This 12-week study evaluated the efficacy and safety of capsaicin 8% patch versus placebo patch in painful diabetic peripheral neuropathy (PDPN). Patients aged 18 years or older with PDPN were ...randomized (1:1) to one 30-minute treatment (capsaicin 8% patch or placebo patch) to painful areas of the feet. Overall, 369 patients were randomized (capsaicin 8% patch, n = 186; placebo patch, n = 183). Percentage reduction in average daily pain score from baseline to between weeks 2 through 8 (the primary end point) was statistically significant for capsaicin 8% patch versus placebo (−27.4% vs −20.9%; P = .025); improvements in pain were observed from week 2 onward. Versus placebo, patients treated with capsaicin 8% patch had a shorter median time to treatment response (19 vs 72 days) and modest improvements in sleep interference scores from baseline to between weeks 2 through 8 (P = .030) and weeks 2 through 12 (P = .020). Apart from application site reactions, treatment-emergent adverse events were similar between groups. No indications of deterioration in sensory perception of sharp, cold, warm, or vibration stimuli were observed. In patients with PDPN, capsaicin 8% patch treatment provided modest pain relief and sleep quality improvements versus a placebo patch, similar in magnitude to other treatments with known efficacy, but without systemic side effects or sensory deterioration.
To our knowledge, this is the first study of the capsaicin 8% patch versus placebo in patients with PDPN to show that one 30-minute capsaicin treatment provides modest improvements in pain and sleep quality. Results confirm the clinical utility of the capsaicin 8% patch in the diabetic population.
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•Capsaicin 8% patch provided effective relief in painful diabetic peripheral neuropathy.•Improvements in sleep quality were modest and significant with capsaicin 8% patch.•Capsaicin 8% patch was well tolerated with no deterioration in sensory perception.•Safety and tolerability were in line with previous studies of capsaicin 8% patch.
Summary
Objective Vitamin D deficiency is common among the elderly and may contribute to cardiovascular disease. The aim of our study was to elucidate whether low serum levels of 25‐hydroxyvitamin D ...25(OH)D are associated with an increased risk of all‐cause and cardiovascular mortality.
Design and patients The Hoorn Study is a prospective population‐based study among older men and women.
Measurements Fasting serum 25(OH)D was determined in 614 study participants at the follow‐up visit in 2000–2001, the baseline for the present analysis. To account for sex differences and seasonal variations of 25(OH)D levels we formed sex‐specific quartiles, which were calculated from the 25(OH)D values of each season.
Results After a mean follow‐up period of 6·2 years, 51 study participants died including 20 deaths due to cardiovascular causes. Unadjusted Cox proportional hazard ratios (HRs; with 95% confidence intervals) for all‐cause and cardiovascular mortality in the first when compared with the upper three 25(OH)D quartiles were 2·24 (1·28–3·92; P = 0·005) and 4·78 (1·95–11·69; P = 0·001), respectively. After adjustment for age, sex, diabetes mellitus, smoking status, arterial hypertension, high‐density lipoprotein‐cholesterol, glomerular filtration rate and waist‐to‐hip ratio, the HRs remained significant for all‐cause 1·97 (1·08–3·58; P = 0·027) and for cardiovascular mortality 5·38 (2·02–14·34; P = 0·001).
Conclusions Low 25(OH)D levels are associated with all‐cause mortality and even more pronounced with cardiovascular mortality, but it remains unclear whether vitamin D deficiency is a cause or a consequence of a poor health status. Therefore, intervention studies are warranted to evaluate whether vitamin D supplementation reduces mortality and cardiovascular diseases.
This 52-week study evaluated the long-term safety and tolerability of capsaicin 8% w/w (179 mg) patch repeat treatment plus standard of care (SOC) versus SOC alone in painful diabetic peripheral ...neuropathy (PDPN).
Phase 3, multinational, open-label, randomised, controlled, 52-week safety study, conducted in Europe. Patients were randomised to capsaicin 8% patch repeat treatment (30 or 60 min; 1-7 treatments with ≥ 8-week intervals) to painful areas of the feet plus SOC, or SOC alone. The primary objective was the safety of capsaicin 8% patch repeat treatment (30 min and 60 min applications) plus SOC versus SOC alone over 52 weeks, assessed by changes in Norfolk Quality of Life-Diabetic Neuropathy (QOL-DN) total score from baseline to end of study (EOS). Secondary safety endpoints included Utah Early Neuropathy Scale (UENS) assessments and standardised testing of sensory perception and reflex function.
