Background Although modifiable cardiovascular disease risk factors are common, some patients eschew ceremonious drug treatments in favor of natural alternatives. Pine bark infusion, a dietary supplement source of antioxidant oligomeric proanthocyanidin complexes, has multiple putative cardiovascular benefits. Studies published to date about the accessory have celebrated methodological limitations. Methods We randomized 130 individuals with increased cardiovascular disease risk to take 200 milligram of a water-based infusion of pine bark ( newton = 64 ; Toyo-FVG, Toyo Bio-Pharma, Torrance, California ; Shinyaku Co, Ltd, Saga, Japan ; besides marketed as Flavagenol in Japan ) or placebo ( n = 66 ) once per day. Blood atmospheric pressure, our basal consequence, and other cardiovascular disease risk factors were measured at baseline and at 6 and 12 weeks. statistical analyses were conducted using regression models. Results Baseline characteristics did not differ between the study groups. Over the 12-week treatment, the sum of systolic and diastolic blood pressures decreased by 1.0 mm Hg ( 95 % confidence interval, −4.2 to 2.1 mm Hg ) in the pine bark extract–treated group and by 1.9 mm Hg ( −5.5 to 1.7 mm Hg ) in the placebo group ( P = .87 ). other outcomes were similarly not significantly different, including consistency multitude index, lipid panel measures, liver-colored transaminase test results, lipoprotein cholesterol particle size, and levels of insulin, lipoprotein ( a ), fasting glucose, and high-sensitivity C-reactive protein. There were no subgroups for whom inhalation of pine bark extract affected cardiovascular disease risk factors.
Conclusions This pine bark extract ( at a dose of 200 mg/d ) was safe but was not associated with improvement in cardiovascular disease risk factors. Although variations among participants, dosages, and chemical preparations could contribute to different findings compared with past studies, our results are coherent with a cosmopolitan bankruptcy of antioxidants to demonstrate cardiovascular benefits. Trial Registration clinicaltrials.gov Identifier : NCT00425945
Although traditional strategies such as prescription medications, dietary changes, and physical activity have proven benefits for reducing cardiovascular disease ( CVD ) risk, a solid population seeks option therapies, including diverse dietary supplements, to lower CVD risk. evidence supports the practice of dietary supplements such as fish petroleum for treat and preventing CVD, but rigorous evidence of efficacy and safety is lacking for most supplements. 1 – 4 In particular, supplements containing antioxidant oligomeric proanthocyanidin complexes ( OPCs ) are normally promoted for cardiovascular health. 5 The OPCs are flavonoids found in gamey concentration in extracts of pomegranate, grape seeds, and ache bark. They have high levels of free-radical scavenge and antioxidant action. 6, 7
Pine bark extract may have potential cardiovascular benefits, particularly for rake blackmail. 8 – 10 A blood pressure–lowering effect of ache bark extract has biologic plausibility because of its ability to antagonize the vasoconstriction caused by epinephrine and noradrenaline through increase activity of endothelial azotic oxide synthase. 9, 11, 12 Pine bark extract has been reported to reduce blood concentrations of endothelin, an endothelial-derived vasoconstrictor. 9 By administering a unite daily drug of pine bark distill, 480 milligram, and vitamin C, 240 milligram, to 24 healthy subjects in an open-label preevaluation and postevaluation, Shand et aluminum 12 found a significant decrease of 7 mm Hg in the bastardly systolic blood pressure at 6 weeks, with a confirm decrease at 12 weeks.
Results of holocene studies besides suggest that pine bark extract may have extra cardiovascular benefits, including enhanced glycemic metamorphosis, 8, 9 reduced torso weight unit, 12 and improved lipid profile. 6, 13 Although these studies provide promise indications for benefits, early studies 6, 12, 14, 15 testify limited or no improvement for these conditions. As with investigations of lineage blackmail, most of these studies were receptive label and did not have a placebo control group. Adequate testing for such a wide used dietary addendum requires rigorous placebo-controlled clinical trials. To far evaluate the cardiovascular benefits of pine bark distill, we investigated the efficacy of pine bark extract on blood pressure and early CVD hazard factors. The primary guess was that pine bark extract would lower blood pressure in a population of corpulence and corpulent participants with baseline prehypertension or high blood pressure. We chose a population at gamble of developing CVD and not taking antihypertensive medications who would be likely to seek dietary supplements as an alternative therapy.
