Abstract
Background
Patients with cancer living in rural areas have inferior cancer outcomes; however, studies examining this association use varying definitions of “rural,” complicating comparisons ...and limiting the utility of the results for policy makers and future researchers.
Methods
Surveillance, Epidemiology, and End Results data (2000-2016) were used to assess risk of cancer mortality and mortality from any cause across 4 definitions of rurality: Urban Influence codes (UIC), National Center for Health Statistics (NCHS), Rural-Urban continuum codes (RUCC), and Index of Relative Rurality. Binary (urban vs rural) and ternary (urban, micropolitan, rural) definitions were evaluated. Multivariable parametric survival models estimated hazards of mortality overall and among 3 cancer groupings: screening related, obesity related, and tobacco related. Definition agreement was also assessed.
Results
Overall, 3 788 273 patients with an incident cancer representing 605 counties were identified. There was little discordance between binary definitions of rural vs urban and moderate agreement at the 3 levels. Adjusted models using binary definitions revealed 15% to 17% greater hazard of cancer mortality in rural compared with urban. At the 3 levels when comparing rural with metropolitan, RUCC and NCHS saw similarly increased hazard ratios; however, Index of Relative Rurality did not. Screening-related cancers saw the highest hazards of mortality and the largest divergence between definitions. Obesity-related and tobacco-related cancers saw similarly increased hazards of mortality at the binary and ternary levels.
Conclusions
Hazard of death is similar across binary definitions; however, this differed when categorized as ternary or continuous, especially among screening-related cancers. Results suggest that study purpose should direct choice of definitions and categorization.
Rural disparities in cancer outcomes have been widely evaluated, but limited evidence is available to describe what characteristics of rural environments contribute to the increased risk of poor ...outcomes. Therefore, this manuscript sought to assess the mediating effects of county characteristics on the relationship between urban/rural status and mortality among patients with cancer, characterize county profiles, and determine at-risk county profiles alongside rural settings.
Patients diagnosed with cancer between 2000 and 2016 were assessed using Surveillance, Epidemiology and End Results data linked to the 2010 Rural-Urban Commuting Codes and 2010 County Health Rankings. There were 757,655 patients representing 596 counties (of 3,143 in the U.S.) and 12 states. Mediation analyses, conducted in 2023, estimated the direct contribution of rurality to 5-year all-cause survival and the contribution of the rural effect indirectly through County Health Ranking domains. Latent class analysis and survival models identified county groupings and estimated the hazard of mortality associated with class membership.
Rankings for premature death, clinical care, and physical environment resulted in rural patients having 17.9%–20.2% less survival time than urban patients. Of this, 4.1%–12.6% of the total excess risk was mediated by these characteristics. Patients living in rural and high-risk county classes saw higher all-cause mortality than those in urban lower-risk counties (hazard ratio=1.04, 95% CI=1.01, 1.08 and 1.07, 95% CI=1.03, 1.11).
Counties with poorer health rankings had increased mortality risks regardless of rurality; however, the poor rankings, notably health behaviors and social and economic factors, elevated the risk for rural counties.
Background
Patients with lymphoma have an increased risk of venous thromboembolism (VTE). The authors examined the risk of VTE and subsequent health care utilization in elderly patients with diffuse ...large B cell lymphoma (DLBCL).
Methods
A total of 5537 DLBCL patients ≥66 years old enrolled in Medicare from the Surveillance, Epidemiology, and End Results registry and a noncancer control group of Medicare beneficiaries (n = 5537) were identified. Cumulative incidence function to examine the risk of VTE 12 months after DLBCL diagnosis was used. Fine and Gray method was used to examine the risk factors associated with VTE risk in multivariable models. Total number of hospitalizations, outpatient visits, and Medicare spending were compared in DLBCL patients with and without VTE.
Results
VTE was diagnosed in 8.3% DLBCL patients and 1.5% controls, yielding an 8.6‐fold higher risk of VTE in DLBCL in adjusted analysis (95% confidence interval CI, 6.62‐11.20; P < .001). Multivariable regression analysis showed that precancer VTE history was associated with an increased risk of developing VTE after a DLBCL diagnosis (hazard ratio HR, 5.39; 95% CI, 4.39‐6.63), and Asian individuals were associated with a lower risk (HR, 0.54; 95% CI, 0.29‐1.00). Patients newly diagnosed with VTE after lymphoma had a 1.7‐fold higher rate of hospitalization and a 1.2‐fold higher rate of outpatient visits compared to those without, resulting in excess Medicare spending of $22,208 in the first year after DLBCL diagnosis.
