Search tips
Search criteria

Results 1-12 (12)

Clipboard (0)

Select a Filter Below

Year of Publication
Document Types
1.  NatHER: protocol for systematic evaluation of trends in survival among patients with HER2-positive advanced breast cancer 
Systematic Reviews  2015;4:133.
Human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) is an aggressive form of breast cancer and is historically associated with poor outcomes compared with HER2-negative MBC. Since 1998, four drugs have been globally approved for the targeted treatment of HER2-positive MBC. Additional advances in patient care—such as improved breast cancer screening, HER2 testing, and supportive care—have also occurred. The objective of this systematic review and meta-analysis is to determine whether there has been a cumulative change in survival over time in patients with HER2-positive advanced breast cancer based on results from interventional clinical trials (ICTs) and observational studies and to compare outcomes across these types of studies.
A systematic search of Medline, EMBASE, and the Cochrane Central Register of Controlled Trials will be performed. Two investigators will independently assess each abstract for inclusion. English language reports of ICTs and observational studies that include patients with HER2-positive advanced breast cancer from 1987 onwards will be considered. The primary outcome of interest is overall survival; secondary outcomes include progression-free survival and safety. Data on clinical outcomes, as well as on study design, study population, treatment/intervention, methodological quality, and outcomes, will be extracted using a structured codebook developed by the authors for this study. Standard and cumulative random effects meta-analysis will be performed to derive pooled risk estimates, both overall and by study design, controlling for covariates such as aggregate demographic and clinical characteristics of patients, treatment/intervention, and study characteristics. Heterogeneity of studies will be evaluated using the I2 statistic. Differences in risk estimates by quality characteristics will be performed using meta-regression.
This study will evaluate current and evolving trends in survival associated with HER2-positive advanced breast cancer over nearly 30 years and will build upon prior, less comprehensive, systematic analyses. This information is important to patients, healthcare providers, and researchers, particularly in the advanced disease setting, in which new therapies have been recently approved. Including observational studies allows us to evaluate real-world effectiveness; useful information will be gained by comparing findings from observational studies with those from ICTs.
Systematic review registration
PROSPERO CRD42014014345
Electronic supplementary material
The online version of this article (doi:10.1186/s13643-015-0118-z) contains supplementary material, which is available to authorized users.
PMCID: PMC4591587  PMID: 26428301
Advanced breast cancer; HER2-positive breast cancer; Interventional controlled trials; Locally advanced breast cancer; Meta-analysis; Metastatic breast cancer; Observational study; Randomized clinical trial; Survival; Systematic review
2.  gems: An R Package for Simulating from Disease Progression Models 
Mathematical models of disease progression predict disease outcomes and are useful epidemiological tools for planners and evaluators of health interventions. The 𝖱 package gems is a tool that simulates disease progression in patients and predicts the effect of different interventions on patient outcome. Disease progression is represented by a series of events (e.g., diagnosis, treatment and death), displayed in a directed acyclic graph. The vertices correspond to disease states and the directed edges represent events. The package gems allows simulations based on a generalized multistate model that can be described by a directed acyclic graph with continuous transition-specific hazard functions. The user can specify an arbitrary hazard function and its parameters. The model includes parameter uncertainty, does not need to be a Markov model, and may take the history of previous events into account. Applications are not limited to the medical field and extend to other areas where multistate simulation is of interest. We provide a technical explanation of the multistate models used by gems, explain the functions of gems and their arguments, and show a sample application.
PMCID: PMC4458858  PMID: 26064082
Monte Carlo simulation; multistate model; 𝖱; survival analysis; prediction; compartmental model
3.  Bridge-to-Decision Therapy With a Continuous-Flow External Ventricular Assist Device in Refractory Cardiogenic Shock of Various Causes 
Circulation. Heart failure  2014;7(5):799-806.
Mortality for refractory cardiogenic shock remains high. In this patient cohort, there have been mixed results in mechanical circulatory support device use as a bridge-to-decision therapy. We evaluated a continuous-flow external ventricular assist device (VAD), CentriMag VAD (Thoratec Corp., Pleasanton, CA), in patients with various causes of refractory cardiogenic shock.
