Outcomes associated with total neoadjuvant therapy with non-operative intent for rectal adenocarcinoma.

Purpose/objectives: To evaluate rates of clinical complete response (cCR), surgery-free survival, permanent ostomy-free survival, and factors associated with these outcomes in patients treated with total neoadjuvant therapy (TNT) with intent for non-operative management of rectal adenocarcinoma. Methods: A retrospective review was conducted of patients treated with TNT for stage II-IV rectal adenocarcinoma (n=45) at our institution between 2013 - 2022 with curative intent. All patients received radiation with concurrent capecitabine and additional chemotherapy, either prior to or following chemoradiation (CRT), with intent for non-operative management. Response rates were determined based on post-treatment MRI and endoscopy. Kaplan-Meier method was utilized to estimate the 1- and 2-year surgery- and permanent ostomy-free survivals. Cox regression was used to evaluate associations between surgery- and permanent ostomy-free survivals and various factors of interest, including patient and tumor characteristics and clinical response. Chi-squared analysis compared rates of cCR and surgery by sequence of TNT modality and cell count ratios. Results: Of the 45 patients treated with TNT, most patients had low-lying rectal tumors with a median distance of 4.1 cm from the anal verge (range, 0.0 - 12.0). Overall, 64.4% (n=29) achieved cCR after TNT. 13 patients (28.9%) underwent surgical resection following TNT, 12 of whom had incomplete response and one who elected to undergo surgery after reaching cCR. At median follow up of 32.0 months (range, 7.1 - 86.1), 22.2% (n=10) of patients had a permanent colostomy, with only 2 of these completed for tumor regrowth after cCR. At one and two years, respectively, surgery-free survival was 77.3% and 66.2%, and permanent ostomy-free survival was 90.9% and 78.2%. Rates of cCR were higher in patients who received CRT first compared to those who received chemotherapy first (72.2% vs. 33.3%, p=0.029) and rates of surgery were also lower in patients who received CRT first compared to those who received chemotherapy first (19.4% vs. 66.7%, p=0.005). On Cox regression model, cCR on 6 month post-CRT endoscopy was associated with surgery-free survival (p=0.006) and permanent ostomy-free survival (p=0.033). Clinical response at earlier follow up points did not predict surgery- nor permanent ostomy-free survival. Conclusion: These results support evidence that TNT may be a non-surgical option for select patients with rectal adenocarcinoma who desire organ preservation. In this investigation at a single institution, the treatment response on 6-month post-CRT endoscopy was the best predictor of surgery- and permanent ostomy-free survival, which are outcomes that are important to patient quality of life. CRT followed by consolidation chemotherapy was associated with higher rates of cCR and lower rates of surgery compared to those treated with induction chemotherapy.

terraFlow, a high-parameter analysis tool, reveals T cell exhaustion and dysfunctional cytokine production in classical Hodgkin's lymphoma.

Immune cells express an incredible variety of proteins; by measuring combinations of these, cell types influencing disease can be precisely identified. We developed terraFlow, a platform that defines cell subsets exhaustively by combinatorial protein expression. Using high-parameter checkpoint-focused and function-focused panels, we studied classical Hodgkin's lymphoma (cHL), where systemic T cells have not been investigated in detail. terraFlow revealed immune perturbations in patients, including elevated activated, exhausted, and interleukin (IL)-17+ phenotypes, along with diminished early, interferon (IFN)γ+, and tumor necrosis factor (TNF)+ T cells before treatment; many perturbations remained after treatment. terraFlow identified more disease-associated differences than other tools, often with better predictive power, and included a non-gating approach, eliminating time-consuming and subjective manual thresholds. It also reports a method to identify the smallest set of markers distinguishing study groups. Our results provide mechanistic support for past reports of immune deficiency in cHL and demonstrate the value of terraFlow in immunotherapy and biomarker studies.

Sustainable Asphalt Mixtures with Enhanced Water Resistance for Flood-Prone Regions Using Recycled LDPE and Carnauba-Soybean Oil Additive.