Conclusions
Elderly patients with DLBCL have an elevated risk of VTE resulting in excess health care utilization. VTE history before DLBCL was associated with increased risk of post‐DLBCL VTE, and Asian individuals were associated with a lower risk of VTE.
Elderly patients with diffuse large B cell lymphoma (DLBCL) have an increased risk of venous thromboembolism (VTE) compared to matched controls without cancer. VTE is associated with increased health care utilization in DLBCL patients.
Identifying which children and young people (CYP) are most vulnerable to serious infection due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is important to guide protective ...interventions. To address this question, we used data for all hospitalizations in England among 0-17 year olds from 1 February 2019 to 31 January 2021. We examined how sociodemographic factors and comorbidities might be risk factors for pediatric intensive care unit (PICU) admission among hospitalizations due to the following causes: Coronavirus Disease 2019 (COVID-19) and pediatric inflammatory multi-system syndrome temporally associated with SARS-CoV-2 (PIMS-TS) in the first pandemic year (2020-2021); hospitalizations due to all other non-traumatic causes in 2020-2021; hospitalizations due to all non-traumatic causes in 2019-2020; and hospitalizations due to influenza in 2019-2020. Risk of PICU admission and death from COVID-19 or PIMS-TS in CYP was very low. We identified 6,338 hospitalizations with COVID-19, of which 259 were admitted to a PICU and eight CYP died. We identified 712 hospitalizations with PIMS-TS, of which 312 were admitted to a PICU and fewer than five CYP died. Hospitalizations with COVID-19 and PIMS-TS were more common among males, older CYP, those from socioeconomically deprived neighborhoods and those who were of non-White ethnicity (Black, Asian, Mixed or Other). The odds of PICU admission were increased in CYP younger than 1 month old and decreased among 15-17 year olds compared to 1-4 year olds with COVID-19; increased in older CYP and females with PIMS-TS; and increased for Black compared to White ethnicity in patients with COVID-19 and PIMS-TS. Odds of PICU admission in COVID-19 were increased for CYP with comorbidities and highest for CYP with multiple medical problems. Increases in odds of PICU admission associated with different comorbidities in COVID-19 showed a similar pattern to other causes of hospitalization examined and, thus, likely reflect background vulnerabilities. These findings identify distinct risk factors associated with PICU admission among CYP with COVID-19 or PIMS-TS that might aid treatment and prevention strategies.
We aimed to describe pre-existing factors associated with severe disease, primarily admission to critical care, and death secondary to SARS-CoV-2 infection in hospitalised children and young people ...(CYP), within a systematic review and individual patient meta-analysis.
We searched Pubmed, European PMC, Medline and Embase for case series and cohort studies published between 1st January 2020 and 21st May 2021 which included all CYP admitted to hospital with ≥ 30 CYP with SARS-CoV-2 or ≥ 5 CYP with PIMS-TS or MIS-C. Eligible studies contained (1) details of age, sex, ethnicity or co-morbidities, and (2) an outcome which included admission to critical care, mechanical invasive ventilation, cardiovascular support, or death. Studies reporting outcomes in more restricted groupings of co-morbidities were eligible for narrative review. We used random effects meta-analyses for aggregate study-level data and multilevel mixed effect models for IPD data to examine risk factors (age, sex, comorbidities) associated with admission to critical care and death. Data shown are odds ratios and 95% confidence intervals (CI).
PROSPERO: CRD42021235338
83 studies were included, 57 (21,549 patients) in the meta-analysis (of which 22 provided IPD) and 26 in the narrative synthesis. Most studies had an element of bias in their design or reporting. Sex was not associated with critical care or death. Compared with CYP aged 1–4 years (reference group), infants (aged <1 year) had increased odds of admission to critical care (OR 1.63 (95% CI 1.40–1.90)) and death (OR 2.08 (1.57–2.86)). Odds of death were increased amongst CYP over 10 years (10–14 years OR 2.15 (1.54–2.98); >14 years OR 2.15 (1.61–2.88)).