Methods and Results
This is a retrospective review of adult patients who underwent surgical CentriMag VAD insertion as bridge-to-decision therapy. From January 2007 through June 2012, 143 patients received CentriMag VAD. The cause of refractory cardiogenic shock was failure of medical management in 71 patients, postcardiotomy shock in 37, graft failure post–heart transplantation in 22, and right ventricular failure post–implantable left VAD in 13. Mean age was 52±16 years, and 71% were in INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) profile 1. Among 158 device runs, device configuration was BiVAD in 67%, isolated right VAD in 26%, and isolated left VAD in 8%. Median duration of support was 14 days (interquartile range, 8–26). Survival was 69% at 30 days and 49% at 1 year. The next destination after the CentriMag VAD was myocardial recovery in 30%, device exchange to an implantable VAD in 15%, and heart transplantation in 18%. The failure of medical management and the graft failure post–heart transplantation groups had higher 30-day survival compared with the postcardiotomy shock group. Major bleeding events occurred in 33% and cerebrovascular accidents in 14%. There was no CentriMag pump failure or thrombosis.
Bridge-to-decision therapy with CentriMag VAD is feasible in a variety of refractory cardiogenic shock settings. Patients with postcardiotomy shock have inferior survival.
PMCID: PMC4369383  PMID: 25027874
heart-assist devices; shock; cardiogenic
4.  Additive Effect of Anemia and Renal Impairment on Long-Term Outcome after Percutaneous Coronary Intervention 
PLoS ONE  2014;9(12):e114846.
Anemia and renal impairment are important co-morbidities among patients with coronary artery disease undergoing Percutaneous Coronary Intervention (PCI). Disease progression to eventual death can be understood as the combined effect of baseline characteristics and intermediate outcomes.
Using data from a prospective cohort study, we investigated clinical pathways reflecting the transitions from PCI through intermediate ischemic or hemorrhagic events to all-cause mortality in a multi-state analysis as a function of anemia (hemoglobin concentration <120 g/l and <130 g/l, for women and men, respectively) and renal impairment (creatinine clearance <60 ml/min) at baseline.
Among 6029 patients undergoing PCI, anemia and renal impairment were observed isolated or in combination in 990 (16.4%), 384 (6.4%), and 309 (5.1%) patients, respectively. The most frequent transition was from PCI to death (6.7%, 95% CI 6.1–7.3), followed by ischemic events (4.8%, 95 CI 4.3–5.4) and bleeding (3.4%, 95% CI 3.0–3.9). Among patients with both anemia and renal impairment, the risk of death was increased 4-fold as compared to the reference group (HR 3.9, 95% CI 2.9–5.4) and roughly doubled as compared to patients with either anemia (HR 1.7, 95% CI 1.3–2.2) or renal impairment (HR 2.1, 95% CI 1.5–2.9) alone. Hazard ratios indicated an increased risk of bleeding in all three groups compared to patients with neither anemia nor renal impairment.
Applying a multi-state model we found evidence for a gradient of risk for the composite of bleeding, ischemic events, or death as a function of hemoglobin value and estimated glomerular filtration rate at baseline.
PMCID: PMC4260949  PMID: 25489846
5.  The Impact of Renal Impairment on Long-Term Safety and Effectiveness of Drug-Eluting Stents 
PLoS ONE  2014;9(9):e106450.
Renal impairment (RI) is associated with impaired prognosis in patients with coronary artery disease. Clinical and angiographic outcomes of patients undergoing percutaneous coronary intervention (PCI) with the use of drug-eluting stents (DES) in this patient population are not well established.
