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Little is known about rates of invasive procedures and associated complications after lung cancer screening (LCS) in nontrial settings.What are the frequency of invasive procedures, complication rates, and factors associated with complications in a national sample of veterans screened for lung cancer?We conducted a retrospective cohort analysis of veterans who underwent LCS in any Veterans Health Administration (VA) facility between 2013 and 2019 and identified veterans who underwent invasive procedures within 10 months of initial LCS. The primary outcome was presence of a complication within 10 days after an invasive procedure. We conducted hierarchical mixed-effects logistic regression analyses to determine patient- and facility-level factors associated with complications resulting from an invasive procedure.Our cohort of 82,641 veterans who underwent LCS was older, more racially diverse, and had more comorbidities than National Lung Screening Trial (NLST) participants. Overall, 1,741 veterans (2.1%) underwent an invasive procedure after initial screening, including 856 (42.3%) bronchoscopies, 490 (24.2%) transthoracic needle biopsies, and 423 (20.9%) thoracic surgeries. Among veterans who underwent procedures, 151 (8.7%) experienced a major complication (eg, respiratory failure, prolonged hospitalization) and an additional 203 (11.7%) experienced an intermediate complication (eg, pneumothorax, pleural effusion). Veterans who underwent thoracic surgery (OR, 7.70; 95% CI, 5.48-10.81), underwent multiple nonsurgical procedures (OR, 1.49; 95% CI, 1.15-1.92), or carried a dementia diagnosis (OR, 3.91; 95% CI, 1.79-8.52) were more likely to experience complications. Invasive procedures were performed less often than in the NLST (2.1% vs 4.2%), but veterans were more likely to experience complications after each type of procedure.These findings may reflect a higher threshold to perform procedures in veteran populations with multiple comorbidities and higher risks of complications. Future work should focus on optimizing the identification of patients whose chance of benefit likely outweighs the complication risks.

There has been an increasing emphasis on placing patients at the center of clinical care and health care research and, in particular, assessing outcomes and experiences from the patient's perspective. One of the most widely used patient-reported outcome instruments is the Veterans RAND 12-item Health Survey (VR-12). This article reviews the VR-12 development and its applications over the last 2 decades, including research and potential uses in clinical care.

BACKGROUND AND OBJECTIVES: Total kidney volume is a validated prognostic biomarker for autosomal dominant polycystic kidney disease. Total kidney volume by magnetic resonance imaging (MRI) and manual segmentation is considered the “reference standard,” but it is time consuming and not readily accessible. By contrast, three-dimensional (3D) ultrasound provides a promising technology for total kidney volume measurements with unknown potential. Here, we report a comparative study of total kidney volume measurements by 3D ultrasound versus the conventional methods by ultrasound ellipsoid and MRI ellipsoid. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This single-center prospective study included 142 patients who completed a standardized 3D ultrasound and MRI. Total kidney volumes by 3D ultrasound and ultrasound ellipsoid were compared with those by MRI. We assessed the agreement of total kidney volume measurements by Bland–Altman plots and misclassification of the Mayo Clinic imaging classes between the different imaging methods, and we assessed prediction of Mayo Clinic imaging classes 1C–1E by average ultrasound kidney length >16.5 cm. RESULTS: Compared with MRI manual segmentation, MRI ellipsoid, 3D ultrasound, and ultrasound ellipsoid underestimated total kidney volume (mean difference: −3%, −9%, and −11%, respectively), with Mayo Clinic imaging classes misclassified in 11%, 21%, and 22% of patients, respectively; most misclassified cases by MRI ellipsoid (11 of 16), 3D ultrasound (23 of 30), and ultrasound ellipsoid (26 of 31) were placed into a lower Mayo Clinic imaging class. Predictions of the high-risk Mayo Clinic imaging classes (1C–1E) by MRI ellipsoid, 3D ultrasound, and ultrasound ellipsoid all yielded high positive predictive value (96%, 95%, and 98%, respectively) and specificity (96%, 96%, and 99%, respectively). However, both negative predictive value (90%, 88%, and 95%, respectively) and sensitivity (88%, 85%, and 94%, respectively) were lower for 3D ultrasound and ultrasound ellipsoid compared with MRI ellipsoid. An average ultrasound kidney length >16.5 cm was highly predictive of Mayo Clinic imaging classes 1C–1E only in patients aged ≤45 years. CONCLUSIONS: Total kidney volume measurements in autosomal dominant polycystic kidney disease by 3D ultrasound and ultrasound ellipsoid displayed similar bias and variability and are less accurate than MRI ellipsoid. Prediction of high-risk Mayo Clinic imaging classes (1C–1E) by all three methods provides high positive predictive value, but ultrasound ellipsoid is simpler to use and more readily available.

