Predicting Hypothetical Willingness to Participate (WTP) in a Future Phase III HIV Vaccine Trial Among High-Risk Adolescents

The present study sought to determine whether the Theory of Planned Behaviour predicted stated hypothetical willingness to participate (WTP) in future Phase III HIV vaccine trials among South African adolescents. Hierarchical logistic regression analyses showed that The Theory of Planned Behaviour (TPB) significantly predicted WTP. Of all the predictors, Subjective norms significantly predicted WTP (OR = 1.19, 95% C.I. = 1.06–1.34). A stepwise logistic regression analysis revealed that Subjective Norms (OR = 1.19, 95% C.I. = 1.07–1.34) and Attitude towards participation in an HIV vaccine trial (OR = 1.32, 95% C.I. = 1.00–1.74) were significant predictors of WTP. The addition of Knowledge of HIV vaccines and HIV vaccine trials, Perceived self-risk of HIV infection, Health-promoting behaviours and Attitudes towards HIV/AIDS yielded non-significant results. These findings provide support for the Theory of Reasoned Action (TRA) and suggest that psychosocial factors may play an important role in WTP in Phase III HIV vaccine trials among adolescents.     

Diabetes mellitus and risk of bladder cancer: a meta-analysis

Aims/hypothesis Epidemiological evidence indicates that individuals with diabetes mellitus have an increased risk of several cancers. We performed a systematic review with meta-analysis to evaluate the association between diabetes and risk of bladder cancer.Methods Pertinent studies were identified by searching MEDLINE (from January 1966 to July 2006) and by reviewing the reference lists of retrieved articles. We included case–control and cohort studies reporting relative risk (RR) estimates with 95% CIs (or data to calculate them) of bladder cancer associated with diabetes. Studies of type 1 diabetes were not included. Summary RRs were calculated using a random-effects model.Results A total of 16 studies (seven case–control studies, three cohort studies and six cohort studies of diabetic patients) fulfilled the inclusion criteria. Analysis of all studies showed that diabetes was associated with an increased risk of bladder cancer, compared with no diabetes (RR = 1.24, 95% CI 1.08–1.42). There was strong evidence of heterogeneity among these studies (p < 0.0001). Stratification by study design found that diabetes was associated with an increased risk of bladder cancer in case–control studies (RR = 1.37, 95% CI 1.04–1.80, p _{heterogeneity} = 0.005) and cohort studies (RR = 1.43, 95% CI 1.18–1.74, p _{heterogeneity} = 0.17), but not in cohort studies of diabetic patients (RR = 1.01, 95% CI 0.91–1.12, p _{heterogeneity} = 0.35).Conclusions/interpretation Findings from this meta-analysis suggest that individuals with diabetes may have a modestly increased risk of bladder cancer.Electronic supplementary material Supplementary material is available in the online version of this article at and is accessible to authorised users.     

A systematic review and meta-analysis of rituximab-based immunochemotherapy for subtypes of diffuse large B cell lymphoma

Addition of rituximab to chemotherapy (R-chemo) has been shown to improve overall survival (OS) in patients with diffuse large B cell lymphoma (DLBCL). Germinal center B cell-like (GCB) subtype of DLBCL has a significantly better clinical outcome than those with non-germinal center B cell-like (non-GCB) subtype. Further research is needed to confirm this difference between those two subtypes treated with R-chemo. We searched for randomized controlled trials that compared R-chemo with identical chemotherapy alone in patients with newly diagnosed or relapsed DLBCL. A random versus fixed effects model was selected according to heterogeneity. Six eligible trials involving 748 adult patients were included in this meta-analysis. Fixed-effects analysis showed OS to be superior for the GCB patients treated with R-chemo (relative risk (RR) = 1.16, 95% confidence interval (CI) = 1.03–1.31, P = 0.02). Superiority was also observed for the GCB subtype under R-chemo with respect to disease control (RR = 1.16, 95% CI = 0.99–1.36) and overall response (RR = 1.19, 95% CI = 0.99–1.99). Both subtypes showed an increased OS (RR = 1.30, 95% CI = 1.11–1.51; RR = 1.89, 95% CI = 1.52–2.35, respectively) and disease control rate (RR = 1.27, 95% CI = 1.05–1.54, P = 0.01; RR = 2.21, 95% CI = 1.68–2.90, respectively) following R-chemo. Therefore, treated with R-chemo, GCB patients still has a significantly better clinical outcome than those with non-GCB subtype.     