This manuscript presents a comprehensive study on the sustainable optimization of asphalt mixtures tailored for regions prone to flooding. The research addresses the challenges associated with water damage to asphalt pavements by incorporating innovative additives. The study centers on incorporating recycled Low-Density Polyethylene (LDPE) and a tailored Carnauba-Soybean Oil Additive, advancing asphalt mixtures with a Control mix, LDPE (5%) + Control, and LDPE (5%) + 3% Oil + Control. A critical aspect of the research involves subjecting these mixtures to 30 wetting and drying cycles, simulating the conditions prevalent in tropical flood-prone areas. The incorporation of innovative additives in asphalt mixtures has demonstrated significant improvements across various performance parameters. Tensile Strength Ratio (TSR) tests revealed enhanced tensile strength, with the LDPE (5%) + 3% Oil-modified mixture exhibiting an impressive TSR of 85.7%. Dynamic Modulus tests highlighted improved rutting resistance, showcasing a remarkable increase to 214 MPa in the LDPE (5%) with a 3% Oil-modified mixture. The Semi-Circular Bending (SCB) test demonstrated increased fracture resistance and energy absorption, particularly in the LDPE (5%) with 3% Oil-modified mixture. Hamburg Wheel-Tracking (HWT) tests indicated enhanced moisture resistance and superior rutting resistance at 20,000 cycles for the same mixture. Cantabro tests underscored improved aggregate shatter resistance, with the LDPE (5%) + 3% Oil-modified mixture exhibiting the lowest weight loss rate at 9.820%. Field tests provided real-world insights, with the LDPE (5%) + 3% Oil mixture displaying superior stability, a 61% reduction in deflection, and a 256% improvement in surface modulus over the control mixture. This research lays the groundwork for advancing the development of sustainable, high-performance road pavement materials, marking a significant stride towards resilient infrastructure in flood-prone areas.

Associations between income and survival in cholangiocarcinoma: A comprehensive subtype-based analysis.

Backgrounds/Aims: Socioeconomic determinants of health are incompletely characterized in cholangiocarcinoma (CCA). We assessed how socioeconomic status influences initial treatment decisions and survival outcomes in patients with CCA, additionally performing multiple sub-analyses based on anatomic location of the primary tumor. Methods: Observational study using the 2018 submission of the Surveillance, Epidemiology, and End Results (SEER)-18 Database. In total, 5,476 patients from 2004-2015 with a CCA were separated based on median household income (MHI) into low income (< 25th percentile of MHI) and high income (> 25th percentile of MHI) groups. Seventy-three percent of patients had complete follow up data, and were included in survival analyses. Survival and treatment outcomes were calculated using R-studio. Results: When all cases of CCA were included, the high-income group was more likely than the low-income to receive surgery, chemotherapy, and local tumor destruction modalities. Initial treatment modality based on income differed significantly between tumor locations. Patients of lower income had higher overall and cancer-specific mortality at 2 and 5 years. Non-cancer mortality was similar between the groups. Survival differences identified in the overall cohort were maintained in the intrahepatic CCA subgroup. No differences between income groups were noted in cancer-specific or overall mortality for perihilar tumors, with variable differences in the distal cohort. Conclusions: Lower income was associated with higher rates of cancer-specific mortality and lower rates of surgical resection in CCA. There were significant differences in treatment selection and outcomes between intrahepatic, perihilar, and distal tumors. Population-based strategies aimed at identifying possible etiologies for these disparities are paramount to improving patient outcomes.

Phase I study targeting newly diagnosed grade 4 astrocytoma with bispecific antibody armed T cells (EGFR BATs) in combination with radiation and temozolomide.