Nasopharyngeal cancer (NPC) is an Epstein-Barr virus (EBV)–positive epithelial malignancy with an extensive inflammatory infiltrate. Traditional RNA-sequencing techniques uncovered only microenvironment signatures, while the gene expression of the tumor epithelial compartment has remained a mystery. Here, we use Smart-3SEQ to prepare transcriptome-wide gene expression profiles from microdissected NPC tumors, dysplasia, and normal controls. We describe changes in biological pathways across the normal to tumor spectrum and show that fibroblast growth factor (FGF) ligands are overexpressed in NPC tumors, while negative regulators of FGF signaling, including SPRY1, SPRY2, and LGALS3, are down-regulated early in carcinogenesis. Within the NF-κB signaling pathway, the critical noncanonical transcription factors, RELB and NFKB2, are enriched in the majority of NPC tumors. We confirm the responsiveness of EBV-positive NPC cell lines to targeted inhibition of these pathways, reflecting the heterogeneity in NPC patient tumors. Our data comprehensively describe the gene expression landscape of NPC and unravel the mysteries of receptor tyrosine kinase and NF-κB pathways in NPC.

ImportanceLung cancer screening (LCS) is underused in the US, particularly in underserved populations, and little is known about factors associated with declining LCS. Guidelines call for shared decision-making when LCS is offered to ensure informed, patient-centered decisions.ObjectiveTo assess how frequently veterans decline LCS and examine factors associated with declining LCS.Design, Setting, and ParticipantsThis retrospective cohort study included LCS-eligible US veterans who were offered LCS between January 1, 2013, and February 1, 2021, by a clinician at 1 of 30 Veterans Health Administration (VHA) facilities that routinely used electronic health record clinical reminders documenting LCS eligibility and veterans’ decisions to accept or decline LCS. Data were obtained from the Veterans Affairs (VA) Corporate Data Warehouse or Medicare claims files from the VA Information Resource Center.Main Outcomes and MeasuresThe main outcome was documentation, in clinical reminders, that veterans declined LCS after a discussion with a clinician. Logistic regression analyses with clinicians and facilities as random effects were used to assess factors associated with declining LCS compared with agreeing to LCS.ResultsOf 43 257 LCS-eligible veterans who were offered LCS (mean [SD] age, 64.7 [5.8] years), 95.9% were male, 84.2% were White, and 37.1% lived in a rural zip code; 32.0% declined screening. Veterans were less likely to decline LCS if they were younger (age 55-59 years: odds ratio [OR], 0.69; 95% CI, 0.64-0.74; age 60-64 years: OR, 0.80; 95% CI, 0.75-0.85), were Black (OR, 0.80; 95% CI, 0.73-0.87), were Hispanic (OR, 0.62; 95% CI, 0.49-0.78), did not have to make co-payments (OR, 0.92; 95% CI, 0.85-0.99), or had more frequent VHA health care utilization (outpatient: OR, 0.70; 95% CI, 0.67-0.72; emergency department: OR, 0.86; 95% CI, 0.80-0.92). Veterans were more likely to decline LCS if they were older (age 70-74 years: OR, 1.27; 95% CI, 1.19-1.37; age 75-80 years: OR, 1.93; 95% CI, 1.73-2.17), lived farther from a VHA screening facility (OR, 1.06; 95% CI, 1.03-1.08), had spent more days in long-term care (OR, 1.13; 95% CI, 1.07-1.19), had a higher Elixhauser Comorbidity Index score (OR, 1.04; 95% CI, 1.03-1.05), or had specific cardiovascular or mental health conditions (congestive heart failure: OR, 1.25; 95% CI, 1.12-1.39; stroke: OR, 1.14; 95% CI, 1.01-1.28; schizophrenia: OR, 1.87; 95% CI, 1.60-2.19). The clinician and facility offering LCS accounted for 19% and 36% of the variation in declining LCS, respectively.Conclusions and RelevanceIn this cohort study, older veterans with serious comorbidities were more likely to decline LCS and Black and Hispanic veterans were more likely to accept it. Variation in LCS decisions was accounted for more by the facility and clinician offering LCS than by patient factors. These findings suggest that shared decision-making conversations in which patients play a central role in guiding care may enhance patient-centered care and address disparities in LCS.