We pooled individual data for 5,011 patients from 3 trials with the exclusive and unrestricted use of DES (SIRTAX - N = 1,012, LEADERS - N = 1,707, RESOLUTE AC - N = 2,292). Angiographic follow-up was available for 1,544 lesions. Outcomes through 2 years were stratified according to glomerular filtration rate (normal renal function: GFR≥90 ml/min; mild RI: 90
Patients with moderate/severe RI had an increased risk of cardiac death or myocardial infarction ([MI], OR 2.14, 95%CI 1.36–3.36), cardiac death (OR 2.21, 95%CI 1.10–4.46), and MI (OR 2.02, 95%CI 1.19–3.43) compared with patients with normal renal function at 2 years follow-up. There was no difference in cardiac death or MI between patients with mild RI compared to those with normal renal function (OR 1.10, 95%CI 0.75–1.61). The risk of target-lesion revascularization was similar for patients with moderate/severe RI (OR 1.17, 95%CI 0.70–1.95) and mild RI (OR 1.16, 95%CI 0.81–1.64) compared with patients with normal renal function. In-stent late loss and in-segment restenosis were not different for patients with moderate/severe RI, mild RI, and normal renal function.
Renal function does not affect clinical and angiographic effectiveness of DES. However, prognosis remains impaired among patients with moderate/severe RI.
PMCID: PMC4153613  PMID: 25184244
BMJ Open  2014;4(9):e005628.
To document overall, racial, ethnic and intent-specific spatiotemporal trends of firearm-related fatality rates (FRF rates) in the USA.
Cross-sectional study per year from 2000 to 2010.
Aggregate count of all people in the USA from 2000 to 2010.
Outcome measures
Data from the Web-based Injury Statistics Query and Reporting System from 2000 to 2010 was used to determine annual FRF rates per 100 000 and by states, race, ethnicity and intent.
The average national 11-year FRF rate was 10.21/100 000, from 3.02 in Hawaii to 18.62 in Louisiana: 60% of states had higher than national rates and 41 states showed no temporal change. The average national FRF rates among African-Americans and Caucasians were 18.51 and 9.05/100 000 and among Hispanics and non-Hispanics were 7.13 and 10.13/100 000; Hispanics had a decreasing change of −0.18, p trend<0.0001. In states with increasing trends (Florida and Massachusetts), Caucasians and non-Hispanics drove the rise; while in states with decreasing trends (California, North Carolina, Arizona, Nevada, New York, Illinois, Maryland), Hispanics and African-Americans drove the fall. The average national FRF rates due to homicides (4.1/100 000) and suicides (5.8/100 000) remained constant, but varied between states.
Endemic national FRF rates mask a wide variation in time trends between states. FRF rates were twice as high in African-Americans than Caucasians but decreased among Hispanics. Efforts to identify state-specific best practices can contribute to changes in national FRF rates that remain high.
PMCID: PMC4185336  PMID: 25239291
Examine the longitudinal effects of personal narratives about mammography and breast cancer compared with a traditional informational approach.
African American women (n=489) ages 40 and older were recruited from low-income neighborhoods in St. Louis, MO and randomized to watch a narrative video comprised of stories from African American breast cancer survivors or a content-equivalent informational video. Effects were measured immediately post-exposure (T2) and at 3- (T3) and 6-month (T4) follow-up. T2 measures of initial reaction included positive and negative affect, trust, identification, and engagement. T3 message-processing variables included arguing against the messages (counterarguing) and talking to family members about the information (cognitive rehearsal). T4 behavioral correlates included perceived breast cancer risk, cancer fear, cancer fatalism, perceived barriers to mammography, and recall of core messages. Structural equation modeling examined inter-relations among constructs.
Women who watched the narrative video (n=244) compared to the informational video (n=245) experienced more positive and negative affect, identified more with the message source, and were more engaged with the video. Narratives, negative affect, identification, and engagement influenced counterarguing, which in turn influenced perceived barriers and cancer fatalism. More engaged women talked with family members more, which increased message recall. Narratives also increased risk perceptions and fear via increased negative affect.
Narratives produced stronger cognitive and affective responses immediately, which in turn influenced message processing and behavioral correlates. Narratives reduced counterarguing and increased cognitive rehearsal, which may increase acceptance and motivation to act on health information in populations most adversely affected by cancer disparities.
PMCID: PMC3217077  PMID: 21895370
mammography; breast cancer survivors; health communication; storytelling; narratives; cancer disparities
BMJ Open  2012;2(5):e001616.