PURPOSE: The purpose of this study was to determine the safety, feasibility, and immunologic responses of treating grade 4 astrocytomas with multiple infusions of anti-CD3 x anti-EGFR bispecific antibody (EGFRBi) armed T cells (EGFR BATs) in combination with radiation and chemotherapy. METHODS: This phase I study used a 3 + 3 dose escalation design to test the safety and feasibility of intravenously infused EGFR BATs in combination with radiation and temozolomide (TMZ) in patients with newly diagnosed grade 4 astrocytomas (AG4). After finding the feasible dose, an expansion cohort with unmethylated O6-methylguanine-DNA methyltransferase (MGMT) tumors received weekly EGFR BATs without TMZ. RESULTS: The highest feasible dose was 80 × 109 EGFR BATs without dose-limiting toxicities (DLTs) in seven patients. We could not escalate the dose because of the limited T-cell expansion. There were no DLTs in the additional cohort of three patients with unmethylated MGMT tumors who received eight weekly infusions of EGFR BATs without TMZ. EGFR BATs infusions induced increases in glioma specific anti-tumor cytotoxicity by peripheral blood mononuclear cells (p < 0.03) and NK cell activity (p < 0.002) ex vivo, and increased serum concentrations of IFN-γ (p < 0.03), IL-2 (p < 0.007), and GM-CSF (p < 0.009). CONCLUSION: Targeting AG4 with EGFR BATs at the maximum feasible dose of 80 × 109, with or without TMZ was safe and induced significant anti-tumor-specific immune responses. These results support further clinical trials to examine the efficacy of this adoptive cell therapy in patients with MGMT-unmethylated GBM. CLINICALTRIALS: gov Identifier: NCT03344250.

Mobile sensing to advance tumor modeling in cancer patients: A conceptual framework.

As mobile and wearable devices continue to grow in popularity, there is strong yet unrealized potential to harness people's mobile sensing data to improve our understanding of their cellular and biologically-based diseases. Breakthrough technical innovations in tumor modeling, such as the three dimensional tumor microenvironment system (TMES), allow researchers to study the behavior of tumor cells in a controlled environment that closely mimics the human body. Although patients' health behaviors are known to impact their tumor growth through circulating hormones (cortisol, melatonin), capturing this process is a challenge to rendering realistic tumor models in the TMES or similar tumor modeling systems. The goal of this paper is to propose a conceptual framework that unifies researchers from digital health, data science, oncology, and cellular signaling, in a common cause to improve cancer patients' treatment outcomes through mobile sensing. In support of our framework, existing studies indicate that it is feasible to use people's mobile sensing data to approximate their underlying hormone levels. Further, it was found that when cortisol is cycled through the TMES based on actual patients' cortisol levels, there is a significant increase in pancreatic tumor cell growth compared to when cortisol levels are at normal healthy levels. Taken together, findings from these studies indicate that continuous monitoring of people's hormone levels through mobile sensing may improve experimentation in the TMES, by informing how hormones should be introduced. We hope our framework inspires digital health researchers in the psychosocial sciences to consider how their expertise can be applied to advancing outcomes across levels of inquiry, from behavioral to cellular.

The Cholangiocarcinoma in the Young (CITY) Study: Tumor Biology, Treatment Patterns, and Survival Outcomes in Adolescent Young Adults With Cholangiocarcinoma.

PURPOSE: Increased awareness of the distinct tumor biology for adolescents and young adults (AYAs) with cancer has led to improvement in outcomes for this population. However, in cholangiocarcinoma (CCA), a paucity of data exist on the AYA population. To our knowledge, we present the largest study to date on AYA disease biology, treatment patterns, and survival outcomes in CCA. METHODS: A multi-institutional cohort of patients with CCA diagnosed with intrahepatic cholangiocarcinoma (ICC) or extrahepatic cholangiocarcinoma (ECC) was used for analysis. Retrospective chart review was conducted on patients who were 50 years old and younger (young; n = 124) and older than 50 years (older; n = 723). RESULTS: Among 1,039 patients screened, 847 patients met eligibility (72% ICC, 28% ECC). Young patients had a larger median tumor size at resection compared with older patients (4.2 v 3.6 cm; P = .048), more commonly had N1 disease (65% v 43%; P = .040), and were more likely to receive adjuvant therapy (odds ratio, 4.0; 95% CI, 1.64 to 9.74). Tumors of young patients were more likely to harbor an FGFR2 fusion, BRAF mutation, or ATM mutation (P < .05 for each). Young patients were more likely to receive palliative systemic therapy (96% v 69%; P < .001), targeted therapy (23% v 8%; P < .001), and treatment on a clinical trial (31% v 19%; P = .004). Among patients who presented with advanced disease, young patients had a higher median overall survival compared with their older counterparts (17.7 v 13.5 months; 95% CI, 12.6 to 22.6 v 11.4 to 14.8; P = .049). CONCLUSION: Young patients with CCA had more advanced disease at resection, more commonly received both adjuvant and palliative therapies, and demonstrated improved survival compared with older patients. Given the low clinical trial enrollment and poor outcomes among some AYA cancer populations, data to the contrary in CCA are highly encouraging.