Early in the coronavirus disease 2019 (COVID-19) crisis, a statewide executive order (PAUSE) severely restricted the movement of New Yorkers from 23 March to 7 June 2020. We used New York City surveillance data for human immunodeficiency virus (HIV), chlamydia, gonorrhea, and syphilis to describe trends in diagnosis and reporting surrounding PAUSE. During PAUSE, the volume of positive HIV/sexually transmitted infection tests, and diagnoses of HIV, chlamydia, gonorrhea, and syphilis declined substantially, reaching a nadir in April before rebounding. Some shifts in characteristics of reported cases were identified.

Probing the biophysical properties of the tumor niche offers a new perspective in cancer mechanobiology, and supports the development of next-generation diagnostics and therapeutics for cancer, in particular for metastasis.

Taste and smell function decline with age, with robust impairment in the very old. Much less is known about taste and smell function in young and middle old. We investigated taste and smell sensitivity via thresholds in a sub-sample of the NutriAct Family Study (NFS), the NFS Examinations cohort (NFSE; N=251, age M=62.5 years). We examined different aspects relating to taste and smell function: the degree to which taste and smell sensitivity relate to another and to taste and smell preferences, the role of gender and age, as well as effects on Quality of Life (QOL). Taste thresholds were highly correlated but no correlation was observed between taste and smell thresholds and between thresholds and preference. Women were more sensitive for both taste and smell than men. We found no effect of age on sensitivity and no effect of sensitivity on QoL. All null-findings were corroborated with Bayesian statistics providing evidence for the null hypotheses. Together our results indicate the independence of taste and smell despite their overlap during sensorial experiences. We found no evidence for age-related sensory decline, which could be due to our sample´s characteristics of non-clinical volunteers with good dental health and 93% non-smokers.

Human papillomavirus (HPV) vaccination and cervical screening prevent cervical cancer effectively. However, there are concerns whether vaccination leads to high-risk sexual behaviors and less intention for cervical screening. We aimed to evaluate the influence of HPV vaccination on high-risk sexual behaviors, and intention for cervical screening among young Chinese females. We also reported the latest HPV vaccination uptake in Hong Kong.A population-based survey was conducted between September 2016 and January 2017. Subjects were school-age girls from twenty-five secondary schools (in-school) and community females between 18 and 27 years (out-school). Demographics, vaccine-related attitudes, intention for cervical screening and participants' sexual behaviors were examined.We surveyed 2260 females from in-school (n = 1664) and out-school (n = 596) settings. 11.5% in-school and 23.5% out-school participants received at least one dose of HPV vaccine. Vaccination was not associated with age (in-school Odds Ratio [OR] 0.99, p = 0.87; out-school OR 1, p = 0.94), ethnicity (in-school OR 0.82, p = 0.72; out-school OR 0, p = 0.98), maternal education (in-school OR for secondary school 1.19, p = 0.43; for post-secondary school 1.28, p = 0.48), underage sex (in-school OR 1.22, p = 0.80; out-school OR 0.63, p = 0.67), earlier sexual exposure (in-school β 0.01, p = 0.99; out-school β 0.13, p = 0.68), multiple sex partners (in-school OR 3.27, p = 0.22; out-school OR 1.16, p = 0.43), and unprotected sex (in-school OR 1.14, p = 0.78; out-school OR 0.60, p = 0.10). Out-school females with higher personal education level was associated with higher vaccine uptake (post-secondary OR 3.4, p 0.001; bachelor's degree or above OR 3.71, p 0.001). More vaccinated females intended for cervical screening (in-school 23.6% vs. 21.1%; out-school 53.6% vs. 43.6%). Costs and knowledge were important factors for non-vaccination and non-intention for cervical screening.HPV vaccination was not associated with earlier and high risk sexual behavior among Chinese young females. Vaccinated Chinese young females had a higher intention for cervical screening.

