Discussing uncertainty and risk in primary care: recommendations of a multi-disciplinary panel regarding communication around prostate cancer screening.

BackgroundShared decision making improves value-concordant decision-making around prostate cancer screening (PrCS). Yet, PrCS discussions remain complex, challenging and often emotional for physicians and average-risk men.ObjectiveIn July 2011, the Centers for Disease Control and Prevention convened a multidisciplinary expert panel to identify priorities for funding agencies and development groups to promote evidence-based, value-concordant decisions between men at average risk for prostate cancer and their physicians.DesignTwo-day multidisciplinary expert panel in Atlanta, Georgia, with structured discussions and formal consensus processes.ParticipantsSixteen panelists represented diverse specialties (primary care, medical oncology, urology), disciplines (sociology, communication, medical education, clinical epidemiology) and market sectors (patient advocacy groups, Federal funding agencies, guideline-development organizations).Main measuresPanelists used guiding interactional and evaluation models to identify and rate strategies that might improve PrCS discussions and decisions for physicians, patients and health systems/society. Efficacy was defined as the likelihood of each strategy to impact outcomes. Effort was defined as the relative amount of effort to develop, implement and sustain the strategy. Each strategy was rated (1-7 scale; 7 = maximum) using group process software (ThinkTank(TM)). For each group, intervention strategies were grouped as financial/regulatory, educational, communication or attitudinal levers. For each strategy, barriers were identified.Key resultsHighly ranked strategies to improve value-concordant shared decision-making (SDM) included: changing outpatient clinic visit reimbursement to reward SDM; development of evidence-based, technology-assisted, point-of-service tools for physicians and patients; reframing confusing prostate cancer screening messages; providing pre-visit decision support interventions; utilizing electronic health records to promote benchmarking/best practices; providing additional training for physicians around value-concordant decision-making; and using re-accreditation to promote training.ConclusionsConference outcomes present an expert consensus of strategies likely to improve value-concordant prostate cancer screening decisions. In addition, the methodology used to obtain agreement provides a model of successful collaboration around this and future controversial cancer screening issues, which may be of interest to funding agencies, educators and policy makers

Cancer Treatment for Dual Eligibles: What Are the Costs and Who Pays?

This study quantifies treatment costs for melanoma and breast, cervical, colorectal, lung, and prostate cancer among patients with dual Medicare and Medicaid eligibility. The analyses use merged Medicare and Medicaid Analytic eXtract enrollment and claims data for dually eligible beneficiaries age18 in Georgia, Illinois, Louisiana, and Maine in 2003 (n=892,001). We applied ordinary least squares regression analysis to estimate annual expenditures attributable to each cancer after controlling for beneficiaries’ age, race/ethnicity, sex, and comorbid conditions, and state fixed effects. Cancers and comorbid conditions were identified on the basis of diagnosis codes on insurance claims. The most prevalent cancers were prostate (38.4 per 1,000 men) and breast (30.7 per 1,000 women). Dual eligibles with the study cancers had higher rates of other chronic conditions such as hypertension and arthritis than other beneficiaries. Total Medicare and Medicaid expenditures for dual eligibles with the study cancers ranged from $30,328 for those with lung cancer to$17,011 for those with breast cancer, compared with $10,664 for beneficiaries without the cancers. However, only 9$256 million ($314 million in 2012 dollars). Dual eligibles with these cancers also had high rates of other medical conditions. These comorbidities should be recognized, both in documenting cancer treatment costs and in developing programs and policies that promote timely cancer diagnosis and treatment

A Single-stranded DNA-binding Protein of Bacteriophage T7 Defective in DNA Annealing

The annealing of complementary strands of DNA is a vital step during the process of DNA replication, recombination, and repair. In bacteriophage T7-infected cells, the product of viral gene 2.5, a single-stranded DNA-binding protein, performs this function. We have identified a single amino acid residue in gene 2.5 protein, arginine 82, that is critical for its DNA annealing activity. Expression of gene 2.5 harboring this mutation does not complement the growth of a T7 bacteriophage lacking gene 2.5. Purified gene 2.5 protein-R82C binds single-stranded DNA with a greater affinity than the wild-type protein but does not mediate annealing of complementary strands of DNA. A carboxyl-terminal-deleted protein, gene 2.5 protein-Delta26C, binds even more tightly to single-stranded DNA than does gene 2.5 protein-R82C, but it anneals homologous strands of DNA as well as does the wild-type protein. The altered protein forms dimers and interacts with T7 DNA polymerase comparable with the wild-type protein. Gene 2.5 protein-R82C condenses single-stranded M13 DNA in a manner similar to wild-type protein when viewed by electron microscopy

Posttraumatic Stress Disorder Symptoms Contribute to Staff Perceived Irritability, Anger, and Aggression After TBI in a Longitudinal Veteran Cohort: A VA TBI Model Systems Study

