Recommendations for ototoxicity surveillance for childhood, adolescent, and young adult cancer survivors: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group in collaboration with the PanCare Consortium.

Childhood, adolescent, and young adult (CAYA) cancer survivors treated with platinum-based drugs, head or brain radiotherapy, or both have an increased risk of ototoxicity (hearing loss, tinnitus, or both). To ensure optimal care and reduce consequent problems-such as speech and language, social-emotional development, and learning difficulties-for these CAYA cancer survivors, clinical practice guidelines for monitoring ototoxicity are essential. The implementation of surveillance across clinical settings is hindered by differences in definitions of hearing loss, recommendations for surveillance modalities, and remediation. To address these deficiencies, the International Guideline Harmonization Group organised an international multidisciplinary panel, including 32 experts from ten countries, to evaluate the quality of evidence for ototoxicity following platinum-based chemotherapy and head or brain radiotherapy, and formulate and harmonise ototoxicity surveillance recommendations for CAYA cancer survivors.

Determining the retention of removable partial dentures.

STATEMENT OF PROBLEM: Removable partial dentures (RPDs) provide a cost-effective treatment for millions of partially edentulous patients worldwide. However, they often fail because of loss of retention. One reason for this problem is lack of precise guidelines for designing retentive RPDs. PURPOSE: The purpose of this in vitro study was to determine the forces produced by food and clasps during mastication to develop an algorithm for predicting RPD retention and to help determine the optimal number of clasps. MATERIAL AND METHODS: The forces that food exerts on acrylic resin teeth during simulated mastication and the retention forces provided by clasps (wrought wire, circumferential, and I-bar) engaging on teeth were measured using a universal testing machine. A statistical analysis was performed with a 1-way ANOVA and repeated-measures ANOVA while the developed algorithm was evaluated by using sensitivity and specificity analysis. RESULTS: The force exerted by food mastication on each individual tooth ranged between 1.7 and 12.2 N, depending on the type of tooth, tooth anatomy, occlusion, and food. The retention force of the clasps after cyclic testing ranged between 2.9 and 14.5 N, depending on the type of tooth abutment and clasp. Using these measurements, an algorithm was developed to predict RPD retention. The algorithm was confirmed experimentally on 36 RPDs, showing a sensitivity of 96%, specificity of 100%, and an accuracy of 97%. CONCLUSIONS: The forces generated by food mastication on teeth varied according to the type of tooth, occlusion, and food. The retention force of RPD clasps varied according to the type of tooth and clasp. An algorithm for predicting RPD retention and determining the optimal number of clasps was developed and validated experimentally.

The cumulative burden of surviving childhood cancer: an initial report from the St Jude Lifetime Cohort Study (SJLIFE).