Cytolytic proteins and peptide toxins are classical virulence factors of several bacterial pathogens which disrupt epithelial barrier function, damage cells and activate or modulate host immune responses. Such toxins have not been identified previously in human pathogenic fungi. Here we identify the first, to our knowledge, fungal cytolytic peptide toxin in the opportunistic pathogen Candida albicans. This secreted toxin directly damages epithelial membranes, triggers a danger response signalling pathway and activates epithelial immunity. Membrane permeabilization is enhanced by a positive charge at the carboxy terminus of the peptide, which triggers an inward current concomitant with calcium influx. C. albicans strains lacking this toxin do not activate or damage epithelial cells and are avirulent in animal models of mucosal infection. We propose the name 'Candidalysin' for this cytolytic peptide toxin; a newly identified, critical molecular determinant of epithelial damage and host recognition of the clinically important fungus, C. albicans.

Hepatocyte growth factor (HGF) has been shown to have anti-fibrotic, pro-angiogenic, and cardioprotective effects; however, it is highly unstable and expensive to manufacture, hindering its clinical translation. Recently, a HGF fragment (HGF-f), an alternative c-MET agonist, was engineered to possess increased stability and recombinant expression yields. In this study, we assessed the potential of HGF-f, delivered in an extracellular matrix (ECM)-derived hydrogel, as a potential treatment for myocardial infarction (MI). HGF-f protected cardiomyocytes from serum-starvation and induced down-regulation of fibrotic markers in whole cardiac cell isolate compared to the untreated control. The ECM hydrogel prolonged release of HGF-f compared to collagen gels, and in vivo delivery of HGF-f from ECM hydrogels mitigated negative left ventricular (LV) remodeling, improved fractional area change (FAC), and increased arteriole density in a rat myocardial infarction model. These results indicate that HGF-f may be a viable alternative to using recombinant HGF, and that an ECM hydrogel can be employed to increase growth factor retention and efficacy.

Two experiments examined competition between an instrumental avoidance response and a Pavlovian safety signal for association with omission of electric shock in a human fear conditioning paradigm. Self-reported shock expectancies and skin conductance responses were consistent with blocking of learning of the instrumental contingency by prior training of the Pavlovian contingency, and vice versa. The results support the idea that a common learning mechanism underlies both Pavlovian and instrumental conditioning. The expectancy data suggest that this learning mechanism is cognitive in nature, and that Pavlovian and instrumental learning involve external and internal attributions, respectively. The procedure may thus serve as a laboratory model for attributional processes involved in the acquisition of threat expectancies in anxiety and anxiety disorders.

Familial aggregation of coronary heart disease (CHD) is thought to account for 50% to 60% of total documented CHD before the age of 60 years.1 First-degree relatives of people with premature CHD (proband) exhibit a risk that is 2 to 12 times greater than that of the general population.2 The National Cholesterol Education Program's Adult Treatment Panel recommends screening patients with a recognized family history of premature CHD, defined as heart disease in men

Despite decades of effort, little progress has been made to improve the treatment of cancer metastases. To leverage the central role of the mechanoenvironment in cancer metastasis, we present a mechanoresponsive cell system (MRCS) to selectively identify and treat cancer metastases by targeting the specific biophysical cues in the tumor niche in vivo. Our MRCS uses mechanosensitive promoter-driven mesenchymal stem cell (MSC)-based vectors, which selectively home to and target cancer metastases in response to specific mechanical cues to deliver therapeutics to effectively kill cancer cells, as demonstrated in a metastatic breast cancer mouse model. Our data suggest a strong correlation between collagen cross-linking and increased tissue stiffness at the metastatic sites, where our MRCS is specifically activated by the specific cancer-associated mechano-cues. MRCS has markedly reduced deleterious effects compared to MSCs constitutively expressing therapeutics. MRCS indicates that biophysical cues, specifically matrix stiffness, are appealing targets for cancer treatment due to their long persistence in the body (measured in years), making them refractory to the development of resistance to treatment. Our MRCS can serve as a platform for future diagnostics and therapies targeting aberrant tissue stiffness in conditions such as cancer and fibrotic diseases, and it should help to elucidate mechanobiology and reveal what cells "feel" in the microenvironment in vivo.