Meta-analysis of medical treatment and placebo treatment for preventing postoperative recurrence in Crohn’s disease (CD)

Introduction  We performed a meta-analysis to compare the clinical and endoscopic recurrence of medical treatment and placebo treatment for preventing postoperative recurrence in Crohn’s disease. Materials and methods  Trials were located through Medline, Embase, the Cochrane Central Register of Controlled Trials, Ovid, Sciencedirect, and Ingenta electronic databases. From 124 articles screened, 14 were identified as randomized placebo-controlled trials and were included for data extraction. Main outcome measures were clinical recurrence, endoscopic recurrence, and severe endoscopic recurrence. The meta-analysis was performed with the fixed-effects model. Result  Fourteen studies with 1,497 participants were analyzed. In the intention-to-treat analysis, medical treatment was associated with a significantly lower incidence of clinical recurrence (relative risk of 0.74, 95% confidence interval 0.64–0.87, P = 0.000], but there were no significant differences in endoscopic recurrence (0.94, 0.83–1.07, P = 0.353) and severe endoscopic recurrence (0.83, 0.60–1.16, P = 0.281) between the two groups. When using per-protocol analysis, the results is similar, medical treatment was associated with a significantly lower incidence of clinical recurrence (0.84, 0.72–0.97, P = 0.020), but there were no significant differences in endoscopic recurrence (0.94, 0.85–1.05, P = 0.268) or severe endoscopic recurrence (0.76, 0.55–1.04, P = 0.084) between the two groups of patients. Conclusions  Medical treatment has a sufficiently beneficial effect on decreasing the risk of clinical postoperative recurrence in patients with CD.     

Methodological quality of randomised controlled trials comparing short-term results of laparoscopic and conventional colorectal resection

Background  Randomised, controlled trials (RCT) and systematic reviews of RCT with meta-analysis are considered to be of highest methodological quality and therefore are given the highest level of evidence (Ia/b). Although, “low-quality” RCT may be downgraded to level of evidence IIb, the methodological quality of each individual RCT is not respected in detail in this classification of the level of evidence. Materials and methods  Within a systematic Cochrane Review of RCT on short-term benefits of laparoscopic or conventional colorectal resections, the methodological quality of all included RCT was evaluated. All RCT were assessed by the Evans and Pollock questionnaire (E and P increasing quality from 0–100) and the Jadad score (increasing quality from 0–5). Results  Publications from 28 RCT printed from 1996 to 2005 were included in the analysis. Methodological quality of RCT was only moderate [E & P 55 (32–84); Jadad 2 (1–5)]. There was a significant correlation between the E & P and the Jadad score (r = 0.788; p < 0.001). Methodological quality of RCT slightly increased with increasing number of patients included (r = 0.494; p = 0.009) and year of publication (r = 0.427; p = 0.03). Meta-analysis of all RCT yielded clinically relevant differences for overall and local morbidity when compared to meta-analysis of “high-quality” (E & P > 70) RCT only. Conclusion  The methodological quality of reports of RCT comparing laparoscopic and open colorectal resection varies considerably. In a systematic review, methodological quality of RCT should be assessed because meta-analysis of “high-quality” RCT may yield different results than meta-analysis of all RCT. This paper was presented during the Surgical Forum of 122nd Congress of the German Surgical Society in Berlin in May 2006.     

Voluntary HIV Testing Among Adults with Severe Mental Illness: Frequency and Associated Factors

Adults with severe mental illness (SMI) are disproportionately affected by HIV/AIDS. This study describes the frequency and associated factors of HIV testing among psychiatric outpatients (N = 150) in a small Northeastern city. A structured clinical interview assessed demographic, psychosocial, behavioral, and psychiatric factors. In the past year, 41% of participants were HIV tested. A hierarchical linear regression model revealed the following multivariate correlates: lower educational attainment, HIV risk behavior, greater social support, homelessness, non-psychotic disorder, borderline personality disorder, and greater treatment utilization. Psychiatric factors remained significant correlates of HIV testing after accounting for psychosocial and behavioral factors. Although HIV testing occurred among a substantial proportion of participants, 45% of individuals who engaged in HIV risk behavior were not tested in the past year. Adults with SMI are in need of interventions promoting routine HIV testing and risk-reduction counseling.     