BACKGROUND: Survivors of childhood cancer develop early and severe chronic health conditions (CHCs). A quantitative landscape of morbidity of survivors, however, has not been described. We aimed to describe the cumulative burden of curative cancer therapy in a clinically assessed ageing population of long-term survivors of childhood cancer. METHODS: The St Jude Lifetime Cohort Study (SJLIFE) retrospectively collected data on CHCs in all patients treated for childhood cancer at the St Jude Children's Research Hospital who survived 10 years or longer from initial diagnosis and were 18 years or older as of June 30, 2015. Age-matched and sex-frequency-matched community controls were used for comparison. 21 treatment exposure variables were included in the analysis, with data abstracted from medical records. 168 CHCs for all participants were graded for severity using a modified Common Terminology Criteria of Adverse Events. Multiple imputation with predictive mean matching was used for missing occurrences and grades of CHCs in the survivors who were not clinically evaluable. Mean cumulative count was used for descriptive cumulative burden analysis and marked-point-process regression was used for inferential cumulative burden analysis. FINDINGS: Of 5522 patients treated for childhood cancer at St Jude Children's Research Hospital who had complete records, survived 10 years or longer, and were 18 years or older at time of study, 3010 (54·5%) were alive, had enrolled, and had had prospective clinical assessment. 2512 (45·5%) of the 5522 patients were not clinically evaluable. The cumulative incidence of CHCs at age 50 years was 99·9% (95% CI 99·9-99·9) for grade 1-5 CHCs and 96·0% (95% CI 95·3-96·8%) for grade 3-5 CHCs. By age 50 years, a survivor had experienced, on average, 17·1 (95% CI 16·2-18·1) CHCs of any grade, of which 4·7 (4·6-4·9) were CHCs of grade 3-5. The cumulative burden in matched community controls of grade 1-5 CHCs was 9·2 (95% CI 7·9-10·6; p<0·0001 vs total study population) and of grade 3-5 CHCs was 2·3 (1·9-2·7, p<0·0001 vs total study population). Second neoplasms, spinal disorders, and pulmonary disease were major contributors to the excess total cumulative burden. Notable heterogeneity in the distribution of CHC burden in survivors with differing primary cancer diagnoses was observed. The cumulative burden of grade 1-5 CHCs at age 50 years was highest in survivors of CNS malignancies (24·2 [95% CI 20·9-27·5]) and lowest in survivors of germ cell tumours (14·0 [11·5-16·6]). Multivariable analyses showed that older age at diagnosis, treatment era, and higher doses of brain and chest radiation are significantly associated with a greater cumulative burden and severity of CHCs. INTERPRETATION: The burden of CHCs in survivors of childhood cancer is substantial and highly variable. Our assessment of total cumulative burden in survivors of paediatric cancer, with detailed characterisation of long-term CHCs, provide data to better inform future clinical guidelines, research investigations, and health services planning for this vulnerable, medically complex population. FUNDING: The US National Cancer Institute, St Baldrick's Foundation, and the American Lebanese Syrian Associated Charities.

Patient satisfaction with laser-sintered removable partial dentures: A crossover pilot clinical trial.

STATEMENT OF PROBLEM: Clinical data regarding newly introduced laser-sintered removable partial dentures (RPDs) are needed before this technique can be recommended. Currently, only a few clinical reports have been published, with no clinical studies. PURPOSE: This clinical trial compared short-term satisfaction in patients wearing RPDs fabricated with conventional or computer-aided design and computer-aided manufacturing (CAD-CAM) laser-sintering technology. MATERIAL AND METHODS: Twelve participants with partial edentulism were enrolled in this pilot crossover double-blinded clinical trial. Participants were randomly assigned to wear cast or CAD-CAM laser-sintered RPDs for alternate periods of 30 days. The outcome of interest was patient satisfaction as measured using the McGill Denture Satisfaction Instrument. Assessments was conducted at 1, 2, and 4 weeks. The participant's preference in regard to the type of prosthesis was assessed at the final evaluation. The linear mixed effects regression models for repeated measures were used to analyze the data, using the intention-to-treat principle. To assess the robustness of potential, incomplete adherence, sensitivity analyses were conducted. RESULTS: Statistically significant differences were found in patients' satisfaction between the 2 methods of RPD fabrication. Participants were significantly more satisfied with laser-sintered prostheses than cast prostheses in regard to general satisfaction, ability to speak, ability to clean, comfort, ability to masticate, masticatory efficiency, and oral condition (P<.05). At the end of the study, 5 participants preferred the laser-sintered, 1 preferred the cast RPD, and 3 had no preference. CONCLUSIONS: The use of CAD-CAM laser-sintering technology in the fabrication of removable partial dentures may lead to better outcomes in terms of patient satisfaction in the short term. The conclusion from this pilot study requires confirmation by a larger randomized controlled trial. CLINICAL TRIAL: ClinicalTrials.gov. A study about patient satisfaction with laser-sintered removable partial dentures; NCT02769715.

Association of Modifiable Health Conditions and Social Determinants of Health With Late Mortality in Survivors of Childhood Cancer.

