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Triple-negative breast cancer (TNBC) is one of the most malignant subtypes of breast cancer with an unsatisfied prognosis. Effective biomarkers could predict the risk and improve patients' survival. Whether LINC00466 possesses the potential to serve as a biomarker of the progression and prognosis of TNBC was evaluated.A total of 122 TNBC patients were included in this study and provided paired clinical tissues. The expression of LINC00466 in TNBC was evaluated by RT-qPCR and evaluated the clinical significance with a series of statistical analyses. The biological effects and the mechanism were investigated in TNBC cells with CCK8, Transwell, and luciferase reporter assays.LINC00466 was significantly upregulated in TNBC and showed close association with the clinical features of patients, which indicates the development, and severity of patients. LINC00466 functioned as a prognostic biomarker predicting the survival of patients and a tumor promoter improving the proliferation, migration, and invasion of TNBC cells through sponging miR-539-5p.LINC00466 promotes the progression of TNBC via regulating miR-539-5p. The inhibition of LINC00466 might be a novel therapeutic strategy for TNBC.

Background Hepatocellular carcinoma (HCC) is one of the most deadly cancer worldwide. Multiple long noncoding RNAs (lncRNAs) are recently identified as crucial oncogenic factors or tumor suppressors. In this study, we explored the functon and mechanism of lncRNA double homeobox A pseudogene 8 (DUXAP8) in the progression of HCC. Methods Expression levels of DUXAP8 in HCC tissue samples were measured using qRT‐PCR. The association between pathological indexes and the expression of DUXAP8 was also analyzed. Human HCC cell lines SMMC‐7721 and QSG‐7701 were used in in vitro studies. CCK‐8 assay was used to assess the effect of DUXAP8 on HCC cell line proliferation. Scratch healing assay and Transwell assay were conducted to detect the effect of DUXAP8 on migration and invasion. Furthermore, dual‐luciferase reporter assay was used to confirm targeting relationship between miR‐422a and DUXAP8. Additionally, Western blot was used to detect the regulatory function of DUXAP8 on pyruvate dehydrogenase kinase 2 (PDK2). Results DUXAP8 expression HCC clinical samples was significantly increased and this was correlated with unfavorable pathological indexes. High expression of DUXAP8 was associated with shorter overall survival time of patients. Its overexpression remarkably facilitated the proliferation, metastasis, and epithelial‐mesenchymal transition of HCC cells. Accordingly, knockdown of it suppressed the malignant phenotypes of HCC cells. Overexpression of DUXAP8 significantly reduced the expression of miR‐422a by sponging it, but enhanced the expression of PDK2. Conclusions DUXAP8 was a sponge of tumor suppressor miR‐422a in HCC, enhanced the expression of PDK2 indirectly, and functioned as an oncogenic lncRNA., DUXAP8 was a sponge of tumor suppressor miR‐422a in HCC, enhanced the expression of PDK2 indirectly, and functioned as an oncogenic lncRNA.

The acute phase protein orosomucoid-1 (Orm1) is mainly expressed by hepatocytes (HPCs) under stress conditions. However, its specific function is not fully understood. Here, we report a role of Orm1 as an executer of HPC proliferation. Increases in serum levels of Orm1 were observed in patients after surgical resection for liver cancer and in mice undergone partial hepatectomy (PH). Transcriptome study showed that Orm1 became the most abundant in HPCs isolated from regenerating mouse liver tissues after PH. Both in vitro and in vivo siRNA-induced knockdown of Orm1 suppressed proliferation of mouse regenerating HPCs and human hepatic cells. Microarray analysis in regenerating mouse livers revealed that the signaling pathways controlling chromatin replication, especially the minichromosome maintenance protein complex genes were uniformly down-regulated following Orm1 knockdown. These data suggest that Orm1 is induced in response to hepatic injury and executes liver regeneration by activating cell cycle progression in HPCs., Highlights • Serum Orm1 levels increased approximately 1.3- to 2.5-folds in both humans and mice after partial hepatectomy. • Transcriptome analysis revealed that Orm1 mostly induced in hepatocytes as a regulator of mouse liver regeneration. • Orm1 knockdown in mice impaired liver regeneration with poor hepatocyte growth and suppressed cell cycle signaling. Orosomucoid-1 (Orm1) is an acute phase protein mainly expressed by hepatocytes under stress conditions. Beginning from the finding that Orm1 was induced after partial hepatectomy in humans and mice, we showed enrichment of Orm1 in regenerating hepatocytes of hepatectomized mice by transcriptome analysis and following culture and animal experiments. Knockdown of Orm1 in mice resulted in decreases in hepatocyte growth accompanying suppressed signaling in controlling chromatin replication. Therefore, Orm1 would be a potential therapeutic and prognostic biomarker for liver diseases, especially after surgical resection of cancer-bearing liver, through its newly found ability to stimulate the cell cycle in regenerating hepatocytes.

Ansamycins are a class of macrolactams with diverse bioactivities, characterized by the unique 3-amino-5-hydroxybenzoic acid moiety. In this study, the ansamycin gene cluster aas in Streptomyces sp. S35 was activated by the constitutive coexpression of two pathway-specific regulator genes aas1 and aas10, and seven novel pentaketide ansamycin aminoansamycins A-G (1-7) were identified. Compound 4 with better antiproliferative activity indicated that the anthranilate analogues are probably promising building blocks for the production of unnatural ansamycins with improved activity.

This study was conducted to explore the diagnostic value of MUC2 gene methylation in pancreatic cancer.Methylation restriction enzyme digestion (Msp I/Hap II) and polymerase chain reaction (PCR) were performed to detect methylation of the MUC2 gene in fecal and blood specimens from seven study subjects with pancreatic cancer (PC), chronic pancreatitis (CP), or normal controls (CON). Simultaneously, blood CA 19-9 levels were detected as a positive indicator of PC.MUC2 methylation was detected in 50% of PC cell lines. In fecal samples, the MUC2 methylation rate in PC (n = 30) was 43.3%, which was significantly higher than those in CP (n = 8, 0%, P 0.05) and CON (n = 20, 5.0%, P 0.05). In blood samples, the MUC2 methylation rate in PC (n = 40) was 52.5%, which was significantly higher than those in CP (n = 15, 0%, P 0.01) and CON (n = 25, 4.0%, P 0.01). For PC diagnosis, MUC2 gene methylation in blood samples showed higher specificity and positive predictive value than CA 19-9. The combined detection in the feces and blood showed a 60% MUC2 methylation rate in PC (n = 10), which was higher than those in the CP (n = 5, 0%, P 0.01) and CON (n = 12, 0%, P 0.01).The study can clearly indicate that combined detection of MUC2 gene methylation in the peripheral blood and feces could be used as a new screening and early diagnosis method for pancreatic cancer.

Objectives Emerging evidence connects serum uric acid (SUA) levels to nonalcoholic fatty liver disease (NAFLD). The objective of this study was to systematically evaluate the association between SUA levels and risk of NAFLD by conducting a meta-analysis of available observational studies. Design and methods We searched for relevant studies in PubMed, Embase, China National Knowledge Infrastructure, and Wanfang databases until October 2014. All observational studies that evaluated SUA levels and NAFLD risks were included. Pooled adjusted odds ratio (OR) and corresponding 95% confidence intervals (CI) were calculated comparing the highest to lowest SUA category. Results Four cross-sectional studies, two prospective studies, and three retrospective studies involving 55,573 participants were identified. In overall risk estimates, the pooled OR of NAFLD occurrence was 1.92 (95% CI: 1.59–2.31) comparing the highest to lowest SUA levels in a random effect model. Subgroup analysis showed that high SUA levels increased the risk of NAFLD in cross-sectional studies (OR: 2.18; 95% CI: 1.58–3.03), retrospective studies (OR 1.82; 95% CI: 1.43–2.33), and prospective studies (OR 1.43; 95% CI: 1.20–1.71). The risk of NAFLD seemed more pronounced among women (OR 1.85; 95% CI: 1.43–2.38) than among men (OR 1.56; 95% CI: 1.30–1.86). Conclusion This meta-analysis suggests that increased SUA level is associated with an exacerbated risk of NAFLD. This increased risk is probably independent of conventional NAFLD risk factors.