Haemoglobin levels are associated with bone mineral density in the elderly: a population-based study

Hypoxemia has been associated with low bone mineral density (BMD) in animal and human models. We assessed the association of haemoglobin levels with ultrasound-derived (UD) T score, Z score and the stiffness index in all 358 subjects aged 75+ living in Tuscania (Italy). Also, we searched for the haemoglobin cutoff levels that might best identify participants with osteoporosis. In the multivariable linear regression analysis, haemoglobin levels were associated among participants with the UD T score [β = 0.13; 95% confidence interval (CI) = 0.01–0.25; p = 0.030], Z score (β = 0.11; 95% CI = 0.01–0.22; p = 0.045) and stiffness index (β = 1.87; 95% CI = 0.51–3.21; p = 0.007) after adjusting for potential confounders. Haemoglobin levels <140 g/L in men and <130 g/L in women best predicted osteoporosis in linear discriminant analysis. Haemoglobin is independently associated with all UD-BMD parameters. Haemoglobin levels <140 g/L in men and 130 g/L in women might be adopted in clinical practice to identify older subjects in whom screening for osteoporosis might yield higher effectiveness.     

The efficacy of diltiazem and glyceryltrinitrate for the medical management of chronic anal fissure: a meta-analysis

Objective The objective of this review is to systematically analyze the prospective randomized controlled trials on the effectiveness of diltiazem (DTZ) and glyceryltrinitrate (GTN) for the pharmacological management of chronic anal fissure (CAF). Materials and methods A systematic review of the literature was undertaken. Prospective randomized controlled trials on the effectiveness of DTZ for the management of CAF were selected according to specific criteria and analyzed to generate summative data. Results Five studies encompassing 263 patients with CAF were retrieved from the electronic databases. Only two randomized controlled trials on 103 patients qualified for the meta-analysis. There were 53 patients in the DTZ group and 50 patients in the GTN group. Both DTZ and GTN were equally effective for the treatment of CAF (random-effect model risk ratio [RR] 0.29 [90.06–1.33] 95% confidence interval [CI], z = 0.62, p = 0.536). However, there was significant heterogeneity between the trials. GTN was associated with higher side effects rate (fixed-effect model RR 0.45 [0.28–0.73] 95% CI, z = −3.22, p = 0.001) and higher headache rate (fixed-effect model RR 0.33 [0.17–0.64] 95% CI, z = −3.27, p = 0.001) as compared to DTZ. There was no statistically significant recurrence rate of CAF between two pharmacotherapies (fixed-effect model RR 0.66 [0.18–2.41] 95% CI, z = −0.62, p = 0.535). Conclusion Both DTZ and GTN are equally effective and can be used for the management of CAF. However, GTN is associated with a higher rate of side effects (headache/anal irritation), and it should be replaced by DTZ. The recurrence rate of CAF after the use of both pharmacotherapies is equal.     

Lipoprotein receptor associated protein (LRPAP1) insertion/deletion polymorphism: association with gallbladder cancer susceptibility