All mucosal surfaces are lined by epithelial cells and are colonised by opportunistic microbes. In health, these opportunistic microbes remain commensal and are tolerated by the immune system. However, when the correct environmental conditions arise, these microbes can become pathogenic and need to be controlled or cleared by the immune system to prevent disease. The mechanisms that enable epithelial cells to initiate the 'danger' signals activated specifically by pathogenic microbes are critical to mucosal defence and homeostasis but are not well understood. Deciphering these mechanisms will provide essential understanding to how mucosal tissues maintain health and activate immunity, as well as how pathogens promote disease. This review focuses on the interaction of the human fungal pathogen Candida albicans with epithelial cells and the epithelial mechanisms that enable mucosal tissues to discriminate between the commensal and pathogenic state of this medically important fungus.

Systemic administration of mesenchymal stem cells (MSCs) affords the potential to ameliorate the symptoms of Multiple Sclerosis (MS) in both preclinical and clinical studies. However, the efficacy of MSC-based therapy for MS likely depends on the number of cells that home to inflamed tissues and on the controlled production of paracrine and immunomodulatory factors. Previously, we reported that engineered MSCs expressing P-selectin glycoprotein ligand-1 (PSGL-1) and Sialyl-Lewis(x) (SLeX) via mRNA transfection facilitated the targeted delivery of anti-inflammatory cytokine interleukin-10 (IL-10) to inflamed ear. Here, we evaluated whether targeted delivery of MSCs with triple PSGL1/SLeX/IL-10 engineering improves therapeutic outcomes in mouse experimental autoimmune encephalomyelitis (EAE), a murine model for human MS. We found PSGL-1/SLeX mRNA transfection significantly enhanced MSC homing to the inflamed spinal cord. This is consistent with results from in vitro flow chamber assays in which PSGL-1/SleX mRNA transfection significantly increased the percentage of rolling and adherent cells on activated brain microvascular endothelial cells, which mimic the inflamed endothelium of blood brain/spinal cord barrier in EAE. In addition, IL-10-transfected MSCs show significant inhibitory activity on the proliferation of CD4(+) T lymphocytes from EAE mice. In vivo treatment with MSCs engineered with PSGL-1/SLeX/IL-10 in EAE mice exhibited a superior therapeutic function over native (unmodified) MSCs, evidenced by significantly improved myelination and decreased lymphocytes infiltration into the white matter of the spinal cord. Our strategy of targeted delivery of performance-enhanced MSCs could potentially be utilized to increase the effectiveness of MSC-based therapy for MS and other central nervous system (CNS) disorders.

Introduction Mesenchymal stem cells (MSCs) are adult multipotent stem cells that possess regenerative and immunomodulatory properties. They have been widely investigated as therapeutic agents for a variety of disease conditions, including tissue repair, inflammation, autoimmunity, and organ transplantation. Importantly, systemically infused MSCs selectively home to primary and metastatic tumors, though the molecular mechanisms of tumor tropism of MSCs remain incompletely understood. We have exploited the active and selective MSCs homing to cancer microenvironments to develop a rapid and selective blood test for the presence of cancer. Methods We tested the concept of using transplanted MSCs as the basis for a simple cancer blood test. MSCs were engineered to express humanized Gaussia luciferase (hGluc). In a minimally invasive fashion, hGluc secreted by MSCs into circulation as a reporter for cancer presence, was assayed to probe whether MSCs co-localize with and persist in cancerous tissue. Results In vitro, hGluc secreted by engineered MSCs was detected stably over a period of days in the presence of serum. In vivo imaging showed that MSCs homed to breast cancer lung metastases and persisted longer in tumor-bearing mice than in tumor-free mice (P < 0.05). hGluc activity in blood of tumor-bearing mice was significantly higher than in their tumor-free counterparts (P < 0.05). Conclusions Both in vitro and in vivo data show that MSCs expressing hGluc can identify and report small tumors or metastases in a simple blood test format. Our novel and simple stem cell-based blood test can potentially be used to screen, detect, and monitor cancer and metastasis at early stages and during treatment.