To evaluate a protocol for a population-based programme targeting the prevention of rheumatic heart disease (RHD) progression by early echocardiographic diagnosis of valvular lesions and timely implementation of secondary prevention.
Observational survey with a subsequent prospective cohort study.
Private boarding school in the urban area of the Sunsari district situated on the foothills of the Lower Himalayan Range in Eastern Nepal.
Fifty-four unselected school-going children 5–15 years of age, 24 girls and 30 boys.
Primary outcome measure
Logistic feasibility of a large-scale population-based screening study using the echocardiographic criteria formulated by the World Heart Federation, with longitudinal follow-up of children with definite or borderline RHD in a prospective cohort study.
Standardised interview, physical examination and screening echocardiography were performed in a three-staged process and took approximately 6 min per child. Socio-economic status was assessed using surrogate markers such as the occupation of the primary caregiver, numbers of rooms at home, car, television, cell phone and internet connection. Physical examination was focused on cardiac auscultation and signs of acute rheumatic fever and targeted echocardiography was performed by an independent examiner without knowledge of the clinical findings. Two children with evidence of borderline RHD were re-examined at B.P. Koirala Institute of Health Sciences and the indication for secondary antibiotic prevention was discussed with the parents and the children. At 6 months of follow-up, echocardiographic findings were stable in both children. Implementation of secondary antibiotic prevention was challenged by impaired awareness of subclinical RHD among parents and inadequate cooperation with family physicians.
This pilot study shows that the methods outlined in the protocol can be translated into a large-scale population-based study. We learned that education and collaboration with teachers, parents and family physicians/paediatricians will be of key importance in order to establish a sustainable programme.
PMCID: PMC3488717  PMID: 23087010
BMJ Open  2012;2(3):e001320.
Rheumatic heart disease (RHD) remains a major contributor to morbidity and mortality in developing countries. The reported prevalence rates of RHD are highly variable and mainly attributable to differences in the sensitivity of either clinical screening to detect advanced heart disease or echocardiographic evaluation where disease is diagnosed earlier across a continuous spectrum. The clinical significance of diagnosis of subclinical RHD by echocardiographic screening and early implementation of secondary prevention has not been clearly established.
Methods and analysis
The authors designed a cross-sectional survey to determine the prevalence of RHD in children from private and public schools between the age of 5 and 15 years in urban and rural areas of Eastern Nepal using both cardiac auscultation and echocardiographic evaluation. Children with RHD will be treated with secondary prevention and enrolled in a prospective cohort study. The authors will compare the prevalence rates by cardiac auscultation and echocardiography, determine risk factors associated with diagnosis and progression of RHD, investigate social and economic barriers for receiving adequate cardiac care and assess clinical outcomes with regular medical surveillance as a function of stage of disease at the time of diagnosis. Prospective clinical studies investigating the impact of secondary prevention for subclinical RHD on long-term clinical outcome will be of central relevance for future health resource utilisation in developing countries.
Ethics and dissemination
The study was considered ethically uncritical and was given an exempt status by the ethics committee at University of Bern, Switzerland. The study has been submitted to the National Nepal Health Research Council and was registered with (NCT01550068). The study findings will be reported in peer-reviewed publications. Identifier
Article summary
Article focus
Study protocol of a population-based evaluation of the prevalence rate of RHD among schoolchildren in Eastern Nepal, with a subsequent prospective longitudinal cohort study assessing long-term clinical outcome of children undergoing secondary prevention for borderline and definite RHD according to the World Heart Federation criteria.
Key messages
RHD remains a major contributor to morbidity and mortality in developing countries.
Echocardiographic screening allows diagnosis of RHD at an earlier stage across a continuous spectrum as compared with cardiac auscultation.
The clinical significance of diagnosis of subclinical RHD by echocardiographic screening and early implementation of secondary prevention has not been clearly established.
Strengths and limitations of this study
The protocol describes a comprehensive approach to implement echocardiographic screening in a high prevalence region as recommended by the WHO and outlines a robust analysis plan to investigate clinical outcome with secondary prevention for subclinical RHD.
