Eliminating children's tobacco smoke exposure: a pathway to bioverified abstinence among low-income maternal smokers in the Babies Living Safe and Smokefree (BLiSS) trial.

BACKGROUND: Identifying behavioral pathways to smoking cessation in high-risk populations, such as low-income maternal smokers, could reduce tobacco disparities. The previous "BLiSS" multilevel intervention trial demonstrated efficacy of the BLiSS intervention in facilitating low-income maternal smokers' bioverified abstinence. This present study examined four putative pathways measured at 3-month end of treatment (Time 2) that could account for the observed intervention effect on smoking abstinence through 12 months (Time 2 - Time 3). METHODS: Nutritionists in community clinics delivering safety net nutrition promotion programs across Philadelphia, Pennsylvania, USA, were trained by trial principal investigators to deliver a brief tobacco intervention informed by the American Academy of Pediatrics best practice guidelines ("Ask, Advise, Refer [AAR]"). After referral, 396 eligible participants were randomized to either a multimodal behavioral intervention (AAR + MBI) or a parallel attention control (AAR + control). Random effects regression analysis tested mediation. RESULTS: Elimination of children's tobacco smoke exposure (TSE) at Time 2 was the only significant mediator of longitudinal smoking abstinence through Time 3. AAR + MBI mothers were more likely to eliminate their children's TSE by Time 2 (OR = 2.11, 95%CI 1.30, 3.42), which was significantly associated with Time 3 abstinence (OR = 6.72, CI 2.28, 19.80). Modeling showed a significant total effect of AAR + MBI on abstinence (OR = 6.21, CI 1.86, 20.71), a direct effect of AAR + MBI on abstinence (OR = 4.80, CI 1.45, 15.94) and an indirect effect through TSE elimination (OR = 1.29, CI 1.06, 1.57). CONCLUSIONS: Integrating smoking cessation interventions with counseling prior to the quit attempt that is designed to facilitate adoption of smokefree home policies and efforts to eliminate children's TSE could enhance the likelihood of long-term abstinence in populations of smokers with elevated challenges quitting smoking.

The critical need to implement and utilize patient-reported measures of function in cancer care delivery.

The study by Smith et al. on the Patient-Reported Outcomes Measurement Information System (PROMIS) Cancer Function Brief 3D Profile shows that it can be used to measure how an individual functions and how his or her function changes during cancer treatments. This is important because most patients will experience a decline in function during cancer treatment and will struggle to fully participate in their life roles. Strong evidence demonstrates that rehabilitation improves function for individuals with cancer; rehabilitation is relatively underutilized. We suggest that using the PROMIS tool as a repeated measure throughout cancer treatment will help to identify those with functional decline who will benefit most from rehabilitation.

Multilevel Intervention for Low-Income Maternal Smokers in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC).

Objectives. To test the efficacy of Babies Living Safe and Smokefree (BLiSS), a multilevel intervention initiated in a citywide safety net health system to improve low-income maternal smokers' abstinence and reduce child tobacco smoke exposure. Methods. This randomized controlled trial in Philadelphia, Pennsylvania (2015-2020), recruited low-income maternal smokers who received a brief smoking intervention (Ask, Advise, Refer [AAR]) from nutrition professionals in the Special Supplemental Nutrition Program for Women, Infants, and Children before randomization to (1) a multilevel intervention (AAR + multimodal behavioral intervention [MBI]; n = 199) or (2) an attention control intervention (AAR + control; n = 197). Results. AAR + MBI mothers had significantly higher 12-month bioverified abstinence rates than did AAR + control mothers (odds ratio [OR] = 9.55; 95% confidence interval [CI] = 1.54, 59.30; P = .015). There were significant effects of time (b = -0.15; SE = 0.04; P < .001) and condition by time (b = -0.19; SE = 0.06; P < .001) on reported child exposure favoring AAR + MBI, but no group difference in child cotinine. Presence of other residential smokers was related to higher exposure. Higher baseline nicotine dependence was related to higher child exposure and lower abstinence likelihood at follow-up. Conclusions. The multilevel BLiSS intervention was acceptable and efficacious in a population that experiences elevated challenges with cessation. Public Health Implications. BLiSS is a translatable intervention model that can successfully improve efforts to address the persistent tobacco-related burdens in low-income communities. Trial Registration. Clinical Trials.gov identifier: NCT02602288. (Am J Public Health. 2022;112(3):472-481. https://doi.org/10.2105/AJPH.2021.306601).

