Determinants of Retinal Microvascular Architecture in Normal Subjects

Background: Recent studies have shown that changes in the retinal microvasculature predict cardiovascular disease (CVD); however, little is known regarding influences on the retinal microvasculature in healthy people without overt cardiovascular or metabolic disease. Methods: We used a semiautomated computerized technique to analyze digitized retinal photographs from a total of 167 healthy people (age range, 45–75 years; 83 female), without clinical CVD, diabetes, or hypertension, randomly sampled from the population‐based Beaver Dam Eye Study. We assessed arteriolar and venular narrowing, arteriolar optimality deviation, and other quantitative aspects of the retinal microvasculature. Results: Arterioles were significantly narrower and longer, had wider branching angles, and were more tortuous than venules. Increased arteriolar length to diameter ratio (an index of ratio arteriolar narrowing) was positively and independently associated with older age and elevated systolic blood pressure. Arteriolar optimality deviation (an index of microvascular endothelial dysfunction) increased with greater body mass index. Current smoking and increased white blood cell (WBC) count was associated with wider venules. After controlling for smoking, WBC was no longer a significant predictor of venular diameter. Conclusions: CVD risk factors are associated with retinal microvascular changes in healthy individuals without evidence of CVD, diabetes, or hypertension. CVD risk factors have different influences on the arteriolar and venular bed.     

Reduced Skeletal Muscle Capillarization and Glucose Intolerance

Objective: Reduced capillarization in hemiparetic skeletal muscle of chronic stroke patients can limit insulin, glucose, and oxygen supply to muscle, thereby contributing to impaired glucose metabolism and cardiovascular deconditioning. We hypothesized that compared to sedentary controls, stroke subjects have reduced skeletal muscle capillarization that is associated with glucose intolerance and reduced peak oxygen consumption (Vo_2peak). Methods: Twelve chronic stroke subjects (ages, 62.1±2.8 years), and matched sedentary controls with impaired (n=12) or normal (n=12) glucose tolerance underwent oral glucose tolerance tests, exercise tests, and vastus lateralis biopsies. Results: Stroke subjects had lower capillarization in hemiparetic muscle than in nonparetic muscle and normal glucose tolerant controls (～22 and ～28%, respectively; P<0.05) and had similar bilateral capillarization, compared to controls with impaired glucose tolerance. Capillary density in hemiparetic muscle inversely correlated with 120‐minute glucose (r=?0.70, P<0.01) and glucose area under the curve (r=?0.78, P<0.01). Vo_2peak was ～40% lower in stroke subjects, compared to controls (P<0.001), but did not correlate with capillarization (P=n.s.). Conclusions: Hemiparetic muscle capillarization is reduced after stroke, and reduced capillarization is associated with glucose intolerance in stroke and control subjects. Interventions to increase skeletal muscle capillarization may prove beneficial for improving glucose metabolism in chronic stroke patients.     

N-Acetylcysteine Added to Volume Expansion with Sodium Bicarbonate Does Not Further Prevent Contrast-Induced Nephropathy: Results from the Cardiac Angiography in Renally Impaired Patients Study

We reviewed data from the multicenter CARE (Cardiac Angiography in Renally Impaired Patients) study to see if benefit could be shown for N -acetylcysteine (NAC) in patients undergoing cardiac angiography who all received intravenous bicarbonate fluid expansion. Four hundred fourteen patients with moderate-to-severe chronic kidney disease were randomized to receive intra-arterial administration of iopamidol-370 or iodixanol-320. All patients were prehydrated with isotonic sodium bicarbonate solution. Each site chose whether or not to administer NAC 1,200 mg twice daily to all patients. Serum creatinine (SCr) levels and estimated glomerular filtration rate were assessed at baseline and 2–5 days after receiving contrast. The primary outcome was a postdose SCr increase 0.5 mg/dL (44.2 μmol/L) over baseline. Secondary outcomes were a postdose SCr increase 25% and the mean peak change in SCr. The NAC group received significantly less hydration (892 ± 236 mL vs. 1016 ± 328 mL; P < 0.001) and more contrast volume (146 ± 74 mL vs. 127 ± 71 mL; P = 0.009) compared with no-NAC group. SCr increases 0.5 mg/dL occurred in 4.2% (7 of 168 patients) in NAC group and 6.5% (16 of 246 patients) in no-NAC group (P = 0.38); rates of SCr increases 25% were 11.9% and 10.6%, respectively (P = 0.75); mean post-SCr increases were 0.07 mg/dL in NAC group versus 0.11 mg/dL in no-NAC group (P = 0.14). In conclusion, addition of NAC to fluid expansion with sodium bicarbonate failed to reduce the rate of contrast-induced nephropathy (CIN) after the intra-arterial administration of iopamidol or iodixanol to high-risk patients with chronic kidney disease.     