Establishment of cancer cell line originating from a patient with high-grade serous ovarian carcinoma.

Aim: Ovarian cancer is a serious malignancy with high prevalence and mortality. Methods: We isolated and characterized an ovarian high-grade serous cancer cell line (M4) from a tumor of a Vietnamese patient with ovarian carcinoma. Results: The M4 cancer cell line showed good proliferation and stability in culture. Morphologically, the M4 cells showed similar characteristics to tumor cells such as a polyhedral shape, large irregular nuclei, high nuclear/cytoplasmic ratio, high nuclear density and expressing cancer markers like CA125, p53 and Ki67 markers. Conclusion: We have successfully isolated and characterized the M4 cell line from a Vietnamese patient with ovarian carcinoma.

Associations between context and affect within the daily lives of cancer caregivers.

PURPOSE: This study used ecological momentary assessment (EMA) to test the association between activity, location, and social company contexts with cancer caregivers' in-the-moment affect to identify precisely when and where to deliver psychological interventions for caregivers. METHODS: Current cancer caregivers (N = 25) received 8 EMA prompts per day for 7 consecutive days. At each prompt, caregivers reported their current positive affect and negative affect, as well as what they were doing, where they were located, and who they were with. Multilevel logistic regressions tested the associations between caregivers' contexts with their own person-mean-centered state (concurrent momentary level) and trait (overall weekly average) positive or negative affect. RESULTS: Caregivers reported lower state negative affect, as well as higher state positive affect, when socializing (ps < .001), when at a public location (ps < .03), and when around their friends, family, spouse/partner, or care recipient (i.e., person with cancer, ps < .02), relative to when not endorsing the context. Caregivers also reported lower state negative affect when eating/drinking or engaging in leisure (ps < .01; but no parallel effects for state positive affect). Caregivers reported higher state negative affect while working, when at their workplace, or when around work colleagues (ps < .001) and lower state positive affect when at home or alone (ps < .03). CONCLUSIONS: Results suggest the pertinence of a behavioral activation framework to mitigate the emotional strain of caregiving. Interventions that facilitate caregivers' ability to socialize with a range of friends and family, including their loved one with cancer, outside of the home may have the strongest positive emotional impact.

Molecular profiling and treatment pattern differences between intrahepatic and extrahepatic cholangiocarcinoma.

BACKGROUND: Treatment patterns for intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) differ, but limited studies exist comparing them. This study examines differences in molecular profiling rates and treatment patterns in these populations, focusing on use of adjuvant, liver-directed, targeted, and investigational therapies. METHODS: This multicenter collaboration included patients with ICC or ECC treated at 1 of 8 participating institutions. Retrospective data were collected on risk factors, pathology, treatments, and survival. Comparative statistical tests were 2-sided. RESULTS: Among 1039 patients screened, 847 patients met eligibility (ICC = 611, ECC = 236). Patients with ECC were more likely than those with ICC to present with early stage disease (53.8% vs 28.0%), undergo surgical resection (55.1% vs 29.8%), and receive adjuvant chemoradiation (36.5% vs 4.2%) (all P < .00001). However, they were less likely to undergo molecular profiling (50.3% vs 64.3%) or receive liver-directed therapy (17.9% vs 35.7%), targeted therapy (4.7% vs 18.9%), and clinical trial therapy (10.6% vs 24.8%) (all P < .001). In patients with recurrent ECC after surgery, the molecular profiling rate was 64.5%. Patients with advanced ECC had a shorter median overall survival than those with advanced ICC (11.8 vs 15.1 months; P < .001). CONCLUSIONS: Patients with advanced ECC have low rates of molecular profiling, possibly in part because of insufficient tissue. They also have low rates of targeted therapy use and clinical trial enrollment. While these rates are higher in advanced ICC, the prognosis for both subtypes of cholangiocarcinoma remains poor, and a pressing need exists for new effective targeted therapies and broader access to clinical trials.

