Brochure intervention to manage bothersome taste changes in pediatric patients receiving cancer therapy.

BACKGROUND: Primary objective was to determine if a patient informational brochure describing potentially useful strategies could help manage specific taste changes. Secondary objective was to describe the specific strategies used and whether the strategies were perceived as being helpful. PROCEDURE: This single-center study included pediatric patients with cancer or hematopoietic cell transplant recipients receiving active treatment who experienced bothersome taste changes in the last month. Participants participated in baseline and follow-up interviews conducted 14-21 days apart. A brochure that listed 16 potentially helpful strategies was provided at baseline. At follow-up, we asked about brochure use and whether it helped. At both interviews, we asked about experienced taste changes, strategies used, and whether strategy helped. RESULTS: Of 100 enrolled participants, different (87%) and bad (72%) taste were most common at baseline. Following the brochure intervention, statistically significant reductions were observed in food tasting different, bad, bland, bitter, sour, and metallic. For most strategies, the proportion of patients who used specific strategies or found them helpful was not significantly different between baseline and follow-up. However, "eating foods you like" was considered helpful in significantly more participants who used the strategy in follow-up (72 out of 89, 80.9%) compared with baseline (55 out of 95, 57.9%; p = .008). Between visits, 81.2% looked at the brochure. Among participants, 53.1% found the brochure helpful, very helpful, or extremely helpful. CONCLUSIONS: A brochure that offered strategies to manage changes in taste helped participants cope with them. Further research should evaluate the brochure using randomized and multicenter trials.

Mucositis reduction with probiotics in children with cancer: a randomised-controlled feasibility study.

BACKGROUND: A recent systematic review and meta-analysis identified a paucity of randomised-controlled trials (RCTs) investigating the use of probiotics to reduce or prevent mucositis and infection in children with cancer. OBJECTIVE: This study evaluated the feasibility of undertaking an RCT and investigated the efficacy of probiotics for reducing or preventing mucositis and infection in children with cancers. SETTING: The Paediatric Oncology and Haematology department at Leeds Teaching Hospital, UK. PATIENTS: Children aged 1 year or older, receiving chemotherapies likely to cause mucositis. INTERVENTIONS: Participants were randomised to receive the probiotic or placebo on day 1-14 of a chemotherapy cycle. Participants were also required to complete a patient diary for 21 days. MAIN OUTCOME MEASURES: To assess whether it is feasible to recruit children diagnosed with cancer who are at risk of developing mucositis to an adequately powered RCT. RESULTS: Between May and November 2019, 34 out of 39 eligible participants were approached. Ten patients were recruited (4 probiotic and 6 placebo) of which 2 participants withdrew. Seven participants partially completed the diary but only two participants completed 80% or more. Eligible participants appeared to prefer giving informal verbal feedback when in direct contact with research and healthcare professionals. CONCLUSION: This study demonstrated that recruitment needs to be improved prior to undertaking an adequately powered RCT. TRIAL REGISTRATION NUMBER: NCT03785938.

Molecular Phylogenetic Analysis of 16S rRNA Sequences Identified Two Lineages of Helicobacter pylori Strains Detected from Different Regions in Sudan Suggestive of Differential Evolution.

