Common variant in GAB2 is associated with late-onset Alzheimer's disease in Han Chinese

BackgroundGRB-associated binding protein 2 (GAB2) may function as a risk factor in the pathogenesis of Alzheimer disease (AD). A recent large genome-wide association study (GWAS) has identified a significant association of rs10793294 polymorphism within the GAB2 gene with AD in Caucasians. While there are no studies on the association of rs10793294 polymorphism with AD risk in the Chinese population.MethodsThe study investigated 358 sporadic late-onset AD (LOAD) and 366 healthy controls matched for sex and age in a Han Chinese population. The rs10793294 polymorphism within the GAB2 gene was genotyped using MALDI-TOF mass spectrometry.ResultsThe C allele of the rs10793294 polymorphism within GAB2 was significantly associated with an increased risk of LOAD (OR = 1.33, 95% CI = 1.04–1.72, P = 0.029). Significance was observed in APOEε4 carriers (genotype P = 0.039, allele P = 0.016). While in APOE ε4 non-carriers, significant differences were observed in alleles (P = 0.039) but not in genotypes (P = 0.304). Logistic regression revealed that rs10793294 polymorphism was still strongly associated with LOAD in dominant model (OR = 2.58, 95% CI = 1.22–5.45, P = 0.013) and additive model (OR = 1.38, 95% CI = 1.05–1.80, P = 0.020) after adjusting for age, gender, and the APOE ε4 status.ConclusionsOur findings implicate GAB2 as a susceptibility gene for LOAD in Han Chinese.     

A single nucleotide polymorphism in LRP2 is associated with susceptibility to Alzheimer's disease in the Chinese population

BackgroundLRP2 (also called megalin) plays a potential key role in the pathogenesis of Alzheimer's disease (AD). Recently, one genome-wide association study has revealed that the rs3755166 (G/A) polymorphism located in the LRP2 promoter is associated with development of AD in Caucasians, while there are no studies on the association LRP2 of with AD risk in Asians.MethodsTo evaluate the relationship between the rs3755166 polymorphism of the LRP2 gene and AD in the ethnic Chinese Han, we conducted a case-control study (n = 361, age > 50) to determine the prevalence of one common single-nucleotide polymorphism (SNP) of LRP2 (rs3755166) in patients with AD in Chinese population of Mainland China, and clarified whether this polymorphism is a risk factor for AD.ResultsThe prevalence of the minor allele (A) in the rs3755166 polymorphism was significantly different in AD patients and control subjects (P < 0.05). The rs3755166 polymorphism was associated with AD in the ethnic Chinese Han (OR = 1.378, 95% CI: 1.017-1.867, P = 0.039), and the results were not influenced by age, gender, or APOE status (P = 0.441, P = 0.94, P = 0.432, respectively).ConclusionOur data revealed the allele (A) of the rs3755166 polymorphism within LRP2 gene may contribute to AD risk in the Chinese Han Population.     

APOC3 -482C>T polymorphism, circulating apolipoprotein C-III and smoking: interrelation and roles in predicting type-2 diabetes and coronary disease

ObjectivesWe determined the relationship of smoking status on APOC3 ­482C>T polymorphism and apolipoprotein C-III (apoC-III) concentrations and the latter two parameters’ influence on risk of diabetes and coronary heart disease (CHD).Design and methodsPrediction of incident cases was assessed at 5.5 years’ follow-up in unselected 519 individuals of a general population genotyped for ­482C>T polymorphism.ResultsFemale sex and current smoking were significantly associated with low circulating apoC-III in subjects without (p ≤ 0.033) than with abdominal obesity (p = 0.053) or than insulin resistant ­482TT homozygotes (p = 0.034) who had 20–30% higher serum apoC-III. Multi-adjusted serum apoC-III was log-linearly associated with fasting triglycerides. ApoC-III levels determined the development of diabetes [RR 1.56 (95%CI 1.21; 2.01)] and CHD [RR 1.38 (1.10; 1.72) for an increment of 14%], after adjustment for confounders.ConclusionAPOC3 ­482TT genotype is associated with high apoC-III concentrations only in the presence of abdominal obesity or insulin resistance, but not in current smokers who remain lean or insulin-sensitive. Rather than APOC3 ­482C>T polymorphism, circulating apoC-III determines cardiometabolic risk.     

