Ebola remains a global threat. In a randomized, controlled trial to assess the safety and immunogenicity of two vaccines against Ebola virus disease in Liberia, no safety signals were found. The ...vaccines elicited immune responses lasting at least 1 year.
Objectives
With HIV treatment prolonging survival and HIV infection now managed as a chronic illness, quality of life (QOL) is important to evaluate in persons living with HIV (PLWH). We assessed at ...study entry the QOL of antiretroviral‐naïve PLWH with CD4 counts > 500 cells/μL in the Strategic Timing of AntiRetroviral Treatment (START) clinical trial.
Methods
QOL was assessed with: (1) a visual analogue scale (VAS) for self‐assessment of overall current health; (2) the Short‐Form 12‐Item Version 2 Health Survey® (SF‐12V2), for which responses are summarized into eight individual QOL domains plus component summary scores for physical health the Physical Health Component Summary (PCS) and mental health the Mental Health Component Summary (MCS). The VAS and eight domain scores were scaled from 0 to 100. Mean QOL measures were calculated overall and by demographic, clinical and behavioural factors.
Results
A total of 4631 participants completed the VAS and 4119 the SF‐12. The mean VAS score (with standard deviation) was 80.9 ± 15.7. Mean SF‐12 domain scores were lowest for vitality (66.3 ± 26.4) and mental health (68.6 ± 21.4), and highest for physical functioning (89.3 ± 23.0) and bodily pain (88.0 ± 21.4). Using multiple linear regression, PCS scores were lower (P < 0.001) for Asians, North Americans, female participants, older participants, and those with less education, longer duration of known HIV infection, alcoholism/substance dependence and body mass index ≥ 30 kg/m2. MCS scores were highest (P < 0.001) for Africans, South Americans and older participants, and lowest for female participants, current smokers and those with alcoholism/substance dependence.
Conclusions
In this primarily healthy population, QOL was mostly favourable, emphasizing that it is important that HIV treatments do not negatively impact QOL. Self‐assessed physical health summary scores were higher than mental health scores. Factors such as older age and geographical region had different effects on perceived physical and mental health.
Antihypertensive therapy is aimed at improving vascular and cardiac health, as well as lowering blood pressure (BP). The benefit of such drugs in untreated patients with borderline BP has not been ...demonstrated. Subjects with BPs ≥130 mm Hg systolic or ≥85 mm Hg diastolic and at least one additional risk factor were randomly assigned to treatment with carvedilol, lisinopril, their combination or placebo. Cardiovascular health was assessed by a disease score (DS), which combines the following tests of cardiovascular function and structure: resting BP, large- and small-artery elasticity (SAE), BP response to exercise, retinal vasculature analysis, electrocardiogram, carotid intima-medial thickness, left ventricular mass, microalbuminuria and N-terminal pro B-type natriuretic peptide. DS was assessed at baseline, after 3 and 9 months of therapy and 1 month after discontinuation of therapy. All active treatment groups displayed a sustained reduction in BP during 9 months of treatment, with the greatest reduction in the cardvedilol+lisinopril group. DS and SAE improved in all the treatment groups but the changes were of borderline significance and exhibited no evidence for progressive improvement from 3 months (functional) to 9 months (structural). All changes were reversed within 1 month after discontinuation of therapy. We conclude that 9 months of treatment with carvedilol, lisinopril or their combination produce a sustained and well-tolerated functional improvement but not a structural improvement, perhaps because of a lack of the nitric oxide-enhancing effects of other agents that inhibit structural changes in the vasculature.
Elevated blood pressure remains a widespread major impediment to health. Obesity and specific dietary factors such as high salt and alcohol intake and low potassium intake adversely affect blood ...pressure. It is a reasonable hypothesis that additional dietary constituents, particularly macronutrients, may also influence blood pressure.