Early postoperative outcomes in implant, pedicled, and free flap reconstruction for breast cancer: an analysis of 23,834 patients from the ACS-NSQIP datasets.

INTRODUCTION: Many patients seek breast reconstruction following mastectomy. Debate exists regarding the best reconstructive option. The authors evaluate outcomes comparing implant, free flap, and pedicled flap reconstruction. METHODS: Patients undergoing implant, pedicled flap, and free flap reconstruction were identified in the 2011-2016 NSQIP database. Demographics were analyzed and covariates were balanced using overlap propensity score. Logistic regression was used for binary outcomes and Gamma GLM for length of stay (LOS). RESULTS: Of 23,834 patients, 87.7% underwent implant, 8.1% free flap, and 4.2% pedicled flap reconstruction. The implant group had the lowest mean operative time (206 min, SD 85.6). Implant patients had less pneumonia (OR 0.09, CI 0.02-0.36, p < 0.01), return to operating room (OR 0.62, CI 0.50-0.75, p < 0.01), venous thromboembolism (VTE) (OR 0.33, CI 0.14-0.79, p = 0.01), postoperative bleeding (OR 0.10, CI 0.06-0.15, p < 0.01), and urinary tract infections (UTI) (OR 0.21, CI 0.07-0.58, p < 0.01) than free flap patients. Pedicled flap patients had less postoperative bleeding (OR 0.69, CI 0.49-0.96, p = 0.03) than free flap patients. Pedicled flap patients had more superficial surgical site infections (p = 0.03), pneumonia (p = 0.02), postoperative bleeding (p < 0.01), VTE (p = 0.04), sepsis (p = 0.05), and unplanned reintubation (p = 0.01) than implant patients. Implant patients had the lowest LOS (1.6 days, p < 0.01). CONCLUSION: Implant reconstruction has less short-term postoperative complications than free flaps and pedicled flap reconstructions. The overall complication rate among all reconstructive modalities remains acceptably low and patients should be informed of all surgical options.

Statistical inference for natural language processing algorithms with a demonstration using type 2 diabetes prediction from electronic health record notes.

The pointwise mutual information statistic (PMI), which measures how often two words occur together in a document corpus, is a cornerstone of recently proposed popular natural language processing algorithms such as word2vec. PMI and word2vec reveal semantic relationships between words and can be helpful in a range of applications such as document indexing, topic analysis, or document categorization. We use probability theory to demonstrate the relationship between PMI and word2vec. We use the theoretical results to demonstrate how the PMI can be modeled and estimated in a simple and straight forward manner. We further describe how one can obtain standard error estimates that account for within-patient clustering that arises from patterns of repeated words within a patient's health record due to a unique health history. We then demonstrate the usefulness of PMI on the problem of predictive identification of disease from free text notes of electronic health records. Specifically, we use our methods to distinguish those with and without type 2 diabetes mellitus in electronic health record free text data using over 400 000 clinical notes from an academic medical center.

Longitudinal follow-up after telephone disclosure in the randomized COGENT study.

PURPOSE: To better understand the longitudinal risks and benefits of telephone disclosure of genetic test results in the era of multigene panel testing. METHODS: Adults who were proceeding with germline cancer genetic testing were randomized to telephone disclosure (TD) with a genetic counselor or in-person disclosure (IPD) (i.e., usual care) of test results. All participants who received TD were recommended to return to meet with a physician to discuss medical management recommendations. RESULTS: Four hundred seventy-three participants were randomized to TD and 497 to IPD. There were no differences between arms for any cognitive, affective, or behavioral outcomes at 6 and 12 months. Only 50% of participants in the TD arm returned for the medical follow-up appointment. Returning was associated with site (p < 0.0001), being female (p = 0.047), and not having a true negative result (p < 0.002). Mammography was lower at 12 months among those who had TD and did not return for medical follow-up (70%) compared with those who had TD and returned (86%) and those who had IPD (87%, adjusted p < 0.01). CONCLUSION: Telephone disclosure of genetic test results is a reasonable alternative to in-person disclosure, but attention to medical follow-up may remain important for optimizing appropriate use of genetic results.