The number of comorbid conditions was associated with increased odds of admission to critical care and death for COVID-19 in a step-wise fashion. Compared with CYP without comorbidity, odds ratios for critical care admission were: 1.49 (1.45–1.53) for 1 comorbidity; 2.58 (2.41–2.75) for 2 comorbidities; 2.97 (2.04–4.32) for ≥3 comorbidities. Corresponding odds ratios for death were: 2.15 (1.98–2.34) for 1 comorbidity; 4.63 (4.54–4.74) for 2 comorbidities and 4.98 (3.78–6.65) for ≥3 comorbidities. Odds of admission to critical care were increased for all co-morbidities apart from asthma (0.92 (0.91–0.94)) and malignancy (0.85 (0.17–4.21)) with an increased odds of death in all co-morbidities considered apart from asthma. Neurological and cardiac comorbidities were associated with the greatest increase in odds of severe disease or death. Obesity increased the odds of severe disease and death independently of other comorbidities. IPD analysis demonstrated that, compared to children without co-morbidity, the risk difference of admission to critical care was increased in those with 1 comorbidity by 3.61% (1.87–5.36); 2 comorbidities by 9.26% (4.87–13.65); ≥3 comorbidities 10.83% (4.39–17.28), and for death: 1 comorbidity 1.50% (0.00–3.10); 2 comorbidities 4.40% (-0.10–8.80) and ≥3 co-morbidities 4.70 (0.50–8.90).
Hospitalised CYP at greatest vulnerability of severe disease or death with SARS-CoV-2 infection are infants, teenagers, those with cardiac or neurological conditions, or 2 or more comorbid conditions, and those who are obese. These groups should be considered higher priority for vaccination and for protective shielding when appropriate. Whilst odds ratios were high, the absolute increase in risk for most comorbidities was small compared to children without underlying conditions.
RH is in receipt of a fellowship from Kidney Research UK (grant no. TF_010_20171124). JW is in receipt of a Medical Research Council Fellowship (Grant No. MR/R00160X/1). LF is in receipt of funding from Martin House Children's Hospice (there is no specific grant number for this). RV is in receipt of a grant from the National Institute of Health Research to support this work (grant no NIHR202322). Funders had no role in study design, data collection, analysis, decision to publish or preparation of the manuscript.
Abstract
Background
Antimicrobial stewardship programs (ASPs) promote the principle of de-escalation: moving from broad- to narrow-spectrum agents and stopping antibiotics when no longer indicated. A ...standard, objective definition of de-escalation applied to electronic data could be useful for ASP assessments.
Methods
We derived an electronic definition of antibiotic de-escalation and performed a retrospective study among 5 hospitals. Antibiotics were ranked into 4 categories: narrow-spectrum, broad-spectrum, extended-spectrum, and agents targeted for protection. Eligible adult patients were cared for on inpatient units, had antibiotic therapy for at least 2 days, and were hospitalized for at least 3 days after starting antibiotics. Number of antibiotics and rank were assessed at 2 time points: day of antibiotic initiation and either day of discharge or day 5. De-escalation was defined as reduction in either the number of antibiotics or rank. Escalation was an increase in either number or rank. Unchanged was either no change or discordant directions of change. We summarized outcomes among hospitals, units, and diagnoses.
Results
Among 39 226 eligible admissions, de-escalation occurred in 14 138 (36%), escalation in 5129 (13%), and antibiotics were unchanged in 19 959 (51%). De-escalation varied among hospitals (median, 37%; range, 31–39%, P < .001). Diagnoses with lower de-escalation rates included intra-abdominal (23%) and skin and soft tissue (28%) infections. Critical care had higher rates of both de-escalation and escalation compared with wards.
Conclusions
Our electronic de-escalation metric demonstrated variation among hospitals, units, and diagnoses. This metric may be useful for assessing stewardship opportunities and impact.
De-escalation of antibiotics is a key principle of antibiotic stewardship, yet there is no standard definition. We proposed an objective, electronic definition of antibiotic de-escalation and present the distribution among infection diagnoses and its variability among hospitals and units.
Background
Regional studies show that children with cancer receive medically intense end‐of‐life (EOL) care, but EOL care patterns, including palliative care utilization in Alabama, remain unknown.
...Methods
This was a retrospective study of 233 children (0‐19 years) who received cancer‐directed therapy at Children's of Alabama and died from 2010 through 2019. Rates and disparities in palliative care utilization and the association between palliative care and intense EOL care, death location, and hospice were examined.
Results
The median death age was 11 years; 62% were non‐Hispanic White. Forty‐one percent had a non–central nervous system (CNS) solid tumor. Fifty‐eight percent received palliative care, and 36% received early palliative care (≥30 days before death). Children without relapsed/refractory disease were less likely to receive palliative care than those who had relapsed/refractory disease (adjusted odds ratio aOR, 0.2; 95% confidence interval CI, 0.1‐0.7). Children with CNS tumors and hematologic malignancies were less likely to have early palliative care (aOR for CNS tumors, 0.4; 95% CI, 0.2‐0.7; aOR for hematologic malignancies, 0.3; 95% CI, 0.2‐0.7) than children with non‐CNS solid tumors. Late palliative care (vs none) was associated with more medically intense care (aOR, 3.3; 95% CI, 1.4‐7.8) and hospital death (aOR, 4.8; 95% CI, 1.9‐11.6). Early palliative care (vs none) was associated with more hospice enrollment (aOR, 3.4; 95% CI, 1.5‐7.6) but not medically intense care (aOR, 1.3; 95% CI, 0.6‐2.9) or hospital death (aOR, 1.8; 95% CI, 0.8‐3.7).
