The diagnosis of ductal carcinoma in situ (DCIS) is increasing, although to the authors' knowledge there is no consensus regarding optimal treatment. This analysis of women treated with ...breast-conserving surgery (BCS) evaluated the impact of radiation therapy (RT) in patient outcomes.
The current study included a population-based sample of 1103 women residing in selected Surveillance, Epidemiology, and End Results (SEER) registries who were diagnosed with DCIS between 1991-1992. Data were obtained from the registry, physician follow-up, and pathology reports. Physicians were contacted in 1999 to determine whether the patient had developed a second event in the ipsilateral breast. For second events, pathology reports were reviewed to determine the presence of in situ or invasive disease. Registry data through 2001 were used to assess death rates and cause of death. Cox proportional hazards and logistic regression models were used to evaluate the rates of second events and breast carcinoma deaths between women treated with and without RT.
Over an average of 91 months, 13.2% of women developed a second event. Rates of second events were 11% for women treated with BCS and RT compared with 15% for women treated with BCS only (adjusted hazards ratio, 0.64; 95% confidence interval, 0.44-0.92). Women receiving RT were significantly less likely to develop invasive breast carcinoma in the ipsilateral breast (adjusted odds ratio, 0.40). By 2001, the rate of death from breast carcinoma was 2.7%; in the group of women treated with BCS only compared with 0.8% in the group of women treated with BCS with RT.
Among a population-based cohort, RT was found to significantly reduce the risk of second events in the ipsilateral breast, particularly invasive tumors, although not to the extent reported in clinical trials.
Home-based HIV testing and counselling (HTC) achieves high uptake, but is difficult and expensive to implement and sustain. We investigated a novel alternative based on HIV self-testing (HIVST). The ...aim was to evaluate the uptake of testing, accuracy, linkage into care, and health outcomes when highly convenient and flexible but supported access to HIVST kits was provided to a well-defined and closely monitored population.
Following enumeration of 14 neighbourhoods in urban Blantyre, Malawi, trained resident volunteer-counsellors offered oral HIVST kits (OraQuick ADVANCE Rapid HIV-1/2 Antibody Test) to adult (≥16 y old) residents (n = 16,660) and reported community events, with all deaths investigated by verbal autopsy. Written and demonstrated instructions, pre- and post-test counselling, and facilitated HIV care assessment were provided, with a request to return kits and a self-completed questionnaire. Accuracy, residency, and a study-imposed requirement to limit HIVST to one test per year were monitored by home visits in a systematic quality assurance (QA) sample. Overall, 14,004 (crude uptake 83.8%, revised to 76.5% to account for population turnover) residents self-tested during months 1-12, with adolescents (16-19 y) most likely to test. 10,614/14,004 (75.8%) participants shared results with volunteer-counsellors. Of 1,257 (11.8%) HIV-positive participants, 26.0% were already on antiretroviral therapy, and 524 (linkage 56.3%) newly accessed care with a median CD4 count of 250 cells/μl (interquartile range 159-426). HIVST uptake in months 13-24 was more rapid (70.9% uptake by 6 mo), with fewer (7.3%, 95% CI 6.8%-7.8%) positive participants. Being "forced to test", usually by a main partner, was reported by 2.9% (95% CI 2.6%-3.2%) of 10,017 questionnaire respondents in months 1-12, but satisfaction with HIVST (94.4%) remained high. No HIVST-related partner violence or suicides were reported. HIVST and repeat HTC results agreed in 1,639/1,649 systematically selected (1 in 20) QA participants (99.4%), giving a sensitivity of 93.6% (95% CI 88.2%-97.0%) and a specificity of 99.9% (95% CI 99.6%-100%). Key limitations included use of aggregate data to report uptake of HIVST and being unable to adjust for population turnover.
Community-based HIVST achieved high coverage in two successive years and was safe, accurate, and acceptable. Proactive HIVST strategies, supported and monitored by communities, could substantially complement existing approaches to providing early HIV diagnosis and periodic repeat testing to adolescents and adults in high-HIV settings.
Abstract Purpose Physical activity is currently commonly summarized by simple composite scores of total activity, such as total metabolic equivalent score (METS), without further information about ...the many specific aspects of activities. We sought to identify more comprehensive physical activity patterns, and their association with cardiovascular disease risk factors. Methods The Northern Manhattan Study is a multiethnic cohort of stroke-free individuals. Questionnaires were used to capture multiple dimensions of leisure-time physical activity. Participants were grouped into METS categories and also into clusters by multivariate mixture modeling of activity frequency, duration, energy expenditure, and number of activity types. Associations between clusters and risk factors were assessed using χ2 tests. Results Using data available in 3293 participants, we identified six model-based clusters that were differentiated by frequency and diversity of activities, rather than activity duration. High activity clusters had lower prevalence of the risk factors compared with those with lower activity; associations with obesity and hypertension remained significant after adjusting for METS ( P = .027, .043). METS and risk factors were not significantly associated after adjusting for the clusters. Conclusions Data-driven clustering method is a principled, generalizable approach to depict physical activity and form subgroups associated with cardiovascular risk factors independently of METS.