Longitudinal outcomes with cancer multigene panel testing in previously tested BRCA1/2 negative patients.

Although multigene panel testing (MGPT) is increasingly utilized in clinical practice, there remain limited data on patient-reported outcomes. BRCA 1/2 negative patients were contacted and offered MGPT. Patients completed pre- and posttest counseling, and surveys assessing cognitive, affective and behavioral outcomes at baseline, postdisclosure and 6 and 12 months. Of 317 eligible BRCA1/2 negative patients who discussed the study with research staff, 249 (79%) enrolled. Decliners were more likely to be older, non-White, and recruited by mail or email. Ninety-five percent of enrolled patients proceeded with MGPT. There were no significant changes in anxiety, depression, cancer specific distress or uncertainty postdisclosure. There were significant but small increases in knowledge, cancer-specific distress and depression at 6-12 months. Uncertainty declined over time. Those with a VUS had significant decreases in uncertainty but also small increases in cancer specific distress at 6 and 12 months. Among those with a positive result, medical management recommendations changed in 26% of cases and 2.6% of all tested. Most BRCA1/2 negative patients have favorable psychosocial outcomes after receipt of MGPT results, although small increases in depression and cancer-specific worry may exist and may vary by result. Medical management changed in few patients.

Inflammation and breast density among female Chinese immigrants: exploring variations across neighborhoods.

PURPOSE: We examined associations of inflammation with breast density, a marker of breast cancer risk, among female Chinese immigrants and explored whether associations varied by neighborhood environment. METHODS: Assessments of serum C-reactive protein (CRP), soluble tumor necrosis factor receptor 2 (sTNFR2), and breast density were performed among 401 Chinese immigrants across the Philadelphia region. Participant addresses were geocoded, with the majority residing in areas representing traditional urban enclaves (i.e., Chinatown and South Philadelphia) or an emerging enclave with a smaller, but rapidly growing Chinese immigrant population (i.e., the Near Northeast). The remainder was classified as residing in non-enclaves. RESULTS: In multivariable adjusted regression models, CRP was inversely associated with dense breast area (p = 0.01). Levels of sTNFR2 were also inversely associated with dense breast area, but these associations varied by neighborhood (interaction p = 0.01); specifically, inverse associations were observed among women residing in the emerging enclave (p = 0.03), but not other neighborhoods. CONCLUSIONS: Among Chinese immigrant women, aggregate analyses that do not take neighborhood context into consideration can mask potential variations in association of inflammatory markers with breast density. Future studies should consider how neighborhood contextual factors may contribute to differential risk pathways.

Preferences for in-person disclosure: Patients declining telephone disclosure characteristics and outcomes in the multicenter Communication Of GENetic Test Results by Telephone study.

Telephone disclosure of cancer genetic test results is noninferior to in-person disclosure. However, how patients who prefer in-person communication of results differ from those who agree to telephone disclosure is unclear but important when considering delivery models for genetic medicine. Patients undergoing cancer genetic testing were recruited to a multicenter, randomized, noninferiority trial (NCT01736345) comparing telephone to in-person disclosure of genetic test results. We evaluated preferences for in-person disclosure, factors associated with this preference and outcomes compared to those who agreed to randomization. Among 1178 enrolled patients, 208 (18%) declined randomization, largely given a preference for in-person disclosure. These patients were more likely to be older (P = 0.007) and to have had multigene panel testing (P < 0.001). General anxiety (P = 0.007), state anxiety (P = 0.008), depression (P = 0.011), cancer-specific distress (P = 0.021) and uncertainty (P = 0.03) were higher after pretest counseling. After disclosure of results, they also had higher general anxiety (P = 0.003), depression (P = 0.002) and cancer-specific distress (P = 0.043). While telephone disclosure is a reasonable alternative to in-person disclosure in most patients, some patients have a strong preference for in-person communication. Patient age, distress and complexity of testing are important factors to consider and requests for in-person disclosure should be honored when possible.

