Summary Background Sodium thiosulfate is an antioxidant shown in preclinical studies in animals to prevent cisplatin-induced hearing loss with timed administration after cisplatin without ...compromising the antitumour efficacy of cisplatin. The primary aim of this study was to assess sodium thiosulfate for prevention of cisplatin-induced hearing loss in children and adolescents. Methods ACCL0431 was a multicentre, randomised, open-label, phase 3 trial that enrolled participants at 38 participating Children's Oncology Group hospitals in the USA and Canada. Eligible participants aged 1–18 years with newly diagnosed cancer and normal audiometry were randomly assigned (1:1) to receive sodium thiosulfate or observation (control group) in addition to their planned cisplatin-containing chemotherapy regimen, using permuted blocks of four. Randomisation was initially stratified by age and duration of cisplatin infusion. Stratification by previous cranial irradiation was added later as a protocol amendment. The allocation sequence was computer-generated centrally and concealed to all personnel. Participants received sodium thiosulfate 16 g/m2 intravenously 6 h after each cisplatin dose or observation. The primary endpoint was incidence of hearing loss 4 weeks after final cisplatin dose. Hearing was measured using standard audiometry and reviewed centrally by audiologists masked to allocation using American Speech-Language-Hearing Association criteria but treatment was not masked for participants or clinicians. Analysis of the primary endpoint was by modified intention to treat, which included all randomly assigned patients irrespective of treatment received but restricted to those assessable for hearing loss. Enrolment is complete and this report represents the final analysis. This trial is registered with ClinicalTrials.gov , number NCT00716976. Findings Between June 23, 2008, and Sept 28, 2012, 125 eligible participants were randomly assigned to either sodium thiosulfate (n=61) or observation (n=64). Of these, 104 participants were assessable for the primary endpoint (sodium thiosulfate, n=49; control, n=55). Hearing loss was identified in 14 (28·6%; 95% CI 16·6–43·3) participants in the sodium thiosulfate group compared with 31 (56·4%; 42·3–69·7) in the control group (p=0·00022). Adjusted for stratification variables, the likelihood of hearing loss was significantly lower in the sodium thiosulfate group compared with the control group (odds ratio 0·31, 95% CI 0·13–0·73; p=0·0036). The most common grade 3–4 haematological adverse events reported, irrespective of attribution, were neutropenia (117 66% of 178 participant cycles in the sodium thiosulfate group vs 145 65% of 224 in the control group), whereas the most common non-haematological adverse event was hypokalaemia (25 17% of 149 vs 22 12% of 187). Of 194 serious adverse events reported in 26 participants who had received sodium thiosulfate, none were deemed probably or definitely related to sodium thiosulfate; the most common serious adverse event was decreased neutrophil count: 26 episodes in 14 participants. Interpretation Sodium thiosulfate protects against cisplatin-induced hearing loss in children and is not associated with serious adverse events attributed to its use. Further research is needed to define the appropriate role for sodium thiosulfate among emerging otoprotection strategies. Funding US National Cancer Institute.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
SARS-CoV-2 has infected nearly 3.7 million and killed 61,722 Californians, as of May 22, 2021. Non-pharmaceutical interventions have been instrumental in mitigating the spread of the coronavirus. ...However, as we ease restrictions, widespread implementation of COVID-19 vaccines is essential to prevent its resurgence. In this work, we addressed the adequacy and deficiency of vaccine uptake within California and the possibility and severity of resurgence of COVID-19 as restrictions are lifted given the current vaccination rates. We implemented a real-time Bayesian data assimilation approach to provide projections of incident cases and deaths in California following the reopening of its economy on June 15, 2021. We implemented scenarios that vary vaccine uptake prior to reopening, and transmission rates and effective population sizes following the reopening. For comparison purposes, we adopted a baseline scenario using the current vaccination rates, which projects a total 11,429 cases and 429 deaths in a 15-day period after reopening. We used posterior estimates based on CA historical data to provide realistic model parameters after reopening. When the transmission rate is increased after reopening, we projected an increase in cases by 21.8% and deaths by 4.4% above the baseline after reopening. When the effective population is increased after reopening, we observed an increase in cases by 51.8% and deaths by 12.3% above baseline. A 30% reduction in vaccine uptake alone has the potential to increase cases and deaths by 35% and 21.6%, respectively. Conversely, increasing vaccine uptake by 30% could decrease cases and deaths by 26.1% and 17.9%, respectively. As California unfolds its plan to reopen its economy on June 15, 2021, it is critical that social distancing and public behavior changes continue to be promoted, particularly in communities with low vaccine uptake. The Centers for Disease Control and Prevention (CDC) recommendation to ease mask-wearing for fully vaccinated individuals despite major inequities in vaccine uptake in counties across the state highlights some of the logistical challenges that society faces as we enthusiastically phase out of this pandemic.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Epidemics of COVID-19 in student populations at universities were a key concern for the 2020-2021 school year. The University of California (UC) System developed a set of recommendations to reduce ...campus infection rates. SARS-CoV-2 test results are summarized for the ten UC campuses during the Fall 2020 term.