Objectives Many studies have compared losartan with other antihypertensive agents in the management of hypertensive patients with hyperuricaemia in China. However, systematic assessment of efficacy and safety between losartan and other antihypertensive agents is still lacking. This meta-analysis sought to evaluate the available randomized controlled trials (RCTs) regarding losartan treatment for hypertensive patients with hyperuricaemia in China. Methods Cochrane Library, PubMed, EMBASE, Chinese National Knowledge Infrastructure, and Wanfang database were searched until December 2013. Only RCTs comparing losartan with other antihypertensive agents for the management of hypertensive patients with hyperuricaemia in Chinese patients were included. Results Thirty-one RCTs with 2754 patients were identified. Losartan reduced serum uric acid levels (weighted mean differences - 1.57 mg/dl, 95% confidence interval -1.83 to -1.30) compared with other antihypertensive agents. No significant differences in the reduction in SBP or DBP were observed. The incidence of adverse events was comparable between losartan and other agents, so no differences were found in dizziness and headache. Losartan generated a lower incidence than angiotensin-converting enzyme inhibitors of reported dry cough (risk ratio 0.19, 95% confidence interval 0.10-0.36). Conclusion There are no significant differences between losartan and other antihypertensive agents in the reduction of blood pressure. However, losartan is superior to other agents in the reduction of serum uric acid levels; it might be a better choice in hypertensive patients with hyperuricaemia.

Tobacco use is the leading preventable cause of death in the United States. Analyzing the ability for different mechanisms to reduce smoking rates can provide healthcare systems with information to establish the most effective smoking cessation efforts. Health insurance provides individuals with direct mechanisms to curb smoking behavior, such as access to smoking cessation resources. Gaining insurance may additionally indirectly influence smoking cessation by altering risk perceptions. Behavioral economic theory suggests that gaining health insurance may reduce current smokers' rate of discounting on the future, which could increase smoking cessation. This article aimed to evaluate the impact of insurance status (i.e., gaining any private (n = 681), gaining only public (n = 647), or remaining uninsured (n = 5,056)) as well as the impact of having a discussion with a healthcare provider about quitting smoking on smoking cessation among current adult smokers who were uninsured at the beginning of their data collection. Data for this study came from the Medical Expenditure Panel Survey 2003 to 2014 database. The study found that while individuals gaining public insurance was not statistically associated with smoking cessation, individuals who gained private insurance were more likely to stop smoking than individuals who remained uninsured (OR: 1.330; 95% CI: 1.019,1.737; p = 0.036). Having a discussion with a healthcare provider about quitting smoking was not associated with smoking cessation. These findings indicate that gaining private insurance may impact smoking behavior through mechanisms other than direct access to physician services.

Background Hepatitis C, caused by a single-stranded RNA virus, has become a global health problem. Infecting millions of individuals in the United States alone, chronic HCV infection can lead to devastating medical problems including cirrhosis and hepatocellular carcinoma. These problems create millions of dollars in health-care costs for treatment and management. This study determines the cost-effectiveness of hepatitis C treatment with the new generation of oral protease inhibitors. Methods A Markov model was constructed to simulate the progression of genotype-1 chronic hepatitis C disease in a cohort of 50-year-old patients. A decision tree, along with the Markov model, was then used to determine duration of disease, treatment success, progression of disease and mortality. At the end of each stage in the model, the cost and quality-adjusted life years (QALY) were summed for each individual. These were then used to calculate the overall cost-effectiveness ratio (CER) using QALY as the unit of effectiveness. Four treatment options were modelled: sofosbuvir with pegylated interferon-α and ribavirin (SOF/PEG-IFN+RBV), sofosbuvir with ribavirin (SOF/RBV), simeprevir with pegylated interferon-α and ribavirin (SMV/ PEG-IFN+RBV) and simeprevir with sofosbuvir (SMV/SOF). Results SOF/PEG-IFN+RBV yielded a CER ratio of $6,796.22/QALY, SMV/PEG-IFN+RBV of $7,642.60/QALY and SMV/SOF of $8,959.11/QALY. SOF/RBV had a higher CER of $16,295.30/QALY. It is important to note however that SMV/SOF had the highest QALY at 19.08. Conclusions After consideration of quality of life, treatment regimens and treatment side effects, the SMV/SOF regimen yields acceptable cost-effectiveness ratios with high QALY.

Falls and fall-related injuries among older community-dwelling adults continue to be a major health concern in the US. Falls are the leading cause of disability and trauma-related death in persons over 65 years of age. This article discusses current approaches in community fall management and challenges with these approaches, and offers some insight for community providers regarding this issue.

Clinical studies have suggested that lipids increase activity of white blood cells. The objective of this study is to examine whether high serum total cholesterol (STC) is associated with periodontitis.A total of 1,061 participants from the 2011 to 2012 National Health and Nutrition Examination Survey who underwent both periodontal examination and laboratory test for STC was included. To examine effects of high STC on periodontitis, odds ratios were calculated, adjusting for age, sex, education, income, smoking status, diabetes, body mass index, and calcium levels.Statistically significant associations were observed between borderline as well as high STC and periodontitis. Study participants with STC between 200 and 239 mg/dL (borderline) were 1.67 times (95% confidence interval [CI]: 1.13 to 2.47) as likely to have periodontitis as those with normal levels (≤199 mg/dL), and those with STC ≥240 mg/dL (high) were 2.22 times (95% CI: 1.27 to 3.87) as likely to have periodontitis as those with normal levels.Positive significant association was observed between STC and periodontitis. Results of the present study provide insight into potential risk factors for periodontitis. High STC levels could be a potential risk factor for the disease; however, further studies need to be conducted to understand the actual relationship between STC levels and periodontitis and to establish causality and directional association.

Recent human studies found that the mRNA expression level of aryl-hydrocarbon receptor nuclear translocator 2 (ARNT2) was positively associated with the prognosis of breast cancer. In this study, we used small interfering RNA techniques to knockdown ARNT2 expression in MCF7 human breast cancer cells, and found that an almost 40% downregulation of ARNT2 mRNA expression increased the expression of sensitive to apoptosis gene (3.36-fold), and decreased the expression of von Hippel-Lindau (0.27-fold) and matrix metalloproteinase-1 (0.35-fold). The metabolite analysis revealed the contents of glucose, glycine, betaine, phosphocholine, pyruvate and lactate involved in the hypoxia-inducible factor (HIF)-1-dependent glycolytic pathway were significantly lower in cells treated with siARNT2. Our results suggested that ARNT2 might play an important role in the modulation of HIF-1-regulated signaling and metabolism.