Participants were 11,342 middle-aged men from the Multiple Risk Factor Intervention Trial (MRFIT). Data from repeat 24-hour dietary recalls (four to five per person) and blood pressure measurements at six annual visits were used to assess relationships, singly and in combination, of dietary macronutrients to blood pressure, adjusted for multiple possible confounders (demographic, dietary, and biomedical). Multiple linear regression was used to assess diet-blood pressure relations in two MRFIT treatment groups (special intervention and usual care), with adjustment for confounders, pooling of coefficients from the two groups (weighted by inverse of variance), and correction of coefficients for regression-dilution bias. In multivariate regression models, dietary cholesterol (milligrams per 1000 kilocalories), saturated fatty acids (percent of kilocalories), and starch (percent of kilocalories) were positively related to blood pressure; protein and the ratio of dietary polyunsaturated to saturated fatty acids were inversely related to blood pressure. These macronutrient-blood pressure findings were obtained in analyses that controlled for body mass, dietary sodium and ratio of sodium to potassium, and alcohol intake, each positively related to blood pressure, and intake of potassium and caffeine, both inversely related to blood pressure.
These data support the concept that multiple dietary factors influence blood pressure; hence, broad improvements in nutrition can be important in preventing and controlling high-normal and high blood pressure.
Dietary isoflavone and lignan phytoestrogens are potential chemopreventive agents. This has led to a need to monitor exposure
to these compounds in human populations and to determine which components ...of a mixed diet contribute to the exposure. Typically,
urinary isoflavonoid excretion is associated with soy consumption and that of lignans is associated with whole grains. However,
other plant foods are known to contain phytoestrogen precursors. The purpose of this study was to examine the association
between urinary isoflavonoid and lignan excretion and intakes of vegetables and fruits (V&F). Isoflavonoids (genistein, daidzein,
O -desmethylangolensin, and equol) and lignans (enterolactone, enterodiol, and matairesinol) were measured in urine collected
for 3 days from 49 male and 49 female volunteers (age, 18–37 years) reporting a wide range of habitual V&F intakes. Dietary
intakes were assessed using 5-day diet records and a food frequency questionnaire. V&F groupings (total V&F, total V, total
F, soyfoods, and V&F grouped by botanical families) were used to assess the relationship between V&F intake and urinary isoflavonoid
and lignan excretion. Pearson correlations were performed. Intake of soyfoods was correlated significantly with urinary genistein
( r = 0.40; P = 0.0001), O -desmethylangolensin ( r = 0.37; P = 0.0002), daidzein ( r = 0.34; P = 0.0007), and the sum of isoflavonoids ( r = 0.39; P = 0.0001). There was no association between equol excretion and soy intake or between the isoflavonoids and any other V&F
groupings. In addition, isoflavonoid excretion was correlated positively with intake of high-fat and processed meats, particularly
among men who did not consume soy. This suggests that, even in the United States, on a Western diet, soyfoods are the primary
contributors to isoflavone intake; however, additional “hidden sources” of soy may also contribute to exposure. In contrast,
a variety of fiber-containing foods contributed to lignan excretion; the sum of the urinary lignans, enterodiol, enterolactone,
and matairesinol, was associated with intake of total F ( r = 0.27; P = 0.008), total V&F ( r = 0.25; P = 0.01), soyfoods ( r = 0.28; P = 0.006), and dietary fiber ( r = 0.36; P = 0.0003). Overall, urinary phytoestrogens (isoflavonoids + lignans) were significantly higher in “high” compared with “low”
V&F consumers. Compared with the “low” V&F group, the “high” group consumed diets that were, on average, higher in fiber and
carbohydrate and soyfoods and lower in fat; thus, the urinary phytoestrogens may also be a useful marker of healthier dietary
patterns.
Skin and soft tissue infections (SSTIs) occur at higher rates among HIV-infected persons, but current trends and risk factors are largely undefined. We evaluated SSTIs among a prospective cohort of ...HIV-infected persons during the late combination antiretroviral therapy (cART) era (2006-2010). Of the 1918 HIV-infected persons evaluated, 379 (20%) developed an SSTI during a median of 3.7 years of follow-up; of these, 118 (31%) developed at least one recurrent SSTI. The incidence rate of SSTIs was 101 (95% confidence interval CI 93-109) cases per 1000 person-years, and rates did not significantly change during the study period. Compared with not receiving cART and having an HIV RNA level >1000 copies/mL, patients receiving cART with an HIV RNA level <1000 copies/mL had a reduced risk of an SSTI (hazard ratio 0.64, 95% CI 0.48-0.86, P < 0.01). In summary, initial and recurrent SSTIs are common among HIV-infected persons, and HIV control is associated with a lower risk of SSTIs.