BACKGROUND: Helicobacter pylori (H. pylori) is ubiquitous among humans and one of the best-studied examples of an intimate association between bacteria and humans. Phylogeny and Phylogeography of H. pylori strains are known to mirror human migration patterns and reflect significant demographic events in human prehistory. In this study, we analyzed the molecular evolution of H. pylori strains detected from different tribes and regions of Sudan using 16S rRNA gene and the phylogenetic approach. Materials and methods. A total of 75 gastric biopsies were taken from patients who had been referred for endoscopy from different regions of Sudan. The DNA extraction was performed by using the guanidine chloride method. Two sets of primers (universal and specific for H. pylori) were used to amplify the 16S ribosomal gene. Sanger sequencing was applied, and the resulted sequences were matched with the sequences of the National Center for Biotechnology Information (NCBI) nucleotide database. The evolutionary aspects were analyzed using MEGA7 software. RESULTS: Molecular detection of H. pylori has shown that 28 (37.33%) of the patients were positive for H. pylori and no significant differences were found in sociodemographic characteristics, endoscopy series, and H. pylori infection. Nucleotide variations were observed at five nucleotide positions (positions 219, 305, 578, 741, and 763-764), and one insertion mutation (750_InsC_751) was present in sixty-seven percent (7/12) of our strains. These six mutations were detected in regions of the 16S rRNA not closely associated with either tetracycline or tRNA binding sites; 66.67% of them were located in the central domain of 16S rRNA. The phylogenetic analysis of 16S rRNA sequences identified two lineages of H. pylori strains detected from different regions in Sudan. The presence of Sudanese H. pylori strains resembling Hungarian H. pylori strains could reflect the migration of Hungarian people to Sudan or vice versa. CONCLUSION: This finding emphasizes the significance of studying the phylogeny of H. pylori strains as a discriminatory tool to mirror human migration patterns. In addition, the 16S rRNA gene amplification method was found useful for bacterial identification and phylogeny.

Systematic review and meta-analysis investigating the efficacy and safety of probiotics in people with cancer.

BACKGROUND/OBJECTIVES: Probiotics are living microorganisms that confer a health benefit on the host when administered. This systematic review and meta-analysis investigates the efficacy and safety of probiotics in adult and paediatric patients diagnosed with cancer. METHODS: A systematic review and meta-analysis was undertaken (PROSPERO registration: CRD42016050252). Randomised controlled trials (RCT), identified through screening multiple databases were included for analysis of efficacy. Non-randomised controlled trials and case reports were included for safety analysis. Outcomes included the reduction in the incidence and severity of diarrhoea, and adverse events. Where possible, data were combined for meta-analysis using a random-effects model. Planned subgroup analyses were not possible through marked heterogeneity of study characteristics. RESULTS: Twenty one studies (N = 2982 participants) were included for assessment of efficacy. Probiotics may reduce the incidence of diarrhoea in patients with cancer [odds ratio (OR) = 0.52, 95% confidence interval (CI) 0.34-0.78, 95% prediction interval (PI) 0.3-0.92, I-sq 36.9%, 5 studies] and the duration of pyrexia [standardised mean difference 0.39 days, 95% CI 0.35-0.43, I-sq 0.01%, 5 studies]. Twenty five studies (N = 2242) were included in the safety analysis. Five case reports showed probiotic-related bacteraemia/fungaemia/positive blood cultures. Definitions and reporting of adverse events were variable and inconsistent. CONCLUSIONS: There remain insufficient studies to assess the true effect of probiotics in people with cancer. Meta-analysis suggests probiotics may be beneficial but further studies are still required. Improved reporting of outcomes and adverse events in clinical trials are required to improve accuracy and confidence of conclusions drawn in future updates.

Survival rates and prognostic predictors of high grade brain stem gliomas in childhood: a systematic review and meta-analysis.

Diagnosis of a pediatric high grade brain stem glioma is devastating with dismal outcomes. This systematic review and meta-analysis was undertaken to determine the survival rates and assess potential prognostic factors including selected interventions. Studies included involved pediatric participants with high grade brain stem gliomas diagnosed by magnetic resonance imaging or biopsy reporting overall survival rates. Meta-analysis was undertaken using a binomial random effects model. Sixty-five studies (2336 participants) were included. Meta-analysis showed 1 year overall survival (OS) of 41% (95% confidence interval (CI) 38-44%, I-sq 52%, 2083 participants), 2 year OS of 15.3% (95% confidence interval 12-20%, I-sq 73.1%, 1329 participants) and 3 year OS of 7.3% (95% confidence interval 5.2-10%, I-sq 26%, 584 participants). Meta-analyses of median overall survival results was not possible due to the lack of reported measures of variance. Subgroup analysis comparing date of study, classification of tumor, use of temozolomide, non-standard interventions or phase 1/2 versus other studies demonstrated no difference in survival outcomes. There was insufficient data to undertake subgroup meta-analysis of patient age, duration of symptoms, K27M histone mutations and AVCR1 mutations. Survival outcomes of high grade brain stem gliomas have remained very poor, and do not clearly vary according to classification, phase of study or use of different therapeutic interventions. Future studies should harmonize outcome and prognostic variable reporting to enable accurate meta-analysis and better exploration of prognosis.

