Background Restless legs syndrome (RLS) is a potentially debilitating sleep disorder that affects a significant percentage of North American and European adults. Although standardized RLS diagnostic criteria are now established and widely accepted, reported prevalence estimates have varied widely. In this paper, we review the literature regarding RLS prevalence in North American and Western European adult populations, examine potential sources of variation, briefly discuss the impact of RLS, and offer recommendations for future research. Methods To identify qualifying studies, we searched 6 scientific databases and scanned bibliographies of relevant review papers and all identified articles. Studies including fewer than 300 participants that did not use any of the 4 standard diagnostic criteria were published prior to 1995, or targeted clinical populations were excluded. Results Thirty-four papers detailing results of large, population-based studies in 16 North American and Western European countries met our inclusion criteria, including 5 multi-country studies (N=69,992 participants) and 29 single country studies (N=163,188 participants); all but one were cross-sectional. Reported general prevalence rates ranged from 4 to 29% of adults, averaging 14.5±8.0% across studies. Reported prevalence averaged higher in primary care populations than in populations derived from random sampling or geographically defined cohorts (19.5±7.9% vs. 12.3±7.2%). Diagnostic and severity criteria differed considerably among studies, as did inclusion criteria, with corresponding variation in prevalence estimates. Prevalence averaged higher in women and older adults; more limited data suggest race/ethnicity, parity, health status, and other factors may also contribute to the observed variation in prevalence. RLS has profound, negative effects on health, well-being, and quality of life, yet detection rates remain low. Conclusions Collectively, these studies indicate that RLS is a common disorder of major clinical and public health significance in the Western industrialized world, affecting between 4 and 29% of adults. The wide variation in reported prevalence likely reflects differences in demographic factors, health status, and other population characteristics; study population source and sampling frame; and inconsistencies in RLS diagnostic criteria and procedures. In addition, prospective studies and corresponding incidence data on RLS are lacking, hindering the evaluation of both causal factors and sequelae.

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Hepatocellular carcinoma (HCC) has emerged as a major cause of cancer deaths globally. The landscape of systemic therapy has recently changed, with six additional systemic agents either approved or awaiting approval for advanced stage HCC. While these agents have the potential to improve outcomes, a survival increase of 2-5 months remains poor and falls short of what has been achieved in many other solid tumor types. The roles of genomics, underlying cirrhosis, and optimal use of treatment strategies that include radiation, liver transplantation, and surgery remain unanswered. Here, we discuss new treatment opportunities, controversies, and future directions in managing HCC.

Identification of the candidate gene responsible for the seed coat colour variation in Brassica juncea was undertaken following an earlier study where two independent loci (BjSc1 and BjSc2) were mapped to two linkage groups, LG A9 and B3 (Padmaja et al. in Theor Appl Genet 111:8-14, 2005). The genome search from BRAD data for the presence of flavonoid genes in B. rapa identified three candidate genes namely, DFR, TT1 and TT8 in the LG A9. Quantitative real-time PCR revealed absence of transcript for the late biosynthetic genes (LBGs) and showed significant reduction of transcript in the TT8 from the developing seeds of yellow-seeded line. While mapping of two DFR genes, the BjuA.DFR and BjuB.DFR did not show perfect co-segregation with the seed coat colour loci, that of the two TT8 genes, BjuA.TT8 and BjuB.TT8 showed perfect co-segregation with the seed coat colour phenotype. The BjuA.TT8 allele from the yellow-seeded line revealed the presence of an insertion of 1,279 bp in the exon 7 and did not produce any transcript as revealed by reverse transcriptase PCR. The BjuB.TT8 allele from the yellow-seeded line revealed the presence of an SNP (C→T) in the exon 7 resulting in a stop codon predicting a truncated protein lacking the C-terminal 8 amino acid residues and produced significantly low level of transcript than its wild-type counterpart. Hence, it is hypothesized that the mutations in both the TT8 genes are required for inhibiting the transcription of LBGs in the yellow-seeded mutant of B. juncea.

BACKGROUND: Depression is common among individuals with osteoarthritis and leads to increased healthcare burden. The objective of this study was to examine excess total healthcare expenditures associated with depression among individuals with osteoarthritis in the US. DESIGN: Adults with self-reported osteoarthritis (n= 1881) were identified using data from the 2010 Medical Expenditure Panel Survey (MEPS). Among those with osteoarthritis, chi-square tests and ordinary least square regressions (OLS) were used to examine differences in healthcare expenditures between those with and without depression. Post-regression linear decomposition technique was used to estimate the relative contribution of different constructs of the Anderson's behavioral model, i.e., predisposing, enabling, need, personal healthcare practices, and external environment factors, to the excess expenditures associated with depression among individuals with osteoarthritis. All analysis accounted for the complex survey design of MEPS. KEY RESULTS: Depression coexisted among 20.6 % of adults with osteoarthritis. The average total healthcare expenditures were $13,684 among adults with depression compared to $9284 among those without depression. Multivariable OLS regression revealed that adults with depression had 38.8 % higher healthcare expenditures (p<0.001) compared to those without depression. Postregression linear decomposition analysis indicated that 50 % of differences in expenditures among adults with and without depression can be explained by differences in need factors. CONCLUSIONS: Among individuals with coexisting osteoarthritis and depression, excess healthcare expenditures associated with depression were mainly due to comorbid anxiety, chronic conditions and poor health status. These expenditures may potentially be reduced by providing timely intervention for need factors or by providing care under a collaborative care model.