Trends in Regionalization of Care and Mortality For Patients Treated With Radical Cystectomy.

BACKGROUND: Regionalization to higher volume centers has been proposed as a mechanism to improve short-term outcomes following complex surgery. OBJECTIVE: The objective of this study was to assess trends in regionalization and mortality for patients undergoing radical cystectomy (RC). RESEARCH DESIGN: An observational study of patients receiving RC in the United States from 2004 to 2013. SUBJECTS: Data for patients receiving RC were extracted from the National Cancer Database. MEASURES: The primary exposure was hospital volume; low-volume hospitals (LVH) included those with <5 RC/year and high-volume hospitals (HVH) were those with ≥30 RC/year. Trends in the volume were assessed, as were 30- and 90-day mortality. Cochrane-Armitage tests were performed for volume, and propensity score-weighted proportional hazard regression was used to assess mortality. RESULTS: A total of 47,028 RC were performed in 1162 hospitals from 2004 to 2013. The proportion of RC at LVH declined from 29% to 17% (P<0.01), whereas that of HVH increased from 16% to 33% (P<0.01). Unadjusted 30- (P=0.02) and 90-day (P<0.001) mortality decreased, and the absolute decrease was greatest at LVH (4.8% vs. 2.6%, P=0.03), whereas rates for HVH remained stable (1.9% vs. 1.4%, P=0.34). Following risk-adjustment, relative to treatment at HVH, treatment at LVH was associated with increased 30-day (hazard ratio: 1.66, 95% CI: 1.53-1.80) and 90-day mortality (hazard ratio: 1.37, 95% confidence interval: 1.30-1.44). CONCLUSIONS: Regionalization of RC to HVH was observed from 2004 to 2013. Treatment at LVH was associated with 66% and 33% relative increases in hazard of death at 30 and 90 days, respectively. These findings support the selective referral of complex cases to higher volume centers.

Prediction of significant estimated glomerular filtration rate decline after renal unit removal to aid in the clinical choice between radical and partial nephrectomy in patients with a renal mass and normal renal function.

OBJECTIVES: To develop a clinically applicable predictive model to quantitate the risk of estimated glomerular filtration rate (eGFR) decline to ≤45 mL/min/1.73 m2 after radical nephrectomy (RN) to better inform decisions between RN and partial nephrectomy (PN). PATIENTS AND METHODS: Our prospectively maintained kidney cancer registry was reviewed for patients with a preoperative eGFR >60 mL/min/1.73 m2 who underwent RN for a localized renal mass. New baseline renal function was indexed. We used multivariable logistic regression to develop a predictive nomogram and evaluated it using receiver-operating characteristic (ROC) analysis. Decision-curve analysis was used to assess the net clinical benefit. RESULTS: A total of 668 patients met the inclusion criteria, of whom 183 (27%) experienced a decline in eGFR to ≤45 mL/min/1.73 m2 . On multivariable analysis, increasing age (P = 0.001), female gender (P < 0.001), and increasing preoperative creatinine level (P < 0.001) were associated with functional decline. We constructed a predictive nomogram that included these variables in addition to comorbidities with a known association with kidney disease, but found that a simplified model excluding comorbidities was equally robust (cross-validated area under the ROC curve was 0.78). Decision-curve analysis showed the net clinical benefit at probabilities >~11%. CONCLUSIONS: The decision to perform RN vs PN is multifaceted. We have provided a simple quantitative tool to help identify patients at risk of a postoperative eGFR of ≤45 mL/min/1.73 m2 , who may be stronger candidates for nephron preservation.

Musashi-2 (MSI2) supports TGF-ß signaling and inhibits claudins to promote non-small cell lung cancer (NSCLC) metastasis.