Importance: Associations between modifiable chronic health conditions (CHCs), social determinants of health, and late mortality (defined as death occurring ≥5 years after diagnosis) in childhood cancer survivors are unknown. Objective: To explore associations between modifiable CHCs and late mortality within the context of social determinants of health. Design, Setting, and Participants: This longitudinal cohort study used data from 9440 individuals who were eligible to participate in the St Jude Lifetime Cohort (SJLIFE), a retrospective cohort study with prospective clinical follow-up that was initiated in 2007 to characterize outcomes among childhood cancer survivors. Eligible individuals had survived 5 or more years after childhood cancer diagnosis, were diagnosed between 1962 and 2012, and received treatment at St Jude Children's Research Hospital were included in mortality estimates. A total of 3407 adult SJLIFE participants (aged ≥18 years) who completed an on-campus assessment were included in risk factor analyses. Vital status, date of death, and cause of death were obtained by linkage with the National Death Index (coverage from inception to December 31, 2016). Deaths occurring before inception of the National Death Index were obtained from the St Jude Children's Research Hospital Cancer Registry. Data were analyzed from June to December 2022. Exposures: Data on treatment exposures and causes of death were abstracted for individuals who were eligible to participate in the SJLIFE study. Information on modifiable CHCs (dyslipidemia, hypertension, diabetes, underweight or obesity, bone mineral deficiency, hypogonadism, hypothyroidism, and adrenal insufficiency, all graded by the modified Common Terminology Criteria for Adverse Events), healthy lifestyle index (smoking status, alcohol consumption, body mass index [calculated as weight in kilograms divided by height in meters squared], and physical activity), area deprivation index (ADI; which measures neighborhood-level socioeconomic disadvantage), and frailty (low lean muscle mass, exhaustion, low energy expenditure, slowness, and weakness) was obtained for participants. Main Outcomes and Measures: National Death Index causes of death were used to estimate late mortality using standardized mortality ratios (SMRs) and 95% CIs, which were calculated based on US mortality rates. For the risk factor analyses (among participants who completed on-campus assessment), multivariable piecewise exponential regression analysis was used to estimate rate ratios (RRs) and 95% CIs for all-cause and cause-specific late mortality. Results: Among 9440 childhood cancer survivors who were eligible to participate in the SJLIFE study, the median (range) age at assessment was 27.5 (5.3-71.9) years, and the median (range) duration of follow-up was 18.8 (5.0-58.0) years; 55.2% were male and 75.3% were non-Hispanic White. Survivors experienced increases in all-cause mortality (SMR, 7.6; 95% CI, 7.2-8.1) and health-related late mortality (SMR, 7.6; 95% CI, 7.0-8.2). Among 3407 adult SJLIFE participants who completed an on-campus assessment, the median (range) age at assessment was 35.4 (17.9-69.8) years, and the median (range) duration of follow-up was 27.3 (7.3-54.7) years; 52.5% were male and 81.7% were non-Hispanic White. Models adjusted for attained age, sex, race and ethnicity, age at diagnosis, treatment exposures, household income, employment status, and insurance status revealed that having 1 modifiable CHC of grade 2 or higher (RR, 2.2; 95% CI, 1.2-4.0; P = .01), 2 modifiable CHCs of grade 2 or higher (RR, 2.6; 95% CI, 1.4-4.9; P = .003), or 3 modifiable CHCs of grade 2 or higher (RR, 3.6; 95% CI, 1.8-7.1, P < .001); living in a US Census block with an ADI in the 51st to 80th percentile (RR, 5.5; 95% CI, 1.3-23.5; P = .02), an ADI in the 81st to 100th percentile (RR, 8.7; 95% CI, 2.0-37.6; P = .004), or an unassigned ADI (RR, 15.7; 95% CI, 3.5-70.3; P < .001); and having frailty (RR, 2.3; 95% CI, 1.3-3.9; P = .004) were associated with significant increases in the risk of late all-cause death. Similar associations were observed for the risk of late health-related death (1 modifiable CHC of grade ≥2: RR, 2.2 [95% CI, 1.1-4.4; P = .02]; 2 modifiable CHCs of grade ≥2: RR, 2.5 [95% CI, 1.2-5.2; P = .01]; 3 modifiable CHCs of grade ≥2: RR, 4.0 [95% CI, 1.9-8.4; P < .001]; ADI in 51st-80th percentile: RR, 9.2 [95% CI, 1.2-69.7; P = .03]; ADI in 81st-100th percentile: RR, 16.2 [95% CI, 2.1-123.7; P = .007], unassigned ADI: RR, 27.3 [95% CI, 3.5-213.6; P = .002]; and frailty: RR, 2.3 [95% CI, 1.2-4.1; P = .009]). Conclusions and Relevance: In this cohort study of childhood cancer survivors, living in a Census block with a high ADI and having modifiable CHCs were independently associated with an increased risk of late death among survivors of childhood cancer. Future investigations seeking to mitigate these factors will be important to improving health outcomes and developing risk-stratification strategies to optimize care delivery to childhood cancer survivors.