Increased left ventricular mass (LVM) by echocardiography is associated with increased risk of cardiovascular disease. Thus, it is of interest to compare the effects of both pharmacological and ...nonpharmacological approaches to the treatment of hypertension on reduction of LVM.
Changes in LV structure were assessed by M-mode echocardiograms in a double-blind, placebo-controlled clinical trial of 844 mild hypertensive participants randomized to nutritional-hygienic (NH) intervention plus placebo or NH plus one of five classes of antihypertensive agents: (1) diuretic (chlorthalidone), (2) beta-blocker (acebutolol), (3) alpha-antagonist (doxazosin mesylate), (4) calcium antagonist (amlodipine maleate), or (5) angiotensin-converting enzyme inhibitor (enalapril maleate). Echocardiograms were performed at baseline, at 3 months, and annually for 4 years. Changes in blood pressure averaged 16/12 mm Hg in the active treatment groups and 9/9 mm Hg in the NH only group. All groups showed significant decreases (10% to 15%) in LVM from baseline that appeared at 3 months and continued for 48 months. The chlorthalidone group experienced the greatest decrease at each follow-up visit (average decrease, 34 g), although the differences from other groups were modest (average decrease among 5 other groups, 24 to 27 g). Participants randomized to NH intervention only had mean changes in LVM similar to those in the participants randomized to NH intervention plus pharmacological treatment. The greatest difference between groups was seen at 12 months, with mean decreases ranging from 35 g (chlorthalidone group) to 17 g (acebutolol group) (P = .001 comparing all groups). Within-group analysis showed that changes in weight, urinary sodium excretion, and systolic BP were moderately correlated with changes in LVM, being statistically significant in most analyses.
NH intervention with emphasis on weight loss and reduction of dietary sodium is as effective as NH intervention plus pharmacological treatment in reducing echocardiographically determined LVM, despite a smaller decrease in blood pressure in the NH intervention only group. A possible exception is that the addition of diuretic (chlorthalidone) may have a modest additional effect on reducing LVM.
The kinetics of colorectal epithelial cell proliferation is altered in patients at increased risk for colon cancer. Calcium administration ameliorates such proliferative changes in rodents. Findings ...in preliminary clinical trials have suggested similar effects in humans.
A randomized, double-blind, placebo-controlled, clinical trial was designed to determine whether calcium supplementation will reduce the colorectal epithelial cell proliferation rate and normalize the distribution of proliferating cells within colorectal crypts (i.e., shift the zone of proliferation from the entire crypt to the lower 60% of the crypt, which is thought to be the normal proliferative zone of the crypt) in patients with sporadic adenomas.
Sporadic adenoma patients (n = 193) were treated with placebo (n = 66), 1.0 g calcium (n = 64), or 2.0 g calcium (n = 63) daily for 6 months. Rectal mucosa biopsy specimens were obtained at base line and at 1-, 2-, and 6-month follow-up. Cell proliferation was measured by detection of S-phase-associated proliferating cell nuclear antigen by immunohistochemical methods. The cell proliferation rate, called labeling index (LI), was calculated as the proportion of labeled cells in the crypts. The deviation of the proliferative zone from the normal location in the lower 60% of the crypt was calculated as the proportion of labeled cells in the upper 40% of the crypt, called distributional index (phi h). The effects of calcium treatment on the LI and phi h were expressed as relative effects--(calcium follow-up/calcium base line)/(placebo follow-up/placebo base line). Calculations and inference testing of the relative effects were accomplished using a repeated-measures mixed model on log-transformed LI and phi h values. All statistical tests were two-sided.
Scorable biopsy specimens were obtained on 170 patients at base line, 164 at 1 month, 161 at 2 months, and 163 at 6 months. The difference in the change in the LI between the combined calcium groups and the placebo group was insignificant, with a relative effect of calcium versus placebo of 0.97 (P = .87). However, for the phi h, the relative effect of calcium versus placebo was 0.50 (P = .05) in the combined calcium groups, 0.56 (P = .16) in the 1.0-g calcium group, and 0.44 (P = .05) in the 2.0-g calcium group.
Calcium supplementation normalizes the distribution of proliferating cells without affecting the proliferation rate in the colorectal mucosa of sporadic adenoma patients.
