Predicting prostate cancer treatment choices: The role of numeracy, time discounting, and risk attitudes

Prostate cancer is the most common cancer among males in the United States and there is lack of consensus as to whether active surveillance (AS) or radical prostatectomy (RP) is the best course of treatment. In this study we examined the role of three overlooked determinants of decision making about prostate cancer treatment in a hypothetical experiment—numeracy, time discounting, and risk taking in 279 men over age 50 without a prior prostate cancer diagnosis. Results showed that AS was the most frequently chosen option. Furthermore, numeracy and time discounting significantly predicted participants’ preference for AS, whereas a propensity to take risks was associated with a preference for RP. Such insights into the factors that affects cancer treatment preferences may improve tailored decision aids and help physicians be better poised to engage in shared decision-making to improve both patient-reported and clinical outcomes

The Baculovirus Uses a Captured Host Phosphatase to Induce Enhanced Locomotory Activity in Host Caterpillars

The baculovirus is a classic example of a parasite that alters the behavior or physiology of its host so that progeny transmission is maximized. Baculoviruses do this by inducing enhanced locomotory activity (ELA) that causes the host caterpillars to climb to the upper foliage of plants. We previously reported that this behavior is not induced in silkworms that are infected with a mutant baculovirus lacking its protein tyrosine phosphatase (ptp) gene, a gene likely captured from an ancestral host. Here we show that the product of the ptp gene, PTP, associates with baculovirus ORF1629 as a virion structural protein, but surprisingly phosphatase activity associated with PTP was not required for the induction of ELA. Interestingly, the ptp knockout baculovirus showed significantly reduced infectivity of larval brain tissues. Collectively, we show that the modern baculovirus uses the host-derived phosphatase to establish adequate infection for ELA as a virion-associated structural protein rather than as an enzyme

Activity pacing for osteoarthritis symptom management: study design and methodology of a randomized trial testing a tailored clinical approach using accelerometers for veterans and non-veterans

<p>Abstract</p> <p>Background</p> <p>Osteoarthritis (OA) is a prevalent chronic disease and a leading cause of disability in adults. For people with knee and hip OA, symptoms (e.g., pain and fatigue) can interfere with mobility and physical activity. Whereas symptom management is a cornerstone of treatment for knee and hip OA, limited evidence exists for behavioral interventions delivered by rehabilitation professionals within the context of clinical care that address how symptoms affect participation in daily activities. Activity pacing, a strategy in which people learn to preplan rest breaks to avoid symptom exacerbations, has been effective as part of multi-component interventions, but hasn't been tested as a stand-alone intervention in OA or as a tailored treatment using accelerometers. In a pilot study, we found that participants who underwent a tailored activity pacing intervention had reduced fatigue interference with daily activities. We are now conducting a full-scale trial.</p> <p>Methods/Design</p> <p>This paper provides a description of our methods and rationale for a trial that evaluates a tailored activity pacing intervention led by occupational therapists for adults with knee and hip OA. The intervention uses a wrist accelerometer worn during the baseline home monitoring period to glean recent symptom and physical activity patterns and to tailor activity pacing instruction based on how symptoms relate to physical activity. At 10 weeks and 6 months post baseline, we will examine the effectiveness of a tailored activity pacing intervention on fatigue, pain, and physical function compared to general activity pacing and usual care groups. We will also evaluate the effect of tailored activity pacing on physical activity (PA).</p> <p>Discussion</p> <p>Managing OA symptoms during daily life activity performance can be challenging to people with knee and hip OA, yet few clinical interventions address this issue. The activity pacing intervention tested in this trial is designed to help people modulate their activity levels and reduce symptom flares caused by too much or too little activity. As a result of this trial, we will be able to determine if activity pacing is more effective than usual care, and among the intervention groups, if an individually tailored approach improves fatigue and pain more than a general activity pacing approach.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01192516">NCT01192516</a></p

Chronic pain, depression and cardiovascular disease linked through a shared genetic predisposition:Analysis of a family-based cohort and twin study