Background Low-density lipoprotein receptor-related protein associated protein (LRPAP1) insertion/deletion polymorphism influences cholesterol homeostasis and may confer risk for gallstone disease and gallbladder carcinoma (GBC) incidence usually parallels with the prevalence of cholelithiosis. Aim We aimed to examine the role of LRPAP1 polymorphism in susceptibility to GBC. Methods Present case control study included 129 proven GBC patients, 183 gallstone patients, and 208 healthy controls. Genotyping was done by polymerase chain reaction–restriction fragment length polymorphism method. Results The D allele of LRPAP1 was significantly higher in GBC patients as compared to gallstone patients (p = 0.013; OR = 1.6, 95% CI = 1.1–2.4). However, II genotype and I allele was associated with reduced risk of GBC as compared to gallstone patients (p = 0.002; OR = 0.1, 95% CI = 0.1–0.6; p = 0.013; OR = 0.6, 95% CI = 0.4–0.8) The increased risk due to D allele was limited to female GBC patients (p = 0.021; OR = 1.8, 95% CI = 1.1–3.0). However, reduced risk due to II genotype and I allele was observed which was also confined to female GBC patients (p = 0.005; OR = 0.1, 95% CI = 0.1–0.6; p = 0.021; OR = 0.5, 95% CI = 0.3–0.8). On comparing GBC patients having gallstone with gallstone patients, high risk was observed in the GBC patients having gallstone due to the presence of D allele (p = 0.032; OR = 1.7, 95% CI = 1.0–2.8). However, low risk was observed because of I allele in GBC patients with gallstone in comparison to gallstone patients (p = 0.032, OR = 0.6, 95% CI = 0.4–0.9). Conclusion It appears that ‘D’ allele may modulate the susceptibility of GBC, and the risk is independent to genetic risk of gallstone.     

Polymorphisms in the gene encoding the voltage-dependent Ca<Superscript>2+</Superscript> channel Ca<Subscript>V</Subscript>2.3 (<Emphasis Type="Italic">CACNA1E</Emphasis>) are associated with type 2 diabetes and impaired insulin secretion

Aims/hypothesis Glucose-stimulated insulin secretion is dependent on the electrical activity of beta cells; hence, genes encoding beta cell ion channels are potential candidate genes for type 2 diabetes. The gene encoding the voltage-dependent Ca²⁺ channel Ca_V2.3 (CACNA1E), telomeric to a region that has shown suggestive linkage to type 2 diabetes (1q21-q25), has been ascribed a role for second-phase insulin secretion. Methods Based upon the genotyping of 52 haplotype tagging single nucleotide polymorphisms (SNPs) in a type 2 diabetes case–control sample (n = 1,467), we selected five SNPs that were nominally associated with type 2 diabetes and genotyped them in the following groups (1) a new case–control sample of 6,570 individuals from Sweden; (2) 2,293 individuals from the Botnia prospective cohort; and (3) 935 individuals with insulin secretion data from an IVGTT. Results The rs679931 TT genotype was associated with (1) an increased risk of type 2 diabetes in the Botnia case–control sample [odds ratio (OR) 1.4, 95% CI 1.0–2.0, p = 0.06] and in the replication sample (OR 1.2, 95% CI 1.0–1.5, p = 0.01 one-tailed), with a combined OR of 1.3 (95% CI 1.1–1.5, p = 0.004 two-tailed); (2) reduced insulin secretion [insulinogenic index at 30 min p = 0.02, disposition index (D _I) p = 0.03] in control participants during an OGTT; (3) reduced second-phase insulin secretion at 30 min (p = 0.04) and 60 min (p = 0.02) during an IVGTT; and (4) reduced D _I over time in the Botnia prospective cohort (p = 0.05). Conclusions/interpretation We conclude that genetic variation in the CACNA1E gene contributes to an increased risk of the development of type 2 diabetes by reducing insulin secretion. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

Long-term follow-up of allogeneic HSCT for CML reveals significant improvement in the outcome over the last decade

Allogeneic hematopoetic stem cell transplantation (HSCT) is still the only curative therapeutic option for chronic myelogenous leukemia (CML). To examine the development of allogeneic HSCT at our center over the past two decades (decade 1: 1984–1994; decade 2: 1995–2005), all CML patients transplanted in first chronic phase (n = 234) were analyzed with respect to patient characteristics, overall survival, transplant-related mortality (TRM), and relapse incidence. The median follow up time was 54 months (range 1–218). The incidence of acute graft vs host disease (GvHD) °II–IV and extensive chronic GvHD were not different between the two decades (p = 0.894 and p = 0.422, respectively). There was also no difference in the relapse incidence (23 vs 26%, p = 0.869). One-year TRM and overall survival were improved in the later decade (33 vs 18%, p = 0.011 and 62 vs 73% at 5 years, p = 0.063, respectively). The major reason for improved outcome in decade 2 was the improved management of acute GvHD and infections in the early phase after transplantation (p = 0.026). In conclusion, the past decade has seen significant improvement in the performance of allogeneic HSCT for CML.     