Objective The aim of this study was to explore race-ethnic differences in the association between plasma lipid components and risk of incident myocardial infarction (MI). Design/methods As part of ...the Northern Manhattan Study, 2,738 community residents without cardiovascular disease were prospectively evaluated. Baseline fasting blood samples were collected, and lipid panel components were analyzed as continuous and categorical variables. Cox proportional hazards models were used to calculate HRs and 95% CIs for incident MI after adjusting for demographic and cardiovascular risk factors. Results The mean age was 68.8 ± 10.4 years; 36.7% were men. Of the participants, 19.9% were non-Hispanic white; 24.9%, non-Hispanic black; and 52.8%, Hispanic (>80% from the Caribbean). Hispanics had lower mean high-density lipoprotein cholesterol (HDL-C) and higher triglycerides (TG)/HDL-C. During a mean 8.9 years of follow-up, there were 163 incident MIs. In the whole cohort, all lipid profile components were associated with risk of MI in the expected directions. However, HDL-C (adjusted HR per 10 mg/dL increase 0.93, 95% CI 0.76-1.12) and TG/HDL-C >2 (adjusted HR 0.89, 95% CI 0.51-1.55) were not predictive of MI among Hispanics but were predictive among non-Hispanic blacks and whites. Triglycerides/HDL-C per unit increase was associated with an 8% higher risk of MI among Hispanics (adjusted HR 1.08, 95% CI 1.04-1.12). Conclusions In Hispanics, low HDL-C and TG/HDL-C >2 were not associated with MI risk. Our data suggest that a different TG/HDL ratio cutoff may be needed among Hispanics to predict MI risk.
Purpose Prior studies have reported that Hispanics have lower cardiovascular disease (CVD) mortality despite a higher burden of risk factors. We examined whether Hispanic ethnicity was associated ...with a lower risk of nonfatal myocardial infarction (MI) coronary death (CD) and vascular death. Methods A total of 2671 participants in the Northern Manhattan Study without clinical CVD were prospectively evaluated. Cox models were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the association of race–ethnicity with nonfatal MI, CD, and vascular death after adjusting for demographic and CVD risk factors. Results Mean age was 68.8 (10.4) years; 52.8% were Hispanic (88% Caribbean-Hispanic). Hispanics were more likely to have hypertension (73.1% vs. 62.2%, p < .001) and diabetes (22.0% vs. 13.3%, p < .001), and less likely to perform any physical activity (50.1% vs. 69.2%, p < .001) compared to non-Hispanic whites (NHW). During a mean 10 years of follow-up there were 154 nonfatal MIs, 186 CD, and 386 vascular deaths. In fully adjusted models, Hispanics had a lower risk of CD (adjusted HR = 0.36, 95% CI: 0.21–0.60), and vascular death (adjusted HR = 0.62, 95% CI: 0.43–0.89), but not nonfatal MI (adjusted HR = 0.95, 95% CI: 0.56–1.60) when compared to NHW. Conclusions We found a “Hispanic paradox” for coronary and vascular deaths, but not nonfatal MI.
Although there are several hazards for patients with implanted pacemakers and defibrillators in the magnetic resonance imaging (MRI) environment, evaluation of lead electrode heating is the most ...complex because of the many influencing variables: patient size, anatomy, body composition, patient position in the bore, scan sequence (radiofrequency power level), lead routing, and lead design. Although clinical studies are an important step in demonstrating efficacy, demonstrating safety through clinical trials alone is not practical because of this complexity.
The purpose of this study was to develop a comprehensive modeling framework to predict the probability of pacing capture threshold (PCT) change due to lead electrode heating in the MRI environment and thus provide a robust safety evaluation.
The lead heating risk was assessed via PCT change because this parameter is the most clinically relevant measure of lead heating. The probability for PCT change was obtained by combining the prediction for power at the electrode–tissue interface obtained via simulations with a prediction for PCT change as a function of radiofrequency power obtained via an in vivo canine study.
The human modeling framework predicted that the probability of a 0.5-V PCT change due to an MRI scan for the Medtronic CapSureFix MRI SureScan model 5086 MRI leads is <1/70,000 for chest scans and <1/10,000,000 for either head scans or lower torso scans.
The framework efficiently models millions of combinations, delivering a robust evaluation of the lead electrode heating hazard. This modeling approach provides a comprehensive safety evaluation that is impossible to achieve using phantom testing, animal studies, or clinical trials alone.