Antibiotic Prescriptions in Lung Cancer and Melanoma Populations: Differences With Potential Clinical Implications in the Immunotherapy Era.

INTRODUCTION: Antibiotic exposure is associated with worse clinical outcomes in patients receiving immune checkpoint inhibitors (ICI). We analyzed antibiotic prescription patterns in lung cancer and melanoma, two malignancies in which ICI are used broadly across stages. METHODS: We performed a retrospective cohort study of adults in the U.S. Veterans Affairs (VA) medical system diagnosed with lung cancer or melanoma from 2003 to 2016. We defined antibiotic exposure as receipt of a prescription for a systemic antibacterial agent between 6 months before and 6 months after cancer diagnosis. Demographics, clinical variables, prescriptions, and diagnostic codes were abstracted from the VA Corporate Data Warehouse. Antibiotic exposure was compared using t tests, Chi-square, and multivariate analyses. RESULTS: A total of 310,321 patients (280,068 lung cancer, 30,253 melanoma) were included in the analysis. Antibiotic exposure was more common among patients with lung cancer (42% vs. 24% for melanoma; P < .001). Among antibiotic-exposed patients, those with lung cancer were more likely to receive prescriptions for multiple antibiotics (47% vs. 30% for melanoma; P < .001). In multivariate analyses, antibiotic exposure was associated with lung cancer diagnosis (HR 1.50; 95% CI, 1.46-1.55), comorbidity score (HR 1.08; 95% CI, 1.08-1.09), non-white race (HR 1.11; 95% CI, 1.06-1.17), and female gender (HR 1.31; 95% CI, 1.24-1.37). CONCLUSION: Among cancer patients, antibiotics are prescribed frequently. Antibiotic exposure is more common in certain cancer types and patient populations. Given the negative effect antibiotic exposure has on immunotherapy outcomes, these observations may have clinical and healthy policy implications.

Potentially inappropriate medications in nursing homes and the community older adults using the French health insurance databases.

PURPOSE: Potentially inappropriate medications (PIMs) have become a major issue in improving prescribing practices and reducing the risk of adverse drug events in older people. However, very few studies have compared exposition to PIMs controlling for differences in demographic and health between nursing home residents (NHRs) and community-dwelling older adults (CDOAs). This study aimed to assess the prescribing pattern of PIMs between NHRs and CDOAs. METHODS: We conducted a cross-sectional study over three months in 2019 using the French Health Insurance databases. The study population included 274 971 NHRs and 4 893 721 CDOAs aged 75 years or over. The prevalence ratio (PR) between NHRs and CDOAs of 17 PIM indicators, based on the Beers and STOPP criteria lists, was assessed using multivariable robust Poisson regression adjusted for age, sex, diseases, and polypharmacy. RESULTS: During the study period, 54% of NHRs and 29% of CDOAs received at least one PIM. After adjustment, the prevalence of PIMs was 33% higher among NHRs compared to CDOAs (aPR = 1.33; 95% CI [1.33-1.34]). NHRs received PIMs related to benzodiazepines (aPR = 1.43; 95% CI [1.42-1.43]), anticholinergic drugs (aPR = 1.29; 95% CI [1.27-1.31]), and at least three central nervous system-active drugs (aPR = 1.94; 95% CI [1.92-1.96]) more frequently. Prevalence of PIMs related to non-steroidal anti-inflammatory drugs (aPR = 0.50; 95% CI [0.48-0.52]) and long-acting benzodiazepines (aPR = 0.84; 95% CI [0.82-0.85]) was lower among NHRs. CONCLUSION: The NHRs were at greater risk for PIM than CDOAs, although differences exist according to the category of PIMs. As the population is aging, it is essential to promote and evaluate interventions in NHs and the community to enhance medication optimization.