Hyperglycaemia is associated with changes in the regional concentrations of glucose and myo-inositol within the brain

Aims/hypothesis  The aim of the study was to assess the effect of hyperglycaemia on regional concentrations of glucose and other substrates within the brain in non-diabetic individuals and in patients with type 1 diabetes. Methods  The brain metabolites of 17 men with type 1 diabetes and 12 age-matched non-diabetic men (22–43 years old) were studied after an overnight fast (plasma glucose 9.2 ± 3.0 vs 4.8 ± 0.5 mmol/l, respectively). N-Acetylaspartate (NAA), creatine, choline, myo-inositol (mI) and glucose in the frontal cortex, frontal white matter and thalamus were quantified with proton magnetic resonance spectroscopy. Results  In the non-diabetic participants, the glucose level was 47% higher (p < 0.01) in the frontal cortex than in the frontal white matter. In contrast, this regional variation was not observed in the diabetic participants, in whom the glucose level in the frontal white matter was 64% higher (p < 0.001) and in the frontal cortex 25% higher (p = 0.033) than that of the non-diabetic participants. In the diabetic participants, the glucose level in each of the three regions studied correlated with fasting plasma glucose (r = 0.88–0.67, p < 0.01). In addition, in the diabetic participants, mI was 20% higher (p < 0.001) and NAA 6% lower (p = 0.037) in the frontal white matter, and mI was 8% higher (p = 0.042) in the frontal cortex, than in the non-diabetic participants. Conclusions/interpretation  In type 1 diabetes, hyperglycaemia is associated with accumulation of glucose and mI in the cortex and in the white matter. The results of this study were presented in abstract form at the 17th Annual Meeting of the Diabetic Neuropathy Study Group (NEURODIAB) of the EASD in Utrecht, the Netherlands, 14–16 September 2007.     

The Association Between the Receipt of Lipid Lowering Therapy and HIV Status Among Veterans Who Met NCEP/ATP III Criteria for the Receipt of Lipid Lowering Medication

OBJECTIVE  To examine the association between HIV infection status and the receipt of lipid lowering therapy based on National Cholesterol Education Program/Adult Treatment Panel (NCEP/ATP III) guidelines and to assess whether HIV viral load and hepatitis C (HCV) status alters that association. PARTICIPANTS AND DESIGN  A cross-sectional analysis of survey, laboratory, and pharmacy data from 1,577 male participants (59% HIV infected) of the Veterans Aging Cohort Five-Site Study, a prospective observational cohort of U.S. veterans with and without HIV infection. MEASUREMENTS  Receipt of lipid lowering therapy obtained from the VA pharmacy benefits management system was the main outcome. RESULTS  The prevalence of lipid lowering therapy among HIV-infected and HIV-uninfected veterans was 15.4% vs. 37.9%, respectively, p < 0.01. Among veterans who met NCEP/ATP III criteria for lipid lowering therapy, HIV-infected veterans had a significantly lower prevalence for the receipt of lipid lowering therapy (adjusted odds ratio (OR) = 0.43, 95% confidence interval (C.I.) 0.28–0.67) as compared with HIV-uninfected veterans. Among HIV-infected veterans, log HIV viral load (adjusted OR = 0.57, 95% CI, 0.41–0.81) and HIV-HCV co-infection (adjusted OR = 0.31, 95% CI = 0.13–0.75) were negatively associated with receipt of lipid lowering therapy. Exposure to HAART was not associated with receipt of lipid lowering therapy. CONCLUSIONS  Among those who met NCEP/ATP III criteria for lipid lowering therapy, HIV-infected veterans, particularly those with high HIV viral loads and HCV co-infection, were significantly less likely to receive lipid lowering therapy. This may be a modifiable mediator of cardiovascular disease among HIV-infected individuals.     