Purpose Some women with early-stage breast cancer are at higher risk of recurrence and can benefit from chemotherapy. We describe patterns of referral, receipt, and completion of chemotherapy among older women at high risk of recurrence. Patients and Methods A total of 2,124 women age 65 years or older who were diagnosed with early-stage breast cancer between 1990 and 1994 and 1996 to 1999 were included; 1,090 of these were at high risk of recurrence. We reviewed medical records to categorize chemotherapy outcomes as follows: did not discuss or were not referred to a medical oncologist (n = 133); discussed and/or referred to a medical oncologist but received no chemotherapy (n = 742); received an incomplete chemotherapy course (n = 29), or received a completed chemotherapy course (n = 186). Results Overall, 19.7% of high-risk women received any chemotherapy, and 86.5% of these women completed their chemotherapy courses. Just greater than 10% of high-risk women did not have a discussion about chemotherapy as part of breast cancer treatment documented in the medical record; these women also received fewer diagnostic assessments of their initial tumors. Conclusion Individuals who receive chemotherapy for early-stage breast cancer are a select subgroup of patients at high risk of recurrence. This study identifies characteristics of women who were referred for and who received chemotherapy, and this study plays an important role in understanding generalizability of studies that examine chemotherapy treatment effectiveness. Outcomes after breast cancer could continue to be improved with increased receipt of chemotherapy among older women at high risk of breast cancer recurrence.

Objectives: To describe hormone therapy (HT) initiation after the 2002 publication of the Women's Health Initiative. Design: Observational cohort (1999-2003) of women ages 40 to 79 years, five health plans, used HT in July 2002 and subsequently discontinued or never used before August 2002. Results: Of discontinuers, 15.8% (3,203 of 20,205) reinitiated HT. Reinitiation was higher among estrogen users (23.8%) versus estrogen with progestin users (11.3%), and lower among those with diabetes (relative risk [RR] = 0.68, 95% CI: 0.61-0.76), cardiovascular disease (RR = 0.87, 95% CI: 0.83-0.92), and hyperlipidemia (RR = 0.83, 95% CI: 0.79-0.88). Only 2.3% (2,072 of 90,261) of never users initiated (August 2002 to December 2003). First-time initiation was associated with cardiovascular disease (RR = 1.17, 95% CI: 1.10-1.25) and hyperlipidemia (RR = 1.24, 95% CI: 1.17-1.33) and was less common among those with diabetes (RR = 0.70, 95% CI: 0.63-0.79). Conclusions: After the Women's Health Initiative, a minority of women reinitiated or became first-time initiators of HT. Women with cardiovascular disease, diabetes, and hyperlipidemia were less likely to reinitiate; women with cardiovascular disease and hyperlipidemia were more likely to be first-time initiators.

Purpose There are more than 2,000,000 breast cancer survivors in the United States today. While surveillance for asymptomatic recurrence and second primary is included in consensus recommendations, the effectiveness of this surveillance has not been well characterized. Our purpose is to estimate the effectiveness of surveillance mammography in a cohort of breast cancer survivors with complete ascertainment of surveillance mammograms and negligible losses to follow-up. Patients and Methods We enrolled 1,846 stage I and II breast cancer patients who were at least 65 years old at six integrated health care delivery systems. We used medical record review and existing databases to ascertain patient, tumor, and therapy characteristics, as well as receipt of surveillance mammograms. We linked personal identifiers to the National Death Index to ascertain date and cause of death. We matched four controls to each breast cancer decedent to estimate the association between receipt of surveillance mammogram and breast cancer mortality. Results One hundred seventy-eight women died of breast cancer during 5 years of follow-up. Each additional surveillance mammogram was associated with a 0.69-fold decrease in the odds of breast cancer mortality (95% CI, 0.52 to 0.92). The protective association was strongest among women with stage I disease, those who received mastectomy, and those in the oldest age group. Conclusion Given existing recommendations for post-therapy surveillance, trials to compare surveillance with no surveillance are unlikely. This large observational study provides support for the recommendations, suggesting that receipt of surveillance mammograms reduces the rate of breast cancer mortality in older patients diagnosed with early-stage disease.

The quality of medical record abstracts is often characterized in a reliability substudy. These results usually indicate agreement, but not the extent to which lack of agreement affects associations observed in the complete data. In this study, medical records were reviewed and abstracted for patients diagnosed with stage I or stage II breast cancer between 1990 and 1994 at one of six US Cancer Research Network sites. For a subsample, interrater reliability data were available. The authors calculated conventional hazard ratios and 95% confidence intervals for the association of demographic, tumor, and treatment characteristics with recurrence rate. These conventional estimates of effect were compared with three sets of estimates and 95% simulation intervals that took account of the uncertainty assessed by lack of agreement in the reliability substudy. The rate of recurrence was associated with increasing cancer stage and with treatment modality but not with demographic characteristics. The hazard ratios and simulation intervals that took account of the reliability data showed that the simulation interval grew wider as the sources of uncertainty taken into account grew more complete, but the associations expected a priori remained readily apparent. While many investigators use reliability data only as a metric for data quality, a more thorough approach can also quantitatively depict the uncertainty in the observed associations.

Objective The study examined the relationship between functional limitation due to chronic diseases and absenteeism among full-time workers. The studied chronic diseases include arthritis/rheumatism, cancer, diabetes, heart disease, hypertension, lung disease, and stroke. Methods We analyzed data from the 2011 to 2013 National Health Interview Survey. Economic impact was determined by workdays lost and lost income. Results Increase in absenteeism was observed for each studied condition. Employees with multiple conditions also saw increase absenteeism. Employers lose 28.2 million workdays annually ($4.95 billion in lost income) due to functional limitation caused by chronic diseases. Conclusions The results show a burden on society due to functional limitation caused by studied chronic diseases. Employers should look into implementing intervention/prevention programs, such as the Chronic Disease Self-Management Programs, to help reduce the cost associated with absenteeism.

Aim To investigate the presence of autoantibodies (aAbs) against interleukin (IL)-17A and IL-17F and observe whether anti-IL-17A or IL-17F aAbs are associated with disease activity in patients with early rheumatoid arthritis (ERA). Methods At present, 60 patients with ERA, 72 patients with osteoarthritis (OA) and 61 healthy controls (HC) have been included in a database. Clinical assessment and laboratory data were recorded. We detected the titer of aAbs against IL-17A and IL-17F using enzyme-linked immunosorbent assay and analyzed the correlation of these aAbs in patients with ERA. Results Our results showed that the levels of aAbs against IL-17A and IL-17F were significantly higher in ERA OA and HC (P

Time delay is the key obstacle for receiving successful stroke treatment. Alteplase therapy must start within 4.5 hours from stroke occurrence. Rapid transport to a primary stroke center (PSC) or acute stroke-ready hospital (ASRH) by the emergency medical system (EMS) paramedics is vital. We determined transport time and destination data for EMS-identified and -delivered stroke suspects in Arkansas during 2013. Our objective was to analyze transport time and the hospital qualification for stroke care across the state.The state's 75 counties were placed into 8 geographical regions (R1-R8). Transport time and hospital qualification were determined for all EMS-identified strokes. Each hospital's stroke care status was categorized as PSC, ASRH, a nonspecialty or unknown care facility (NSCF), out-of-state, or nonapplicable designation facilities.There were 9588 EMS stroke ground transports with median within-region transport times of 29-40 minutes. Statewide, only 65% of EMS-transported stroke patients were transported to either PSC (12%) or ASRH (53%) facilities. One-third of the patients (30.6%) were delivered to NSCFs, where acute stroke therapy may rarely be performed. Regions with the highest suspected-stroke cases per capita also had the highest percentage of transports to NSCFs.With only a few PSCs in Arkansas, EMS agencies should prioritize transporting stroke patients to ASRHs when PSCs are not regionally located.