Serum brain-derived neurotrophic factor in patients with type 2 diabetes mellitus: Relationship to glucose metabolism and biomarkers of insulin resistance

ObjectivesThe aims of this study were to measure serum levels of brain-derived neurotrophic factor (BDNF) in patients with type 2 diabetes mellitus (T2DM) and to investigate the association of these BDNF levels with biomarkers of glucose metabolism and insulin resistance.Design and methodsWe studied 112 patients with T2DM and 80 age- and gender-matched control subjects.ResultsSerum BDNF levels were significantly lower in patients with T2DM compared to control subjects (15.5 ± 5.2 ng/mL vs. 20.0 ± 7.3 ng/mL, P < 0.01). In patients with T2DM, BDNF levels were significantly higher in females than in males (P < 0.01). In the female patients, BDNF was positively related to immunoreactive insulin (IRI) (ρ = 0.458, P < 0.05) and HOMA-R (ρ = 0.444, P < 0.05). Stepwise multiple regression analysis showed a significant relationship between BDNF and IRI (F = 5.294, P < 0.05) in female patients with diabetes.ConclusionsThese findings suggest that BDNF may contribute to glucose metabolism.     

Association between serum retinol-binding protein 4 and small dense low-density lipoprotein cholesterol levels in young adult women

BackgroundSerum retinol-binding protein 4 (RBP4) and small dense low-density lipoprotein (sdLDL) have been suggested to be associated with insulin resistance, but no information is available on the relationship between RBP4 and sdLDL.MethodsWe determined serum RBP4, sdLDL-cholesterol, and other metabolic variables on 38 young women, aged 19–29 years. The homeostatic model assessment of insulin resistance (HOMA-IR) was used for the estimation of insulin resistance.ResultsIn simple regression analyses, RBP4 levels had significant correlations with total cholesterol (r = 0.354, P = 0.029), LDL-cholesterol (r = 0.396, P = 0.014), and sdLDL-cholesterol (r = 0.510, P = 0.001) levels. The sdLDL-cholesterol levels also correlated significantly with total cholesterol (r = 0.402, P = 0.012), LDL-cholesterol (r = 0.627, P < 0.001) and triglycerides (r = 0.449, P = 0.005). Stepwise multiple regression analyses showed only sdLDL-cholesterol (β coefficient (ß) = 0.510, P = 0.001) level was a significant independent predictor of RBP4 levels (adjusted R² = 0.240), whereas RBP4 (ß = 0.289, P = 0.026) level was one of major factors affecting sdLDL-cholesterol levels (adjusted R² = 0.519). There was no significant association of HOMA-IR with RBP4 or sdLDL levels.ConclusionsWe showed an independent linkage between serum RBP4 and sdLDL-cholesterol levels in young adult women. These findings may contribute to understanding of lipoprotein metabolisms involved in diabetes and cardiovascular disease.     

Monocyte chemoattractant protein 1-2518 A/G polymorphism and susceptibility to type 2 diabetes in a Chinese population

BackgroundHyperglycemia could accelerate monocyte chemoattractant protein 1 (MCP-1) production in monocytes and vascular endothelial cells. Recently, a genetic polymorphism (–2518 A/G) located in MCP-1 gene promoter has been found that could influence the expression of MCP-1. A large cohort study of Caucasians reported that MCP-1 G–2518 gene variant was negatively correlated with the prevalence of insulin resistance and type 2 diabetes. However, it is unclear whether this polymorphism is associated with type 2 diabetes in Han Chinese.MethodsWe conducted a population-based case–control study of 416 type 2 diabetes cases and 416 controls.ResultsCompared with the wild genotype AA, MCP-1 G–2518 gene variant could significantly decrease the prevalence of type 2 diabetes in Han Chinese (adjusted OR = 0.49, 95% CI 0.32–0.77, P < 0.0001). The results of stratified analyses indicated that a decreased risk of type 2 diabetes related with variant genotypes was evident in younger participants (age ≤ 50) (adjusted OR = 0.35, 95% CI 0.20–0.61, P < 0.0001), and similar results were observed in males (adjusted OR = 0.37, 95% CI 0.21–0.66, P = 0.001) and urban participants (adjusted OR = 0.35, 95% CI 0.21–0.58, P < 0.0001). In addition, a statistically significant difference was observed between MCP-1–2518 A/G polymorphism and waist to hip ratio.ConclusionsOur present pilot study indicated that MCP-1 G–2518 gene variant could significantly decrease the risk of type 2 diabetes in a Chinese population.     