UC mitigation efforts included protocols for the arrival of students living on-campus students, non-pharmaceutical interventions, daily symptom monitoring, symptomatic testing, asymptomatic surveillance testing, isolation and quarantine protocols, student ambassador programs for health education, campus health and safety pledges, and lowered density of on-campus student housing. We used data from UC campuses, the UC Health-California Department of Public Health Data Modeling Consortium, and the U.S. Census to estimate the proportion of each campus' student populations that tested positive for SARS-CoV-2 and compared it to the fraction individuals aged 20-29 years who tested positive in their respective counties.
SARS-CoV-2 cases in campus populations were generally low in September and October 2020, but increased in November and especially December, and were highest in early to mid-January 2021, mirroring case trajectories in their respective counties. Many students were infected during the Thanksgiving and winter holiday recesses and were detected as cases upon returning to campus. The proportion of students who tested positive for SARS-CoV-2 during Fall 2020 ranged from 1.2% to 5.2% for students living on campus and was similar to students living off campus. For most UC campuses the proportion of students testing positive was lower than that for the 20-29-year-old population in which campuses were located.
The layered mitigation approach used on UC campuses, informed by public health science and augmented perhaps by a more compliant population, likely minimized campus transmission and outbreaks and limited transmission to surrounding communities. University policies that include these mitigation efforts in Fall 2020 along with SARS-CoV-2 vaccination, may alleviate some local concerns about college students returning to communities and facilitate resumption of normal campus operations and in-person instruction.
Full text
Available for:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Long-term safety of topical calcineurin inhibitors is not well understood. APPLES (A Prospective Pediatric Longitudinal Evaluation to Assess the Long-Term Safety of Tacrolimus Ointment for the ...Treatment of Atopic Dermatitis; NCT00475605) examined incidence of lymphoma and other cancers in a pediatric population with atopic dermatitis.
To quantify incident malignancies during 10 years in children with atopic dermatitis who used topical tacrolimus for ≥6 weeks.
Standardized incidence ratios for cancer events were analyzed relative to sex-, age-, and race-matched control data from national cancer registries.
There were 7954 eligible patients enrolled at 314 sites in 9 countries. During 44,629 person-years, 6 confirmed incident cancers occurred (standardized incidence ratio, 1.01; 95% confidence interval, 0.37-2.20). No lymphomas occurred.
Observational prospective cohort study.