Effect of Rater Training on Reliability and Accuracy of Mini-CEX Scores: A Randomized, Controlled Trial

Background  Mini-CEX scores assess resident competence. Rater training might improve mini-CEX score interrater reliability, but evidence is lacking. Objective  Evaluate a rater training workshop using interrater reliability and accuracy. Design  Randomized trial (immediate versus delayed workshop) and single-group pre/post study (randomized groups combined). Setting  Academic medical center. Participants  Fifty-two internal medicine clinic preceptors (31 randomized and 21 additional workshop attendees). Intervention  The workshop included rater error training, performance dimension training, behavioral observation training, and frame of reference training using lecture, video, and facilitated discussion. Delayed group received no intervention until after posttest. Measurements  Mini-CEX ratings at baseline (just before workshop for workshop group), and four weeks later using videotaped resident–patient encounters; mini-CEX ratings of live resident–patient encounters one year preceding and one year following the workshop; rater confidence using mini-CEX. Results  Among 31 randomized participants, interrater reliabilities in the delayed group (baseline intraclass correlation coefficient [ICC] 0.43, follow-up 0.53) and workshop group (baseline 0.40, follow-up 0.43) were not significantly different (p = 0.19). Mean ratings were similar at baseline (delayed 4.9 [95% confidence interval 4.6–5.2], workshop 4.8 [4.5–5.1]) and follow-up (delayed 5.4 [5.0–5.7], workshop 5.3 [5.0–5.6]; p = 0.88 for interaction). For the entire cohort, rater confidence (1 = not confident, 6 = very confident) improved from mean (SD) 3.8 (1.4) to 4.4 (1.0), p = 0.018. Interrater reliability for ratings of live encounters (entire cohort) was higher after the workshop (ICC 0.34) than before (ICC 0.18) but the standard error of measurement was similar for both periods. Conclusions  Rater training did not improve interrater reliability or accuracy of mini-CEX scores. Clinical trials registration  clinicaltrials.gov identifier NCT00667940 Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Interstitial lung disease in polymyositis and dermatomyositis

The aim of the study was to estimate the prevalence, characteristics, and prognostic factors of interstitial lung disease (ILD) in patients with polymyositis (PM) and dermatomyositis (DM). The medical records of 151 PM/DM patients treated at Chang Gung Memorial Hospital between January, 2000 and June, 2007 were retrospectively reviewed. Thirty of 151 (19.9%) PM/DM patients had developed ILD. Older age at PM/DM onset, anti-Jo-1 antibody, and arthritis/arthralgia were associated with the presence of ILD (p = 0.004, p = 0.008, and p = 0.026, respectively). Anti-Jo-1 was initially excluded from the multivariate analysis because only 80 patients underwent the test. An older age at onset above 45 years (odds ratio 3.28, 95% confidence interval (CI) 1.15–9.34, p = 0.026) and arthritis/arthralgia at onset (odds ratio (OR) 2.57, 95% CI 1.09–6.08, p = 0.032) were the two independent risk factors for developing ILD. If anti-Jo-1 was included in the multivariate analysis (n = 80), then an older age at onset above 45 years (OR 7.30, 95% CI 1.70–31.40, p = 0.008) and anti-Jo-1 positive (OR 7.89, 95% CI 1.18–52.87, p = 0.033) were associated with ILD, while arthritis/arthralgia was no longer significant (OR 2.64, 95% CI 0.70–10.01, p = 0.153). Of the 30 ILD patients, 16 (53.3%) died. The survival time was significantly shorter in ILD patients than in patients without ILD (p < 0.001). Poor survival in ILD patients was associated with male gender (p = 0.039), a Hamman–Rich-like presentation (p = 0.039), and a clinical diagnosis of acute interstitial pneumonia (p = 0.007).     

Midlife muscle strength and human longevity up to age 100 years: a 44-year prospective study among a decedent cohort