VO(2)max in patients with chronic pain: comparative analysis with objective and subjective tests of disability

ObjectivesTo establish the level of maximal aerobic capacity in patients with chronic pain of different etiologies and to compare these results with different parameters of disability.Patients and methodsA cycloergometer exercise test with VO₂max measurement, fatigue assessment and objective and subjective disability parameter testing was performed on 155 patients (mean age 42.1 ± 9.9 years) classified into three groups: patients with chronic lower back pain, patients with an upper limb musculoskeletal disorder, and patients with multifocal chronic pain.ResultsThe mean VO₂max value was 22.18 mL/min/kg. There was no statistically significant difference in VO₂max between the three groups. The patients with poorest aerobic condition were older (P < 0.007), were on sick leave longer (P < 0.03), had weaker Sorensen test (P < 0.01) and P.I.L.E. (P < 0.004) results, had more perceived fatigue (P < 0.04), a higher mean BMI (P < 0.0001) and gained more weight during sick leave (P < 0.02).DiscussionNumerous studies have examined loss of aerobic capacity due to chronic low back pain with contradictory results. This is probably due to variability of in the methods used to measure or calculate VO₂max as well as to the variability in the studied populations.ConclusionIt seems appropriate to offer patients with chronic pain multidisciplinary exercise rehabilitation programs.     

A genetic variant in the gene encoding adrenomedullin predicts the development of dysglycemia over 6.4 years in Chinese

BackgroundAdrenomedullin, a vasodilatory peptide, facilitates the differentiation of pre-adipocytes, and affects lipolysis and glucose uptake. We investigated the association of common single nucleotide polymorphisms (SNPs) in the gene encoding adrenomedullin (ADM) with dysglycemia in the Hong Kong Chinese population.MethodsFour SNPs were genotyped in 1391 subjects without dysglycemia at baseline from the Hong Kong Cardiovascular Risk Factor Prevalence Study-2, which had a median follow-up time of 6.4 years. Dysglycemia included impaired fasting glucose, impaired glucose tolerance, and diabetes according to the WHO 1998 criteria. At follow-up, 382 subjects had developed dysglycemia.ResultsIn stepwise logistic regression, the SNP rs11042725 was a significant independent predictor of the development of dysglycemia (OR = 1.31, P = 0.012), together with baseline age (P < 0.001), plasma triglycerides (P < 0.001), body mass index (P = 0.004), 2-h glucose after oral glucose tolerance test (P < 0.001), homeostasis model assessment of insulin resistance index (P = 0.045), and follow-up duration (P = 0.009). The association was more significant in women (P = 0.002) and in subjects without regular exercise (P = 0.001).ConclusionsOur study suggests a potential role of genetic variants in the ADM gene in the development of dysglycemia in our local Chinese population.     

Association among retinol-binding protein 4, small dense LDL cholesterol and oxidized LDL levels in dyslipidemia subjects