The cancer incidence was as expected, given matched background data. This finding provides no support for the hypothesis that topical tacrolimus increases long-term cancer risk in children with atopic dermatitis.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background Toxic epidermal necrolysis (TEN) is a serious drug eruption that results in death in approximately 25% to 50% of patients. There is controversy over whether SCORTEN accurately predicts ...mortality or if treatment interventions such as intravenous immunoglobulin (IVIg) can alter mortality. Objectives We sought to determine whether SCORTEN accurately predicts mortality in this cohort, whether IVIg improved survival, and which drugs and medical comorbidities impacted mortality. Methods We summarize our experience prospectively over 5 years and 82 patients. Patients either received supportive care, intravenous immunoglobulin, or cyclosporine as treatment. All patients had a SCORTEN on admission, an offending drug on record, and a list of medical comorbidities. Results Of the 82 patients, 29% died from TEN. SCORTEN accurately predicted mortality in this cohort with an area under the curve (AUC) of 0.83 in a receiver operator curve (ROC) analysis. A Kaplan-Meier curve did not show improved mortality if patients received IVIg versus supportive care ( P = .9). Medications most often responsible for TEN were trimethoprim/sulfamethoxazole, followed by anticonvulsants, nonsteroidal anti-inflammatories, and allopurinol. Limitations This prospective cohort study design is not as ideal as patients presenting for a randomized controlled trial. Conclusions SCORTEN was an accurate predictor of mortality in this cohort. Age older than 40 years, the presence of metabolic syndrome and/or gout, higher body surface area involvement, higher SCORTEN, and higher number of medical comorbidities statistically significantly increased risk of death. IVIg did not significantly alter mortality. Although the highest number of cases was due to trimethoprim/sulfamethoxazole, the greatest proportion of deaths was due to allopurinol.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Background
Stagnant outcomes for adolescents and young adults (AYAs) 15–39 years of age with cancer are partly attributed to poor enrollment onto clinical trials. Initiatives have focused on ...increasing accrual, but changes at the population‐level are unknown. We examined patterns of clinical trial participation over time in AYA patients with cancer.
Procedure
We utilized medical record data from AYAs in two population‐based National Cancer Institute Patterns of Care Studies identified through the Surveillance, Epidemiology and End Results Program. Among 3135 AYAs diagnosed with non‐Hodgkin lymphoma (NHL), Hodgkin lymphoma, acute lymphoblastic leukemia (ALL), and sarcoma, we used multivariate logistic regression to evaluate patient and provider characteristics associated with clinical trial enrollment. Interaction terms evaluated variation in clinical trial enrollment across patient and provider characteristics by year of diagnosis.
Results
From 2006 to 2012–2013, clinical trial participation increased from 14.8% to 17.9% (P < 0.01). Adjusting for patient and provider characteristics, we found lower clinical trial enrollment among those who were older at diagnosis, diagnosed with NHL vs ALL, treated by adult hematologist/oncologists only (vs pediatric hematologist/oncologists), and of non‐Hispanic Black race/ethnicity (vs non‐Hispanic White) (P < 0.05 for all). Interaction analyses indicate improved clinical trial enrollment from 2006 to 2012–2013 among young adults 25–29 years of age and the uninsured.
Conclusions
Although disparities in enrollment onto clinical trials remain for AYAs with cancer, our study identified increasing overall clinical trial participation over time. Further, we identify promising trends in enrollment uptake among AYAs 25–29 years of age and the uninsured.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background
Adolescent and young adult (AYA) cancer survivors experience psychological distress often because of cancer and its treatment. However, no prior studies have evaluated the additional ...medical expenditures and health care utilization associated with psychological distress in AYA cancer survivors.
Methods
AYA cancer survivors and a comparison matched group of adults with no history of cancer were identified from 2011‐2016 Medical Expenditure Panel Survey data. Medical expenditures and health care utilization were evaluated with multivariable regression models.
Results
AYA cancer survivors were more likely to have psychological distress (11.5% of 1757) than adults with no history of cancer (5.8% of 5227). The prevalence of psychological distress was found to be high many years after the diagnosis, with 11.2% reporting distress ≥20 years after their cancer diagnosis. AYA cancer survivors with psychological distress were more likely to smoke and have chronic conditions and were less likely to exercise regularly in comparison with AYAs with no history of psychological distress. AYA cancer survivors with psychological distress had additional annual medical expenses ($4415; 95% CI, $993‐$9690), office visits (2.80; 95% CI, 0.23‐6.15), and use of prescription medications/medication renewals (11.58; 95% CI, 5.70‐19.47) in comparison with AYA cancer survivors without psychological distress. Additional annual medical expenses of psychological distress were $2600 higher in AYA cancer survivors than adults without a history of cancer ($1802; 95% CI, $440‐$3791).