The natural history of chronic hepatitis C (CHC) remains to be defined in patients with end-stage renal disease (ESRD).To determine the clinical presentation of CHC and the factors associated with stage III-IV fibrosis in patients with CHC and ESRD.The study included patients with CHC and ESRD (n = 91) or normal renal function (NRF, n = 159). Both groups were matched for mean age, gender, history of alcohol use, and estimated duration of hepatitis C virus (HCV) infection.Presentation of CHC and ESRD was independently associated with non-Caucasian ethnicity (OR = 3.24, p= 0.0003), a history of diabetes mellitus (DM, OR = 7.911, p0.0001), and lower frequencies of being obese (OR = 0.457, p= 0.035), of having hepatic steatosis (OR = 0.372, p= 0.003), and stage III-IV fibrosis (OR = 0.403, p= 0.016). After adjusting for serum levels of alpha-fetoprotein (AFP) and HCV RNA, CHC, and ESRD were independently associated with lower frequencies of elevated alanine aminotransferase (ALT, OR = 0.175, p= 0.02) and aspartate aminotransferase (AST, OR = 0.169, p= 0.04), but higher frequencies of AST/ALT ratio1 (OR = 7.173, p= 0.002) and hypoalbuminemia (OR = 9.567, p= 0.0007). Compared to patients with NRF and stage III-IV fibrosis, those with ESRD and stage III-IV fibrosis had a significantly higher frequency of a history of DM (OR = 8.014, p= 0.0031) and lower frequency of elevated AST (OR = 0.054, p= 0.004), which were independent of the frequencies of lower levels of ALT and albumin, and AST/ALT ratio1. In patients with CHC and ESRD, the presence of stage III-IV fibrosis was significantly associated with hepatic steatosis (OR = 4.523, p= 0.012) and thrombocytopenia (OR = 4.884, p= 0.044), which were independent of the frequencies of a history of DM, splenomegaly, and a higher level of AST.CHC and ESRD are independently associated with a higher frequency of a history of DM, but lower frequencies of being obese, and having hepatic steatosis, stage III-IV fibrosis, and elevated transaminases. In patients with CHC and ESRD, stage III-IV fibrosis is not associated with a history of DM, but is independently associated with hepatic steatosis and thrombocytopenia.

High-throughput genomic mutation screening for primary tumors has characteristically been expensive, labor-intensive, and inadequate to detect low levels of mutation in a background of wild-type signal. We present a new, combined PCR and colorimetric approach that is inexpensive, simple, and can detect the presence of 1% mutation in a background of wild-type. We compared manual dideoxy sequencing of p53 for eight lung cancer samples to a novel assay combining a primer extension step and an enzymatic colorimetric step in a 96-well plate with covalently attached oligonucleotide sequences. For every sample, we were able to detect the presence or absence of the specific mutation with a statistically significant difference between the sample optical density (OD) and the background OD, with a sensitivity and specificity of 100%. This assay is straightforward, accurate, inexpensive, and allows for rapid, high-throughput analysis of samples, making it ideal for genomic mutation or polymorphism screening studies in both clinical and research settings.

Solid pseudopapillary neoplasm (SPN) of the pancreas is a rare, clinicopathologically distinct neoplasm with a tendency to affect young women. The histogenesis of SPN is not well defined. Pancreatic endocrine neoplasms (PENs) are also uncommon tumors of the pancreas.Our comprehensive review of the literature did not yield any reported cases of collision tumors of the above two neoplasms. We report a case of such a collision tumor in a 45-year-old man.This tumor was an incidental finding on computed tomography, followed by fine-needle aspiration confirmation of a tumor that was initially diagnosed as an SPN only. A histologic examination of a 2.1-cm mass following distal pancreatectomy revealed a 0.7-cm PEN partly engulfed by an SPN. The tumors showed different morphologic and immunohistochemical features, confirming the presence of a collision tumor.A comparative analysis of immunoprofiles of these tumors yielded interesting findings, enabling us to postulate that SPNs may originate from a multipotential primordial cell that may follow different differentiation pathways, such as endocrine, epithelial, and acinar. The ultrastructures and immunophenotypic characteristics appear to support this hypothesis.