Overall, 468 patients were randomised (30 min plus SOC, n = 156; 60 min plus SOC, n = 157; SOC alone, n = 155). By EoS, mean changes in Norfolk QOL-DN total score from baseline estimated mean difference versus SOC alone; 90% CI for difference were: 30 min plus SOC, -27.6% -20.9; -31.7, -10.1; 60 min plus SOC, -32.8% -26.1; -36.8, -15.4; SOC alone, -6.7%. Mean changes difference versus SOC alone in UENS total score by EoS versus baseline were: 30 min plus SOC, -2.1 -0.9; -1.8, 0.1; 60 min plus SOC, -3.0 -1.7; -2.7, -0.8; SOC alone, -1.2. No detrimental deterioration was observed in any of the Norfolk or UENS subscales by EoS with capsaicin. Also, no worsening in sensory perception testing of sharp, warm, cold and vibration stimuli was found with capsaicin by EoS. Capsaicin treatment was well tolerated and the most frequent treatment-emergent adverse events were application site pain (30 min, 28.2%; 60 min, 29.3%), burning sensation (30 min, 9.0%; 60 min, 9.6%) and application site erythema (30 min, 7.7%; 60 min, 8.9%).
In patients with PDPN, capsaicin 8% patch repeat treatment plus SOC over 52 weeks was well tolerated with no negative functional or neurological effects compared with SOC alone.
ClinicalTrials.gov registration: NCT01478607 . Date of registration November 21, 2011; retrospectively registered.
Context: Low adiponectin concentrations are associated with the presence of an adverse cardiovascular disease (CVD) risk profile.
Objective: We studied the predictive value of adiponectin levels for ...all-cause and CVD mortality and CVD morbidity.
Design, Setting, and Participants: This was a population-based cohort study in Hoorn, The Netherlands, which started in 1989 and included 2484 participants, aged 50–75 yr.
Main Outcome Measures: Hazard ratios (HRs) with 95% confidence interval per sd change in log-adiponectin for all-cause and CVD mortality and CVD morbidity were calculated.
Results: Adiponectin was determined for 1077 men and 1248 women. Higher adiponectin reduced the risk of nonfatal CVD in women HR with 95% confidence interval 0.72 (0.61–0.90) in women and 0.92 (0.79–1.06) in men, but not the risk of all-cause or CVD mortality. In contrast, after adjustment for cardiovascular risk factors, higher adiponectin was a significant predictor of all-cause and CVD mortality HR for CVD mortality 1.45 (1.10–1.92) in women and 1.30 (1.04–1.63) in men. Higher adiponectin was associated with an increased risk of CVD mortality in people with prevalent CVD HR 1.27 (0.98–1.63) and with reduced risk in people without HR 0.90 (0.73–1.11). After adjustment for cardiovascular risk factors, the HRs for CVD mortality were 1.60 (1.14–2.23) for patients with and 1.38 (1.06–1.80) for patients without prevalent CVD.
Conclusions: High levels of adiponectin predict mortality, in particular in patients with prevalent CVD. We hypothesize that adiponectin protects against metabolic and vascular diseases, but in patients already afflicted with CVD, adiponectin is compensatory up-regulated and, therefore, indicates a high mortality risk.
This analysis of the RASH trial (NCT01729481) aimed at gaining a better understanding of the "Burden of Therapy" (BOTh
) in pancreatic ductal adenocarcinoma (PDAC). In the RASH study, 150 patients ...with newly diagnosed metastatic PDAC were treated with gemcitabine plus erlotinib (gem/erlotinib) for four weeks. Patients who developed a skin rash during this four-week run-in phase continued with the gem/erlotinib treatment, while rash-negative patients were switched to FOLFIRINOX. The study demonstrated a 1-year survival rate of rash-positive patients who received gem/erlotinib as first-line treatment that was comparable to previous reports of patients receiving FOLFIRINOX. To understand whether these comparable survival rates may be accompanied by better tolerability of the gem/erlotinib treatment compared to FOLFIRINOX, the BOTh
methodology was used to continuously quantify and depict the burden of therapy generated by treatment emergent events (TEAEs). Sensory neuropathy was significantly more common in the FOLFIRINOX arm, and prevalence as well as severity increased over time. In both arms, the BOTh
associated with diarrhea decreased over the course of treatment. The BOTh
caused by neutropenia was comparable in both arms but decreased in the FOLFIRINOX arm over time, possibly due to chemotherapy dose reductions. Overall, gem/erlotinib was associated with a slightly higher overall BOTh
, but the difference was not statistically significant (
= 0.6735). In summary, the BOTh
analysis facilitates the evaluation of TEAEs. In patients fit for intense chemotherapeutic regimens, FOLFIRINOX is associated with a lower BOTh
than gem/erlotinib.