Conclusions
Fifty‐eight percent of children dying of cancer in Alabama receive palliative care, but EOL care varies with the receipt and timing (early vs late) of palliative care. Whether this variation reflects differences in child and family preferences or systemic factors (eg, hospice access) remains unknown.
Pediatric cancer decedents receive intense care at the end of life. However, early palliative care reduces the intensity of end‐of‐life care.
High intensity focused ultrasound (HIFU) rapidly and non-invasively destroys tumor tissue. Here, we sought to assess the immunomodulatory effects of MR-guided HIFU and its combination with the innate ...immune agonist CpG and checkpoint inhibitor anti-PD-1. Mice with multi-focal breast cancer underwent ablation with a parameter set designed to achieve mechanical disruption with minimal thermal dose or a protocol in which tumor temperature reached 65 °C. Mice received either HIFU alone or were primed with the toll-like receptor 9 agonist CpG and the checkpoint modulator anti-PD-1. Both mechanical HIFU and thermal ablation induced a potent inflammatory response with increased expression of Nlrp3, Jun, Mefv, Il6 and Il1β and alterations in macrophage polarization compared to control. Furthermore, HIFU upregulated multiple innate immune receptors and immune pathways, including Nod1, Nlrp3, Aim2, Ctsb, Tlr1/2/4/7/8/9, Oas2, and RhoA. The inflammatory response was largely sterile and consistent with wound-healing. Priming with CpG attenuated Il6 and Nlrp3 expression, further upregulated expression of Nod2, Oas2, RhoA, Pycard, Tlr1/2 and Il12, and enhanced T-cell number and activation while polarizing macrophages to an anti-tumor phenotype. The tumor-specific antigen, cytokines and cell debris liberated by HIFU enhance response to innate immune agonists.
Background
Disparities in end‐of‐life (EOL) care for children with cancer remain understudied. We addressed this gap by examining patterns of EOL care, with a focus on location of death and hospice ...utilization.
Methods
We used MarketScan – a nationally representative dataset with Medicaid and commercial claims to conduct a retrospective observational study of children with cancer who died between 2011 and 2017 at age ≤21 years. We examined rates of (a) home death, (b) hospice utilization, (c) and medically intense interventions in the last 30 days (e.g., intubation).
Results
Of the 1492 children in the cohort, 44% had Medicaid and 56% commercial insurance; 71% carried a solid tumor diagnosis, and 37% were between the ages of 15 and 21 years at the time of death. Forty percent died at home; children with Medicaid were less likely to die at home (relative risk RR = 0.82, 95% confidence interval CI: 0.73–0.92; reference: commercial). Forty‐five percent enrolled in hospice, for a median of 2 days. Hospice enrollment rates did not vary with insurance. However, children with Medicaid spent less time enrolled (incidence rate ratio IRR = 0.22, 95% CI: 0.17–0.27). Among children with Medicaid, Black children were less likely to die at home (RR = 0.69, 95% CI: 0.52–0.92) and enroll on hospice (RR = 0.71, 95% CI: 0.55–0.91) than non‐Hispanic White children. Medically intense interventions did not vary with insurance or race.
Conclusion
Only 40% of children with cancer die at home, and the duration of hospice enrollment is short. EOL care varies significantly with insurance. It is imperative that we determine if these patterns and disparities represent EOL preferences, provider biases, or differences in quality or availability of hospice.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has the potential for rapid transmission in congregate settings. We describe the multidisciplinary response to an outbreak of coronavirus ...disease (COVID-19) in a large homeless shelter in Chicago, Illinois, USA. The response to the outbreak included 4 rounds of mass PCR testing of all staff and residents and subsequent isolation of persons who tested positive for SARS-CoV-2. We further describe the dynamics of the shelter outbreak by fitting a modified susceptible-exposed-infectious-recovered compartmental model incorporating the widespread SARS-CoV-2 testing and isolation measures implemented in this shelter. Our model demonstrates that rapid transmission of COVID-19 in the shelter occurred before the outbreak was detected; rates of transmission declined after widespread testing and isolation measures were put in place. Overall, we demonstrate the feasibility of mass PCR testing and isolation in congregate settings and suggest the necessity of prompt response to suspected COVID-19 outbreaks in homeless shelters.
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