To explore the subcellular localization of ataxin-3 and the effect of polyglutamine (polyQ) expansion mutation on the morphology of mitochondrion, golgi apparatus and endoplasmic reticulum.Transient transfection was employed to build cell models expressing wild-type or mutant ataxin-3 proteins. Indirect immunofluorescence was applied to identify markers of organelle membrane. The results were observed under a laser scanning confocal microscope.No co-localization was observed for ataxin-3 protein and mitochondrial marker TOM20, but the percentage of cells with mitochondrial fragmentation has increased in cells expressing mutant ataxin-3 (P0.05). No co-localization was observed for ataxin-3 protein and golgi marker GM130, and mutant ataxin-3 did not cause golgi fragmentation. Wide type and polyQ-expanded ataxin-3 both showed partial co-localization with ER marker calnexin. The latter showed more overlap with calnexin, and the overlapping signals were mostly located in the places where aggregates were situated.PolyQ-expanded ataxin-3 protein may indirectly affect the integrity of mitochondria, but may cause no effect on the structure and functions of golgi apparatus. Endoplasmic reticulum may be another place where extended ataxin-3 protein can induce cytotoxicity in addition to the nucleus.

This meta-analysis revealed that diabetic adults had a twofold greater risk of hip fractures compared with non-diabetic populations, and this association was more pronounced in type 1 diabetes. The relationship between diabetes mellitus and risk of hip fracture yielded conflicting results. We conducted a meta-analysis to investigate the association between diabetes mellitus and the risk of hip fractures based on observational studies. We conducted a systematic literature search of PubMed and Embase databases through May 2015. We selected cohort and case–control studies providing at least age-adjusted risk ratio (RR) and corresponding 95 % confidence intervals (CI) of hip fractures among diabetic and non-diabetic subjects. Moreover, we pooled the female-to-male RR of hip fractures from studies that reported gender-specific risk estimate in a single study. Twenty-one studies involving 82,293 hip fracture events among 6,995,272 participants were identified. Diabetes mellitus was associated with an increased risk of hip fractures (RR 2.07; 95 % CI 1.83–2.33) in a random effects model. Subgroup analysis indicated that excess risk of hip fracture was more pronounced in type 1 diabetes (RR 5.76; 95 % CI 3.66–9.07) than that in type 2 diabetes (RR 1.34; 95 % CI 1.19–1.51). The pooled female-to-male RR of hip fractures was 1.09 (95 % CI 0.93–1.28). Individuals with diabetes mellitus have an excessive risk of hip fractures, and this relationship is more pronounced in type 1 diabetes. The association between diabetes and hip fracture risk is similar in men and women.

Purpose A substantial literature describes age-dependent variations in breast cancer treatment, showing that older women are less likely to receive standard treatment than younger women. We sought to identify patient and tumor characteristics associated with the nonreceipt of standard primary tumor and systemic adjuvant therapies. Patients and Methods We studied 1,859 women age 65 years or older with stage I and II breast cancer diagnosed between 1990 and 1994 who were cared for in six geographically dispersed community-based health care systems. We collected demographic, tumor, treatment, and comorbidity data from electronic data sources, including cancer registry, administrative, and clinical databases, and from subjects' medical records. Results Women 75 years of age or older and women with higher comorbidity indices were more likely to receive nonstandard primary tumor therapy, to not receive axillary lymph node dissection, and to not receive radiation therapy after breast-conserving surgery (BCS). Asian women were less likely to receive BCS, and African American women were less likely to be prescribed tamoxifen. Although nonreceipt of most therapies was associated with a lower baseline risk of recurrence, an important minority of high-risk women (16% to 30%) did not receive guideline therapies. Conclusion Age is an independent risk factor for nonreceipt of effective cancer therapies, even when comorbidity and risk of recurrence are taken into account. Information regarding treatment effectiveness in this age group and tools that allow physicians and patients to estimate the benefits versus the risks of therapies, taking into account age and comorbidity burden, are critically needed.

OBJECTIVE: In the absence of trial results that are applicable to the target population, nested case-control studies might be an alternative to full-cohort analysis. We compared relative and absolute estimates of associations in an influenza vaccine study using both designs.STUDY DESIGN AND SETTING: Data from elderly persons enrolled during six consecutive influenza seasons were used (147,551 person-periods). The endpoints "hospitalization for pneumonia or influenza" (P&I) or "death" were used combined and separately to define three types of cases. Controls for the case-control samples were randomly selected from the remainder of the total cohort at different ratios (1:1 to 1:4). Logistic regression analysis was used to assess adjusted vaccine effectiveness (VE). Sampling fractions were used to determine the number needed to treat to prevent one outcome. Receiver-operator-curve analysis was conducted to estimate the area under the curve (AUC) as a measure of discriminative capacity of the prognostic model.RESULTS: In all, 978 P and I hospitalizations and 1,339 deaths were observed. The adjusted estimates of relative estimates (VE, AUC) and their corresponding 95% confidence intervals were virtually the same using both study designs, notably when the case-control ratio was high (1:4).CONCLUSION: A nested case-control design can provide valid and precise estimates of associations and is a cost-effective alternative for full-cohort analysis.

BACKGROUND: Uncertainties among health care providers and patients about the risk of serious influenza-associated complications and the potential benefits of vaccination may contribute to unsatisfactorily low influenza vaccination rates. To quantify the risk of serious outcomes (hospitalization due to pneumonia or influenza or death due to any cause) during influenza seasons, we developed a clinical prediction rule for the probability of hospitalization due to pneumonia or influenza or death among elderly persons.METHODS: We developed the clinical prediction rule using data from linked administrative databases in a cohort of 16,280 noninstitutionalized and unvaccinated elderly persons. Validation of the rule was conducted in 5 unvaccinated and 6 vaccinated cohorts, each consisting of >11,000 elderly members of 3 managed care organizations. Logistic regression was used to produce a prognostic score on the basis of the following predictors: age; sex; presence of pulmonary, cardiac, and renal disease; dementia or stroke and cancer; number of outpatient visits; and hospitalization due to pneumonia or influenza during the previous year.RESULTS: Reliability of the regression model was good (P=.65, by goodness-of-fit test), and it discriminated well between those who did and those who did not experience an outcome (area under the receiver-operating curve, 0.83; 95% confidence interval, 0.81-0.85). Validation revealed moderately lower but acceptable discriminating values (0.72-0.81). In the derivation cohort, the prognostic accuracy of the rule was high when a cutoff score for the upper 50th percentile was used: > or =10 of 1000 subjects with a score in the upper 50th percentile were predicted to have an outcome, and 89% of all outcomes were observed in this high-risk group, whereas CONCLUSIONS: This prediction rule may be a useful tool to complement other age-based strategies, to further encourage vaccination, especially among those at the highest risk of serious complications due to influenza.