Conclusions
These results highlight the substantial economic burden associated with psychological distress in AYA cancer survivors. This research could inform survivorship care plans and interventions addressing the psychological needs of AYA cancer survivors.
Psychological distress in adolescent and young adult cancer survivors is associated with substantial increases in health care expenses and utilization. Using survivorship care plans that acknowledge psychological needs can mitigate the impact of psychological distress in adolescent and young adult cancer survivors.
Full text
Available for:
BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Suboptimal adherence to self-administered medications is a common problem. The purpose of this study was to determine the effectiveness of a video-game intervention for improving adherence and other ...behavioral outcomes for adolescents and young adults with malignancies including acute leukemia, lymphoma, and soft-tissue sarcoma.
A randomized trial with baseline and 1- and 3-month assessments was conducted from 2004 to 2005 at 34 medical centers in the United States, Canada, and Australia. A total of 375 male and female patients who were 13 to 29 years old, had an initial or relapse diagnosis of a malignancy, and currently undergoing treatment and expected to continue treatment for at least 4 months from baseline assessment were randomly assigned to the intervention or control group. The intervention was a video game that addressed issues of cancer treatment and care for teenagers and young adults. Outcome measures included adherence, self-efficacy, knowledge, control, stress, and quality of life. For patients who were prescribed prophylactic antibiotics, adherence to trimethoprim-sulfamethoxazole was tracked by electronic pill-monitoring devices (n = 200). Adherence to 6-mercaptopurine was assessed through serum metabolite assays (n = 54).
Adherence to trimethoprim-sulfamethoxazole and 6-mercaptopurine was greater in the intervention group. Self-efficacy and knowledge also increased in the intervention group compared with the control group. The intervention did not affect self-report measures of adherence, stress, control, or quality of life.
The video-game intervention significantly improved treatment adherence and indicators of cancer-related self-efficacy and knowledge in adolescents and young adults who were undergoing cancer therapy. The findings support current efforts to develop effective video-game interventions for education and training in health care.
OBJECTIVE:Our objective was to compare outcomes of a restrictive to a liberal red cell transfusion strategy in 20% or more total body surface area (TBSA) burn patients. We hypothesized that the ...restrictive group would have less blood stream infection (BSI), organ dysfunction, and mortality.
BACKGROUND:Patients with major burns have major (>1 blood volume) transfusion requirements. Studies suggest that a restrictive blood transfusion strategy is equivalent to a liberal strategy. However, major burn injury is precluded from these studies. The optimal transfusion strategy in major burn injury is thus needed but remains unknown.
METHODS:This prospective randomized multicenter trial block randomized patients to a restrictive (hemoglobin 7–8 g/dL) or liberal (hemoglobin 10–11 g/dL) transfusion strategy throughout hospitalization. Data collected included demographics, infections, transfusions, and outcomes.
RESULTS:Eighteen burn centers enrolled 345 patients with 20% or more TBSA burn similar in age, TBSA burn, and inhalation injury. A total of 7054 units blood were transfused. The restrictive group received fewer blood transfusionsmean 20.3 ± 32.7 units, median = 8 (interquartile range3, 24) versus mean 31.8 ± 44.3 units, median = 16 (interquartile range7, 40) in the liberal group (P < 0.0001, Wilcoxon rank sum). BSI incidence, organ dysfunction, ventilator days, and time to wound healing (P > 0.05) were similar. In addition, there was no 30-day mortality difference9.5% restrictive versus 8.5% liberal (P = 0.892, χ test).
CONCLUSIONS:A restrictive transfusion strategy halved blood product utilization. Although the restrictive strategy did not decrease BSI, mortality, or organ dysfunction in major burn injury, these outcomes were no worse than the liberal strategy (Clinicaltrials.gov identifier NCT01079247).
PDF