These results support further study of whether alterations in colon cell proliferative kinetics represent true intermediate steps in colon carcinogenesis that can be used to investigate the etiology and prevention of, and whether a higher calcium consumption can reduce the risk of, colon cancer.
Higher intakes of vegetables and fruits are associated with a lower risk of certain human cancers. A biomarker of vegetable
and fruit intake would be a valuable research tool. A cross-sectional study ...assessed the association between plasma carotenoid
concentrations and intakes of vegetables and fruits. Plasma carotenoids (alpha-carotene, beta-carotene, lutein, beta-cryptoxanthin,
and lycopene) were measured in 50 male and 49 female participants, aged 18-37 years, with a wide range of habitual vegetable
and fruit intakes. Dietary intakes were assessed via a food frequency questionnaire. Intake of vegetables and fruits and high
carotenoid foods were measured. The sum of the plasma carotenoids (excluding lycopene) was highly correlated with intake of
total vegetables and fruits (r = 0.59). Of the individual plasma carotenoids, plasma alpha-carotene had the highest correlation
with intakes of both total vegetables (r = 0.50) and total fruits (r = 0.58). Intakes of foods with high carotenoid contents
were correlated with their corresponding plasma concentrations as follows: high beta-carotene foods (r = 0.41); high lutein
foods (r = 0.46); and high lycopene foods (r = 0.11). Multiple regression analyses showed that intake of total vegetables
and fruits was the most significant determinant of each plasma carotenoid except lycopene. The utility of combining the plasma
carotenoids as biomarkers of vegetable and fruit intake was assessed by a stepwise regression of total vegetable and fruit
intake on plasma carotenoids. Significant determinants of intake of total vegetables and fruits were alpha-carotene, beta-cryptoxanthin,
lutein, and energy intake (R2 = 0.53).
Problems with sexual function have been a long-standing concern in the treatment of hypertension and may influence the choice of treatment regimens and decisions to discontinue drugs. The Treatment ...of Mild Hypertension Study (TOMHS) provides an excellent opportunity for examination of sexual function and effects of treatment on sexual function in men and women with stage I diastolic hypertension because of the number of drug classes studied, the double-blind study design, and the long-term follow-up. TOMHS was a double-blind, randomized controlled trial of 902 hypertensive individuals (557 men, 345 women), aged 45 to 69 years, treated with placebo or one of five active drugs (acebutolol, amlodipine maleate, chlorthalidone, doxazosin maleate, or enalapril maleate). All participants received intensive lifestyle counseling regarding weight loss, dietary sodium reduction, alcohol reduction (for current drinkers), and increased physical activity. Sexual function was ascertained by physician interviews at baseline and annually during follow-up. At baseline, 14.4% of men and 4.9% of women reported problems with sexual function. In men, 12.2% had problems obtaining and/or maintaining an erection; 2.0% of women reported a problem having an orgasm. Erection problems in men at baseline were positively related to age, systolic pressure, and previous antihypertensive drug use. The incidences of erection dysfunction during follow-up in men were 9.5% and 14.7% through 24 and 48 months, respectively, and were related to type of antihypertensive therapy. Participants randomized to chlorthalidone reported a significantly higher incidence of erection problems through 24 months than participants randomized to placebo (17.1% versus 8.1%, P = .025). Incidence rates through 48 months were more similar among treatment groups than at 24 months, with nonsignificant differences between the chlorthalidone and placebo groups. Incidence was lowest in the doxazosin group but was not significantly different from the placebo group. Incidence for acebutolol, amlodipine, and enalapril groups was similar to that in the placebo group. In many cases, erection dysfunction did not require withdrawal of medication. Disappearance of erection problems among men with problems at baseline was common in all groups but greatest in the doxazosin group. Incidence of reported sexual problems in women was low in all treatment groups. In conclusion, long-term incidence of erection problems in treated hypertensive men is relatively low but is higher with chlorthalidone treatment. Effects of erection dysfunction with chlorthalidone appear relatively early and are often tolerable, and new occurrences after 2 years are unlikely. The rate of reported sexual problems in hypertensive women is low and does not appear to differ by type of drug. Similar incidence rates of erection dysfunction in placebo and most active drug groups caution against routine attribution of erection problems to antihypertensive medication. (Hypertension. 1997;29:8-14.)
PDF
