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Aim Sodium-phosphate-containing colonoscopy preparations cause renal failure by the development of calcium phosphate nephropathy. Although Fleet's Phospho-Soda has been removed from the US market, sodium phosphate tablets sold as OsmoPrep and Visicol remain available. Our aim was to analyse renal risks of the sodium phosphate tablets. Method We conducted a retrospective study using the US Food and Drug Administration Adverse Event Reporting System, a voluntary reporting system available for public access. Renal adverse events were identified using search terms including renal impairment, increased blood urea nitrogen, increased creatinine, renal failure, acute renal failure, chronic renal failure, acute phosphate nephropathy, nephrocalcinosis, renal tubular necrosis, haemodialysis, nephropathy toxic, dialysis, peritoneal dialysis, renal injury, renal tubular disorder, decreased glomerular filtration rate and decreased creatinine clearance. Patient age, gender and body weight were compared with data for the general population in the National Health and Nutrition Examination Survey (NHANES). Results In total 2 097 223 files were extracted from the US Food and Drug Administration website for 2004-2008 and the first 9 months of 2009. Of these, 178 patients on tablet preparations (71% women) were identified, with increasing numbers of renal adverse drug reactions reported from tablet preparations each year. The mean weight for women with renal complications from tablet preparations was 68.57 ± 1.78 kg, significantly lower than the national average weight of 74 ± 0.5 kg for the same age group ( P = 0.003) in NHANES. Conclusion Renal adverse drug reactions from sodium phosphate tablets are more common in women with a mean body weight lower than the national average weight. [ABSTRACT FROM AUTHOR]

The escalating drug addiction crisis in the United States underscores the urgent need for innovative therapeutic strategies. This study embarked on an innovative and rigorous strategy to unearth potential drug repurposing candidates for opioid and cocaine addiction treatment, bridging the gap between transcriptomic data analysis and drug discovery. We initiated our approach by conducting differential gene expression analysis on addiction-related transcriptomic data to identify key genes. We propose a novel topological differentiation to identify key genes from a protein-protein interaction network derived from DEGs. This method utilizes persistent Laplacians to accurately single out pivotal nodes within the network, conducting this analysis in a multiscale manner to ensure high reliability. Through rigorous literature validation, pathway analysis and data-availability scrutiny, we identified three pivotal molecular targets, mTOR, mGluR5 and NMDAR, for drug repurposing from DrugBank. We crafted machine learning models employing two natural language processing (NLP)-based embeddings and a traditional 2D fingerprint, which demonstrated robust predictive ability in gauging binding affinities of DrugBank compounds to selected targets. Furthermore, we elucidated the interactions of promising drugs with the targets and evaluated their drug-likeness. This study delineates a multi-faceted and comprehensive analytical framework, amalgamating bioinformatics, topological data analysis and machine learning, for drug repurposing in addiction treatment, setting the stage for subsequent experimental validation. The versatility of the methods we developed allows for applications across a range of diseases and transcriptomic datasets., (© The Author(s) 2024. Published by Oxford University Press.)