Rates of breast cancer (BC) and colorectal cancer (CRC) screening are particularly low among poor and minority patients. Multifaceted interventions have been shown to improve cancer-screening rates, yet the relative impact of the specific components of these interventions has not been assessed. Identifying the specific components necessary to improve cancer-screening rates is critical to tailor interventions in resource limited environments. To assess the relative impact of various components of the reminder, recall, and outreach (RRO) model on BC and CRC screening rates within a safety net practice. Pragmatic randomized trial. Men and women aged 50–74 years past due for CRC screen and women aged 40–74 years past due for BC screening. We randomized 1,008 patients to one of four groups: (1) reminder letter; (2) letter and automated telephone message (Letter + Autodial); (3) letter, automated telephone message, and point of service prompt (Letter + Autodial + Prompt); or (4) letter and personal telephone call (Letter + Personal Call). Documentation of mammography or colorectal cancer screening at 52 weeks following randomization. Compared to a reminder letter alone, Letter + Personal Call was more effective at improving screening rates for BC (17.8 % vs. 27.5 %; AOR 2.2, 95 % CI 1.2–4.0) and CRC screening (12.2 % vs. 21.5 %; AOR 2.0, 95 % CI 1.1–3.9). Compared to letter alone, a Letter + Autodial + Prompt was also more effective at improving rates of BC screening (17.8 % vs. 28.2 %; AOR 2.1, 95 % CI 1.1–3.7) and CRC screening (12.2 % vs. 19.6 %; AOR 1.9, 95 % CI 1.0–3.7). Letter + Autodial was not more effective than a letter alone at improving screening rates. The addition of a personal telephone call or a patient-specific provider prompt were both more effective at improving mammogram and CRC screening rates compared to a reminder letter alone. The use of automated telephone calls, however, did not provide any incremental benefit to a reminder letter alone.

Cancer screening rates are suboptimal for low-income patients. To assess an intervention to increase cancer screening among patients in a safety-net primary care practice. Patients at an inner-city family practice who were overdue for cancer screening were randomized to intervention or usual care. Screening rates at 1 year were compared using the chi-square test, and multivariable analysis was performed to adjust for patient factors. All average-risk patients at an inner-city family practice overdue for mammography or colorectal cancer (CRC) screening. Patients’ ages were 40 to 74 years (mean 53.9, SD 8.7) including 40.8 % African Americans, 4.2 % Latinos, 23.2 % with Medicaid and 10.9 % without any form of insurance. The 6-month intervention to promote cancer screening included letters, automated phone calls, prompts and a mailed Fecal Immunochemical Testing (FIT) Kit. Rates of cancer screening at 1 year. Three hundred sixty-six patients overdue for screening were randomly assigned to intervention (n = 185) or usual care (n = 181). Primary analysis revealed significantly higher rates of cancer screening in intervention subjects: 29.7 % vs. 16.7 % for mammography (p = 0.034) and 37.7 % vs. 16.7 % for CRC screening (p = 0.0002). In the intervention group, 20 % of mammography screenings and 9.3 % of CRC screenings occurred at the early assessment, while the remainder occurred after repeated interventions. Within the CRC intervention group 44 % of screened patients used the mailed FIT kit. On multivariable analysis the CRC screening rates remained significantly higher in the intervention group, while the breast cancer screening rates were not statistically different. A multimodal intervention significantly increased CRC screening rates among patients in a safety-net primary care practice. These results suggest that relatively inexpensive letters and automated calls can be combined for a larger effect. Results also suggest that mailed screening kits may be a promising way to increase average-risk CRC screening.

Background There are limited data regarding interventions designed to improve cancer screening rates in safety-net practices with "real world" patients. Objective To examine the impact of a multimodal intervention on mammography and colorectal cancer (CRC) screening rates in a safety-net practice caring for under-served patients. Methods At an inner-city family medicine practice, all patients past due for mammography or CRC screening were assigned to receive or not receive a screening promotion intervention based on their medical record number. The 12-month intervention included outreach to patients (tailored letters, automated and personal phone calls) and point-of-care patient and clinician prompts. The trial was registered at clinicaltrials.gov, NCT00818857. Results We enrolled 469 participants aged 40 to 74 years, including 28% African Americans, 5% Latinos, 25% with Medicaid, and 10% without any form of insurance. Participants in the intervention group showed statistically significantly higher rates of cancer screening; rates were 41 % vs 16.8% for mammography and 28.8% vs 10% for CRC screening. These findings were confirmed in multivariable analysis. Similar relative improvements in screening were seen across race, ethnicity, socioeconomic status, and insurance groups. Discussion A multimodal intervention shows promise for improving rates of mammography and colorectal cancer screening within a safety-net practice. Further study will identify the most cost-effective components of the intervention.