Activation of protooncogenes and inactivation of putative tumor suppressor genes are genetic lesions considered to be important in lung carcinogenesis. Fifty-four cases of non-small-cell lung cancer ...(23 adenocarcinomas, 23 squamous-cell carcinomas, and 8 large-cell carcinomas) were examined for loss of DNA sequences at 13 polymorphic genetic loci. Loss of heterozygosity was seen more frequently in squamous-cell carcinoma than in adenocarcinoma. The loss of DNA sequences from the short arm of chromosome 17 (D17S1 locus) was detected in 8 of 9 heterozygous cases of squamous-cell carcinoma and in only 2 of 11 heterozygous cases of adenocarcinomas. Furthermore, in 7 of these 8 squamous-cell carcinomas, loss of heterozygosity from chromosome 17 was accompanied by loss of DNA sequences from chromosome 11. The spectrum of allelic sequences lost from chromosome 11 was, however, similar in every type of carcinoma studied, and the data show two regions commonly deleted from chromosome 11 (11pter-p15.5 and 11p13-q13) that may have a role in the pathogenesis of all these types of non-small-cell bronchogenic carcinoma. Loss of DNA sequences from chromosome 3 was seen in 16 of 31 cases where the constitutive DNA was heterozygous--i.e., informative. These data included only 6 of 16 cases where loss of heterozygosity involved a chromosomal locus previously shown to be lost consistently in small-cell lung cancer (DNF15S2). Loss of heterozygosity at the chromosome 13q locus, D13S3, was seen in 9 of 21 informative cases, and in 2 cases, both adenocarcinomas, duplication of the intact DNA sequences suggested the possibility that mitotic recombination had occurred. Frequent DNA sequence deletions, including those from chromosome 17, in squamous-cell carcinomas may reflect the extensive mutagenic and clastogenic effects of tobacco smoke that may lead to inactivation of putative tumor-suppressor genes.
Patients surgically treated for infection after extremity fractures are typically discharged with a 6- to 12-week antibiotic regimen. Intravenous (IV) antibiotics are associated with significant cost ...and potential complications of deep vein thrombosis, line clotting, and sepsis. Many of the pathogens that cause musculoskeletal infection have both oral (PO) and IV antibiotic options with adequate bioavailability and antibacterial effect, yet IV antibiotics remain the standard of care absent evidence that PO options are clinically as efficacious. The POvIV study is a prospective, multicenter, randomized trial to compare PO with IV antibiotic therapy in patients with postoperative wound infections after extremity fractures. Patients between the ages of 18 and 84 who have a culture-positive surgical site infection after internal fixation for fracture repair or arthrodesis are approached for this study, and if they provide consent, are randomly assigned to receive either PO or IV antibiotics. Antibiotic selection is based on culture and sensitivity results. Randomization determines the route of administration. Patients are followed for 1 year after study enrollment. This study will be the largest prospective randomized trial to evaluate the safety and effectiveness of PO antibiotic use for treatment of postoperative wound infections. Results will inform clinician decisions on antibiotic delivery in patients with postoperative wound infections.
Abstract Purpose To examine whether the survival benefit of exercise is modified by obesity. Methods In the Northern Manhattan Study, we collected baseline sociodemographics and cardiovascular ...disease risk factors. The primary exposure was leisure-time physical activity (LTPA) and the outcomes were total, vascular, and nonvascular deaths (non-VaD). LTPA was defined as any versus none and metabolic equivalent score category (total activity weighted by intensity). We used Cox models to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). Results A total of 3298 participants (mean age 69 years, 52% Hispanic, 63% women) were followed over a mean of 11.8 years with 1589 total deaths (641 vascular, 819 nonvascular). Any activity (adjusted HR: 0.84, 95% CI: 0.75–0.94) was associated with reduced risk of all-cause mortality and non-VaD, but not VaD. We found an interaction ( P < .05) of LTPA with body mass index (BMI) less than 30 for all-cause and vascular mortality. Any LTPA was associated with reduced all-cause mortality (adjusted HR: 0.77, 95% CI: 0.68–0.87) and VaD (adjusted HR: 0.79, 95% CI: 0.65–0.97) only among those with BMI less than 30. Conclusions We found no evidence of an independent survival benefit of LTPA among those with BMI more than 30. The health benefits of exercise should be considered in the context of obesity.
The finished sequence of human chromosome 20 comprises 59,187,298 base pairs (bp) and represents 99.4% of the euchromatic DNA. A single contig of 26 megabases (Mb) spans the entire short arm, and ...five contigs separated by gaps totalling 320 kb span the long arm of this metacentric chromosome. An additional 234,339 bp of sequence has been determined within the pericentromeric region of the long arm. We annotated 727 genes and 168 pseudogenes in the sequence. About 64% of these genes have a 5' and a 3' untranslated region and a complete open reading frame. Comparative analysis of the sequence of chromosome 20 to whole-genome shotgun-sequence data of two other vertebrates, the mouse Mus musculus and the puffer fish Tetraodon nigroviridis, provides an independent measure of the efficiency of gene annotation, and indicates that this analysis may account for more than 95% of all coding exons and almost all genes.
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