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1,397 result(s) for "Robinson, Susan"
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A literature review on the representativeness of randomized controlled trial samples and implications for the external validity of trial results
Randomized controlled trials (RCTs) are conducted under idealized and rigorously controlled conditions that may compromise their external validity. A literature review was conducted of published English language articles that reported the findings of studies assessing external validity by a comparison of the patient sample included in RCTs reporting on pharmaceutical interventions with patients from everyday clinical practice. The review focused on publications in the fields of cardiology, mental health, and oncology. A range of databases were interrogated (MEDLINE; EMBASE; Science Citation Index; Cochrane Methodology Register). Double-abstract review and data extraction were performed as per protocol specifications. Out of 5,456 de-duplicated abstracts, 52 studies met the inclusion criteria (cardiology, n = 20; mental health, n = 17; oncology, n = 15). Studies either performed an analysis of the baseline characteristics (demographic, socioeconomic, and clinical parameters) of RCT-enrolled patients compared with a real-world population, or assessed the proportion of real-world patients who would have been eligible for RCT inclusion following the application of RCT inclusion/exclusion criteria. Many of the included studies concluded that RCT samples are highly selected and have a lower risk profile than real-world populations, with the frequent exclusion of elderly patients and patients with co-morbidities. Calculation of ineligibility rates in individual studies showed that a high proportion of the general disease population was often excluded from trials. The majority of studies (n = 37 [71.2 %]) explicitly concluded that RCT samples were not broadly representative of real-world patients and that this may limit the external validity of the RCT. Authors made a number of recommendations to improve external validity. Findings from this review indicate that there is a need to improve the external validity of RCTs such that physicians treating patients in real-world settings have the appropriate evidence on which to base their clinical decisions. This goal could be achieved by trial design modification to include a more representative patient sample and by supplementing RCT evidence with data generated from observational studies. In general, a thoughtful approach to clinical evidence generation is required in which the trade-offs between internal and external validity are considered in a holistic and balanced manner.
Extraglandular ocular involvement and morbidity and mortality in primary Sjögren’s Syndrome
Purpose To report the significance of extraglandular ocular involvement and long-term systemic morbidity and mortality in primary Sjögren’s Syndrome (SS). Methods This retrospective, longitudinal cohort study included consecutive patients with primary SS evaluated at a tertiary referral center. An electronic chart review was performed and all available data were extracted from clinic visits between October 1999 and March 2019. The primary outcome measures included occurrence of extraglandular ocular manifestations of SS, serological markers, prevalence of malignancy, and incidence of death. Results One hundred and twenty-six SS patients with minimum 3 years of follow-up (median 9.6, range 3.0–15.9 years, total of 1,235 patient-years) were included. Of those, 10 patients with inflammatory keratolysis or scleritis had 2.3 times greater likelihood of death compared to the rest of the cohort (OR = 2.3, 95% confidence interval [CI] 0.5 to 4.0, p = 0.01) due to SS related complications. The lifetime prevalence of any malignancy in the entire cohort was 15.5%. The most common hematologic malignancy was non-Hodgkin’s lymphoma (4.8%) and the most common solid malignancy was breast cancer (6.0%). Men SS patients were more likely to have a history of or concurrent malignancy compared to women (30.0% versus 13.7%, p = 0.16) and double the mortality (OR = 2.1, 95% CI 0.09 to 1.4, p = 0.04), independent of malignancy. Conclusions SS patients with serious ocular manifestations, particularly men, may be at greater risk for mortality due to SS complications. The eye seems to be the barometer of systemic disease activity.
Essential Caribbean
Ready to experience the Caribbean? The experts at Fodor's are here to help. Fodor's Essential Caribbean travel guide is packed with top recommendations, detailed maps of the Caribbean, and exclusive tips from locals. Whether you want to stay at an all-inclusive resort, find the best beaches, or snorkel or scuba dive at some of the world's best coral reefs, this user-friendly guidebook will help you plan it all out. Our local writers vet every recommendation to ensure that you not only make the most of your time, but that you also have all the most up-to-date and essential information you need to plan the perfect trip. This new edition has been FULLY-REDESIGNED with a new layout and beautiful images for more intuitive travel planning!