Methods
We conducted a randomized, placebo-controlled, double-blind, parallel-group clinical trial. A sum of 130 corpulence and corpulent adults with systolic blood pressure above that considered optimum ( 125-160 millimeter Hg ) were enrolled between January 31, 2007, and May 31, 2008. Participants were randomly assigned on a 1:1 ratio to take 200 magnesium of a french nautical pine bark educe ( Toyo-FVG, Toyo Bio-Pharma, Torrance, California ; Toyo Shinyaku Co, Ltd, Saga, Japan ; besides marked as Flavagenol in Japan ). randomization was performed using the permute stuff method ( block size, 6 ) stratified by sex. Participants and all study staff ( including clinicians ) were blinded until study completion. Data were collected at service line and at 6 and 12 weeks after randomization, with a restrict 3-week visit to assess adverse events. statistical analyses were conducted using arrested development models. The learn protocol was approved by the Stanford University Institutional Review Board, Stanford, California.
Participants
Participants were recruited from the local community by radio and print advertisements. Among 2411 individuals who completed the initial riddle by telephone and on-line, 643 were identified who were not taking diabetes medicine, high blood pressure medicine, or any dietary supplements within the past calendar month aside from the recommended casual measure of multivitamins ( Figure 1 ). These individuals were invited to attend clinical riddle at the Stanford Prevention Research Center. The inclusion criteria were fleshy or fleshiness class I ( body bulk index [ BMI ] calculated as weight in kilograms divided by stature in meters squared, 25.0-34.9 ) and prehypertensive or hypertensive systolic lineage atmospheric pressure ( 125-160 millimeter Hg ). many participants had suboptimal lipoprotein profiles and high-sensitivity C-reactive protein levels, but those with fast levels exceeding the following were excluded : 450 mg/dL for triglycerides, 126 mg/dL for lineage glucose, or 200 mg/dL for low-density lipoprotein cholesterol ( LDL-C ) ( to convert triglycerides level to millimoles per liter, breed by 0.0113 ; glucose level to millimoles per liter, breed by 0.0555 ; and cholesterol level to millimoles per liter, multiply by 0.0259 ). These measurements for eligibility screen were obtained by point-of-care screen ( LDX and GDX analyzers ; Cholestech Corporation, Hayward, California ). 16 Individuals eligible at clinical screen were invited to attend a report orientation session, during which informed accept was obtained. randomization followed the completion of 2 baseline visits.
randomization
The sketch presenter ( Toyo Shinyaku Co, Ltd ) provided the researchers with ache bark excerpt and placebo study tablets labeled “ A ” and “ B. ” Computer-generated, sex-stratified, block permutation lists were generated by the research analyst and were provided to the pharmacy staff. At the decision of the second gear service line travel to, pharmacy staff dispensed survey tablet A or discipline tablet B accordingly. Participants were equally likely to be randomized to receive either study tablet. Pharmacy staff had no role in subject recruitment, judgment, or follow-up. Investigators and all cogitation staff were blinded to treatment assignment until all survey results were collected, at which time the study sponsor revealed which tablet, A or B, contained ache bark press out.
Study tablets and attachment
Study tablets of pine bark infusion contained 50 mg each and were vacuum packed in sachets with each containing 4 tablets ( 200 milligram ). This dose was selected based on the midrange of administration in past studies and the OPC capacity of this pine bark press out compared with other formulations. This formulation of ache bark extract is extracted from the milled bark of Pinus pinaster ( besides known as Pinus maritime and Pinus maritimus ) using heated water. The educe is concentrated by dehydration and according to the manufacturer contains approximately 40 % proanthocyanidin oligomers ( dimer, trimer, and tetramer ), 42 % early polyphenols, and 18 % other substances. The extract is subsequently compounded with excipients of palatinit boodle, caramel, sucrose, fatty acerb ester, and calcium stearate. The placebo tablets consisted of these like excipients.