Non-small cell lung cancer (NSCLC) has a 5-y survival rate of ∼16%, with most deaths associated with uncontrolled metastasis. We screened for stem cell identity-related genes preferentially expressed in a panel of cell lines with high versus low metastatic potential, derived from NSCLC tumors of Kras(LA1/+);P53(R172HΔG/+) (KP) mice. The Musashi-2 (MSI2) protein, a regulator of mRNA translation, was consistently elevated in metastasis-competent cell lines. MSI2 was overexpressed in 123 human NSCLC tumor specimens versus normal lung, whereas higher expression was associated with disease progression in an independent set of matched normal/primary tumor/lymph node specimens. Depletion of MSI2 in multiple independent metastatic murine and human NSCLC cell lines reduced invasion and metastatic potential, independent of an effect on proliferation. MSI2 depletion significantly induced expression of proteins associated with epithelial identity, including tight junction proteins [claudin 3 (CLDN3), claudin 5 (CLDN5), and claudin 7 (CLDN7)] and down-regulated direct translational targets associated with epithelial-mesenchymal transition, including the TGF-ß receptor 1 (TGFßR1), the small mothers against decapentaplegic homolog 3 (SMAD3), and the zinc finger proteins SNAI1 (SNAIL) and SNAI2 (SLUG). Overexpression of TGFßRI reversed the loss of invasion associated with MSI2 depletion, whereas overexpression of CLDN7 inhibited MSI2-dependent invasion. Unexpectedly, MSI2 depletion reduced E-cadherin expression, reflecting a mixed epithelial-mesenchymal phenotype. Based on this work, we propose that MSI2 provides essential support for TGFßR1/SMAD3 signaling and contributes to invasive adenocarcinoma of the lung and may serve as a predictive biomarker of NSCLC aggressiveness.

Anti-Müllerian hormone and risk of ovarian cancer in nine cohorts.

Animal and experimental data suggest that anti-Müllerian hormone (AMH) serves as a marker of ovarian reserve and inhibits the growth of ovarian tumors. However, few epidemiologic studies have examined the association between AMH and ovarian cancer risk. We conducted a nested case-control study of 302 ovarian cancer cases and 336 matched controls from nine cohorts. Prediagnostic blood samples of premenopausal women were assayed for AMH using a picoAMH enzyme-linked immunosorbent assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using multivariable-adjusted conditional logistic regression. AMH concentration was not associated with overall ovarian cancer risk. The multivariable-adjusted OR (95% CI), comparing the highest to the lowest quartile of AMH, was 0.99 (0.59-1.67) (Ptrend : 0.91). The association did not differ by age at blood draw or oral contraceptive use (all Pheterogeneity : ≥0.26). There also was no evidence for heterogeneity of risk for tumors defined by histologic developmental pathway, stage, and grade, and by age at diagnosis and time between blood draw and diagnosis (all Pheterogeneity : ≥0.39). In conclusion, this analysis of mostly late premenopausal women from nine cohorts does not support the hypothesized inverse association between prediagnostic circulating levels of AMH and risk of ovarian cancer.

Comparative Effectiveness and Risks of Bowel Preparation Before Elective Colorectal Surgery.

OBJECTIVE: The objective of this study was to determine the relationship between bowel preparation and surgical site infections (SSIs), and also other postoperative complications, after elective colorectal surgery. BACKGROUND: SSI is a major source of postoperative morbidity/costs after colorectal surgery. The value of preoperative bowel preparation to prevent SSI remains controversial. METHODS: We analyzed 32,359 patients who underwent elective colorectal resections in the American College of Surgeons National Surgery Quality Improvement Program database from 2012 to 2014. Univariable and multivariable analyses were performed; propensity adjustment using patient/procedure characteristics was used to account for nonrandom receipt of bowel preparation. RESULTS: 26.7%, 36.6%, 3.8%, and 32.9% of patients received no bowel preparation, mechanical bowel preparation (MBP), oral antibiotics (OA), and MBP + OA, respectively. After propensity adjustment, MBP was not associated with decreased risk of SSI compared with no bowel preparation. In contrast, both OA and OA + MBP were associated with decreased risk of any SSI (adjusted odds ratio 0.49, 95% confidence interval 0.38-0.64; and adjusted odds ratio 0.45, 95% confidence interval 0.40-0.50, respectively) compared with no bowel preparation. OA and MBP + OA were associated with decreased risks of anastomotic leak, postoperative ileus, readmission, and also shorter length of stay (all P < 0.05). Bowel preparation was not associated with increased risk of cardiac/renal complications compared with no preparation. CONCLUSIONS: The use of MBP alone before elective colorectal resection to prevent SSI is ineffective and should be abandoned. In contrast, OA and MBP + OA are associated with decreased risks of SSI and are not associated with increased risks of other adverse outcomes compared with no preparation. Prospective studies to determine the efficacy of OA are warranted; in the interim, MBP + OA should be used routinely before elective colorectal resection to prevent SSI.