Background: Population-level vaccine efficacy is a critical component of understanding COVID-19 risk, informing public health policy, and mitigating disease impacts. Unlike individual-level clinical trials, population-level analysis characterizes how well vaccines worked in the face of real-world challenges like emerging variants, differing mobility patterns, and policy changes., Methods: In this study, we analyze the association between time-dependent vaccination rates and COVID-19 health outcomes for 48 U.S. states. We primarily focus on case-hospitalization risk (CHR) as the outcome of interest, using it as a population-level proxy for disease burden on healthcare systems. Performing the analysis using Generalized Additive Models (GAMs) allowed us to incorporate real-world nonlinearities and control for critical dynamic (time-changing) and static (temporally constant) factors. Dynamic factors include testing rates, activity-related engagement levels in the population, underlying population immunity, and policy. Static factors incorporate comorbidities, social vulnerability, race, and state healthcare expenditures. We used SARS-CoV-2 genomic surveillance data to model the different COVID-19 variant-driven waves separately, and evaluate if there is a changing role of the potential drivers of health outcomes across waves., Results: Our study revealed a strong and statistically significant negative association between vaccine uptake and COVID-19 CHR across each variant wave, with boosters providing additional protection during the Omicron wave. Higher underlying population immunity is shown to be associated with reduced COVID-19 CHR. Additionally, more stringent government policies are generally associated with decreased CHR. However, the impact of activity-related engagement levels on COVID-19 health outcomes varied across different waves. Regarding static variables, the social vulnerability index consistently exhibits positive associations with CHR, while Medicaid spending per person consistently shows a negative association. However, the impacts of other static factors vary in magnitude and significance across different waves., Conclusions: This study concludes that despite the emergence of new variants, vaccines remain highly correlated with reduced COVID-19 harm. Therefore, given the ongoing threat posed by COVID-19, vaccines remain a critical line of defense for protecting the public and reducing the burden on healthcare systems., (© 2024. The Author(s).)

Background: Since the US reported its first COVID-19 case on January 21, 2020, the science community has been applying various techniques to forecast incident cases and deaths. To date, providing an accurate and robust forecast at a high spatial resolution has proved challenging, even in the short term., Method: Here we present a novel multi-stage deep learning model to forecast the number of COVID-19 cases and deaths for each US state at a weekly level for a forecast horizon of 1-4 weeks. The model is heavily data driven, and relies on epidemiological, mobility, survey, climate, demographic, and SARS-CoV-2 variant frequencies data. We implement a rigorous and robust evaluation of our model-specifically we report on weekly performance over a one-year period based on multiple error metrics, and explicitly assess how our model performance varies over space, chronological time, and different outbreak phases., Findings: The proposed model is shown to consistently outperform the CDC ensemble model for all evaluation metrics in multiple spatiotemporal settings, especially for the longer-term (3 and 4 weeks ahead) forecast horizon. Our case study also highlights the potential value of variant frequencies data for use in short-term forecasting to identify forthcoming surges driven by new variants., Interpretation: Based on our findings, the proposed forecasting framework improves upon the available state-of-the-art forecasting tools currently used to support public health decision making with respect to COVID-19 risk., Funding: This work was funded the NSF Rapid Response Research (RAPID) grant Award ID 2108526 and the CDC Contract #75D30120C09570., Competing Interests: Declaration of interests The authors declare no potential conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Different from less developed countries, 80% of children with cancers in the United States are cured. Traditional chemotherapy drugs are the mainstay of therapies; new targeted medications have become available recently. Using publicly available data, we created a database of cancer drugs with paediatric malignancy indications approved by 31 October 2020 in China and the United States. We compared numbers, type, indications and listing on the World Health Organization Model List of Essential Medicines for Children (WHO EMLc) between the two countries, assessed the correlation between paediatric indications and cancer incidences, and described evidence supporting approvals of targeted medications in the two settings. Our study showed that by 31 October 2020, 31 and 39 cancer drugs available in China and the United States were approved for use in children, corresponding to 137 and 102 paediatric cancer indications, respectively. About half of these drugs (17 in China and 18 in the United States) were listed on the WHO EMLc. The correlation between indications and burden of disease was higher in the United States (r = 0.68) than China (r = 0.59). More traditional chemotherapy drugs were approved in China (n = 27) than the United States (n = 19). Of 20 targeted childhood anticancer medicines approved in the United States, mainly on the basis of single arm trials (27/32 indications, 84.4%), only four were approved for paediatric indications in China, at a median of 2.8 years after US Food and Drug Administration approval. A harmonised, evidence-based regulatory framework is needed to ensure approvals of needed, safe and efficacious childhood cancer drugs across the world., (© 2021 UICC.)