Participants in either study group were instructed to take 4 tablets at the same time each good morning. Tablets were distributed at service line and at 3 and 6 weeks. Adherence was tracked by counting returned tablets at 3, 6, and 12 weeks. Tablet count was conducted by drugstore staff, who had no direct patient reach. Participants were asked to refrain from changing their diet, losing burden, and beginning new dietary supplements or medications during the study. Three-day food records were administered at service line and at 12 weeks to monitor changes in diet, particularly intake of antioxidant-rich foods. Participants were queried about their consumption of dietary supplements and medications at screening and were asked to report any changes.
Outcomes
Two sets of resting rake press measurements, the primary result, were obtained over a 3-day interval at baseline and at 12 weeks, and a single set was obtained at 6 weeks. All blood pressures were measured by register nurses trained in the cogitation protocol using a blood pressure monitor ( Dinamap ; Critikon Corporation, Tampa, Florida ). To obtain a stay blood coerce, participants sat restfully for 5 minutes before the first measurement. All measurements were obtained with participants in a seat position, with their feet and ankles uncrossed, using the correctly sleeve. At each clinic sojourn, 3 lineage blackmail measurements were obtained, with at least 1 infinitesimal elapsing between the first and second measurements and with at least 3 minutes elapsing between the moment and third base measurements. Blood pressure for a given time compass point ( baseline, 6, and 12 weeks ) was calculated by taking the mean of all readings after discarding the first read of each sidereal day.
Fasting ( ≥10 hours ) rake samples were collected once at 6 weeks and doubly ( with 3-5 days between tests ) at baseline and at 12 weeks. Insulin, fasting glucose, and glycated hemoglobin levels were used to assess glucose metamorphosis. lipid panel measures ( high-density lipoprotein cholesterol [ HDL-C ], LDL-C, and triglycerides ) and lipoprotein cholesterol particle size results were used to assess plasma lipoprotein cholesterol visibility. High-sensitivity C-reactive protein level was used as a meter of systemic inflammation. Alanine transaminase and aspartate transaminase levels assured intersection base hit. Assessment of lipoprotein cholesterol atom size and levels of glycated hemoglobin, lipoprotein ( a ), and high-sensitivity C-reactive protein was conducted by an away lab ( Liposcience, Raleigh, North Carolina ). All early tests were performed at Stanford Hospital and Clinics Laboratory. Both laboratories are regulated by the Clinical Laboratory Improvement Act.
Height was measured once at baseline to the nearest tenth of an inch using a wall-mounted stadiometer. Body weight was measured to the nearest one-tenth of a hammer once at 6 weeks and on 2 different days at service line and at 12 weeks using a calibrated poise scale. waist circumference was measured to the nearest one-tenth of an column inch in the horizontal plane around the abdomen at the tied of minimal circumference.
adverse events and adverse effects were assessed using a survey administered at 3, 6, and 12 weeks. The adverse events and adverse effects questionnaire asked about symptoms normally reported in past studies of pine bark educe, hospital and hand brake department visits, new diagnoses, and changes in existing diagnoses. Participants were instructed to contact study staff if they experienced adverse events between report visits. In accession, we monitored report data for lift rake imperativeness, liver-colored function test results, and levels of glucose, triglycerides, and LDL-C.
statistical analysis
comparison of the ache bark extract and placebo groups on service line demographic and clinical characteristics was assessed by t test for continuous variables and by Pearson intersection here and now correlation χ2 examination for categoric variables. The primary result was the blend deepen in systolic and diastolic blood pressures from baseline to 12 weeks. We hypothesized that this sum would decrease by at least 7 millimeter Hg in the pine bark extract group relative to the placebo group after 12 weeks. After projecting 10 % participant grinding over 12 weeks, a sample size of 130 participants ( 65 per study group ) was calculated to provide 75 % ability for detecting an effect size of 0.5 ( beggarly divided by standard deviation ) at α = .05.
Following our a priori primary analysis plan, the effect of pine bark extract on the primary result, 12-week blood pressure deepen, was examined using a regression exemplary with 12-week blood pressure transfer as the subject variable and with service line blood coerce as a covariate. Although demographic variables were not importantly unlike between groups at baseline, we evaluated them as covariates in this regression exemplar. none were included in the concluding models because they were not significant statistically at P < .20. secondary outcomes were assessed using exchangeable regression models. Changes in rake blackmail and in secondary coil outcomes were analyzed at 6 weeks using this like method acting. Because the 6-week outcomes did not differ from those noted at 12 weeks, we present lone our analysis of 12-week outcomes. We besides analyzed the datum on an intent-to-treat footing, with the survive observation collected carry forward for participants with missing data at follow-up. As expected given limited loss to follow-up, the findings were about identical and are not presented. Missing adhesiveness data were conservatively calculated as if the player had consumed no study tablets. All statistical tests were 2-tailed, and the doorsill significance level was P < .05. statistical psychoanalysis was conducted using commercially available software ( SAS, interpretation 9.1 ; SAS Institute Inc, Cary, North Carolina ).