Investigation of reward learning and feedback sensitivity in non-clinical participants with a history of early life stress
Early life stress (ELS) is an important risk factor for the development of depression. Impairments in reward learning and feedback sensitivity are suggested to be an intermediate phenotype in depression aetiology therefore we hypothesised that healthy adults with a history of ELS would exhibit reward processing deficits independent of any current depressive symptoms. We recruited 64 adults with high levels of ELS and no diagnosis of a current mental health disorder and 65 controls. Participants completed the probabilistic reversal learning task and probabilistic reward task followed by depression, anhedonia, social status, and stress scales. Participants with high levels of ELS showed decreased positive feedback sensitivity in the probabilistic reversal learning task compared to controls. High ELS participants also trended towards possessing a decreased model-free learning rate. This was coupled with a decreased learning ability in the acquisition phase of block 1 following the practice session. Neither group showed a reward induced response bias in the probabilistic reward task however high ELS participants exhibited decreased stimuli discrimination. Overall, these data suggest that healthy participants without a current mental health diagnosis but with high levels of ELS show deficits in positive feedback sensitivity and reward learning in the probabilistic reversal learning task that are distinct from depressed patients. These deficits may be relevant to increased depression vulnerability.
Birth Weights in Sickle Cell Disease Pregnancies: A Cohort Study
Pregnancy in women with Sickle Cell Disease (SCD) has been linked with an increased incidence of adverse foetal outcomes when compared to women without haemoglobinopathies (HbAA). There's a paucity of data into foetal outcomes for infants born to women with SCD. Customised growth charts have been demonstrated to be better than population-based growth charts at identifying unhealthy small babies. We analysed the mean birth weight and customised birth weight centiles of infants born to mothers with SCD versus mothers with HbAA genotype, to quantify the risk of having a smaller baby. Birth weight and birth weight centiles were analysed for 88 women with SCD (50 HbSS; 38 HbSC) and 176 controls (HbAA). Statistically significant differences were seen in the mean birth weight (P value = 0.004) and the mean birth weight centiles (P value = 0.016). We conclude that SCD is a risk factor for having a smaller baby.
The best American mystery stories 2016
The Best American Mystery Stories 2016 is a feast of both literary crime and hard-boiled detection, featuring a seemingly innocent murderer, a drug dealer in love, a drunken prank gone terribly wrong, and plenty of other surprising twists and turns.
NEK7 phosphorylation of cortactin modulates the migratory capacity of cells expressing EML4-ALK V3
EML4-ALK is a common oncogenic driver of non-small cell lung cancer. Distinct EML4-ALK variants cause different rates of disease progression, with patients expressing variant 3 (V3) exhibiting accelerated metastasis. Cells expressing EML4-ALK V3 develop a mesenchymal-like morphology and enhanced migration that is dependent on the NEK9 and NEK7 kinases. However, downstream substrates of these kinases relevant to these phenotypes are largely unknown. Here, we show that the actin-binding protein cortactin is phosphorylated by NEK7 within the F-actin-binding region (ABR) and that depletion of cortactin abrogates the morphological and migration phenotypes induced by EML4-ALK V3. Expression of constitutively active mutants of NEK9 or NEK7 causes similar cortactin-dependent morphological and migration changes. Cortactin co-localises with NEK7 and EML4-ALK V3 at branched filopodia-like extensions that are also generated upon expression of a cortactin protein with phospho-mimetic mutations in the ABR. In contrast, phospho-null mutations dissociate cortactin from F-actin. We propose that EML4-ALK V3 alters cell morphology and promotes directed cell migration by modulating the actin cytoskeleton via NEK7-mediated phosphorylation of cortactin within its ABR.