ObjectivesTo investigate retinol-binding protein 4 (RBP4), small dense low-density lipoprotein cholesterol (sdLDL-C) and oxidized low-density lipoprotein (ox-LDL) levels and their associations in dyslipidemia subjects.Design and methodsWe determined RBP4, sdLDL-C, ox-LDL levels in 150 various dyslipidemia subjects and 50 controls. The correlation analysis and multiple linear regression analysis were performed.ResultsThe RBP4, sdLDL-C and ox-LDL levels were found increased in various dyslipidemia subjects. The sdLDL-C levels were positively correlated with RBP4 (r = 0.273, P = 0.001) and ox-LDL (r = 0.273, P = 0.001). RBP4 levels were also correlated with ox-LDL (r = 0.167, P = 0.043). The multiple regression analysis showed that only sdLDL-C was a significant independent predictor for RBP4 (β coefficient = 0.219, P = 0.009; adjusted R² = 0.041) and ox-LDL (β coefficient = 0.253, P = 0.003; adjusted R² = 0.057) levels, respectively.ConclusionsThe independent associations of sdLDL-C with RBP4 and ox-LDL were observed in dyslipidemia subjects. RBP4 may play an important role in lipid metabolism of atherosclerosis, particularly in formation of sdLDL.     

Characterization of chemosensory alterations in advanced cancer reveals specific chemosensory phenotypes impacting dietary intake and quality of life

ContextTaste and smell (chemosensory) alterations are common and distressing among advanced cancer patients, but their specific nature is poorly described and seldom linked to dietary intake. Details of altered chemosensory perception may help to explain food intake behaviors.ObjectivesOur goal was to characterize chemosensory alterations and their relationship with dietary intake and quality of life (QOL).MethodsAdult advanced cancer patients (n = 192) completed a chemosensory self-assessment questionnaire to characterize changes in their sense of smell and four basic tastes (sweet, sour, salty, and bitter) since the onset of cancer, three-day food record, and QOL questionnaire.ResultsPatients experienced either no alteration in any basic tastes and sense of smell sensations (26% of patients) or one of three altered chemosensory phenotypes: 1) stronger sensations overall (42%), 2) weaker sensations overall (18%), or 3) mixed (some sensations stronger and others weaker, 14%). For individual sensations (sweet, sour, salty, bitter, and smell), stronger sensation was twice more prevalent than weaker sensation (P = 0.035). Patients reporting chemosensory alteration consumed 20%–25% fewer calories per day (P = 0.0018), experienced greater weight loss (P = 0.0036), and had poorer QOL scores (P = 0.0176) compared with patients with no alterations, but results did not vary by chemosensory phenotype. Chemosensory alterations were not related to tumor type (P = 0.884), gender (P = 0.286), or nausea (P = 0.278).ConclusionChemosensory alterations predict dietary intake and QOL; the identification of chemosensory phenotypes provides a rationale to adjust the properties of foods and dietary recommendations in function of the specific nature of these changes.     

The feasibility and the effects of cycloergometer interval-training on aerobic capacity and walking performance after stroke. Preliminary study

BackgroundAfter stroke, the early and persistent decline in aerobic capacity leads to diminish walking capacities. The aim of the study is to investigate the effects of aerobic cycloergometer interval-training on the walking performances in subacute and chronic stroke survivors.MethodA prospective design was used. Fourteen patients whose stroke had occurred more than 3 months and less than 2 years performed an aerobic training session with a cycloergometer for 8 weeks. A maximal exercise test, a 6-min walking test, a 20-m test and an isokinetic muscle strength test were realized before and after training session.ResultsThere was a significant increase after aerobic training in maximal power (Pmax) (mean 23.2%, P < 0.0001), in VO_2peak (mean 14.8%, P = 0.04), and in the knee extension and flexion muscle peak torque on the nonparetic side and extension on the paretic side in isokinetic mode (mean from 13 to 29%, P = from 0.019 to P = 0.0007) and in the walking performances on the 6-min walk test (mean 15.8%, P = 0.0002).ConclusionPatients with subacute and chronic stroke can improve aerobic capacity, muscle strength and walking performances after cycloergometer interval-training. Although these results must be interpreted with caution considering the small size of our sample, they suggest that aerobic training is a safe and potentially effective training after stroke and an alternative to walking treadmill training.     