Lessons Learned: The combination of anlotinib and S-1 exhibited good antitumor activity in third- or later-line treatment for stage IV non-small cell lung cancer (NSCLC). Combination therapy of anlotinib with S-1 has manageable toxicities in patients with NSCLC., Background: This study aimed to evaluate the efficacy and safety of anlotinib combined with S-1 as a third- or later-line treatment for patients with stage IV non-small cell lung cancer (NSCLC). Anlotinib was approved in 2018 by the Chinese Food and Drug Administration (FDA) as a third-line treatment for patients with refractory advanced NSCLC and is under study in the U.S. and Europe., Methods: Simon's phase II clinical trial design with an α error of 5% and a power β of 80% was used, anticipating a 10% objective response rate (ORR) of anlotinib and a 30% ORR of anlotinib combined with S-1; the required sample size was 29. A total of 29 patients were enrolled in the clinical trial. Patients were treated with anlotinib plus S-1 over a 21-day treatment course until disease progression or unacceptable toxic effects. If the efficacy was assessed as stable disease, partial response, or complete response after six cycles, anlotinib was maintained until disease progression or death. The primary endpoint was the objective response rate. Somatic mutations were not required for study enrollment., Results: The median follow-up time was 11.1 months. Objective responses were observed in 11 of 29 (37.9%) patients making up the intention-to-treat population, which reached the target primary endpoint of 30% ORR. The median overall and progression-free survival were 16.7 and 5.8 months, respectively. The most common grade 3 adverse events (AEs) were gastrointestinal, including nausea, vomiting and diarrhea, fatigue, and hypertension. No grade 4 treatment-related AEs or treatment-related deaths occurred., Conclusion: The combination of anlotinib with S-1 in the third- or later-line treatment of stage IV NSCLC shows promising antitumor activity and manageable toxicity in patients with NSCLC; phase III trials will be planned in the future., (© AlphaMed Press; the data published online to support this summary are the property of the authors.)

The disjunct distribution between East Asia and North America is one of the best established biogeographic patterns. A robust phylogeny is fundamental for understanding the biogeographic histories of taxa with this distribution pattern. Tsuga (hemlock) is a genus of Pinaceae with a typical intercontinental disjunct distribution in East Asia and eastern and western North America, and its phylogeny has not been completely reconstructed in previous studies. In this study, we reconstructed a highly resolved phylogeny of Tsuga using 881 nuclear genes, 60 chloroplast genes and 23 mitochondrial genes and explored its biogeographic and reticulate evolutionary history. The results of phylogenetic analysis, molecular dating and ancestral area reconstruction indicate that Tsuga very likely originated from North America in the late Oligocene and dispersed from America to East Asia via the Bering Land Bridge during the middle Miocene. In particular, we found complex reticulate evolutionary pattern among the East Asian hemlock species. T. sieboldii possibly originated from hybridization with the ancestor of T. chinensis from mainland China and T. forrestii as the paternal donor and the ancestor of T. diversifolia and T. ulleungensis as the maternal donor. T. chinensis (Taiwan) could have originated by hybridization together with T. sieboldii and then evolved independently after dispersal to the Taiwan Island, subsequently experiencing mitochondrial DNA introgression with T. chinensis from mainland China. Moreover, our study found that T. chinensis from western China is more closely related to T. forrestii than to T. chinensis from eastern China. The nonmonophyletic T. chinensis needs taxonomic reconsideration., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The Chinese paddlefish (Psephurus gladius), one of the world's largest freshwater fish, was last seen alive in 2003; they are presumed now to be extinct. In fish, germ cell transplantation is currently known as one of the most powerful assisted reproductive technologies for the conservation of endangered species. In the event that a Chinese paddlefish is unexpectedly caught in the near future, we aimed to develop an experimental strategy to produce paddlefish gametes in the gonads of surrogate sturgeon. Spermatogonia were collected from the testes of 2.5-year-old immature male American paddlefish (Polyodon spathula), the species most closely related to the Chinese paddlefish, by Percoll gradient centrifugation, and transplanted into the peritoneal cavity of Yangtze sturgeon (Acipenser dabryanus) larvae at 7-8 days post-hatch. At two months post-transplantation, donor-derived spermatogonia had efficiently colonized in the recipient gonads and proliferated. A PCR analysis developed to detect xenogenic donor-derived mtDNA sequences in recipient gonads revealed that American paddlefish germ cells survived for at least seven months after transplantation in the gonads of Yangtze sturgeon recipients. These results show that the somatic microenvironment of Yangtze sturgeon gonads was able to support the colonization, proliferation, and survival of xenogeneic germ cells from a different taxonomic family. This study provides key information that could lead to future restoration of Chinese paddlefish using germ cell transplantation., Competing Interests: Declaration of competing interest The authors declare that they have no conflict of interest., (Copyright © 2020. Published by Elsevier Inc.)