PURPOSE Germline mutations in the homologous recombination genes BRCA1, BRCA2, and PALB2 confer an increased risk for pancreatic ductal adenocarcinoma (PDAC). Tumors associated with mutations in homologous recombination genes are sensitive to DNA-damaging agents. We retrospectively studied patients with resected PDAC and a pathogenic germline mutation in one of these three genes. The planned analyses included overall survival (OS) and changes therein when platinum chemotherapy was used in the perioperative setting. MATERIALS AND METHODS Thirty-two individuals with pathogenic germline mutations in BRCA1, BRCA2, or PALB2 and resected PDAC (mutation positive) were matched in a 1:2 fashion to patients who were noncarriers or untested (mutation negative) by age, year of diagnosis, stage, and sex. Patients were identified via one of two available databases at University of Pennsylvania: the Basser Center for BRCA Registry or the electronic medical record. The primary outcome was OS. RESULTS Patients in the mutation-positive group had a median OS (mOS) of 46.6 months; those in the mutation-negative group had an mOS of 23.2 months (hazard ratio [HR], 0.49; 95% CI, 0.27 to 0.88). With platinum exposure in the perioperative setting, mOS in the mutation-positive group had not yet been met versus a mOS of 23.1 months in the mutation-negative group (HR, 0.12; 95% CI, 0.01 to 1.00). When neither group was treated with platinum, there was no significant OS difference between groups (HR, 0.52; 95% CI 0.12 to 2.24). Patients in the mutation-positive group who received perioperative treatment with platinum had a trend toward improved mOS compared with those who did not (HR, 0.15; 95% CI, 0.02 to 1.23; P = .07). CONCLUSION Platinum-based chemotherapy may confer a survival benefit in patients with resected PDAC and a pathogenic germline BRCA1, BRCA2, or PALB2 mutation. Knowledge of a germline mutation may be important to determine best choice of perioperative chemotherapy.

The objectives of this study are to illustrate the effects of immortal time bias (ITB) using an oncology outcomes database and quantify through simulations the magnitude and direction of ITB when different analytical techniques are used. A cohort of 11 626 women who received neoadjuvant chemotherapy and underwent mastectomy with pathologically positive lymph nodes were accrued from the National Cancer Database (2004-2008). Standard Cox regression, time-dependent (TD), and landmark models were used to compare overall survival in patients who did or did not receive postmastectomy radiation therapy (PMRT). Simulation studies showing ways to reduce the effect of ITB indicate that TD exposures should be included as variables in hazard-based analyses. Standard Cox regression models comparing overall survival in patients who did and did not receive PMRT showed a significant treatment effect (hazard ratio [HR]: 0.93, 95% confidence interval [CI]: 0.88-0.99). Time-dependent and landmark methods estimated no treatment effect with HR: 0.97, 95% CI: 0.92 to 1.03 and HR: 0.98, 95% CI, 0.92 to 1.04, respectively. In our simulation studies, the standard Cox regression model significantly overestimated treatment effects when no effect was present. Estimates of TD models were closest to the true treatment effect. Landmark model results were highly dependent on landmark timing. Appropriate statistical approaches that account for ITB are critical to minimize bias when examining relationships between receipt of PMRT and survival.

Background: Restless legs syndrome (RLS) is a common and distressing sensorimotor disorder of unknown etiology. While the epidemiology of RLS has been examined in several North American and European studies, research on RLS and RLS burden in poor, rural populations, including those residing in Appalachia, remains sparse. In this study, we investigated RLS prevalence in an Appalachian primary care population and examined the association of RLS to demographic factors, lifestyle characteristics, sleep quality, and mood disorders. Methods: Participants of this anonymous survey study were community-dwelling adults aged ≥ 18 years visiting one of 4 West Virginia primary care clinics. Data gathered included detailed information on sleep patterns, demographic characteristics, lifestyle factors, and health/medical history; the survey also included questions specifi c to RLS diagnosis and severity. Response rates were excellent, with 68% of eligible adults contacted returning completed surveys (N = 1,424/2,087). Pregnant women (N = 65) and those with missing data on key variables (N = 142) were excluded from the analyses. Results: Of the 1,217 participants included in the fi nal analytic sample, 19.6% (18.2% with symptoms at least once/month) met the 4 IRLSSG diagnostic criteria in the absence of positional discomfort or leg cramps; 14.5% reported RLS symptoms at least once/week and 10.1% indicated symptoms ≥ 3×/week. Excluding respondents with diabetes, kidney disease, or anemia