Analytical model of I-bar clasps for removable partial dentures.

OBJECTIVE: Clasps of removable partial dentures (RPDs) often suffer from fatigue stress that leads to plastic deformation, loss of retention, and RPD failure. Recently, computer-based technologies were proposed to optimize clasp geometry design. The objective of this study was to create an analytic model of I-bar clasps for computer-aided design (CAD)-RPD. METHODS: The analytical model based on mechanical laws was established to simulate I-bar clasp retention, and optimize its design. The model considered the lengths of the vertical (L1) and horizontal (L2) arms of the I-bar as well as the radius (r) of its half-round cross-section. The analytical model was validated with mechanical experiments evaluating the retention of cobalt-chromium (Co-Cr) clasps in vitro and compared with finite element analysis (FEA). RESULTS: The analytical model was in good agreement with the mechanical experiments and FEA, and showed that I-bar clasp design could provide optimal mechanical performance as long as the length of arms (L1 and L2) do not exceed 6 mm. Clasps with L1 > 8 mm and L2 > 9 mm presented stress values exceeding the fatigue limit of Co-Cr. The proposed solution was to increase the radius of I-bar to conserve the initial mechanical performance of Co-Cr. SIGNIFICANCE: Co-Cr I-bar clasps perform best on teeth with reduced mesiodistal dimensions (canine and premolar), and their designs could be optimized to prevent stress from reaching the yield strength and the fatigue failure limit.

An analytical model to design circumferential clasps for laser-sintered removable partial dentures.

OBJECTIVE: Clasps of removable partial dentures (RPDs) often suffer from plastic deformation and failure by fatigue; a common complication of RPDs. A new technology for processing metal frameworks for dental prostheses based on laser-sintering, which allows for precise fabrication of clasp geometry, has been recently developed. This study sought to propose a novel method for designing circumferential clasps for laser-sintered RPDs to avoid plastic deformation or fatigue failure. METHODS: An analytical model for designing clasps with semicircular cross-sections was derived based on mechanics. The Euler-Bernoulli elastic curved beam theory and Castigliano's energy method were used to relate the stress and undercut with the clasp length, cross-sectional radius, alloy properties, tooth type, and retention force. Finite element analysis (FEA) was conducted on a case study and the resultant tensile stress and undercut were compared with the analytical model predictions. Pull-out experiments were conducted on laser-sintered cobalt-chromium (Co-Cr) dental prostheses to validate the analytical model results. RESULTS: The proposed circumferential clasp design model yields results in good agreement with FEA and experiments. The results indicate that Co-Cr circumferential clasps in molars that are 13mm long engaging undercuts of 0.25mm should have a cross-section radius of 1.2mm to provide a retention of 10N and to avoid plastic deformation or fatigue failure. However, shorter circumferential clasps such as those in premolars present high stresses and cannot avoid plastic deformation or fatigue failure. SIGNIFICANCE: Laser-sintered Co-Cr circumferential clasps in molars are safe, whereas they are susceptible to failure in premolars.

Removable partial denture alloys processed by laser-sintering technique.