Validation of a classification system for treatment-related mortality in children with cancer.

BACKGROUND: Death not directly due to cancer has been termed 'treatment-related mortality' (TRM). Appreciating the differences between TRM and disease-related death is critical in directing strategies to improve supportive care, interventions delivered or disease progression. Recently, a global collaboration developed and validated a consensus-based classification tool and attribution system. OBJECTIVES: To evaluate the reliability of the newly developed consensus-based definition of TRM and explore the use of the cause-of-death attribution system outside the centre it was initially validated (Toronto, Canada). In the initial study, reviewers listed multiple causes of death. In this study, reviewers identified a primary cause for simplicity. SETTING: The paediatric haematology and oncology department at Leeds Teaching Hospital in Leeds, UK. PARTICIPANTS: Two consultants and two clinical research associates (CRAs). METHODS: Thirty medical records of the most recent deaths in children with cancer, 2 and 4 weeks prior to death, were anonymised and presented to the participants. Reviewers independently classified deaths as 'treatment related mortality' or 'not treatment related' according to the algorithm developed. When TRM occurred, reviewers applied the cause-of-death attribution system to identify the primary cause of death. Inter-relater reliability was assessed using the kappa statistic (k). MAIN OUTCOME: Inter-relater reliability between CRA and consultants. RESULTS: Reliability of the classification was deemed 'very good' between CRA and consultants (k=0.86, 95% CI 0.72 to 0.97). Ten deaths were classified as TRM, of which infection was the most frequent cause identified. Reviewers disagreed on the primary cause of death (eg, respiratory vs infection) when applying the cause-of-death attribution system in six cases and probable and possible causes in four cases. The study identified how the algorithm may not detect TRM in patients receiving non-curative therapy. CONCLUSIONS: The classification and cause of death attribution system could be implemented in different healthcare settings. Adaptation of the classification tool in patients receiving non-curative interventions and the cause of death attribution system should be considered.

Critical review of current clinical practice guidelines for antifungal therapy in paediatric haematology and oncology.

PURPOSE: The incidence of invasive fungal disease (IFD) is rising, but its treatment in paediatric haematology and oncology patients is not yet standardised. This review aimed to critically appraise and analyse the clinical practice guidelines (CPGs) that are available for paediatric IFD. METHODS: Electronic searches of MEDLINE, MEDLINE in-Process & Other non-Indexed Citations, the Guidelines International Network (GIN), guideline.gov and Google were performed and combined fungal disease (Fung* OR antifung*OR Candida* OR Aspergill*) with prophylaxis or treatment (prophyl* OR therap* OR treatment). All guidelines were assessed using the AGREE II tool and recommendations relating to prophylaxis, empirical treatment and specific therapy were extracted. RESULTS: Nineteen guidelines met the inclusion criteria. The AGREE II scores for the rigour of development domain ranged from 11 to 92 % with a median of 53 % (interquartile range 32-69 %). Fluconazole was recommended as antifungal prophylaxis in all nine of the included guidelines which recommended a specific drug. Liposomal amphotericin B was recommended in all five guidelines giving empirical therapy recommendations. Specific therapy recommendations were given for oral or genital candidiasis, invasive candida infection, invasive aspergillosis and other mould infections. CONCLUSIONS: In many areas, recommendations were clear about appropriate practice but further clarity was required, particularly relating to the decision to discontinue empirical antifungal treatment, the relative benefits of empiric and pre-emptive strategies and risk stratification. Future CPGs could consider working to published guideline production methodologies and sharing summaries of evidence appraisal to reduce duplication of effort, improving the quality and efficiency of CPGs in this area.