To test the substitution hypothesis, that community-based care reduces the probability of institutional placement for at-risk elderly.The closure of the Social Health Maintenance Organization (Social HMO) at HealthPartners (HP) in Minnesota in 1994 and the continuation of the Social HMO at Kaiser Permanente Northwest (KPNW) in Oregon/Washington comprised a "natural experiment." Using multinomial logistic regression analyses, we followed cohorts of Social HMO enrollees for up to 5 years, 1995 to 1999. To adjust for site effects and secular trends, we also followed age- and gender-matched Medicare-Tax Equity and Fiscal Responsibility Act (TEFRA) cohorts, enrolled in the same HMOs but not in the Social HMOs.All enrollees in the Social HMO for at least 4 months in 1993 and an age-gender matched sample of Medicare-TEFRA enrollees. To be included, individuals had to be alive and have a period out of an institution after January 1, 1995 (total n = 18,143).The primary data sources were the electronic databases at HP and KPNW. The main outcomes were long-term nursing home placement (90+ days) or mortality. Covariates were age, gender, a comorbidity index, and geographic site effect.Adjusting for variations in the 2 sites, we found no difference in probability of mortality between the 2 cohorts, but approximately a 40% increase in long-term institutional placement associated with the termination of the Social HMO at HealthPartners (odds ratio, 1.43; 95% confidence interval, 1.15-1.79).The Social HMO appears to help at-risk elderly postpone long-term nursing home placement.

This serial cohort study assessed the risk of hospitalization or death associated with influenza and the effectiveness of influenza vaccination among subgroups of elderly members of 3 managed-care organizations in the United States. Data on baseline characteristics and outcomes were obtained from computerized databases. A total of 122,974 (1996-1997 season) and 158,454 (1997-1998 season) persons were included in the cohorts. Among unvaccinated persons, hospitalizations for pneumonia/influenza or death occurred in 8.2 of 1000 healthy and 38.4 of 1000 high-risk persons in year 1, and in 8.2 of 1000 healthy and 29.3 of 1000 high-risk persons in year 2. After adjustments, vaccination was associated with a 48% reduction in the incidence of hospitalization or death (95% confidence interval [CI], 42-52) in year 1 and 31% (95% CI, 26-37) in year 2. Effectiveness estimates were statistically significant and generally consistent across the healthy and high-risk subgroups. The absolute risk reduction, however, was 2.4- to 4.7-fold higher among high-risk than among healthy elderly persons. All elderly individuals may substantially benefit from vaccination. However, the impact of influenza is greater in persons with high-risk medical conditions.

Summary Background Dahuang zhechong formula has been used for the treatment of chronic hepatitis B, but its efficacy on the liver fibrosis is conflicting. We performed a meta-analysis to quantitatively investigate the efficacy of Dahuang zhechong formula as an adjunctive therapy treatment for liver fibrosis in patients with hepatitis B. Methods We searched the PubMed, EMBASE, VIP database, China National Knowledge Infrastructure, and Wanfang database through January 2014. Only randomized controlled trials investigating Dahuang zhechong formula as an adjunctive therapy treatment for liver fibrosis in patients with chronic hepatitis B were selected. Results Seventeen trials involving 1212 patients were included. Dahuang zhechong formula reduced serum hyaluronic acid level (standardized mean difference [SMD]=−1.27; 95% confidence interval [CI]: −1.72 to −0.83), type-III procollagen level (SMD=−1.71; 95%CI: −2.34 to −1.09), type-IV collagen level (SMD=−1.06; 95%CI: −1.41 to −0.70), and laminin level (SMD=−0.75; 95%CI: −0.89 to −0.62). In particular, subgroup analyses showed that patients who did not receive anti-viral agents have achieved a greater reduction in serum fibrosis markers. Conclusions Dahuang zhechong formula appears to reduce serum biomarkers of liver fibrosis in patients with chronic hepatitis B. However, robust conclusions cannot be reached due to the methodological flaws of the included trials.

This study developed methods and determined the impact of influenza vaccination on elderly persons in 3 large health plans: Kaiser Permanente Northwest, HealthPartners, and Oxford Health Plans. Data for the 1996-1997 and 1997-1998 seasons were extracted from administrative databases. Subjects were health plan members > or = 65 years old. Comorbid conditions collected from the preceding year were used for risk adjustment with logistic regression. The virus-vaccine match was excellent for year 1 and fair for year 2. Both years, during peak and total periods, vaccination reduced all causes of death and hospitalization for pneumonia and influenza: hospitalizations were reduced by 19%-20% and 18%-24% for years 1 and 2, respectively, and deaths were reduced by 60%-61% and 35%-39% for the same periods. These results show that all elderly persons should be immunized annually for influenza. The methods used in this study are an efficient cost-effective way to study vaccine impact and similar questions.

Background/purposeAcyclic retinoid (ACR) is a promising chemopreventive agent for hepatocellular carcinoma (HCC) that selectively inhibits the growth of HCC cells (JHH7) but not normal hepatic cells (Hc). To better understand the molecular basis of the selective anti-cancer effect of ACR, we performed nuclear magnetic resonance (NMR)-based and capillary electrophoresis time-of-flight mass spectrometry (CE-TOFMS)-based metabolome analyses in JHH7 and Hc cells after treatment with ACR.Methodology/principal findingsNMR-based metabolomics revealed a distinct metabolomic profile of JHH7 cells at 18 h after ACR treatment but not at 4 h after ACR treatment. CE-TOFMS analysis identified 88 principal metabolites in JHH7 and Hc cells after 24 h of treatment with ethanol (EtOH) or ACR. The abundance of 71 of these metabolites was significantly different between EtOH-treated control JHH7 and Hc cells, and 49 of these metabolites were significantly down-regulated in the ACR-treated JHH7 cells compared to the EtOH-treated JHH7 cells. Of particular interest, the increase in adenosine-5'-triphosphate (ATP), the main cellular energy source, that was observed in the EtOH-treated control JHH7 cells was almost completely suppressed in the ACR-treated JHH7 cells; treatment with ACR restored ATP to the basal levels observed in both EtOH-control and ACR-treated Hc cells (0.72-fold compared to the EtOH control-treated JHH7 cells). Moreover, real-time PCR analyses revealed that ACR significantly increased the expression of pyruvate dehydrogenase kinases 4 (PDK4), a key regulator of ATP production, in JHH7 cells but not in Hc cells (3.06-fold and 1.20-fold compared to the EtOH control, respectively).Conclusions/significanceThe results of the present study suggest that ACR may suppress the enhanced energy metabolism of JHH7 cells but not Hc cells; this occurs at least in part via the cancer-selective enhancement of PDK4 expression. The cancer-selective metabolic pathways identified in this study will be important targets of the anti-cancer activity of ACR.

Recent randomized trials have indicated that the risks of hormone therapy for menopausal women may outweigh the benefits. The purpose of this study was to describe how health plans responded to the findings of the Women's Health Initiative (WHI) estrogen plus progestin trial. We surveyed five health plans affiliated with the HMO Research Network and the Cancer Research Network to document the response of each plan to the WHI in terms of patient and provider education and guidelines. Every health plan issued responses within 3 months of WHI's termination in a variety of formats. Recommendations were relatively consistent across the organizations. Given the documented changes in hormone therapy use in these five health plans in the post-WHI era, we conclude that attempts on the part of each organization to educate patients and providers about the implications of the WHI may have contributed to the observed changes in hormone therapy use.

Priorities for improving the health of our nation include rebuilding the public health infrastructure through increasing assessment, policy development, and assurance capacities in our communities. Capacity building necessitates formalizing and strengthening public health practice linkages to achieve Year 2000 objectives. Determining progress in achieving objectives requires development of public health infrastructure surveillance and data system capabilities. The Tracking Center of Tracking and Outreach Program for St. Louis (TOPS), through unique collaboration among academic and practice partners, laid the foundation for a Regional Integrated Information System (RIIS) by developing a centralized maternal-child health data base for prenatal and pediatric care providers. The RIIS model provides an example of a capacity building system designed to provide public health surveillance, assessment, planning, and evaluation capabilities. Medical Subject Headings (MeSH): health information systems, prenatal care, immunization, maternal-child health care, public health surveillance.