Removable partial dentures (RPDs) are traditionally made using a casting technique. New additive manufacturing processes based on laser sintering has been developed for quick fabrication of RPDs metal frameworks at low cost. The objective of this study was to characterize the mechanical, physical, and biocompatibility properties of RPD cobalt-chromium (Co-Cr) alloys produced by two laser-sintering systems and compare them to those prepared using traditional casting methods. The laser-sintered Co-Cr alloys were processed by the selective laser-sintering method (SLS) and the direct metal laser-sintering (DMLS) method using the Phenix system (L-1) and EOS system (L-2), respectively. L-1 and L-2 techniques were 8 and 3.5 times more precise than the casting (CC) technique (p < 0.05). Co-Cr alloys processed by L-1 and L-2 showed higher (p < 0.05) hardness (14-19%), yield strength (10-13%), and fatigue resistance (71-72%) compared to CC alloys. This was probably due to their smaller grain size and higher microstructural homogeneity. All Co-Cr alloys exhibited low porosity (2.1-3.3%); however, pore distribution was more homogenous in L-1 and L-2 alloys when compared to CC alloys. Both laser-sintered and cast alloys were biocompatible. In conclusion, laser-sintered alloys are more precise and present better mechanical and fatigue properties than cast alloys for RPDs. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1174-1185, 2018.

Genetic Risk for Subsequent Neoplasms Among Long-Term Survivors of Childhood Cancer.

Purpose Childhood cancer survivors are at increased risk of subsequent neoplasms (SNs), but the germline genetic contribution is largely unknown. We assessed the contribution of pathogenic/likely pathogenic (P/LP) mutations in cancer predisposition genes to their SN risk. Patients and Methods Whole-genome sequencing (30-fold) was performed on samples from childhood cancer survivors who were ≥ 5 years since initial cancer diagnosis and participants in the St Jude Lifetime Cohort Study, a retrospective hospital-based study with prospective clinical follow-up. Germline mutations in 60 genes known to be associated with autosomal dominant cancer predisposition syndromes with moderate to high penetrance were classified by their pathogenicity according to the American College of Medical Genetics and Genomics guidelines. Relative rates (RRs) and 95% CIs of SN occurrence by mutation status were estimated using multivariable piecewise exponential regression stratified by radiation exposure. Results Participants were 3,006 survivors (53% male; median age, 35.8 years [range, 7.1 to 69.8 years]; 56% received radiotherapy), 1,120 SNs were diagnosed among 439 survivors (14.6%), and 175 P/LP mutations were identified in 5.8% (95% CI, 5.0% to 6.7%) of survivors. Mutations were associated with significantly increased rates of breast cancer (RR, 13.9; 95% CI, 6.0 to 32.2) and sarcoma (RR, 10.6; 95% CI, 4.3 to 26.3) among irradiated survivors and with increased rates of developing any SN (RR, 4.7; 95% CI, 2.4 to 9.3), breast cancer (RR, 7.7; 95% CI, 2.4 to 24.4), nonmelanoma skin cancer (RR, 11.0; 95% CI, 2.9 to 41.4), and two or more histologically distinct SNs (RR, 18.6; 95% CI, 3.5 to 99.3) among nonirradiated survivors. Conclusion The findings support referral of all survivors for genetic counseling for potential clinical genetic testing, which should be prioritized for nonirradiated survivors with any SN and for those with breast cancer or sarcoma in the field of prior irradiation.

Impact of microparticles on UV disinfection of indigenous aerobic spores.

Numerous studies have shown that the efficacy of ultraviolet (UV) disinfection can be hindered by the presence of particles that can shield microorganisms. The main objective of this study was to determine to what extent natural particulate matter can shield indigenous spores of aerobic spore-forming bacteria (ASFB) from UV rays. The extent of the protective shielding was assessed by comparing the inactivation rates in three water fractions (untreated, dispersed and filtered on an 8 microm membrane) using a collimated beam apparatus with a low-pressure lamp emitting at 254 nm. Levels of inactivation were then related to the distribution and abundance of particles as measured by microflow imaging. Disinfection assays were completed on two source waters of different quality and particle content. A protocol was developed to break down particles and disperse aggregates (addition of 100mg/L of Zwittergent 3-12 and blending at 8000 rpm for 4 min). Particle size distribution (PSD) analysis confirmed a statistically significant decrease in the number of particles for diameter ranges above 5 microm following the dispersion protocol and 8 microm filtration. The fluence required to reach 1-log inactivation of ASFB spores was independent of particle concentration, while that required to reach 2-log inactivation or more was correlated with the concentration of particles larger than 8 microm (R(2)>0.61). Results suggest that natural particulate matter can protect indigenous organisms from UV radiation in waters with elevated particle content, while source water with low particle counts may not be subject to this interference.