Background: The COVID-19 pandemic has powerfully shaped people's lives. The current work investigated the emotional and behavioral reactions people experience in response to COVID-19 through their internet searches. We hypothesised that when the prevalence rates of COVID-19 increase, people would experience more fear, which in turn would predict more searches for protective behaviors, health-related knowledge, and panic buying., Methods: Prevalence rates of COVID-19 in the United States, the United Kingdom, Canada, and Australia were used as predictors. Fear-related emotions, protective behaviors, seeking health-related knowledge, and panic buying were measured using internet search volumes in Google Trends., Results: We found that increased prevalence rates of COVID-19 were associated with more searches for protective behaviors, health knowledge, and panic buying. This pattern was consistent across four countries, the United States, the United Kingdom, Canada, and Australia. Fear-related emotions explained the associations between COVID-19 and the content of their internet searches., Conclusions: Findings suggest that exposure to COVID-19 prevalence and fear-related emotions may motivate people to search for relevant health-related information so as to protect themselves from the pandemic., (© 2020 International Association of Applied Psychology.)

Background: Within 4 months of COVID-19 first being reported in the USA, it spread to every state and to more than 90% of all counties. During this period, the US COVID-19 response was highly decentralised, with stay-at-home directives issued by state and local officials, subject to varying levels of enforcement. The absence of a centralised policy and timeline combined with the complex dynamics of human mobility and the variable intensity of local outbreaks makes assessing the effect of large-scale social distancing on COVID-19 transmission in the USA a challenge., Methods: We used daily mobility data derived from aggregated and anonymised cell (mobile) phone data, provided by Teralytics (Zürich, Switzerland) from Jan 1 to April 20, 2020, to capture real-time trends in movement patterns for each US county, and used these data to generate a social distancing metric. We used epidemiological data to compute the COVID-19 growth rate ratio for a given county on a given day. Using these metrics, we evaluated how social distancing, measured by the relative change in mobility, affected the rate of new infections in the 25 counties in the USA with the highest number of confirmed cases on April 16, 2020, by fitting a statistical model for each county., Findings: Our analysis revealed that mobility patterns are strongly correlated with decreased COVID-19 case growth rates for the most affected counties in the USA, with Pearson correlation coefficients above 0·7 for 20 of the 25 counties evaluated. Additionally, the effect of changes in mobility patterns, which dropped by 35-63% relative to the normal conditions, on COVID-19 transmission are not likely to be perceptible for 9-12 days, and potentially up to 3 weeks, which is consistent with the incubation time of severe acute respiratory syndrome coronavirus 2 plus additional time for reporting. We also show evidence that behavioural changes were already underway in many US counties days to weeks before state-level or local-level stay-at-home policies were implemented, implying that individuals anticipated public health directives where social distancing was adopted, despite a mixed political message., Interpretation: This study strongly supports a role of social distancing as an effective way to mitigate COVID-19 transmission in the USA. Until a COVID-19 vaccine is widely available, social distancing will remain one of the primary measures to combat disease spread, and these findings should serve to support more timely policy making around social distancing in the USA in the future., Funding: None., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Importance: Mammography screening currently relies on subjective human interpretation. Artificial intelligence (AI) advances could be used to increase mammography screening accuracy by reducing missed cancers and false positives., Objective: To evaluate whether AI can overcome human mammography interpretation limitations with a rigorous, unbiased evaluation of machine learning algorithms., Design, Setting, and Participants: In this diagnostic accuracy study conducted between September 2016 and November 2017, an international, crowdsourced challenge was hosted to foster AI algorithm development focused on interpreting screening mammography. More than 1100 participants comprising 126 teams from 44 countries participated. Analysis began November 18, 2016., Main Outcomes and Measurements: Algorithms used images alone (challenge 1) or combined images, previous examinations (if available), and clinical and demographic risk factor data (challenge 2) and output a score that translated to cancer yes/no within 12 months. Algorithm accuracy for breast cancer detection was evaluated using area under the curve and algorithm specificity compared with radiologists' specificity with radiologists' sensitivity set at 85.9% (United States) and 83.9% (Sweden). An ensemble method aggregating top-performing AI algorithms and radiologists' recall assessment was developed and evaluated., Results: Overall, 144 231 screening mammograms from 85 580 US women (952 cancer positive ≤12 months from screening) were used for algorithm training and validation. A second independent validation cohort included 166 578 examinations from 68 008 Swedish women (780 cancer positive). The top-performing algorithm achieved an area under the curve of 0.858 (United States) and 0.903 (Sweden) and 66.2% (United States) and 81.2% (Sweden) specificity at the radiologists' sensitivity, lower than community-practice radiologists' specificity of 90.5% (United States) and 98.5% (Sweden). Combining top-performing algorithms and US radiologist assessments resulted in a higher area under the curve of 0.942 and achieved a significantly improved specificity (92.0%) at the same sensitivity., Conclusions and Relevance: While no single AI algorithm outperformed radiologists, an ensemble of AI algorithms combined with radiologist assessment in a single-reader screening environment improved overall accuracy. This study underscores the potential of using machine learning methods for enhancing mammography screening interpretation.