Background Little information is available on geographic disparity of human papillomavirus (HPV) vaccination among women aged 18–26 years in the U.S. Genital HPV is the most common sexually transmitted infection in the U.S. Persistent HPV infection with oncogenic types can cause cervical cancer. Purpose This study utilized data collected from the 2010 National Health Interview Survey (NHIS). It identified geographic variability and other factors contributing to the disparities in HPV vaccine series initiation in a nationally representative sample of women aged 18–26 years. Methods The study utilized data collected from 1867 women who participated in the Cancer Control Module Supplement of the 2012 NHIS. A multivariable logistic regression model was used to assess characteristics associated with initiation of the HPV series. Analyses were performed in 2012. Results After adjusting for other characteristics, women living in the West and North Central/Midwest had 54% and 20% greater odds of initiating the HPV series, respectively, compared with those living in the Northeast. Other factors associated with HPV series initiation were younger age, Hispanic background, being single/never married, childlessness, a history of HPV, and current alcohol use. Factors correlated with failure to initiate the HPV series were: not having insurance, living below the 200% poverty level, not being a high school graduate, not currently using hormone-based birth control, most recent Pap >1 year ago, no regular provider, last clinic visit ≥12 months ago, and never having received the hepatitis B vaccine. Conclusions Results demonstrate disparity in HPV vaccine uptake by region of residence in the U.S. among young women. Further research is needed to understand the factors contributing to this geographic disparity. Evaluation of vaccination policies and practices associated with higher coverage regions might help characterize effective methods to improve HPV vaccination among women aged 18–26 years.

Thalidomide is increasingly used in anticancer and anti-inflammation therapies. However, it is known for its teratogenicity and ability to induce peripheral neuropathy, although the mechanisms underlying its neurological effect in humans are unclear. In this study, we investigated the effect of thalidomide on the metabolism and neuronal differentiation of human neural progenitor cells. We found that levels of tyrosine, phenylalanine, methionine and glutathione, which are involved in dopamine and methionine metabolism, were decreased following thalidomide treatment. Morphological analysis revealed that treatment with 100 nM thalidomide, which is much lower than clinical doses, significantly decreased the number of dopaminergic (tyrosine hydroxylase-positive) neurons, compared with control cells. Our results suggest that these adverse neurological effects of thalidomide should be taken into consideration prior to its use for the treatment of neurodegenerative and other diseases.

To compare the effects of prophylactic anticonvulsant use of phenytoin and carbamazepine on the cognitive and emotional status of the patient after brain injury.Double-blind, placebo-controlled study with assessments before and after withdrawal from drug treatment.Patients had been initially treated by neurosurgeons at a university hospital and were followed up during the study on an outpatient basis.Forty of 64 patients receiving phenytoin and 42 of 127 patients receiving carbamazepine from 6 to 44 months for seizure prophylaxis after brain injury met study criteria and were assigned to continue or discontinue treatment. Groups were balanced for age, sex, race, weight, intelligence, type of injury, duration of therapy, and drug plasma concentration at screening.A battery of neuropsychological tests was administered twice during a 4-week baseline period, at the end of a 4- to 5-week period of continued drug treatment or placebo, and after 4 weeks of not receiving medication.Attention and concentration, psychomotor speed, memory, verbal fluency, and emotional state.No significant differences were found in the performance of patients in medication and placebo groups for either drug at the end of the placebo phase. Patients in the combined groups showed significant improvement (P.01) on several measures of motor and speeded performance following cessation of drug treatment. Multivariate analyses showed additional differences between phenytoin and carbamazepine and also suggested a significant practice effect on some measures used.Both phenytoin and carbamazepine seem to have negative effects on cognitive performance, particularly on tasks with significant motor and speed components. Practice effects were noted and may account for much of the improvement when patients stopped taking the drugs. Overall effects of the drugs were small and of limited clinical significance, but differences among subjects were noted that may affect selection of a particular drug for the individual patient.

To evaluate the effects of providing appropriateness criteria through guideline-based electronic health record (EHR) decision support for high-tech diagnostic imaging (HTDI) procedures.Chart audits were performed on a random sample of adult primary care orders for 3 HTDI procedures (computed tomography [CT] and magnetic resonance imaging [MRI] of the head, and MRI of the lumbar spine) before and after implementation of an EHR decision support system.Level of appropriateness, abnormal findings, and apparent effects on patient care.A total of 299 eligible audits were performed. Decision support was associated with a 20% to 36% drop in spine MRI and head CT orders, but head MRI order volume was unaffected. Combined results for the 3 procedures showed that a larger proportion of studies ordered after implementing decision support (89.2% vs 79.5%, P = .02) fit appropriateness criteria, and more postimplementation studies had A ratings (highest utility rating) (81.8% vs 70%, P = .04). However, there were no differences in the proportion of tests with positive findings (42/132 vs 28/120, P = .16 among procedures that met definite criteria) or the proportion with a likely impact on patients (6.6% vs 10.8%, P = .07).These data support the feasibility of using chart audits to assess the relationship between appropriateness criteria and HTDI orders. Although introduction of EHR clinical decision support for diagnostic imaging orders was associated with reduced volume and increased appropriateness of orders, there was little apparent impact on either findings or patients.

To identify factors associated with delayed radiotherapy (RT) in older women with early-stage breast cancer.We studied 541 women ageor=65 years diagnosed with early-stage breast cancer in 1990-1994 at 5 integrated healthcare delivery systems and treated with breast-conserving surgery and RT, but not chemotherapy. We examined whether demographic, tumor, or treatment characteristics were associated with RT delays of8 weeks postsurgery using chi(2) tests and multivariable logistic regression.Seventy-six women (14%) had delayed RT, with a median delay of 14 weeks. Even though they had insurance and access to care, nonwhite and Hispanic women were much more likely than white women to have delayed RT (odds ratio = 3.3; 95% confidence interval = 1.7, 10) in multivariable analyses that controlled for demographic and clinical variables.Timely RT should be facilitated through physician and patient education, navigation, and notification programs to improve quality of care. Queues for RT appointments should be evaluated on an ongoing basis to ensure adequate access. Future research should examine modifiable barriers to RT timeliness and whether delays impact long-term outcomes.

Little is known about the risk of recurrence >5 years after diagnosis among older breast cancer survivors. A community-based population of women ≥65 years diagnosed with early-stage breast cancer who survived disease free for 5 years was followed for 5 additional years or until a diagnosis of breast cancer recurrence, second primary, death, or loss to follow-up. These 5-year disease-free survivors (N = 1,277) had primary breast cancers that were node negative (77%) and estrogen receptor positive or unknown (86%). Five percent (n = 61) developed a recurrence between 5 and 10 years after diagnosis: 25% local, 9.8% regional, and 66% distant. Women who were node positive [hazard ratio (HR), 3.9; 95% confidence interval (95% CI), 1.5-10], had poorly differentiated tumors (HR, 2.5; 95% CI, 0.9-6.6), or who received breast conserving surgery without radiation therapy (HR, 2.4; 95% CI, 1.0-5.8) had higher recurrence rates compared with node negative, well differentiated, and receipt of mastectomy, respectively. Not receiving adjuvant tamoxifen, compared with receiving adjuvant tamoxifen, was also positively associated with late recurrence among women with estrogen receptor–positive/unknown tumors. Although relatively few women experience a late recurrence, most recurrences present as advanced disease, which is difficult to treat in older women. This study of late recurrence emphasizes that the risk, although small, is not negligible even in this group at high risk of death due to competing causes. (Cancer Epidemiol Biomarkers Prev 2009;18(11):2979–83)