Objective: Higher dairy consumption has been suggested to reduce the risk of obesity and metabolic disturbances. The aim of our study was to investigate the prospective association between dairy ...consumption and changes in weight and metabolic disturbances.
Methods and Procedures: Baseline dairy intake (servings/day) was assessed by a semi‐quantitative food‐frequency questionnaire in 1,124 participants of the Hoorn Study. Linear and logistic regression analyses were performed to investigate the association between dairy intake and 6.4‐year change in weight, fat distribution, and metabolic risk factors (glucoses, lipids, blood pressure) and the incidence of metabolic syndrome (MS).
Results: Baseline dairy consumption was not associated with changes in fasting and post‐load glucose concentrations, serum lipid levels (high‐density lipoprotein‐cholesterol, low‐density lipoprotein‐cholesterol, and triglycerides), or blood pressure, nor with the risk of developing the MS in 6.4 years (odds ratio with 95% confidence interval was 0.86 (0.52–1.42) comparing highest with lowest quartile of dairy consumption). In subjects with BMI < 25 kg/m2, higher dairy consumption was significantly associated with an increase in BMI, weight, waist, and a decrease in high‐density lipoprotein.
Discussion: Our results do not support the hypothesis that a higher dairy consumption protects against weight gain and development of metabolic disturbances in a Dutch elderly population.
BACKGROUND:Dairy consumption has been postulated to reduce the risk of obesity and metabolic disturbances. OBJECTIVE:The aim of this study was to evaluate the associations of dairy consumption with ...body weight and other components of the metabolic syndrome. DESIGN:We used cross-sectional data for 2064 men and women aged 50-75 y who participated in the Hoorn Study. The metabolic syndrome was defined according to the National Cholesterol Education Program Expert Panel. Dairy consumption was assessed by using a semiquantitative food-frequency questionnaire. RESULTS:The median consumption of total dairy products was 4.1 servings/d. After adjustment for potential confounders (ie, dietary factors, physical activity, smoking, income, educational level, and antihypertensive medication), total dairy consumption was significantly associated with lower diastolic blood pressure (β ± SE: -0.31 ± 0.12 mm Hg/serving) and higher fasting glucose concentrations (0.04 ± 0.02 mmol/L per serving), but not with body weight or other metabolic variables (ie, lipids, postload glucose, or insulin). When different dairy products were distinguished, borderline significant (P < 0.10) inverse associations were observed for dairy desserts, milk, and yogurt with systolic (-1.26 ± 0.58, -0.57 ± 0.34, and -1.28 ± 0.74 mm Hg/serving, respectively) and diastolic (-0.58 ± 0.31, -0.57 ± 0.18, and -0.35 ± 0.40 mm Hg/serving, respectively) blood pressure, whereas cheese consumption was positively associated with body mass index (0.15 ± 0.08/serving). CONCLUSION:In an elderly Dutch population, higher dairy consumption was not associated with lower weight or more favorable levels of components of the metabolic syndrome, except for a modest association with lower blood pressure.