Objective To examine the relationship between staff perceived irritability, anger, and aggression and posttraumatic stress disorder (PTSD) in veterans with traumatic brain injury (TBI) of all severity levels. Design Longitudinal cohort design. Setting Veterans Affairs Polytrauma Transitional Rehabilitation Programs. Participants Veterans and service members with TBI of all severity levels enrolled in the Veterans Affairs Polytrauma Rehabilitation Centers’ Traumatic Brain Injury Model System national database (N=240). Interventions Not applicable. Main Outcome Measure Univariable and multivariable logistic regression modeling was used to examine the association between irritability, anger, and aggression and potential risk factors, including PTSD symptoms. Irritability, anger, and aggression was measured as a single construct using an item from the Mayo-Portland Adaptability Inventory-4 that was rated by program staff at admission and discharge from the inpatient rehabilitation program. PTSD symptoms were assessed using the PTSD Checklist–Civilian Version. Results PTSD symptoms uniquely predicted program staff-rated irritability, anger, and aggression at discharge even after controlling for severity of TBI, age, male sex, education, and annual earnings. The model explained 19% of the variance in irritability, anger, and aggression. Conclusions When TBI severity and PTSD symptoms were considered simultaneously in a sample of veterans, only PTSD symptoms predicted staff-rated irritability, anger, and aggression. Given the negative outcomes linked with irritability, anger, and aggression, veterans may benefit from assessment and treatment of PTSD symptoms within rehabilitation settings

Impact of Pre-Exposure History and Host Genetics on Antibody Avidity Following Norovirus Vaccination

Background: Development of high avidity, broadly neutralizing antibodies (Abs) is a priority after vaccination against rapidly evolving, widely disseminated viruses like human norovirus. After vaccination with a multivalent GI.1 and GII.4c norovirus virus-like particle (VLP) vaccine candidate adjuvanted with alum and monophosphoryl lipid A (MPL), blockade Ab titers peaked early, with no increase in titer following a second vaccine dose. Methods: Blockade Ab relative avidity was evaluated by measuring the slope of blockade Ab neutralization curves. Results: Blockade Ab avidity to the GI.1 vaccine component peaked at day 35 (7 days after dose 2). Avidities to heterotypic genogroup I VLPs were not sustained at day 35 after vaccination or GI.1 infection, as measured from archived sera. Only secretor-positive participants maintained high avidity blockade Ab to GI.1 at day 180. Avidity to the GII.4c vaccine component peaked at day 7, remained elevated through day 180, and was not secretor dependent. Avidity to an immunologically novel GII.4 strain VLP correlated with preexisting Ab titer to an ancestral strain Epitope A. Conclusions: Host genetics and pre-exposure history shape norovirus vaccine Ab responses, including blockade Ab avidity. Avidity of potentially neutralizing Ab may be an important metric for evaluating vaccine responses to highly penetrant viruses with cross-reactive serotypes

Oligonucleotide ligation assay detects HIV drug resistance associated with virologic failure among antiretroviral-naive adults in Kenya

Background: Transmitted drug resistance (TDR) is increasing in some areas of Africa. Detection of TDR may predict virologic failure of first-line non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based antiretroviral therapy (ART). We evaluated the utility of a relatively inexpensive oligonucleotide ligation assay (OLA) to detect clinically relevant TDR at time of ART initiation. Methods: Pre-ART plasmas from ART-naive Kenyans initiating an NNRTI-based fixed-dose combination ART in a randomized adherence trial conducted in 2006 were retrospectively analyzed by OLA for mutations conferring resistance to NNRTI (K103N, Y181C, and G190A) and lamivudine (M184V). Post-ART plasmas were analyzed for virologic failure (≥1,000 copies/mL) at 6 month intervals over 18-month follow-up. Pre-ART plasmas of those with virologic failure were evaluated for drug resistance by consensus and 454-pyrosequencing. Results: Among 386 participants, TDR was detected by OLA in 3.89% [95% Confidence Interval (CI), 2.19-6.33], and was associated with a 10-fold higher rate of virologic failure [Hazard Ratio (HR), 10.39; 95% CI, 3.23-32.41; p Conclusions: Detection of TDR by a point mutation assay may prevent use of sub-optimal ART

Country differences in the diagnosis and management of coronary heart disease : a comparison between the US, the UK and Germany

Background The way patients with coronary heart disease (CHD) are treated is partly determined by non-medical factors. There is a solid body of evidence that patient and physician characteristics influence doctors' management decisions. Relatively little is known about the role of structural issues in the decision making process. This study focuses on the question whether doctors' diagnostic and therapeutic decisions are influenced by the health care system in which they take place. This non-medical determinant of medical decision-making was investigated in an international research project in the US, the UK and Germany. Methods Videotaped patients within an experimental study design were used. Experienced actors played the role of patients with symptoms of CHD. Several alternative versions were taped featuring the same script with patients of different sex, age and social status. The videotapes were shown to 384 randomly selected primary care physicians in the three countries under study. The sample was stratified on gender and duration of professional experience. Physicians were asked how they would diagnose and manage the patient after watching the video vignette using a questionnaire with standardised and open-ended questions. Results Results show only small differences in decision making between British and American physicians in essential aspects of care. About 90% of the UK and US doctors identified CHD as one of the possible diagnoses. Further similarities were found in test ordering and lifestyle advice. Some differences between the US and UK were found in the certainty of the diagnoses, prescribed medications and referral behaviour. There are numerous significant differences between Germany and the other two countries. German physicians would ask fewer questions, they would order fewer tests, prescribe fewer medications and give less lifestyle advice. Conclusion Although all physicians in the three countries under study were presented exactly the same patient, some disparities in the diagnostic and patient management decisions were evident. Since other possible influences on doctors treatment decisions are controlled within the experimental design, characteristics of the health care system seem to be a crucial factor within the decision making process