Fixation methods in pediatric cochlear implants: retrospective review of an evolution of 3 techniques.

OBJECTIVE: To review 3 techniques of cochlear implant (CI) fixation used by a single surgeon for the fixation of 320 consecutive CIs in a pediatric population and associated complications. STUDY DESIGN: Case series with chart review. SETTING: Tertiary referral children's hospital. SUBJECTS AND METHODS: Patients receiving CIs between July 1995 and July 2009 were reviewed. Clinical information obtained included age at implant, implant type, duration of follow-up, method of implant fixation (intraosseous suture ligature, prolene mesh with titanium screws, and a small periosteal pocket with periosteal sutures), and postoperative complications of fixation (migration or extrusion). RESULTS: Three hundred twenty consecutive CIs were reviewed: 64 of which were bilateral (42 staged, 22 concurrent). The median age at implantation was 3.6 years (range, 8 months to 20 years). Manufacturers included Cochlear (223) and Advanced Bionics Corporation (97). Median follow-up was 26 months (range, 1 month to 12.7 years). The intraosseous suture ligation method of fixation was used for 182 CIs. Ninety-eight CIs were fixed using a small piece of polypropylene mesh and titanium screws. Forty implants were secured by using a tight periosteal pocket and placing the suture through the periosteum and soft tissue to collar the receiver in a modified well. No complications of device migration or extrusion were noted, nor were there any intracranial complications. Device failure occurred in 13 (4%) patients requiring explantation and reimplantation, but these were unrelated to surgical technique or fixation. CONCLUSIONS: This study illustrates that with an evolution toward less invasive and less complex methods of fixation, there has not been an associated increase in fixation-related complications.

MRSA and non-MRSA otorrhea in children: a comparative study of clinical course.

OBJECTIVE: To test the perception that post-tympanostomy tube otorrhea caused by methicillin-resistant Staphylococcus aureus (MRSA) is a more virulent disease than otorrhea caused by other pathogens by analyzing the clinical differences and disease courses in children diagnosed with otorrhea caused by MRSA bacteria vs non-MRSA bacteria. DESIGN: Retrospective review. SETTING: Tertiary children's hospital. PATIENTS: We retrospectively examined the medical records of children who presented to a tertiary children's hospital from January 1, 2003, to December 31, 2008, with otorrhea that occurred after tympanostomy tube insertion. MAIN OUTCOME MEASURES: Otorrhea culture records were used to group the 1079 patients into those whose otitis media was due to MRSA (n = 170) and those with non-MRSA otitis media (n = 909). From the non-MRSA group, we randomly selected an age-matched group of 170 and examined the differences between the MRSA and age-matched non-MRSA groups in organisms isolated by culture, demographic factors (including type of medical insurance), medical history, treatments, surgical procedures performed, audiometric data, and other admissions for infection-related illnesses. RESULTS: The overall incidence of MRSA in this series was about 16% (170 of 1079 patients). Of the 170 eligible children in each age-matched group, 135 with MRSA otorrhea and 141 with non-MRSA otorrhea had data in every category selected for statistical analysis. The groups did not differ significantly in type of insurance; history of tympanostomy tube placement, cholesteatoma, or prematurity; number or type (minor/major) of surgical procedures performed; or risk of subsequent infection-related diagnoses. More patients in the MRSA group received intravenous antibiotic therapy (11% vs 3.6%; P < .001). CONCLUSION: In this study, a diagnosis of otorrhea due to MRSA did not carry an increased risk for surgical procedures or infection-associated sequelae compared with a diagnosis of non-MRSA otorrhea.