Results
Baseline data and survey retentiveness
No significant differences were noted in the baseline characteristics of the pine bark excerpt group ( normality = 64 ) vs the placebo group ( n = 66 ) ( table 1 ). coherent with our recruitment of a population with lineage pressures above the normal ( 120/80 millimeter Hg ) range, the bastardly ( SD ) blood pressures at baseline were 132.6 ( 10.9 ) /78.6 ( 7.9 ) millimeter Hg for the pine bark extract group and 133.2 ( 10.9 ) /79.9 ( 7.7 ) millimeter Hg for the placebo group. early mean levels were within convention or clinically acceptable ranges at baseline except for high-sensitivity C-reactive protein ( 2.6 [ SD, 2.8 ] mg/L for the pine bark extract group and 2.6 [ SD, 2.9 ] mg/L for the placebo group ) ; C-reactive protein charge to nanomoles per liter, reproduce by 9.524 ).
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Of 130 randomized participants, 7 participants ( 4 in the ache bark press out group and 3 in the placebo group ) dropped out before the 6-week data collection orient, and 2 participants in the placebo group dropped out after the 6-week data solicitation item, for a 93.1 % retention pace ( Figure 1 ). Of 4 participants in the pine bark extract group who dropped out, 2 were concerned about possible adverse effects of the supplement, 1 began a blood pressure medicine, and 1 began cancer treatments. Of 5 participants in the placebo group who dropped out, 1 moved extinct of the area, 2 were concerned about the cost and clock of traveling to study visits, and 2 were lost to follow-up.
Study pad and diet
The hateful study pill attachment rates were 90.1 % in the ache bark educe group and 92.6 % in the placebo group ( P = .35 ). The median adhesiveness was 96.4 % in both groups. failure to consume at least 50 % of study tablets was evenly likely in both groups ( 5 % for both, P = .97 ). We analyzed changes in multiple dietary variables between the 2 groups from service line to 12 weeks, none of which were statistically significant except for potassium consumption ( 75 milligram in the pine bark press out group vs −293 magnesium in the placebo group, P = .03 ). Intake of fruit ( P = .24 ) and vegetables ( P = .16 ), the primary dietary sources of antioxidants, did not change differentially between the groups.
effect of pine bark extract on blood blackmail
At 6 weeks, systolic and diastolic blood pressure changes were insignificant, with systolic plus diastolic blood pressure decreasing by 1.1 mm Hg in the intervention group and by 1.2 mm Hg in the placebo group ( Figure 2 ). After 12 weeks, blood press changes from baseline remained nonsignificant ( P = .87 ). The pine bark extract group had a 0.1–mm Hg ( 95 % confidence time interval [ CI ], −2.2 to 2.0 mm Hg ) decrease in systolic blood coerce and a 0.9–mm Hg ( −2.2 to 0.4 mm Hg ) decrease in diastolic blood atmospheric pressure ( total decrease in blood pressure, 1.0 millimeter Hg ; −4.2 to 2.1 mm Hg ) from baseline to 12 weeks ( Figure 2 and Figure 3 and Figure 4 ). The placebo group had a 1.6–mm Hg ( 95 % CI, −4.0 to 0.9 mm Hg ) decrease in systolic blood pressure and a 0.35–mm Hg ( −1.8 to 1.0 mm Hg ) decrease in diastolic rake pressure ( entire decrease in rake atmospheric pressure, 1.9 millimeter Hg ; 95 % CI, −5.5 to 1.7 mm Hg ) from service line to 12 weeks.