Objective: To investigate the prevalence, demographic characteristics and social life function of mental disorders in the rural left behind elderly aged 60 years and older in Gansu. Methods: Between November 2017 and June 2018, a multi-stage stratified cluster sampling method was used to randomly select the rural left behind elderly aged 60 years and older in Gansu, and totally 6 000 elderly were enrolled. By using the extended general health questionnaire (GHQ-12) and the American Handbook for Diagnosis and Statistics of Mental Disorders (DSM-Ⅳ) Axis Ⅰ Disorders Formal Clinical Examination Patient Edition, all the included subjects were screened and diagnosed. Functional status was assessed by the Global Assessment Function scale (GAF). Statistical analysis of the prevalence of various mental illnesses, as well as the differences in the prevalence of different gender, marital status and age groups was performed. Results: Totally, 6 000 subjects completed the survey. The adjusted current prevalence of any mental disorder was 20.11% (95% CI 17.70%-22.85%). The six most prevalent specific disorders were major depressive disorder (9.20%), pain disorder (2.71%), mood disorder due to the body condition (2.08%), generalized anxiety disorder (1.99%), anxiety disorder not otherwise specified (1.15%) and dysthymic disorder (0.84%). The lifetime prevalence of mental disorders was 20.54% (95% CI 18.40%-23.39%). The overall current prevalence of mental disorders was higher in women (242.89‰) than in men (119.55‰), and the unmarried (248.37‰) was higher than those married (187.53‰). There was no significant difference in the prevalence of mental disorders among different age groups ( P >0.05). The GAF score of mental disorders was 56±11, and 71.82% was moderate to severe functional impairment. Conclusions: The prevalence of mental disorders is high in rural left-behind population aged 60 years and over in Gansu Province. Major depression is a condition that deserves special attention.