Goals To determine the risk factors for stage 3 and 4 fibrosis in a large cohort of U.S. patients with chronic hepatitis C (CHC). Background Multiple host and viral factors affect the outcomes of CHC. Further defining the pathogenic roles of these factors in CHC progression will lead to improving management of this disease. Study Retrospective study of a large cohort of US patients with CHC. Results Of the 460 patients, 331 were males and 129 were females with mean age of 48.4+/-8.0 years, and 191 (41.7%) had stage 3 and 4 fibrosis. Clinically, a multivariate analysis revealed that age of > or =60 years at presentation, the estimated duration of hepatitis C virus (HCV) infection > or =25 years, a body mass index > or =30 kg/m, and a history of diabetes mellitus were independently associated with stage 3 and 4 fibrosis, after adjusting for history of alcohol use. Laboratorially, a multivariate analysis revealed that aspartate aminotransferase (AST) > or =2 x upper limit of normal (ULN), alpha fetoprotein > or =15 microg/L, and presence of grade 2 and 3 steatosis were independently associated with stage 3 and 4 fibrosis, after adjusting for alanine aminotransferase > or =2 x upper limit of normal, AST/alanine aminotransferase ratio > or =1, HCV genotyping, transferrin saturation, and a histology activity index score > or =7. Conclusions The present study indicated that elderly, longer duration of HCV infection, obesity, and history of diabetes mellitus are independent clinical parameters associated with advanced fibrosis, whereas elevated AST, alpha fetoprotein, and presence of grade 2 and 3 steatosis are independent laboratorial parameters associated with stage 3 and 4 fibrosis in patients with CHC.

To examine the health status of elderly veteran enrollees, stratified by age group, and compare with nonveteran populations.Cross-sectional study.Outpatient.A total of 1,406,049 veteran enrollees were surveyed, and 887,775 returned the questionnaire (63.1%). Of these, 663,729 (74%) were aged 65 and older.Patient demographics, comorbid conditions, and health status, which was assessed using the Veterans 36-item short form (SF-36), a reliable and valid measure of health-related quality of life (HRQoL).Elderly veteran enrollees are a group with poor health status across all scales of the Veterans SF-36. Significant decline in HRQoL was found in patients grouped by increasing age (65-74, 75-84, andor =85). Of the Veterans SF-36 scales, the role physical and role emotional scales and physical functioning presented the largest decrements by age group. The elderly veteran enrollees had poorer health status than older people enrolled in Medicare managed care, ranging from 0.5 to 1 standard deviations worse.Elderly veteran enrollees have substantial disease burden, as reflected by major impairments across multiple dimensions of HRQoL. These findings bear important implications for use of services, suggesting that the Veterans Health Administration will require considerable resources to provide care for its aging population.

Aluminum is a recognized neurotoxin in dialysis encephalopathy and may also be implicated in the etiology of neurodegenerative disease, particularly Alzheimer's disease. Alzheimer's disease is suspected to be associated with oxidative stress, possibly due to the pro-oxidant properties of beta-amyloid present in the senile plaques. The underlying mechanism by which this occurs is not well understood although interactions between amyloid and iron have been proposed. The presence of low molecular weight iron compounds can stimulate free radical production in the brain. This study provides a possible explanation whereby both aluminum and beta-amyloid can potentiate free radical formation by stabilizing iron in its more damaging ferrous (Fe2+) form which can promote the Fenton reaction. The velocity, at which Fe2+ is spontaneously oxidized to Fe3+ at 37 degrees C in 20 mM Bis-Tris buffer at pH 5.8, was significantly slowed in the presence of aluminum salts. A parallel effect of prolongation of stability of soluble ferrous ion, was found in the presence of beta-amyloid fragment (25-35). Ascorbic acid, known to potentiate the pro-oxidant properties of iron, was also capable of markedly stabilizing ferrous ions.