Cardiac Resynchronization Therapy in Non‐Left Bundle Branch Block Morphologies

Introduction: In select patients with systolic heart failure, cardiac resynchronization therapy (CRT) has been shown to improve quality of life, exercise capacity, ejection fraction (EF), and survival. Little is known about the response to CRT in patients with right bundle branch block (RBBB) or non‐specific intraventricular conduction delay (IVCD) compared with traditionally studied patients with left bundle branch block (LBBB). Methods: We assessed 542 consecutive patients presenting for the new implantation of a CRT device. Patients were placed into one of three groups based on the preimplantation electrocardiogram morphology: LBBB, RBBB, or IVCD. Patients with a narrow QRS or paced ventricular rhythm were excluded. The primary endpoint was long‐term survival. Secondary endpoints were changes in EF, left ventricular end‐diastolic and systolic diameter, mitral regurgitation, and New York Heart Association (NYHA) functional class. Results: Three hundred and thirty‐five patients met inclusion criteria of which 204 had LBBB, 38 RBBB, and 93 IVCD. There were 32 deaths in the LBBB group, 10 in the RBBB, and 27 in the IVCD group over a mean follow up of 3.4 ± 1.2 years. In multivariate analysis, no mortality difference amongst the three groups was noted. Patients with LBBB had greater improvements in most echocardiographic endpoints and NYHA functional class than those with IVCD and RBBB. Conclusion: There is no difference in 3‐year survival in patients undergoing CRT based on baseline native QRS morphology. Patients with RBBB and IVCD derive less reverse cardiac remodeling and symptomatic benefit from CRT compared with those with a native LBBB. (PACE 2010; 590–595)     

25-Hydroxyvitamin D levels in prevalent Australian dialysis patients

Aim:   Vitamin D deficiency is a common problem in the general population. A high frequency of vitamin D deficiency in the pre-dialysis and dialysis populations has been observed overseas, but there is limited information regarding vitamin D levels in Australian dialysis patients.
Method:   We measured 25-hydroxyvitamin D levels in 120 haemodialysis (HD) and 31 peritoneal dialysis (PD) patients. We defined vitamin D deficiency as a level <50 nmol/L and insufficiency as a level of 50–74 nmol/L. We assessed for correlation between vitamin D levels and markers of bone and mineral metabolism, age, sex, dialysis type, dialysis duration, haemoglobin and erythropoietin dose.
Results:   Of the HD patients, 59 (49%) were frankly deficient and 39 (33%) had insufficiency. Of the PD patients, 24 (77%) were frankly deficient and 6 (19%) had insufficiency. Overall, only 23 patients (19%) had sufficient levels of vitamin D. Vitamin D levels were significantly lower in PD patients ( P  = 0.001), in females ( P  = 0.002) and in those with diabetic nephropathy ( P  = 0.03). There was no correlation between vitamin D levels and markers of bone and mineral metabolism, age, dialysis duration, haemoglobin or erythropoietin dose.
Conclusion:   Vitamin D deficiency and insufficiency were very common in this cohort of prevalent Australian dialysis patients. Lower levels were associated with PD as treatment modality, female sex and diabetic nephropathy.     

Drug injecting in patients in New Zealand Methadone Maintenance Treatment programs: An anonymous survey