Objective: In recent years, vitamin D has been shown to possess a wide range of immunomodulatory effects. Although there is extensive amount of research on vitamin D, we lack a comprehensive understanding of the prevalence of vitamin D deficiency or the mechanism by which vitamin D regulates the human immune system. This study examined the prevalence and correlates of vitamin D deficiency and the relationship between vitamin D and the immune system in healthy individuals., Methods: Healthy individuals (n = 774) comprised of European-Americans (EA, n = 470), African-Americans (AA, n = 125), and Native Americans (NA, n = 179) were screened for 25-hydroxyvitamin D [25(OH)D] levels by ELISA. To identify the most noticeable effects of vitamin D on the immune system, 20 EA individuals with severely deficient (<11.3 ng/mL) and sufficient (>24.8 ng/mL) vitamin D levels were matched and selected for further analysis. Serum cytokine level measurement, immune cell phenotyping, and phosphoflow cytometry were performed., Results: Vitamin D sufficiency was observed in 37.5% of the study cohort. By multivariate analysis, AA, NA, and females with a high body mass index (BMI, >30) demonstrate higher rates of vitamin D deficiency (p<0.05). Individuals with vitamin D deficiency had significantly higher levels of serum GM-CSF (p = 0.04), decreased circulating activated CD4+ (p = 0.04) and CD8+ T (p = 0.04) cell frequencies than individuals with sufficient vitamin D levels., Conclusion: A large portion of healthy individuals have vitamin D deficiency. These individuals have altered T and B cell responses, indicating that the absence of sufficient vitamin D levels could result in undesirable cellular and molecular alterations ultimately contributing to immune dysregulation.

Unlabelled: In our journey to achieve Magnet designation, we sought to increase staff nurses' research participation and teach them about the research process by conducting a corporate-wide study, a blind taste test, using potato chips., Purpose: To compare 3 varieties of the same-brand potato chips for overall preference and perception of healthiness. We hypothesized that the potato chip the nurses liked the best would not be the chip they perceived as the healthiest., Methods: For this institutional review board-approved study, nurses were recruited via (1) randomly selected units and (2) a convenience sample during cafeteria lunch hours. After informed consent was obtained, nurses rated each potato chip in a blinded manner, based on appearance, crispiness, flavor, saltiness, and greasiness. They indicated which potato chip they perceived to be the healthiest and which they preferred overall, and they completed an anonymous demographic questionnaire., Results: A total of 263 nurses participated, with 78% being staff nurses. Regular (full fat) was most preferred (37.6%), whereas fat free was least preferred (16%) and also considered the healthiest (45.2%) (P < .0001)., Conclusions: Nurses preferred the regular chip and chose the fat-free chip as the healthiest, proving our hypothesis that the preferred chip would not be considered the healthiest., Implications: This study was easy, feasible, and helped promote systemwide nursing research.

Objectives: The development of robust Accreditation Council for Graduate Medical Education (ACGME) systems-based practice (SBP) training and validated evaluation tools has been generally challenging for emergency medicine (EM) residency programs. The purpose of this paper is to report the results of a consensus workgroup session of the 2010 Council of Emergency Medicine Residency Directors (CORD) Academic Assembly with the following objectives: 1) to discuss current and preferred local and regional methods for teaching and assessing SBP and 2) to develop consensus within the CORD community using the modified Delphi method with respect to EM-specific SBP domains and link these domains to specific SBP educational and evaluative methods., Methods: Consensus was developed using a modified Delphi method. Previously described taxonomy generation methodology was used to create a SBP taxonomy of EM domain-specific knowledge, skills, and attitudes (KSA). The steps in the process consisted of: 1) an 11-question preconference survey, 2) a vetting process conducted at the 2010 CORD Academic Assembly, and 3) the development and ranking of domain-specific SBP educational activities and evaluation criteria for the specialty of EM., Results: Rank-order lists were created for preferred SBP education and evaluation methods. Expert modeling, informal small group discussion, and formal small group activities were considered to be the optimal methods to teach SBP. Kruskal-Wallis testing revealed that these top three items were rated significantly higher than self-directed learning projects and lectures (p = 0.0317). Post hoc test via permutation testing revealed that the difference was significant between expert modeling and formal small group activity (adjusted p = 0.028), indicating that expert modeling was rated significantly higher than formal small group activity. Direct observation methods were the preferred methods for evaluation. Multiple barriers to training and evaluation were elucidated. We developed a consensus taxonomy of domains that were felt to be most essential and reflective of the practice of EM: multitasking, disposition, and patient safety. Learning formats linked to the domains were created and specific examples of local best practices collected. Domain-specific anchors of observable actions for the three domains were created., Conclusions: This consensus process resulted in the development of a taxonomy of EM-specific domains for teaching and observable tasks for evaluating SBP. The concept of SBP is interlinked with the other general competencies and difficult to separate. Rather than develop specific SBP evaluation tools to measure the competency directly, SBP competency evaluation should be considered one element of a coordinated effort to teach and evaluate the six ACGME general competencies., (© 2011 by the Society for Academic Emergency Medicine.)