Objective To evaluate the effectiveness of methods that control for confounding by indication, we compared breast cancer recurrence rates among women receiving adjuvant chemotherapy with those who did not. Study Design and Setting In a medical record review-based study of breast cancer treatment in older women ( n =1798) diagnosed between 1990 and 1994, our crude analysis suggested that adjuvant chemotherapy was positively associated with recurrence (hazard ratio [HR]=2.6; 95% confidence interval [CI]=1.9, 3.5). We expected a protective effect, so postulated that the crude association was confounded by indications for chemotherapy. We attempted to adjust for this confounding by restriction, multivariable regression, propensity scores (PSs), and instrumental variable (IV) methods. Results After restricting to women at high risk for recurrence ( n =946), chemotherapy was not associated with recurrence (HR=1.1; 95% CI=0.7, 1.6) using multivariable regression. PS adjustment yielded similar results (HR=1.3; 95% CI=0.8, 2.0). The IV-like method yielded a protective estimate (HR=0.9; 95% CI=0.2, 4.3); however, imbalances of measured factors across levels of the IV suggested residual confounding. Conclusion Conventional methods do not control for unmeasured factors, which often remain important when addressing confounding by indication. PS and IV analysis methods can be useful under specific situations, but neither method adequately controlled confounding by indication in this study.

The objectives were to estimate the incidence of neonatal herpes simplex virus (HSV) infections and to assess the utility of surveillance methods for neonatal herpes in 2 managed care populations. We identified potential cases using 15 discharge International Classification of Diseases 9th Revision Clinical Modification (ICD-9) codes for neonatal HSV and other diseases clinically consistent with this diagnosis. We also searched laboratory databases for positive HSV tests and investigated deaths during the neonatal period. We performed medical chart review using a standardized form. Two pediatric infectious disease specialists reviewed the forms of infants who had a positive HSV test or received a herpes-related diagnosis and made a determination as confirmed probable or not a case. Among 270703 infants born from 1997 to 2002 we identified 737 potential cases and completed medical chart abstraction for 699 (95%). Final review identified 35 confirmed or probable cases of neonatal HSV and the incidence was 12.9 per 100000 live births. Only 24 (69%) of the 35 cases were confirmed by laboratory testing. Among the 24 confirmed cases 22 (92%) received an ICD-9 code of 054.xx or 771.2. Among the 60 infants that received an ICD-9 code of 054.xx or 771.2 only 31 (52%) were confirmed or probable cases of neonatal HSV after final review. About 30% of neonatal HSV cases were not laboratory confirmed. The use of ICD-9 codes of 054.xx and 771.2 was a sensitive but not specific method to identify cases of neonatal herpes. (authors)

Purpose Five years of adjuvant tamoxifen therapy for estrogen receptor (ER) –positive breast cancer is more effective than 2 years of use. However, information on tamoxifen discontinuation is scanty. We sought to identify predictors of tamoxifen discontinuation among older women with breast cancer. Patients and Methods Within six health care delivery systems, we identified women ≥ 65 years old diagnosed with stage I to IIB ER-positive or indeterminant breast cancer between 1990 and 1994 who had filled a prescription for adjuvant tamoxifen. We observed them for 5 years after initial tamoxifen prescription. We used automated pharmacy records to validate tamoxifen prescription information abstracted from medical records. The primary end point was tamoxifen discontinuation, operationalized as ever discontinuing tamoxifen during 5 years of follow-up. We used Cox proportional hazards to identify predictors of tamoxifen discontinuation. Results Of 961 women who were prescribed tamoxifen, 49% discontinued tamoxifen before the completion of 5 years. Discontinuers were more likely to be aged 75 to less than 80 years (v < 70 years; hazard ratio [HR] = 1.41; 95% CI, 1.06 to 1.87), be aged ≥ 80 years (HR = 2.02; 95% CI, 1.53 to 2.66), have an increase in Charlson Comorbidity Index at 3 years from diagnosis (HR = 1.52; 95% CI, 1.18 to 1.95), have an increase in the number of cardiopulmonary comorbidities at 3 years (HR = 1.75; 95% CI, 1.34 to 2.28), have indeterminant ER status (v ER-positive status; HR = 1.36; 95% CI, 1.00 to 1.85), and have received breast-conserving surgery (BCS) without radiotherapy (v mastectomy; HR = 1.62; 95% CI, 1.18 to 2.22). Conclusion Attention to nonadherence among older women at risk of discontinuation, particularly those receiving BCS without radiotherapy, might improve breast cancer outcomes for these women.

Purpose Many studies have reported body mass index (BMI) increases the risk of breast cancer recurrence and breast cancer–specific mortality. Few studies have reported or examined whether breast cancer treatment differs by BMI. The purpose of this study was to examine the association between BMI at breast cancer diagnosis and receipt of appropriate primary tumor therapy and adjuvant therapy. Methods We identified 897 women age ≥ 65 years diagnosed with stage I or II breast cancer from 1990 to 1999 at five health care organizations. We used medical records to confirm demographics, tumor characteristics, treatment, comorbid conditions, and to calculate BMI at diagnosis (< 25 kg/m2, n = 328; 25 to < 30 kg/m2, n = 305; 30 to < 35 kg/m2, n = 188; ≥ 35 kg/m2, n = 76). We defined primary therapy based on National Guidelines as receiving breast-conserving surgery with radiation therapy and axillary node dissection, simple mastectomy with axillary node dissection, or modified radical mastectomy (73% overall); adjuvant therapy was defined as receipt of hormonal therapy, chemotherapy, or both (60% overall). Results The median BMI was 26.7 kg/m2 (range, 14.6 to 61.2). The proportion of women receiving primary therapy and adjuvant therapy was lowest for women less than 25 kg/m2 (69% and 56%, respectively) and greatest for obese I (78% and 64%, respectively). There were no differences in receipt of primary or adjuvant treatment across BMI in univariate or multivariable models (after adjusting for age, stage, comorbidity, diagnosis year, and hormone receptor positivity). Conclusion Receipt of appropriate primary therapy and adjuvant therapy is not associated with BMI in older women with access to health care. Additional research in larger samples and more diverse settings is needed.

Annual surveillance mammography is recommended for follow-up of women with a history of breast cancer. We examined surveillance mammography among breast cancer survivors who were enrolled in integrated healthcare systems.Women in this study were 65 or older when diagnosed with early stage invasive breast cancer (N = 1,762). We assessed mammography use during 4 years of follow-up, using generalized estimating equations to account for repeated measurements.Eighty-two percent had mammograms during the first year after treatment; the percentage declined to 68.5% in the fourth year of follow-up. Controlling for age and comorbidity, women who were at higher risk of recurrence by being diagnosed at stage II or receiving breast-conserving surgery (BCS) without radiation therapy were less likely to have yearly mammograms (compared to stage I, odds ratio [OR] for stage IIA 0.72, confidence interval [CI] 0.59, 0.87, OR for stage IIB 0.75, CI 0.57, 1.0; compared to BCS with radiation, OR 0.58, CI 0.43, 0.77). Women with visits to a breast cancer surgeon or oncologist were more likely to receive mammograms (OR for breast cancer surgeon 6.0, CI 4.9, 7.4, OR for oncologist 7.4, CI 6.1, 9.0).Breast cancer survivors who are at greater risk of recurrence are less likely to receive surveillance mammograms. Women without a visit to an oncologist or breast cancer surgeon during a year have particularly low rates of mammography. Improvements to surveillance care for breast cancer survivors may require active participation by primary care physicians and improvements in cancer survivorship programs by healthcare systems.