BACKGROUND: Depression and chronic pain are the two most important causes of disability (Global Burden of Disease Study 2013). They occur together more frequently than expected and both conditions have been shown to be co-morbid with cardiovascular disease. Although shared socio-demographic risk factors (e.g. gender, deprivation) might explain the co-morbidity of these three conditions, we hypothesised that these three long-term, highly prevalent conditions co-occur and may be due to shared familial risk, and/or genetic factors. METHODS AND FINDINGS: We employed three different study designs in two independent cohorts, namely Generation Scotland and TwinsUK, having standardised, validated questionnaire data on the three traits of interest. First, we estimated the prevalence and co-occurrence of chronic pain, depression and angina among 24,024 participants of a population-based cohort of extended families (Generation Scotland: Scottish Family Health Study), adjusting for age, gender, education, smoking status, and deprivation. Secondly, we compared the odds of co-morbidity in sibling-pairs with the odds in unrelated individuals for the three conditions in the same cohort. Lastly, examination of similar traits in a sample of female twins (TwinsUK, n = 2,902), adjusting for age and BMI, allowed independent replication of the findings and exploration of the influence of additive genetic (A) factors and shared (C) and non-shared (E) environmental factors predisposing to co-occurring chronic widespread pain (CWP) and cardiovascular disease (hypertension, angina, stroke, heart attack, elevated cholesterol, angioplasty or bypass surgery). In the Generation Scotland cohort, individuals with depression were more than twice as likely to have chronic pain as those without depression (adjusted OR 2·64 [95% CI 2·34-2·97]); those with angina were four times more likely to have chronic pain (OR 4·19 [3·64-4·82]); those with depression were twice as likely to have angina (OR 2·20 [1·90-2·54]). Similar odds were obtained when the outcomes and predictors were reversed and similar effects seen among sibling pairs; depression in one sibling predicted chronic pain in the other (OR 1·34 [1·05-1·71]), angina predicted chronic pain in the other (OR 2·19 [1·63-2·95]), and depression, angina (OR 1·98 [1·49-2·65]). Individuals with chronic pain and angina showed almost four-fold greater odds of depression compared with those manifesting neither trait (OR 3·78 [2·99-4·78]); angina showed seven-fold increased odds in the presence of chronic pain and depression (OR 7·76 [6·05-9·95]) and chronic pain nine-fold in the presence of depression and angina (OR 9·43 [6·85-12·98]). In TwinsUK, the relationship between CWP and depression has been published (R = 0.34, p<0.01). Considering the CWP-cardiovascular relationship, the most suitable model to describe the observed data was a combination of A, C and E, with a small but significant genetic predisposition, shared between the two traits (2·2% [95% CI 0·06-0·23]). CONCLUSION: We found an increased co-occurrence of chronic pain, depression and cardiovascular disease in two independent cohorts (general population-based cohort, twins cohort) suggesting a shared genetic contribution. Adjustment for known environmental influences, particularly those relating to socio-economic status (Generation Scotland: age, gender, deprivation, smoking, education; Twins UK: age,BMI) did not explain the relationship observed between chronic pain, depression and cardiovascular disease. Our findings from two independent cohorts challenge the concept of traditional disease boundaries and warrant further investigation of shared biological mechanisms

Genetic-Background Modulation of Core and Variable Autistic-Like Symptoms in Fmr1 Knock-Out Mice

International audienc

Clinical implementation of rapid CYP2C19 genotyping to guide antiplatelet therapy after percutaneous coronary intervention