Mentally ill people may face barriers to receiving elective surgical procedures as a result of societal stigma and the cognitive, behavioral, and interpersonal deficits associated with mental illness. Using data from a cohort of elderly Medicare beneficiaries in 2007, we examined whether the mentally ill have less access than people without mental illness to several common procedures that are typically not for emergencies and are performed at the discretion of the provider and the patient. Results suggest that Medicare patients with mental illness are 30-70 percent less likely than others to receive these "referral-sensitive" surgical procedures. Those who did undergo an elective procedure generally experienced poorer outcomes both in the hospital and after discharge. Efforts to improve access to and outcomes of nonpsychiatric care for mentally ill patients are warranted.

Objective: To explore the role of hereditary and environmental factors on the development of stress urinary incontinence in a large cohort of identical and nonidentical twins., Methods: This is a large, population-based, classic twin study of twin sisters recruited to complete a health survey at the world's largest annual twins festival during 2003-2008. Concordance rates were calculated and structural equation models were used to estimate the contribution of genetic effects compared with environmental factors toward the development of stress urinary incontinence., Results: Eight hundred eighty-two twin sister pairs (n=1,764), including 765 identical and 117 nonidentical twin sister pairs, completed the questionnaires. Sequential structural equation modeling revealed that common environmental factors contributed 77.6% (95% confidence interval [CI], 41.4-83.8; P<.001) of the variance and unique environmental factors contributed 20.9% (95% CI, 15.8-26.7; P<.001) of the variance. The effect of genetics was not statistically significant at 1.49% (95% CI, 0.0-38.8; P=.46)., Conclusion: Female stress urinary incontinence is more a consequence of environmental risk factors than heredity. This epidemiologic insight should be considered in preventive health efforts., Level of Evidence: II.

Background & Aims: Cigarette smoking is an established risk factor for pancreatic cancer, but there is conflicting evidence regarding the effects of alcohol consumption. The effects of cigarettes and alcohol on age of sporadic pancreatic cancer diagnosis have not been examined; we evaluated the independent and synergistic effects of lifetime cigarette smoking and alcohol consumption on age at pancreatic cancer diagnosis in the United States., Methods: We analyzed data on cigarette smoking and alcohol consumption from the IMPAC Services, Inc Cancer Information Resource File (CIRF), collected from June 1, 1993, to December 31, 2003, for 29,239 reported, histologically confirmed cases of pancreatic adenocarcinoma. We also analyzed data on cigarette smoking and alcohol consumption for 820 histologically confirmed cases of pancreatic adenocarcinoma from the University of Michigan Pancreatic Cancer Registry (UMPCR), collected from January 2004 to October 2007., Results: Current cigarette smokers were diagnosed at significantly younger ages than never smokers, according to data from the CIRF and UMPCR (8.3 and 6.3 y, respectively); the UMPCR data indicated dose effects. Past and current alcohol consumption were associated with younger age at diagnosis in both databases. Current smokers who were current drinkers were diagnosed significantly earlier (CIRF, 10.2 y; UMPCR, 8.6 y) than abstainers. Past cigarette smoking was associated modestly with younger diagnosis age., Conclusions: Cigarette smoking and alcohol consumption were associated with younger age at pancreatic cancer presentation and have a combined effect on diagnosis age. Past cigarette smoking is less influential. Smoking cessation programs could help prevent pancreatic cancer.