BACKGROUND. The association between common breast cancer therapies and recurrences and second primary breast cancers in older women is unclear, although older women are less likely to receive common therapies. METHODS. Women aged ≥65 years who were diagnosed with stage I or II breast cancer and who underwent mastectomy or breast-conserving surgery (BCS) from 1990 to 1994 were identified from automated data from 6 healthcare systems and then were followed for 10 years or until breast cancer recurrence, disenrollment, or death. Trained abstractors reviewed medical records to obtain recurrence, tumor, treatment and demographic data. The authors used proportional hazards models to examine predictors of recurrent and second primary breast cancers adjusted for demographic and tumor factors. RESULTS. Of 1837 eligible women, 34% were ages 65 to 69 years, 46% were ages 70 to 79 years, and 20% were aged ≥80 years. In multivariable models that used mastectomy as the reference group, BCS without radiation therapy was associated with an increased risk of any recurrent and second primary breast cancer (hazard ratio [HR], 1.6; 95% confidence interval [CI], 1.1–2.3), particularly with the subgroup of women with local and regional recurrence (HR, 3.5; 95% CI, 2.0–6.0). Tamoxifen use for

Background The purpose of this study was to compare the rates of all-cause and breast cancer–specific mortality after breast-conserving surgery (BCS) only, BCS plus radiation therapy (RT), mastectomy, and the receipt of adjuvant tamoxifen in a large population-based cohort of older women with early-stage disease. Study Design This cohort study was conducted within six US integrated health-care delivery systems. Automated administrative databases, medical records, and tumor registries were used to identify women aged 65 years or older who received BCS or mastectomy to treat stage I or II breast cancer diagnosed from January 1, 1990, through December 31, 1994. We compared cause-specific 10-year mortality rates across treatment categories by fitting Cox proportional hazards models adjusted for demographics and tumor characteristics. Results We identified 1,837 women having operations for stage I or II breast cancer. Compared with women receiving mastectomy, those receiving BCS without RT were twice as likely to die of breast cancer (adjusted hazards ratio [HR]=2.19, 95% confidence interval [CI], 1.51 to 3.18). Breast cancer mortality rates were similar between women receiving BCS plus RT and women receiving mastectomy (adjusted HR=1.08, 95% CI, 0.79 to 1.48). In the subset of 886 chemotherapy-naive women treated with tamoxifen, those treated with tamoxifen for less than 1 year had a substantially higher breast cancer mortality rate than those exposed 5 years or more (adjusted HR=6.26, 95% CI, 3.10 to 12.64). Conclusions Our findings indicate that older women receiving BCS alone have higher rates of breast cancer death than those receiving BCS + RT or mastectomy and that the survival benefit from tamoxifen increases with increasing duration of treatment.

Background The choice between paper data collection methods and electronic data collection (EDC) methods has become a key question for clinical researchers. There remains a need to examine potential benefits, efficiencies, and innovations associated with an EDC system in a multi-center medical record review study. Methods A computer-based automated menu-driven system with 658 data fields was developed for a cohort study of women aged 65 years or older, diagnosed with invasive histologically confirmed primary breast cancer (N = 1859), at 6 Cancer Research Network sites. Medical record review with direct data entry into the EDC system was implemented. An inter-rater and intra-rater reliability (IRR) system was developed using a modified version of the EDC. Results Automation of EDC accelerated the flow of study information and resulted in an efficient data collection process. Data collection time was reduced by approximately four months compared to the project schedule and funded time available for manuscript preparation increased by 12 months. In addition, an innovative modified version of the EDC permitted an automated evaluation of inter-rater and intra-rater reliability across six data collection sites. Conclusion Automated EDC is a powerful tool for research efficiency and innovation, especially when multiple data collection sites are involved.

Background In 1999, the American Academy of Pediatrics and U.S. Public Health Service recommended suspending the birth dose of hepatitis B vaccine due to concerns about potential mercury exposure. A previous report found that overall national hepatitis B vaccination coverage rates decreased in association with the suspension. It is unknown whether this underimmunization occurred uniformly or was associated with how providers changed their practices for the timing of hepatitis B vaccine doses. We evaluate the impact of the birth dose suspension on underimmunization for the hepatitis B vaccine series among 24-month-olds in five large provider groups and describe provider practices potentially associated with underimmunization following the suspension. Methods Retrospective cohort study of children enrolled in five large provider groups in the United States (A-E). Logistic regression was used to evaluate the association between the birth dose suspension and a child's probability of being underimmunized at 24 months for the hepatitis B vaccine series. Results Prior to July 1999, the percent of children who received a hepatitis B vaccination at birth varied widely (3% to 90%) across the five provider groups. After the national recommendation to suspend the hepatitis B birth dose, the percent of children who received a hepatitis B vaccination at birth decreased in all provider groups, and this trend persisted after the policy was reversed. The most substantial decreases were observed in the two provider groups that shifted the first hepatitis B dose from birth to 5–6 months of age. Accounting for temporal trend, children in these two provider groups were significantly more likely to be underimmunized for the hepatitis B series at 24 months of age if they were in the birth dose suspension cohort compared with baseline (Group D OR 2.7, 95% CI 1.7 – 4.4; Group E OR 3.1, 95% CI 2.3 – 4.2). This represented 6% more children in Group D and 9% more children in Group E who were underimmunized in the suspension cohort compared with baseline. Children in the reversal cohort in these groups remained significantly more likely to be underimmunized compared with baseline. In contrast, in a third provider group where the typical timing of the third dose was unchanged and in two other provider groups whose hepatitis B vaccination schedules were unaffected by the birth dose suspension, hepatitis B vaccination coverage either was maintained or improved. Conclusion When the hepatitis B birth dose was suspended, provider groups that moved the first dose of vaccination to 5–6 months of age or later had decreases in hepatitis B vaccine coverage at 24 months. These findings suggest that as vaccine policy changes occur, providers could attempt to minimize underimmunization by adopting vaccination schedules that minimize delays in the recommended timing of vaccine doses.

Improvements in cancer detection and treatment have resulted in increasing numbers of breast cancer survivors. Information regarding the use of mammography by breast cancer survivors is limited.The use of surveillance mammography was examined over a 5-year period in a retrospective cohort of women ageor=55 years who were diagnosed with incident primary breast cancer (1996-1997) while enrolled in 1 of 4 geographically diverse integrated health systems.Of the 797 women included in the study, 80% (n=636) underwent mammograms during the first year after treatment for breast cancer. The percentage of women having mammograms during each yearly period decreased significantly over time. In multivariable analyses, older women with comorbid illnesses or those with late-stage disease were less likely to undergo mammograms, whereas those who underwent breast-conserving therapy (adjusted odds ratio [OR] of 1.38 [95% confidence interval (95% CI), 1.09-1.75]) were more likely to have mammograms. Women who had outpatient visits with a gynecologist (adjusted OR of 3.49 [95% CI, 2.55-4.79]), or a primary care physician (adjusted OR of 2.21 [95% CI, 1.73-2.82]) during the year were more likely to undergo mammograms in that year.The use of mammography among breast cancer survivors declines over time. Efforts are needed to increase awareness among healthcare providers and breast cancer survivors of the value of follow-up mammography. The current findings highlight the importance of maintaining ongoing contact with primary care physicians and gynecologists.