Background: The higher risk of type 2 diabetes in persons with a high waist-to-hip ratio (WHR) or waist-to-thigh ratio (WTR) has mostly been attributed to increased visceral fat accumulation. ...However, smaller hip or thigh circumference may also explain the predictive value of the WHR or WTR for type 2 diabetes. Objective: This study considered prospectively the association of hip and thigh circumferences, independent of waist circumference, with the incidence of type 2 diabetes. Design: The Hoorn Study is a population-based cohort study of diabetes. A total of 1357 men and women aged 50–75 y and nondiabetic at baseline participated in the 6-y follow-up examination. Glucose tolerance was assessed by use of a 75-g oral-glucose-tolerance test. Baseline anthropometric measurements included body mass index (BMI) and waist, hip, and thigh circumferences. Results: Logistic regression analyses showed that a 1-SD larger hip circumference gave an odds ratio (OR) for developing diabetes of 0.55 (95% CI: 0.36, 0.85) in men and 0.63 (0.42, 0.94) in women, after adjustment for age, BMI, and waist circumference. The adjusted ORs for a 1-SD larger thigh circumference were 0.79 (0.53, 1.19) in men and 0.64 (0.46, 0.93) in women. In contrast with hip and thigh circumferences, waist circumference was positively associated with the incidence of type 2 diabetes in these models (ORs ranging from 1.60 to 2.66). Conclusion: Large hip and thigh circumferences are associated with a lower risk of type 2 diabetes, independently of BMI, age, and waist circumference, whereas a larger waist circumference is associated with a higher risk.
BACKGROUND:Inadequate vitamin D status is common in many populations around the world. OBJECTIVE:The aim was to evaluate potentially modifiable determinants of vitamin D status in an older ...population. DESIGN:This was a cross-sectional study from a population-based cohort including 538 white Dutch men and women aged 60-87 y. Vitamin D status was assessed by plasma 25-hydroxyvitamin D 25(OH)D concentrations. RESULTS:In the winter period, 51% of the subjects had 25(OH)D concentrations <50.0 nmol/L. Greater body fatness and less time spent on outdoor physical activity were associated with worse vitamin D status. Regular use of vitamin D-fortified margarine products odds ratio (OR) in a comparison of intake of >=20 g/d with none: 0.41; 95% CI: 0.20, 0.86; P for trend < 0.001, fatty fish (OR for servings of >=2/mo versus none: 0.41; 95% CI: 0.16, 1.04; P for trend = 0.01), and vitamin D-containing supplements (OR for >= 1/d versus none: 0.33; 95% CI: 0.17, 0.63; P for trend < 0.001) were inversely associated with vitamin D inadequacy 25(OH)D <50.0 nmol/L. We estimated that combined use of margarine products (20 g/d), fatty fish (100 g/wk), and vitamin D supplements (>=1/d) was associated with a 16.8 nmol/L higher 25(OH)D concentration than was the use of none of these. However, none of the participants reached these intakes for all 3 factors. CONCLUSION:Because few foods are vitamin D-fortified and the amounts of vitamin D in supplements are low, it is difficult to achieve adequate vitamin D status through increasing intakes in the Netherlands and in countries with similar policies.
Waist and hip circumferences have been shown to have independent and opposite associations with glucose levels. Waist circumference is positively associated with glucose levels, whereas hip ...circumference is negatively associated. It is unclear which tissues are involved in the pathophysiological mechanism causing these associations. The main goal was to determine which tissue in the trunk and legs, fat or lean tissue, is associated with measures of glucose metabolism.
In 623 participants of the third examination of the Hoorn Study, whole-body dual-energy X-ray absorptiometry was performed to determine fat and lean soft-tissue mass in the trunk and legs. Fasting and 2-h postload glucose levels after 75-g oral glucose tolerance test (OGTT) were determined. After exclusion of known diabetic patients, cross-sectional analyses were performed in 275 men aged 60-87 years (140 with normal glucose metabolism, 92 with impaired glucose metabolism; and 43 with diabetes) and in 281 women (148 with normal glucose metabolism, 90 with impaired glucose metabolism, and 43 with diabetes).
Greater trunk fat mass was associated with higher glucose levels after adjustment for age, trunk lean mass, leg lean mass, and leg fat mass. Standardized beta (95% CI) in men were 0.44 (0.25-0.64) for fasting and 0.41 (0.22-0.60) for postload glucose. For women, these values were 0.49 (0.35-0.63) and 0.47 (0.33-0.61), respectively. In contrast, in the same regression models, a larger leg fat mass was associated with lower glucose levels. Standardized beta in men were -0.24 (-0.43 to -0.05) and -0.12 (-0.31 to 0.07) and in women -0.24 (-0.37 to -0.10) and -0.27 (-0.40 to -0.13) for fasting and postload glucose, respectively. In these models, larger leg lean mass was also associated with lower glucose levels but was only statistically significant in men.
If trunk fat is taken into account, accumulation of fat in the legs seems to be protective against a disturbed glucose metabolism, particularly in women. Further research is needed to unravel underlying pathophysiological mechanisms.
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