Fabrication of Porous Fe-Based Metal-Organic Complex for the Enhanced Delivery of 5-Fluorouracil in In Vitro Treatment of Cancer Cells.

Metal-organic complexes are one of the most studied materials in the last few decades, which are fabricated from organic ligands and metal ions to form robust frameworks with porous structures. In this work, iron-1,4-benzenedicarboxylic-polyethylene glycol (Fe-BDC-PEG) with a porous structure was successfully constructed by an iron(III) benzene dicarboxylate and polyethylene glycol diacid. The drug-delivery properties of the resultant Fe-BDC-PEG were tested for the loading and release of the 5-fluorouracil compound. The maximal loading capacity of Fe-BDC-PEG for 5-fluorouracil was determined to be 348.22 mg/g. The drug release of 5-fluorouracil-loaded Fe-BDC-PEG after 7 days was 92.69% and reached a maximum of 97.52% after 10 days. The 7 day and acute oral toxicity of Fe-BDC-PEG in mice were studied. The results show that no reasonable change or mortality was observed upon administration of Fe-BDC-PEG complex in mice at 10 g/kg body weight. When the uptake of Fe-BDC-PEG particles in mice was continued for 7 consecutive days, the mortality, feed consumption, body weight, and daily activity were negligibly changed.

CSF3R T618I mutated chronic myelomonocytic leukemia: A proliferative subtype with a distinct mutational profile.

Chronic myelomonocytic leukemia (CMML) is a clonal myeloid neoplasm characterized by sustained monocytosis and mutations in TET2, ASXL1, SRSF2, SETBP1, NRAS, and KRAS. We describe a rare case of CSF3R T618I mutated CMML that has a proliferative phenotype, myelodysplasia, and additional mutations in ASXL1, SETBP1, KRAS, and PTPN11. Comparing the clinicopathologic features of this case to previously reported cases of CSF3R T618I mutated CMML and CSF3R non-T618I mutated CMML, CSF3R T618I seems to define a unique proliferative subtype of CMML with a distinct mutational profile. The diagnostic challenges and molecular pathogenesis associated with this case are also briefly discussed.

Quantification of human enteric viruses as alternative indicators of fecal pollution to evaluate wastewater treatment processes.

We investigated the potential use and quantification of human enteric viruses in municipal wastewater samples of Winnipeg (Manitoba, Canada) as alternative indicators of contamination and evaluated the processing stages of the wastewater treatment plant. During the fall 2019 and winter 2020 seasons, samples of raw sewage, activated sludge, effluents, and biosolids (sludge cake) were collected from the North End Sewage Treatment Plant (NESTP), which is the largest wastewater treatment plant in the City of Winnipeg. DNA (Adenovirus and crAssphage) and RNA enteric viruses (Pepper mild mottle virus, Norovirus genogroups GI and GII, Rotavirus Astrovirus, and Sapovirus) as well as the uidA gene found in Escherichia coli were targeted in the samples collected from the NESTP. Total nucleic acids from each wastewater treatment sample were extracted using a commercial spin-column kit. Enteric viruses were quantified in the extracted samples via quantitative PCR using TaqMan assays. Overall, the average gene copies assessed in the raw sewage were not significantly different (p-values ranged between 0.1023 and 0.9921) than the average gene copies assessed in the effluents for DNA and RNA viruses and uidA in terms of both volume and biomass. A significant reduction (p-value ≤ 0.0438) of Adenovirus and Noroviruses genogroups GI and GII was observed in activated sludge samples compared with those for raw sewage per volume. Higher GCNs of enteric viruses were observed in dewatered sludge samples compared to liquid samples in terms of volume (g of sample) and biomass (ng of nucleic acids). Enteric viruses found in gene copy numbers were at least one order of magnitude higher than the E. coli marker uidA, indicating that enteric viruses may survive the wastewater treatment process and viral-like particles are being released into the aquatic environment. Viruses such as Noroviruses genogroups GI and GII, and Rotavirus were detected during colder months. Our results suggest that Adenovirus, crAssphage, and Pepper mild mottle virus can be used confidently as complementary viral indicators of human fecal pollution.

Implementation and Uptake of Rural Lung Cancer Screening.