We studied prospectively the midlife handgrip strength, living habits, and parents’ longevity as predictors of length of life up to becoming a centenarian. The participants were 2,239 men from the Honolulu Heart Program/Honolulu–Asia Aging Study who were born before the end of June 1909 and who took part in baseline physical assessment in 1965–1968, when they were 56–68 years old. Deaths were followed until the end of June 2009 for 44 years with complete ascertainment. Longevity was categorized as centenarian (≥100 years, n = 47), nonagenarian (90–99 years, n = 545), octogenarian (80–89 years, n = 847), and ≤79 years (n = 801, reference). The average survival after baseline was 20.8 years (SD = 9.62). Compared with people who died at the age of ≤79 years, centenarians belonged 2.5 times (odds ratio (OR) = 2.52, 95% confidence interval (CI) = 1.23–5.10) more often to the highest third of grip strength in midlife, were never smokers (OR = 5.75 95% CI = 3.06–10.80), had participated in physical activity outside work (OR = 1.13 per daily hour, 95% CI = 1.02–1.25), and had a long-lived mother (≥80 vs. ≤60 years, OR = 2.3, 95% CI = 1.06–5.01). Associations for nonagenarians and octogenarians were parallel, but weaker. Multivariate modeling showed that mother’s longevity and offspring’s grip strength operated through the same or overlapping pathway to longevity. High midlife grip strength and long-lived mother may indicate resilience to aging, which, combined with healthy lifestyle, increases the probability of extreme longevity.     

Tissue specificity of insulin resistance in humans: fat in the liver rather than muscle is associated with features of the metabolic syndrome

Aims/hypothesis The aim of this study was to investigate whether intrahepatic and intramyocellular fat are related to insulin resistance in these respective tissues or to the metabolic syndrome. Methods Hepatic (insulin 1.8 pmol kg⁻¹ min⁻¹ combined with [3-³H]glucose) and muscle (insulin 6.0 pmol kg⁻¹ min⁻¹) insulin sensitivity were measured on separate occasions in 45 non-diabetic men (age 42 ± 1 years, BMI 26.2 ± 0.6 kg/m²) using the euglycaemic–hyperinsulinaemic clamp. Liver fat and intramyocellular lipid (IMCL) were measured by proton magnetic resonance spectroscopy and body composition by magnetic resonance imaging. We also determined fasting serum insulin and adiponectin concentrations, components of the metabolic syndrome and maximal oxygen consumption. Results In participants with high [median 12.0% (interquartile range 5.7–18.5%)] vs low [2.0% (1.0–2.0%)] liver fat, fasting serum triacylglycerols (1.6 ± 0.2 vs 1.0 ± 0.1 mmol/l, p = 0.002) and fasting serum insulin (55 ± 4 vs 32 ± 2 pmol/l, p < 0.0001) were increased and serum HDL-cholesterol (1.26 ± 0.1 vs 1.48 ± 0.1 mmol/l, p = 0.02) and fasting serum adiponectin (9.5 ± 1.2 vs 12.2 ± 1.2 μg/ml, p = 0.05) decreased. In participants with high [19.5% (16.0–26.0%)] vs low [5.0% (2.3–7.5%)] IMCL, these parameters were comparable. Liver fat was higher in participants with [10.5% (3.0–18.0%)] than in those without [2.0% (1.5–6.0%), p = 0.010] the metabolic syndrome, even independently of obesity, while IMCL was comparable. Insulin suppression of glucose rate of appearance and serum NEFA was significantly impaired in the high liver fat group. Conclusions/interpretation Fat accumulation in the liver rather than in skeletal muscle is associated with features of the metabolic syndrome, i.e. increased fasting serum triacylglycerols and decreased fasting serum HDL-cholesterol, as well as with hyperinsulinaemia and low adiponectin.     

Barriers to Obtaining Waivers to Prescribe Buprenorphine for Opioid Addiction Treatment Among HIV Physicians