Gamma-glutamyl transferase level predicts the development of hypertension in Hong Kong Chinese

BackgroundPlasma activities of alkaline phosphatase, alanine aminotransferase (ALT), aspartate aminotransferase, and γ-glutamyl transferase (GGT) are often increased in cardiometabolic diseases. We investigated if hypertension is associated with increased activities of these plasma markers.MethodsWe included 235 hypertensive and 708 normotensive subjects (mean age 47.3 ± 9.6 and 58.0 ± 10.2 years respectively) from the Hong Kong Cardiovascular Risk Factor Prevalence Study-2 (CRISPS-2) in 2000–2004 who had drank < 1/week. In the follow-up study in 2005–2008 (CRISPS-3), 126 out of the 708 subjects had developed hypertension.ResultsRaised plasma ALT (OR = 1.22 per SD of log-transformed level, P = 0.045) and GGT (OR = 1.38 per SD of log-transformed level, P = 0.001) levels were associated with hypertension at baseline in CRISPS-2 after adjusting for covariates. Among subjects not on anti-hypertensive medications, plasma ALP, ALT and GGT were related to blood pressure (P < 0.01). In subjects normotensive at CRISPS-2, plasma GGT, but not ALP, ALT and AST, was an independent predictor of new-onset hypertension at CRISPS-3 (OR = 1.38 per SD of log-transformed level, P = 0.020 and OR = 2.68 for 3rd tertile vs. 1st tertile, P = 0.004) after adjusting for covariates.ConclusionsAmong the 4 plasma markers, increased GGT activity is the strongest predictor for existing and new-onset hypertension in Hong Kong Chinese.     

ChREBP gene polymorphisms are associated with coronary artery disease in Han population of Hubei province

BackgroudChREBP regulates lipogenesis and glucose utilization in the liver. Current reports suggest a contradictive association between rs3812316 of this gene and triglyceride level. We hypothesized the polymorphisms in ChREBP gene were associated with CAD in Chinese population.MethodsThe ChREBP gene polymorphisms were analyzed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods in 200 controls and 310 CAD patients. Serum lipids and glucose concentrations were measured in all subjects. Haplotypes were constructed based on rs3812316, rs7798357 and rs1051921. All the data were analyzed using SPSS14.0, PLINK1.07 and SHEsis software.ResultsThe rare allele G of rs3812316 was significantly lower in the CAD group after adjusting for age, sex, BMI, SBP and DBP (OR^a = 0.589, 95%CI = 0.361–0.961, P = 0.034). No significant differences between cases and controls were found in genotype or allele distributions of rs7798357, rs17145750 and rs1051921. Haplotype CGC was significant higher in CAD group (P < 0.01, OR = 2.364, 95%CI = 1.608–3.474), while haplotypes GGC, CGT, CCC were significant lower in CAD group (P < 0.05).ConclusionsThe rs3812316 and the haplotypes in ChREBP gene appeared to be related to high susceptibility to CAD.     

Pro-inflammatory and anti-inflammatory cytokines in acute ischemic stroke and their relation to early neurological deficit and stroke outcome

ObjectivesOur aim was to explore (i) the difference in concentration of IL-6, TNF-α and IL-10 between acute ischemic stroke patients and control individuals; (ii) the association of plasma cytokine concentration with stroke severity at admission assessed by NIHSS and stroke outcome in 90 days assessed by Barthel index (BI) and modified Rankin scale (mRS).Materials and methodsStudy included 68 stroke patients admitted within 12 h of symptoms onset and 71 controls.ResultsIL-6 was increased in patients relative to controls (P = 0.035) and this increase was associated with severe stroke (P = 0.007) and worse outcome (P = 0.030 and 0.019; assessed by BI and mRS, respectively), whereas IL-10 was decreased (P = 0.044) and associated with better outcome (P = 0.043). TNF-α did not differ between studied groups (P = 0.302).ConclusionsIncreased IL-6 and reduced IL-10 concentrations are present in early stroke period and are associated with a degree of neurological deficit and/or stroke outcome.     