Since access to education is a marker of socioeconomic status, restriction of screening to school going children is subjected to selection bias likely to underestimate the real disease burden related to RHD in Eastern Nepal.
Cultural sensitivity with education programmes and focus group discussions will anticipate the potential social stigma of a diagnosis with a heart condition during childhood and increase public awareness.
PMCID: PMC3371575  PMID: 22685225
Patient education and counseling  2010;81S1:S22-S33.
This study examined the effects (affective reactions, cognitive reactions and processing, perceived benefits and barriers and intent to screen) of targeted Peripheral + Evidential (PE) and Peripheral+Evidential+Socio-cultural (PE+SC) colorectal cancer communications.
This study was a two-arm randomized control study of cancer communication effects on affective, cognitive processing, and behavioral outcomes over a 22-week intervention. There were 771 African American participants, 45 to 75 years, participating in the baseline survey related to CRC screening. Three follow-up interviews that assessed intervention effects on affective response to the publications, cognitive processing, and intent to obtain CRC screening were completed.
There were no statistically significant differences between PE and PE+SC intervention groups for affect, cognitive processing or intent to screen. However, there were significant interactions effects on outcome variables.
The advantages and disadvantages of PE+SC targeted cancer communications and implications of sex differences are considered.
Practice Implications
While there do not appear to be significant differences in behavioral outcomes when using PE and PE+SC strategies, there appear to be subtle differences in affective and cognitive processing outcomes related to medical suspicion and ethnic identity, particularly as it relates to gender.
PMCID: PMC2988986  PMID: 20702056
Patient education and counseling  2010;81(Suppl):S6-14.
Compare effects of narrative and informational videos on use of mammography, cancer-related beliefs, recall of core content and a range of reactions to the videos.
African American women (n=489) ages 40 and older were recruited from low-income neighborhoods in St. Louis, MO and randomly assigned to watch a narrative video comprised of stories from African American breast cancer survivors (Living Proof) or a content-equivalent informational video using a more expository and didactic approach (Facts for Life). Effects were measured immediately post-exposure and at 3- and 6-month follow-up.
The narrative video was better liked, enhanced recall, reduced counterarguing, increased breast cancer discussions with family members and was perceived as more novel. Women who watched the narrative video also reported fewer barriers to mammography, more confidence that mammograms work, and were more likely to perceive cancer as an important problem affecting African Americans. Use of mammography at 6-month follow-up did not differ for the narrative vs. informational groups overall (49% vs. 40%, p=.20), but did among women with less than a high school education (65% vs. 32%, p<.01), and trended in the same direction for those who had no close friends or family with breast cancer (49% vs. 31%, p=.06) and those who were less trusting of traditional cancer information sources (48% vs. 30%, p=.06).
Narrative forms of communication may increase the effectiveness of interventions to reduce cancer health disparities.
Narratives appear to have particular value in certain population sub-groups; identifying these groups and matching them to specific communication approaches may increase effectiveness.
PMCID: PMC3146295  PMID: 21071167
PPAR Research  2007;2008:276581.
The primary aim of this study was to examine prospectively the associations between 5 peroxisome proliferator-activated receptor (PPAR) single nucleotide polymorphisms (SNPs) and cardiovascular morbidity and mortality in a community-based cohort study in Washington County, Maryland. Data were analyzed from 9,364 Caucasian men and women participating in CLUE-II. Genotyping on 5 PPAR polymorphisms was conducted using peripheral DNA samples collected in 1989. The followup period was from 1989 to 2003. The results showed that there were no statistically significant associations between the PPAR SNPs and cardiovascular deaths or events. In contrast, statistically significant age-adjusted associations were observed for PPARG rs4684847 with both baseline body mass and blood pressure, and for PPARG rs709158, PPARG rs1175543, and PPARD rs2016520 with baseline cholesterol levels. Future studies should be conducted to confirm these findings and to explore the associations in populations with greater racial and ethnic diversity.
PMCID: PMC2233806  PMID: 18288282

Results 1-12 (12)