancer results from genomic sequencing (GS). METHODS: Qualitative study, using semi-structured interviews with patients who underwent GS within a trial. Thematic analysis employing constant comparison was used. Two coders coded transcripts, with use of a third coder to resolve conflicts. RESULTS: 25 patients participated: female (22), >50 years (18), European (12), Ashkenazi Jewish (5), Middle Eastern (3), or other ethnicity (5), with breast cancer history (20). Patients' perceptions of the utility of cancer GS results hinged on whether they triggered clinical action. For example, when patients were enrolled into high-risk breast cancer surveillance programs for low/moderate risk breast cancer genes, they perceived the results to be very "useful" and of moderate-high utility. In contrast, patients receiving low/moderate risk or primary variants of uncertain significance results without clinical action perceived results as "concerning," leading to harms, such as hypervigilance about cancer symptoms. Overall, having supportive relatives or providers enhanced perceptions of utility. CONCLUSION: Patients' perceptions of cancer GS results hinged on whether they triggered clinical management. Consequently, patients who received results without clinical action became hypervigilant, experiencing harms. Our findings call for a need to develop practice interventions to support patients with cancer undergoing GS.

Effect of Free Medicine Distribution on Health Care Costs in Canada Over 3 Years: A Secondary Analysis of the CLEAN Meds Randomized Clinical Trial.

Importance: Few interventions are proven to reduce total health care costs, and addressing cost-related nonadherence has the potential to do so. Objective: To determine the effect of eliminating out-of-pocket medication fees on total health care costs. Design, Setting, and Participants: This secondary analysis of a multicenter randomized clinical trial using a prespecified outcome took place across 9 primary care sites in Ontario, Canada (6 in Toronto and 3 in rural areas), where health care services are generally publicly funded. Adult patients (≥18 years old) reporting cost-related nonadherence to medicines in the past 12 months were recruited between June 1, 2016, and April 28, 2017, and followed up until April 28, 2020. Data analysis was completed in 2021. Interventions: Access to a comprehensive list of 128 medicines commonly prescribed in ambulatory care with no out-of-pocket costs for 3 years vs usual medicine access. Main Outcome and Measures: Total publicly funded health care costs over 3 years, including costs of hospitalizations. Health care costs were determined using administrative data from Ontario's single-payer health care system, and all costs are reported in Canadian dollars with adjustments for inflation. Results: A total of 747 participants from 9 primary care sites were included in the analysis (mean [SD] age, 51 [14] years; 421 [56.4%] female). Free medicine distribution was associated with a lower median total health care spending over 3 years of $1641 (95% CI, $454-$2792; P = .006). Mean total spending was $4465 (95% CI, -$944 to $9874) lower over the 3-year period. Conclusions and Relevance: In this secondary analysis of a randomized clinical trial, eliminating out-of-pocket medication expenses for patients with cost-related nonadherence in primary care was associated with lower health care spending over 3 years. These findings suggest that eliminating out-of-pocket medication costs for patients could reduce overall costs of health care. Trial Registration: ClinicalTrials.gov Identifier: NCT02744963.

Anticoagulant use and associated outcomes in older patients receiving home palliative care: a retrospective cohort study.

BACKGROUND: The benefits and harms of anticoagulants for people near the end of life are not well understood, nor is it known what proportion of patients discontinue these medications. We aimed to characterize anticoagulant use in older recipients of home palliative care and describe patient and provider characteristics, as well as outcomes associated with anticoagulant discontinuation in this group. METHODS: Using linked administrative health databases, we conducted a population-based cohort study of patients aged 66 years and older who initiated home palliative care in Ontario from 2010 to 2018. We calculated the prevalence of anticoagulant use. We used multilevel logistic regression models to assess patient (e.g., sociodemographic, comorbidities) and physician (e.g., demographic, training, practice) factors associated with anticoagulant discontinuation after initiation of home palliative care. We defined discontinuation as either primary (no anticoagulant claim within 1.5 times the days' supply of the previous prescription) or secondary (no subsequent anticoagulant claim at any time after the index date). In secondary analyses, we used cause-specific hazards regression to explore subsequent thrombotic and bleeding events associated with anticoagulant discontinuation, and multivariable logistic regression for location of death. RESULTS: We identified 98 089 recipients of home palliative care, of whom 15.5% were taking anticoagulants at the time of the first palliative care visit. Depending on the definition of discontinuation, 18.0% to 24.4% of patients discontinued anticoagulants after the first home palliative care visit. Compared with warfarin, use of a direct oral anticoagulant (adjusted odds ratio [OR] 0.49, 95% confidence interval [CI] 0.43-0.56) and low-molecular-weight heparin (adjusted OR 0.56, 95% CI 0.47-0.66) were associated with a lower likelihood of discontinuation. Few patient or physician characteristics - and no comorbidities or indications for therapeutic anticoagulation - were associated with discontinuation. Anticoagulant discontinuation after beginning home palliative care was associated with similar rates of thrombosis (adjusted hazard ratio [HR] 1.06, 95% CI 0.81-1.39), lower rates of bleeding (adjusted HR 0.75, 95% CI 0.62-0.90) and a higher likelihood of a home death (adjusted OR 1.22, 95% CI 1.09-1.36) compared with continuing anticoagulation. INTERPRETATION: Among recipients of home palliative care in Ontario, anticoagulant use is common, and discontinuation is not influenced by comorbidities or indication for anticoagulation. Physician preference may play an important role; patients should be made aware of their options toward the end of life and supported in shared decision-making.