Introduction and Aims. To investigate the prevalence and nature of injecting behaviour among patients on Methadone Maintenance Treatment (MMT) programs. Design and Methods. A self‐reported questionnaire was handed to 423 patients enrolled in MMT across six clinics in the lower North Island of New Zealand. Results. A total of 151 patients responded, giving a 35.6% response rate. One hundred and twenty (79.5%) respondents reported they had injected methadone while enrolled in MMT, 84 (55.6%) had injected methadone in the last year and of those 43 (35.8%) had injected methadone in the last week. Reasons given for injecting of methadone included: rapid onset of effect, needle fixation and euphoria. Time on the methadone programme was negatively associated with ever injecting methadone [odds ratio (95% CI) 0.92 (0.85–0.99), P = 0.029] and injecting other substances [odds ratio (95% CI) 0.93(0.87–1.0), P = 0.046]. More frequent pharmacy‐observed consumption was associated with increased injecting of other substances [odds ratio (95% CI) 1.32 (1.09–1.59), P = 0.005] but not methadone. The time a person had been enrolled on the methadone programme was associated with decreased use of other substances [odds ratio (95% CI) 0.93 (0.87–1.0), P = 0.046]. Discussion and Conclusions. Many individuals on MMT continue to inject their methadone. In this sample, the frequency of injection of methadone did not correlate with prescribed dose or takeaway arrangements. The beneficial impact of time on the programme emphasises the importance of retention in treatment. It is suggested that these results also indicate a need for routine education concerning safe injecting.[Judson G, Bird R, O'Connor P, Bevin T, Loan R, Schroder M, McGrath R, Weatherall M, Moriarty H, Robinson G. Drug injecting in patients in New Zealand Methadone Maintenance Treatment programs: An anonymous survey. Drug Alcohol Rev 2009]     

Psychopathology in methamphetamine‐dependent adults 3 years after treatment

Introduction and Aims. Although psychiatric symptoms are frequently observed in methamphetamine (MA) users, little is known about the prevalence of psychiatric disorders in MA‐dependent individuals. This is the first study to examine the association of psychiatric disorders with substance use and psychosocial functioning in a large sample of MA users 3 years after treatment. We predicted that psychiatric diagnoses and severity would be associated with substance use and poorer overall functioning over the 3 year post‐treatment course. Design and Methods. Participants (N = 526) received psychosocial treatment for MA dependence as part of the Methamphetamine Treatment Project and were reassessed for psychosocial functioning and substance use at a mean of 3 years after treatment initiation. DSM‐IV psychiatric diagnoses were assessed at follow‐up using the Mini‐International Neuropsychiatric Interview. Psychosocial functioning was assessed using the Addiction Severity Index. Results. Overall, 48.1% of the sample met criteria for a current or past psychiatric disorder other than a substance use disorder. Consistent with prior reports from clinical samples of cocaine users, this rate was largely accounted for by mood disorders, anxiety disorders and antisocial personality. Those with an Axis I psychiatric disorder evidenced increased MA use and greater functional impairment over time relative to those without a psychiatric disorder. Discussion and Conclusions. This initial investigation of psychiatric diagnoses in MA users after treatment indicates elevated rates of Axis I and II disorders in this population and underscores the need for integrated psychiatric assessment and intervention in drug abuse treatment settings.[Glasner‐Edwards S, Mooney LJ, Marinelli‐Casey P, Hillhouse M, Ang A, Rawson RA, The Methamphetamine Treatment Project Corporate Authors. Psychopathology in methamphetamine‐dependent adults 3 years after treatment. Drug Alcohol Rev 2009]     

A cost‐effectiveness analysis of modafinil therapy for psychostimulant dependence

Introduction and Aims. To examine the cost‐effectiveness of modafinil (200 mg daily) plus counselling compared with placebo for the treatment of psychostimulant dependence. Design and Methods. Cost and outcome data were collected alongside two randomised controlled trials of modafinil 200 mg daily over 10 weeks for methamphetamine (n = 74) and cocaine dependence (n = 8), respectively. Incremental cost‐effectiveness ratios representing the additional costs to achieve a given outcome were calculated for both the change in the number of stimulant‐free days and quality‐adjusted life years 12 weeks post‐treatment. Results. The incremental cost‐effectiveness ratio indicated that it would cost an additional $AUD79 to achieve an extra stimulant‐free day with modafinil compared with placebo. This result was not statistically significant, but appeared to be a robust estimate after sensitivity analysis. Counselling, whether received within program or from other services, improved the cost‐effectiveness of modafinil relative to placebo. Discussion and Conclusions. Strategies to improve the uptake of counselling are recommended as cost‐effective.[Shearer J, Shanahan M, Darke S, Rodgers C, van Beek I, McKetin R, Mattick RP. A cost‐effectiveness analysis of modafinil therapy for psychostimulant dependence. Drug Alcohol Rev 2010]