EHR phenotyping via jointly embedding medical concepts and words into a unified vector space.

BACKGROUND: There has been an increasing interest in learning low-dimensional vector representations of medical concepts from Electronic Health Records (EHRs). Vector representations of medical concepts facilitate exploratory analysis and predictive modeling of EHR data to gain insights about the patterns of care and health outcomes. EHRs contain structured data such as diagnostic codes and laboratory tests, as well as unstructured free text data in form of clinical notes, which provide more detail about condition and treatment of patients. METHODS: In this work, we propose a method that jointly learns vector representations of medical concepts and words. This is achieved by a novel learning scheme based on the word2vec model. Our model learns those relationships by integrating clinical notes and sets of accompanying medical codes and by defining joint contexts for each observed word and medical code. RESULTS: In our experiments, we learned joint representations using MIMIC-III data. Using the learned representations of words and medical codes, we evaluated phenotypes for 6 diseases discovered by our and baseline method. The experimental results show that for each of the 6 diseases our method finds highly relevant words. We also show that our representations can be very useful when predicting the reason for the next visit. CONCLUSIONS: The jointly learned representations of medical concepts and words capture not only similarity between codes or words themselves, but also similarity between codes and words. They can be used to extract phenotypes of different diseases. The representations learned by the joint model are also useful for construction of patient features.

Anti-Mullerian hormone and endometrial cancer: a multi-cohort study.

BACKGROUND: The Mullerian ducts are the embryological precursors of the female reproductive tract, including the uterus; anti-Mullerian hormone (AMH) has a key role in the regulation of foetal sexual differentiation. Anti-Mullerian hormone inhibits endometrial tumour growth in experimental models by stimulating apoptosis and cell cycle arrest. To date, there are no prospective epidemiologic data on circulating AMH and endometrial cancer risk. METHODS: We investigated this association among women premenopausal at blood collection in a multicohort study including participants from eight studies located in the United States, Europe, and China. We identified 329 endometrial cancer cases and 339 matched controls. Anti-Mullerian hormone concentrations in blood were quantified using an enzyme-linked immunosorbent assay. Conditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CI) across tertiles and for a doubling of AMH concentrations (ORlog2). Subgroup analyses were performed by ages at blood donation and diagnosis, oral contraceptive use, and tumour characteristics. RESULTS: Anti-Mullerian hormone was not associated with the risk of endometrial cancer overall (ORlog2: 1.07 (0.99-1.17)), or with any of the examined subgroups. CONCLUSIONS: Although experimental models implicate AMH in endometrial cancer growth inhibition, our findings do not support a role for circulating AMH in the aetiology of endometrial cancer.

Assessing the relative influence of hospital and surgeon volume on short-term mortality after radical cystectomy.

OBJECTIVES: To assess the relationship between surgeon (SV) and hospital volume (HV) on mortality after radical cystectomy (RC). PATIENTS AND METHODS: We queried the National Cancer Database (NCDB) for adult patients undergoing RC between 2010 and 2013. We calculated average volume for each surgeon and hospital. Using propensity-scored weights for combined volume groups with a proportional hazards regression model, we compared the associations between HV and SV with 90-day survival after RC. RESULTS: A total of 19 346 RCs were performed at 927 hospitals by 2 927 surgeons in the period 2010-2013. The median (interquartile range) HV and SV were 12.3 (5.0-35.5) and 4.3 (1.3-12.3) cases, respectively. For HV, 90-day unadjusted mortality was 8.5% in centres with <5 cases/year (95% confidence interval [CI] 7.7-9.3) and 5.6% in those with >30 cases/year (95% CI 5.0-6.2). For SV, 90-day mortality was 8.1% for surgeons with <5 cases/year (95% CI 7.6-8.6) and 4.0% for those with >30 cases/year (95% CI 2.8-5.2; all P < 0.05). The 30-day mortality rate was lowest for the combined HV-SV groups with HV >30, ranging from 1.6% to 2.1%. CONCLUSIONS: In hospitals reporting to the NCDB, volume was associated with improved mortality after RC. These associations appear to be driven by hospital- rather than surgeon-level effects. An elevated SV had a beneficial effect on mortality at the highest-volume hospitals. These findings inform efforts to regionalize complex surgical care and improve quality at community and safety net hospitals.