OBJECTIVE: Given the higher rates of tobacco use along with increased mortality specific to lung cancer in rural settings, low-dose CT (LDCT)-based lung cancer screening could be particularly beneficial to such populations. However, limited radiology facilities and increased geographical distance, combined with lower income and education along with reduced patient engagement, present heightened barriers to screening initiation and adherence. METHODS: In collaboration with community leaders and stakeholders, we developed and implemented a community-based lung cancer screening program, including telephone-based navigation and tobacco cessation counseling support, serving 18 North Texas counties. Funding was available to support clinical services costs where needed. We collected data on LDCT referrals, orders, and completion. RESULTS: To raise awareness for lung cancer screening, we leveraged our established collaborative network of more than 700 community partners. In the first year of operation, 107 medical providers referred 570 patients for lung cancer screening, of whom 488 (86%) were eligible for LDCT. The most common reasons for ineligibility were age (43%) and insufficient tobacco history (20%). Of 381 ordered LDCTs, 334 (88%) were completed. Among screened patients, 61% were current smokers and 36% had insurance coverage for the procedure. The program cost per patient was $430. DISCUSSION: Implementation, uptake, and completion of LDCT-based lung cancer screening is feasible in rural settings. Community outreach, health promotion, and algorithm-based navigation may support such efforts. Given low lung cancer screening rates nationally and heightened lung cancer risk in rural populations, similar programs in other regions may be particularly impactful.

Use of Proton Pump Inhibitors and Risk of Pancreatic Cancer: A Nationwide Case-Control Study Based on the French National Health Data System (SNDS).

BACKGROUND: Only a few studies investigated the association between proton pump inhibitor (PPI) use and pancreatic cancer, with inconsistent results. Moreover, these studies had a number of methodologic limitations. Our objective was to assess this association in a nationwide case-control study. METHODS: We used the French National Health Data System (SNDS), covering 99% of the French population since 2006. Incident cases of pancreatic cancer, identified between 2014 and 2018, were matched with up to four controls on year of birth, sex, frequency of hospitalization within 8 years prior to index date, and department of residence. Associations between PPIs and pancreatic cancer were estimated using conditional logistic regression models adjusted for sociodemographic characteristics, risk factors of pancreatic cancer (including diabetes mellitus, tobacco-related diseases, and morbid obesity), and other comorbidities. RESULTS: A total of 23,321 cases of pancreatic cancer (mean age, 69.8 years; 51.7% males) and 75,937 matched controls were included. Overall, 77.8% of cases and 75.5% of controls were PPI ever users. Ever (vs. never) PPI use was associated with an increased risk of pancreatic cancer [adjusted OR (aOR) = 1.05, 95% confidence interval (CI), 1.01-1.09]. A dose-response relationship was observed [1-30 cumulative defined daily dose (cDDD): aOR = 0.92, 95% CI, 0.87-0.97; 31-180 cDDD: aOR = 1.05, 95% CI, 1.00-1.11; 181-1,080 cDDD: aOR = 1.18, 95% CI, 1.12-1.24; >1,080 cDDD: aOR = 1.17, 95% CI, 1.10-1.23]. CONCLUSIONS: On the basis of these findings, a slight increase in the risk of pancreatic cancer associated with high cumulative doses of PPIs cannot be excluded. IMPACT: Given the overuse of PPIs, efforts should be continued to limit treatments to appropriate indications and durations.

Decreasing trends in potentially inappropriate medications in older people: a nationwide repeated cross-sectional study.