Objective: To evaluate the impact of administration context (embedded versus stand-alone) on the reliability and validity of the FACT Head and Neck Symptom Index (FHNSI)., Methods: Ninety-eight patients with head and neck cancer were randomized to one of two assessment conditions to evaluate the FHNSI's context (items administered embedded within the FACT-H&N or as stand-alone scale) and order of administration in the battery., Results: Planned comparisons on the item and scale levels revealed no systematic order or context differences. The embedded and stand-alone versions of the FHNSI showed high internal consistency (Cronbach's alpha 0.79-0.87). Correlations were high between the FHNSI versions and the physical and functional well-being scales of the FACT-H&N (0.70-0.84) and measures of pain intensity (-0.73, -0.74) and depression (-0.71, -0.74); moderate to large with the Performance Status Scale for Head and Neck subscales (PSS-HN; 0.46-0.71); and low with an anxiety measure (0.30, 0.34). Both FHNSI versions differentiated patients grouped by performance status (p < .0001, p < .0001) and global rating of change (p < .0001, p < 0.01). The FHNSI's minimally important difference range was 3-4 points., Conclusion: The FHNSI is a reliable and valid symptom index, which can be administered alone or scored using items embedded within the FACT-H&N.

Objectives: Using patient and expert provider input, we previously developed a 15-item index of the most important symptoms and concerns of people being treated for advanced kidney cancer, the Functional Assessment of Cancer Therapy - Kidney Symptom Index (FKSI). These 15 concerns are a mixture of disease-related symptoms and treatment-related side effects. As a result, it may be difficult to assign an informative label to the score defined as the summation of these 15 most important concerns. Because one of the primary goals of treating advanced kidney cancer is the relief of disease-related symptoms, we set out to differentiate from the list of 15 symptoms those that are predominantly attributable to kidney cancer itself rather than its treatment, and to evaluate this abbreviated FKSI - Disease-Related Symptoms (FKSI-DRS)., Methods: Survey results from 18 experienced clinical experts were summarized to separate DRS from other concerns more arguably attributable to treatment side effects. This nine-item FKSI-DRS was then validated on a sample of 141 people with kidney cancer., Results: The FKSI-DRS is reliable (internal consistency range = 0.75-0.78; test-retest reliability intraclass correlation = 0.85), and valid, separating groups by performance status and the patient's own global rating of change. The likely minimally important difference in the FKSI-DRS is in the range of 2-3 points., Conclusions: The FKSI-DRS is a reliable, valid, and responsive brief index of the most important symptoms associated with advanced kidney cancer.

Background: This single-institution long-term prospective study was performed in the setting of community service screening mammography to evaluate the association between the methods of breast cancer detection and survival rates., Methods: From 1994 through 2001, data on 1237 patients with breast cancer were collected concurrent with definitive surgical treatment and entered into a comprehensive database., Results: Mammography was the sole method of detection for 517 (44%) of 1179 Tis-T2 breast cancers. Fifty-seven percent of invasive cancers detectable by mammography alone were less than 1 cm in diameter. For 1049 patients with invasive cancers, the 5-year overall observed survival rates were 94% for 372 whose cancers were detectable by mammogram alone and 87% for 677 whose cancers were detectable by palpation (alone or in combination with mammography) (P = .0002)., Conclusions: Most of the contribution to breast cancer mortality reduction is from the detection of small nonpalpable cancers, not from adjuvant therapy.

Cancer patients who have limited literacy skills or English language proficiency are particularly vulnerable to receiving sub-optimal care. Outcome measurement in these patients may provide new insight into previously undetected problems. This report describes the development and testing of a Spanish language, multimedia program for quality of life (QOL) assessment. Pilot testing was conducted with 30 Latino cancer patients with a range of education levels and computer experience. Patients found the program easy to use and understand. The "Talking Touchscreen" is a practical, user-friendly method that provides greater opportunities to assess QOL in Spanish-speaking patients with a range of literacy skills.