Background Illicit drug use is common among HIV-infected individuals. Buprenorphine enables physicians to simultaneously treat HIV and opioid dependence, offering opportunities to improve health outcomes. Despite this, few physicians prescribe buprenorphine. Objective To examine barriers to obtaining waivers to prescribe buprenorphine. Design Cross-sectional survey study. Participants 375 physicians attending HIV educational conferences in six cities in 2006. Approach Anonymous questionnaires were distributed and analyzed to test whether confidence addressing drug problems and perceived barriers to prescribing buprenorphine were associated with having a buprenorphine waiver, using chi-square, t tests, and logistic regression. Results 25.1% of HIV physicians had waivers to prescribe buprenorphine. In bivariate analyses, physicians with waivers versus those without waivers were less likely to be male (51.1 vs 63.7%, p < .05), more likely to be in New York (51.1 vs 29.5%, p < .01), less likely to be infectious disease specialists (25.5 vs 41.6%, p < .05), and more likely to be general internists (43.6 vs 33.5%, p < .05). Adjusting for physician characteristics, confidence addressing drug problems (adjusted odds ratio [AOR] = 2.05, 95% confidence interval [95% CI] = 1.08–3.88) and concern about lack of access to addiction experts (AOR = 0.56, 95% CI = 0.32–0.97) were significantly associated with having a buprenorphine waiver. Conclusions Among HIV physicians attending educational conferences, confidence addressing drug problems was positively associated with having a buprenorphine waiver, and concern about lack of access to addiction experts was negatively associated with it. HIV physicians are uniquely positioned to provide opioid addiction treatment in the HIV primary care setting. Understanding and remediating barriers HIV physicians face may lead to new opportunities to improve outcomes for opioid-dependent HIV-infected patients.     

Evaluating the association of common LMNA variants with type 2 diabetes and quantitative metabolic phenotypes in French Europids

Aims/hypothesis In the present study, we sought to examine the evidence that LMNA variants are associated with type 2 diabetes and quantitative metabolic traits in French Europid individuals. Methods We genotyped 24 single nucleotide polymorphisms (SNPs) spanning the LMNA gene in 3,093 case–control participants. The association between LMNA SNPs and quantitative metabolic traits was also examined in the 1,674 normoglycaemic adults who made up the control cohort. Results SNP rs505058, a synonymous SNP (D446D) in exon 7, showed nominal evidence of association with type 2 diabetes [p = 0.003, odds ratio (OR) 1.30 (95% CI 1.09–1.56)] in French Europids. A meta-analysis of available rs505058 genotype data from 7,819 participants provided support for a modest association of rs505058 with type 2 diabetes [p = 0.003, OR 1.19 (95% CI 1.06–1.35)]. We found no evidence (p = 0.91) that the tag SNP rs4641 is associated with type 2 diabetes. However, a meta-analysis of all available rs4641 genotype data in a total of 15,591 participants produced borderline evidence of association [p = 0.054, OR 1.05 (95% CI 1.00–1.11)]. SNP rs6669212, in the 3′ untranslated region of LMNA, exhibited suggestive associations with WHR (p = 0.013), fasting serum levels of total cholesterol (p = 0.023) and triacylglycerol (p = 0.015). We emphasise that these quantitative trait associations are not corrected for multiple testing. Conclusions/interpretation The available data do not support a major effect of common LMNA variation on type 2 diabetes susceptibility in northern Europeans. Further large-scale studies are required to conclusively establish the extent to which LMNA variants have an impact on quantitative metabolic traits. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorised users.     

Increased serum levels of advanced glycation endproducts predict total, cardiovascular and coronary mortality in women with type 2 diabetes: a population-based 18 year follow-up study

Aims/hypothesis AGEs, modification products formed by glycation or glycoxidation of proteins and lipids, have been linked to premature atherosclerosis in patients with diabetes. We investigated whether increased serum levels of AGEs predict total, cardiovascular (CVD) or CHD mortality in a population-based study. Subjects and methods Serum levels of AGEs were determined by immunoassay in a random sample of 874 Finnish diabetic study participants (488 men, 386 women), aged 45–64 years. These participants were followed for 18 years for total, CVD and CHD mortality. Results Multivariate Cox regression models revealed that serum levels of AGEs were significantly associated with total (p = 0.002) and CVD mortality (p = 0.021) in women, but not in men. Serum levels of AGEs in the highest sex-specific quartile predicted all-cause (hazards ratio [HR] 1.51; 95% confidence intervals [CI], 1.14–1.99; p = 0.004), CVD (HR 1.56; 95% CI 1.12–2.19; p = 0.009), and CHD (HR 1.68; 95% CI 1.11–2.52; p = 0.013) mortality in women, even after adjustment for confounding factors, including high-sensitivity C-reactive protein. Conclusions/interpretation Increased serum levels of AGEs predict total and CVD mortality in women with type 2 diabetes. B. K. Kilhovd and A. Juutilainen contributed equally to this study.