© 2018 The Author(s). Background: The CYP2C19 nonfunctional genotype reduces clopidogrel effectiveness after percutaneous coronary intervention (PCI). Following clinical implementation of CYP2C19 genotyping at University Florida (UF) Health Shands Hospital in 2012, where genotype results are available approximately 3 days after PCI, testing was expanded to UF Health Jacksonville in 2016 utilizing a rapid genotyping approach. We describe metrics with this latter implementation. Methods: Patients at UF Health Jacksonville undergoing left heart catheterization with intent to undergo PCI were targeted for genotyping using the Spartan RX™ system. Testing metrics and provider acceptance of testing and response to genotype results were examined, as was antiplatelet therapy over the 6 months following genotyping. Results: In the first year, 931 patients, including 392/505 (78%) total patients undergoing PCI, were genotyped. The median genotype test turnaround time was 96 min. Genotype results were available for 388 (99%) PCI patients prior to discharge. Of 336 genotyped PCI patients alive at discharge and not enrolled in an antiplatelet therapy trial, 1/6 (17%) poor metabolizers (PMs, with two nonfunctional alleles), 38/93 (41%) intermediate metabolizers (IMs, with one nonfunctional allele), and 119/237 (50%) patients without a nonfunctional allele were prescribed clopidogrel (p = 0.110). Clopidogrel use was higher among non-ACS versus ACS patients (78.6% vs. 42.2%, p < 0.001). Six months later, among patients with follow-up data, clopidogrel was prescribed in 0/4 (0%) PMs, 33/65 (51%) IMs, and 115/182 (63%) patients without a nonfunctional allele (p = 0.008 across groups; p = 0.020 for PMs versus those without a nonfunctional allele). Conclusion: These data demonstrate that rapid genotyping is clinically feasible at a high volume cardiac catheterization facility and allows informed chronic antiplatelet prescribing, with lower clopidogrel use in PMs at 6 months

Self-collected dried blood spots as a tool for measuring ovarian reserve in young female cancer survivors.

Study questionAre female young cancer survivors (YCS) able to self-collect high-quality dried blood spots (DBSs) at home to provide biospecimens for studying ovarian reserve?Summary answerYCS can self-collect high-quality DBS specimens in non-clinical settings, and anti-Mullerian hormone (AMH) levels can be assayed in such specimens.What is known alreadyLarge-scale biosample collection is a barrier to studying ovarian reserve in YCS. DBS collected by research personnel has high acceptability. AMH levels measured in DBS are highly correlated with those measured by serum-based methods.Study design, size, durationIn a prospective cohort study, YCS were recruited to self-collect DBS samples. AMH levels were assayed in 112 samples.Participants/materials, setting, methodsYCS participants, ages 18-44, were recruited from a nationwide longitudinal cohort and DBS collection materials were posted to them. AMH levels were assayed by the Ansh DBS AMH ELISA and compared according to participant characteristics.Main results and the role of chanceAmong 163 potential participants, 123 (75%) were enrolled. Of those enrolled, 112 (91%) were able to complete DBS self-collection and submit mailed samples adequate for measuring AMH. Participants (mean age 31.6 [SD 5.5]) were 85% white, 87% college graduates and 46% reported higher income. Common cancer types were lymphoma and leukemia (34%), breast cancer (30%) and thyroid or skin cancer (8%). The geometric mean (95% confidence interval) AMH level in DBS samples was 0.24 ng/ml (0.16-0.36). In adjusted analysis, AMH levels for survivors of breast cancer (0.02 ng/ml [0.01-0.07]) or leukemia/lymphoma (0.03 ng/ml [0.01-0.08]) were lower than the levels in thyroid or skin cancer survivors (0.12 ng/ml [0.03-0.44]). Pelvic radiation remained associated with lower AMH levels (0.20 ng/ml [0.10-0.40] in unexposed versus 0.02 ng/ml [0.01-0.06] in exposed). Amenorrheic survivors had AMH levels (0.02 ng/ml [0.01-0.06]) that were lower than those of YCS with 7-9 (0.09 ng/ml [0.03-0.32]) or ≥10 (0.17 ng/ml [0.08-0.37]) menstrual periods in the past year.Limitations, reasons for cautionThe results are generalizable to a population of highly educated, higher income YCS. It is unclear how generalizable the results are to other populations.Wider implications of the findingsSelf-collected DBS is a patient-friendly and minimally invasive tool for studying ovarian reserve in geographically diverse populations.Study funding/competing interestsResearch related to the development of this paper was supported by the National Institutes of Health, grants UL1 RR024926 pilot and HD080952-02, and by the American Cancer Society MRSG-08-110-01-CCE. The authors report no competing interests