BACKGROUND: Potentially Inappropriate Medications (PIMs) and polypharmacy are widely used indicators of suboptimal prescribing for older people. The aim of this study was to describe the changes in the prevalence of PIMs and polypharmacy among people aged 75 years and over between 2011 and 2019 in France. METHODS: PIMs and polypharmacy were assessed among people aged 75 years and over every two years between 2011 and 2019 using the French health insurance data system. Sixteen PIM criteria from the 2015 Beers and STOPP lists were assessed. Polypharmacy (5 to 9 drugs) and hyper-polypharmacy (≥10 drugs) were defined based on the average number of drugs dispensed per quarter. The Annual Percent Change (APC) and 95%CI were assessed using linear regression models after standardization of the prevalence on age and sex. RESULTS: The study population included 5,777,645 individuals over 75 years old in 2011 and 6,328,155 in 2019. The prevalence of PIMs decreased from 49.6 to 39.6% over the study period (APC: - 1.19% [- 1.35;-1.04]). Of the sixteen indicators assessed, the prevalence of thirteen decreased between 2011 and 2019. Benzodiazepines were the most frequent PIMs (34.7% in 2011 to 26.9% in 2019), followed by anticholinergic drugs (12.1% in 2011 to 8.3% in 2019), oral non-steroidal anti-inflammatory drugs (11.4 to 7.8%), and PIMs related to antihypertensive drugs (7.4 to 6.0%). Overall, women and individuals aged 85 years and older were more likely to receive PIMs. The prevalence of hyper-polypharmacy decreased from 30.5 to 25.9% over the study period. CONCLUSION: This study, which is the first to assess the change in prevalence of PIMs and polypharmacy over time from comprehensive health data in France, highlights that PIMs and hyper-polypharmacy declined between 2011 and 2019. However, PIMs remains frequent for older people and often involves benzodiazepines.

Prevalence and Significance of Potential Pharmacokinetic Drug-Drug Interactions Among Patients with Lung Cancer: Implications for Clinical Trials.

BACKGROUND: The overall prevalence of potential drug-drug interactions (DDIs) among patients with lung cancer is unknown. OBJECTIVE: The objective of this study was to determine the prevalence of potential DDIs and major DDIs among individuals newly diagnosed with lung cancer in a national cohort. PATIENTS AND METHODS: We performed a retrospective cross-sectional study of adult patients in the United States Veterans' Affairs (VA) medical system diagnosed with lung cancer between 2003 and 2016. The primary endpoint was the prevalence of prescriptions for medications associated with any potential DDIs during the 3 months leading up to and including the date of lung cancer diagnosis. The secondary endpoint was the prevalence of prescriptions associated with major DDIs during the same time period. RESULTS: Overall, 280,068 patients were included in the study; 55.9% of patients were prescribed medications associated with potential DDIs, while 5.3% received prescriptions for medications associated with major DDIs. Among the 20 most commonly prescribed drugs associated with potential DDIs, only two were associated with major DDIs. CONCLUSION: Medications with potential DDIs are prescribed to the majority of patients with lung cancer; however, only about 5% of patients are prescribed medications with major DDIs that might be prohibited in certain clinical trials.

Feasibility of ecological momentary assessment to study depressive symptoms among cancer caregivers.

OBJECTIVE: Ecological momentary assessment (EMA) may help with the development of more targeted interventions for caregivers' depression, yet the use of this method has been limited among cancer caregivers. This study aimed to demonstrate the feasibility of EMA among cancer caregivers and the use of EMA data to understand affective correlates of caregiver depressive symptoms. METHODS: Caregivers (N = 25) completed a depressive symptom assessment (Patient Health Questionnaire-8) and then received eight EMA survey prompts per day for 7 days. EMA surveys assessed affect on the orthogonal dimensions of valence and arousal. Participants completed feedback surveys regarding the EMA protocol at the conclusion of the week-long study. RESULTS: Of 32 caregivers approached, 25 enrolled and participated (78%), which exceeded the a priori feasibility cutoff of 55%. The prompt completion rate (59%, or 762 of 1,286 issued) did not exceed the a priori cutoff of 65%, although completion was not related to caregivers' age, employment status, physical health quality of life, caregiving stress, or depressive symptoms or the patients' care needs (ps > 0.22). Caregivers' feedback about their study experience was generally positive. Mixed-effects location scale modeling showed caregivers' higher depressive symptoms were related to overall higher reported negative affect and lower positive affect, but not to affective variability. CONCLUSIONS: Findings from this feasibility study refute potential concerns that an EMA design is too burdensome for distressed caregivers. Clinically, findings suggest the potential importance of not only strategies to reduce overall levels of negative affect, but also to increase opportunities for positive affect.