Association between serum cortisol and testosterone levels, opioid therapy, and symptom distress in patients with advanced cancer

ContextPatients with advanced cancer often experience symptoms such as pain, anorexia, and fatigue. Opioid therapy for the management of cancer pain may result in neurohormonal dysfunction that may contribute to a patient’s symptom burden.ObjectivesTo examine the association between serum cortisol and testosterone levels, opioid therapy, and symptom distress in patients with cancer.MethodsA retrospective chart review was performed on 77 consecutive patients with advanced cancer referred for symptoms of fatigue or cachexia. We collected information regarding cortisol levels (am or random), testosterone levels (men only), morphine equivalent daily dose (MEDD), and symptom severity measured by the Edmonton Symptom Assessment Scale. Nonparametric correlation analysis was performed.ResultsThe median age was 63 years (range 24–79), and 62% were men (n = 48). Most patients had gastrointestinal (n = 33, 43%) or thoracic (n = 21, 27%) malignancies and were Caucasian (n = 46, 60%). The median random cortisol level was 19.1 μg/dL (Q1–Q3, 13.4–23.8 [normal, 4.3–22.4]), which correlated with MEDD (Spearman coefficient, 0.25, P = 0.032) and symptoms including pain (0.50, P < 0.001), fatigue (0.29, P = 0.012), nausea (0.34, P = 0.003), depression (0.24, P = 0.032), and anxiety (0.25, P = 0.031). Pain and nausea remained significant after Bonferroni correction. Median morning cortisol level (n = 28) was 20.6 μg/dL (Q1–Q3, 16.6–25.4) and significantly correlated with pain (0.55, P = 0.003) after Bonferroni correction. Patients with a MEDD <30 mg/day had a mean random cortisol level of 16.6 μg/dL, whereas patients with a MEDD ≥30 mg/day had a mean random cortisol level of 20.6 μg/dL (P = 0.01). In 44 male patients with cancer, MEDD was inversely correlated with the total testosterone level (?0.52, P = 0.001).ConclusionIn patients with advanced cancer, elevated random cortisol levels were associated with pain and opioid use, although abnormally low levels of cortisol were found to be infrequent. Patients on higher opioid therapy (MEDD >30) had increased cortisol levels, and male patients had lower testosterone levels. Our study suggests that opioid therapy in patients with advanced cancer may inhibit gonadal function while sparing the adrenal axis. Future studies are needed.     

Identification of pharmacogenetic predictors of lipid-lowering response to atorvastatin in Chilean subjects with hypercholesterolemia

BackgroundStatins are normally the first-line therapy for hypercholesterolemia (HC); however, the lipid-lowering response shows high interindividual variation. We investigated the effect of four polymorphisms in CYP3A4, CYP3A5 and ABCB1 genes on response to atorvastatin and CYP3A4 activity in Chilean subjects with HC.MethodsA total of 142 hypercholesterolemic individuals underwent atorvastatin therapy (10 mg/day/1 month). Serum lipid levels before and after treatment were measured. Genetic variants in CYP3A4 (? 290A>G, rs2740574), CYP3A5 (6986A>G, rs776746) and ABCB1 (2677G>A/T, rs2032582 and 3435C>T, rs1045642) were analyzed by PCR-RFLP. CYP3A4 enzyme activity in urine samples was assessed through determination of 6β-hydroxycortisol/cortisol free ratio (6βOHC/FC).ResultsAfter 4 weeks of therapy, a significant reduction in total cholesterol (TC) and LDL-c was observed (P < 0.001). The G allele for ? 290A>G polymorphism was related to higher percentage of variation in TC and LDL-c (P < 0.001). Moreover, same allele was associated with higher HDL-c variation (P = 0.017). In addition, CYP3A4 enzyme activity was lower in subjects carrying this polymorphism (P = 0.009). No differences were observed for CYP3A5 and ABCB1 variants.ConclusionOur results suggest that presence of G allele for ? 290A>G polymorphism determines a better response to atorvastatin, being also associated with lower CYP3A4 activity in vivo, causing an increased atorvastatin activity.     

Association study: SLC6A18 gene and myocardial infarction

ObjectiveSLC6A18 (solute carrier family 6, member 18) acts as a specific transporter for neurotransmitters, amino acids and osmolytes such as betaine, taurine and creatine. The aim of the present study was to investigate the relationship between the human SLC6A18 gene and myocardial infarction (MI) in a Japanese population.MethodsUsing 5 single nucleotide polymorphisms in the SLC6A18 gene (rs7728646, rs4975625, rs12522796, rs4975623 and rs7447815) we performed a case-control study based on each SNP and haplotype in 289 MI patients and 223 controls.ResultsLogistic regression analysis revealed that the frequency of the CC + CG genotype of rs7447815 was significantly higher in all patients and the male MI patients than in controls (P = 0.005, P = 0.036, respectively). The frequency of the T-C haplotype (rs7728646–rs7447815) was significantly higher for the MI patients when compared with controls (P = 0.037).ConclusionsThese results suggest that SLC6A18 or neighboring genes are associated with increased susceptibility to MI.     