Distress and Financial Distress in Adults With Cancer: An Age-Based Analysis.

Background: Although financial distress is commonly recognized in patients with cancer, it may be more prevalent in younger adults. This study sought to evaluate disparities in overall and financial distress in patients with cancer as a function of age. Methods: This was a single-center cross-sectional study of patients with solid malignancies requiring cancer therapy. The patient questionnaire included demographics, financial concerns, and measures of overall and financial distress. Data analyses compared patients in 3 age groups: young (<50 years), middle-aged (50-64 years), and elderly (≥65 years). Results: The cohort included 119 patients (median age, 62 years; 52% female; 84% white; 100% insured; 36% income ≥$75,000). Significant financial concerns included paying rent/mortgage (P=.003) and buying food (P=.032). Impact of Event Scale (IES) results revealed significant distress in 73% young, 64% middle-aged, and 44% elderly patients. The mean Distress Thermometer (DT) score was 6.1 (standard deviation [SD], 2.9) for young patients, 5.4 (SD, 2.6) for middle-aged, and 4.4 (SD, 3.3) for elderly patients. Young patients were more likely than elderly patients to have a higher IES distress score (P=.016) and DT score (P=.048). The mean InCharge score was lowest (indicating greatest financial distress) in the young group and progressed with age: 5.0 (SD, 1.9), 5.7 (SD, 2.7), and 7.4 (SD, 1.9), respectively (P<.001). Multivariable analyses revealed that the relationship between financial distress and overall distress was strongest in the middle-age group; as the DT increased by 1 point, the InCharge scores decreased by 0.52 (P<.001). Conclusions: Overall and financial distress are more common in young and middle-aged patients with cancer. There are several factors, including employment, insurance, access to paid sick leave, children, and education, that affect younger and middle-aged adults and are less of a potential stressor for elderly individuals.

Nedd9 restrains renal cystogenesis in Pkd1-/- mice.

Mutations inactivating the cilia-localized Pkd1 protein result in autosomal dominant polycystic kidney disease (ADPKD), a serious inherited syndrome affecting ∼ 1 in 500 people, in which accumulation of renal cysts eventually destroys kidney function. Severity of ADPKD varies throughout the population, for reasons thought to involve differences both in intragenic Pkd1 mutations and in modifier alleles. The scaffolding protein NEDD9, commonly dysregulated during cancer progression, interacts with Aurora-A (AURKA) kinase to control ciliary resorption, and with Src and other partners to influence proliferative signaling pathways often activated in ADPKD. We here demonstrate Nedd9 expression is deregulated in human ADPKD and a mouse ADPKD model. Although genetic ablation of Nedd9 does not independently influence cystogenesis, constitutive absence of Nedd9 strongly promotes cyst formation in the tamoxifen-inducible Pkd1fl/fl;Cre/Esr1(+) mouse model of ADPKD. This cystogenic effect is associated with striking morphological defects in the cilia of Pkd1(-/-);Nedd9(-/-) mice, associated with specific loss of ciliary localization of adenylase cyclase III in the doubly mutant genotype. Ciliary phenotypes imply a failure of Aurora-A activation: Compatible with this idea, Pkd1(-/-);Nedd9(-/-) mice had ciliary resorption defects, and treatment of Pkd1(-/-) mice with a clinical Aurora-A kinase inhibitor exacerbated cystogenesis. In addition, activation of the ADPKD-associated signaling effectors Src, Erk, and the mTOR effector S6 was enhanced, and Ca(2+) response to external stimuli was reduced, in Pkd1(-/-);Nedd9(-/-) versus Pkd1(-/-) mice. Together, these results indicated an important modifier action of Nedd9 on ADPKD pathogenesis involving failure to activate Aurora-A.