Exploring generalizability in a study of costs for community-based palliative care

ContextPalliative care researchers face challenges recruiting and retaining study subjects.ObjectivesThis article investigates selection, study site, and participation biases to assess generalizability of a cost analysis of palliative care program (PCP) clients receiving care at home.MethodsStudy subjects’ sociodemographic, geographic, survival, disease, and treatment characteristics were compared for the same year and region with those of three populations. Comparison I was with nonstudy subjects enrolled in the PCP to assess selection bias. Comparison II was with adults who died of cancer to assess study site bias. Comparison III was with study-eligible persons who declined to participate in order to assess participation bias.ResultsComparison I: When compared with the other 1010 PCP clients, the 50 study subjects were on average 3.6 years younger (P = 0.03), enrolled 70 days longer in the PCP (P < 0.001), lived 6.7 km closer to the PCP (P < 0.0001), and were more likely to have cancer (96.0% vs. 86.4%, P = 0.05). Comparison II: Compared with all cancer decedents, the 45 study subjects who died of cancer were on average 7.0 years younger (P < 0.001), lived 2.7 km closer to the PCP (P < 0.001), and were more likely to have had radiotherapy (62.2% vs. 33.8%, P < 0.0001) and medical oncology (28.9% vs. 14.8%, P = 0.01) consultations. Comparison III: The 50 study subjects lived on average 42 days longer after their diagnosis (P = 0.03) and 2.6 km closer to the PCP (P = 0.01) than the 110 eligible persons who declined to participate.ConclusionIf the study findings are applied to populations that differ from the study subjects, inaccurate conclusions are possible.     

Association between self-reported sleep disturbance and other symptoms in patients with advanced cancer

ContextSleep disturbance (SD) is a significant source of distress for patients with cancer. Studies of patients with advanced cancer receiving palliative care to identify symptoms associated with the severity of SD are limited.ObjectivesIn this study, we sought to identify the symptoms measured by the Edmonton Symptom Assessment Scale (ESAS) that are associated with SD, as measured by the Pittsburgh Sleep Quality Index (PSQI). Secondary aims of the study were to determine the association between occurrences of SD with occurrences of other symptoms and screening performance of the ESAS-Sleep item against the PSQI.MethodsWe reviewed the completed ESAS and PSQI assessments of 101 patients with advanced cancer who were receiving palliative care and had been admitted to prospective clinical trials previously initiated by us. Patients with a PSQI score of ≥5 were considered to have an SD. The frequency and severity of the ESAS symptoms items, their correlation with each other, the PSQI score, and the screening performance of the ESAS-Sleep item were calculated.ResultsThe median age of patients was 60 years. Most were white non-Hispanic (73%), had lung or breast cancer (41%), and were diagnosed with SD (85%). The PSQI score was correlated with the ESAS items of pain (r = 0.27, P = 0.006), dyspnea (r = 0.25, P < 0.001), well-being (r = 0.35, P < 0.0001), and sleep (r = 0.44, P < 0.0001). Compared with patients without SD, those with SD were more likely to report pain (P = 0.0132), depression (P = 0.019), anxiety (P = 0.01), and a poorer sense of well-being (P = 0.035). An ESAS-Sleep item cutoff score of ≥3 (of 10) resulted in a sensitivity of 74% and a specificity of 73%.ConclusionSD is associated with increased frequency of pain, depression, anxiety, and a worse sense of well-being. These four symptoms should be assessed in all patients with advanced cancer with a complaint of SD. The ideal cutoff point of the ESAS-Sleep item for screening for SD is a score of ≥3. More research is needed to better characterize this frequent and distressing syndrome.