secondary outcomes
Changes in secondary CVD risk factors from baseline to 12 weeks were assessed for glycemic metabolism, plasma lipoprotein cholesterol measures, systemic excitement, and measures of adiposity. Differences from baseline to 12 weeks between the pine bark press out group and the placebo group did not reach statistical meaning except for BMI, which increased in the ache bark press out group ( from 29.0 to 29.1 ) and decreased in the placebo group ( from 28.4 to 28.3 ) ( group exchange difference, 0.20 ; 95 % CI, 0.03-0.39 ; P = .02 ) ( table 2 ).
adverse effects
adverse events were reported by 43 participants in the pine bark extract group and by 42 participants in the placebo group and did not differ in asperity or by specific symptom. At 6 weeks and at 12 weeks, participants ‘ coverage of particular symptoms was common and equally frequent in both groups. At 12 weeks, the most normally reported symptoms were headache ( 45.5 % in the pine bark excerpt group vs 45.2 % in the placebo group ), sleepiness ( 40.9 % vanadium 45.2 % ), frequent micturition ( 38.6 % vanadium 31.0 % ), gastrointestinal tract discomfort ( 38.6 % volt 35.7 % ), and insomnia ( 34.1 % v 31.0 % ). In the pine bark distill group, there was 1 hospitalization and no emergency department visits. In the placebo group, there were no hospitalizations and 2 emergency department visits. No meaning differences were noted between the 2 groups in liver alanine transaminase or aspartate transaminase test results at 6 weeks or at 12 weeks ( table 2 ).
Subgroup analyses
We assessed whether an effect of pine bark distill might be limited to particular participant subgroups because player baseline variables were within the convention rate for many outcomes. Analyses were performed for subgroups defined by sex, slant, BMI, waist circumference above and below the medial for age, baseline systolic lineage imperativeness of 130 mm Hg or higher, ratio of sum cholesterol level to HDL-C degree of 3.5 or higher, and levels of glucose, cholesterol, triglycerides, glycated hemoglobin, and high-sensitivity C-reactive protein. There were no meaning differences in lineage imperativeness among any subgroups, while sporadic statistically significant differences, as might be expected by chance, were found for other outcomes. Despite our extensive subgroup analysis, the only suggestion of an impression was for participants with baseline systolic rake blackmail of 130 mm Hg or higher, among whom the mean ( SD ) lipoprotein ( a ) tied decreased by 2 ( 10 ) nmol/L among 37 individuals in the pine bark extract group ( baseline level, 37 nmol/L ) and increased by 4 ( 10 ) nmol/L among 38 individuals in the placebo group ( 47 nmol/L ).
comment
Our aim was to determine the effects of ache bark excerpt on rake pressure and other CVD risk factors in fleshy and corpulent adults with higher-than-optimal systolic blood pressure. The study used a randomize, placebo-controlled, double-blind clinical trial design and achieved a sample distribution size larger than most previous studies of ache bark excerpt. No significant effects on blood pressure, plasma lipoprotein cholesterol profile, glycemic metamorphosis, or incendiary markers were observed between the pine bark extract group and the placebo group. furthermore, when we limited our analysis to subgroups with more extreme values of numerous risk factors, we besides failed to detect an effect of this ache bark extract ( at 200 mg/d ) on outcomes.
Our findings are coherent with a growing body of experimental and clinical test tell that dietary supplements, particularly antioxidant supplementation, do not have a beneficial effect on heart disease. 17 – 20 Vivekananthan et aluminum 20 performed a meta-analysis of large randomize clinical trials of vitamin E and beta carotene treatment and showed that they were ineffective for CVD prevention. In accession, the Women ‘s Health Initiative 19 followed up 161 000 women for 7.9 years, and observation data showed no association between multivitamin function and CVD. Clinical, experimental, and meta-analysis studies 17, 18, 21 besides showed that megadoses of vitamins were nonprotective against diverse cancers. Some studies 17, 20 besides link antioxidant addendum consumption to increased mortality risk.
several studies 8, 12, 22 reported that pine bark extract decreases rake pressure. Shand et aluminum 12 observed a decrease of 7 mm Hg in systolic plus diastolic rake pressures combined for 24 participants taking ache bark extract ( 480 mg/d ) for 12 weeks, while Hosseini et alabama 22 noted a decrease in systolic lineage pressure for 11 participants taking ache bark excerpt ( 200 mg/d ) for 8 weeks. however, both of these studies lacked a comparison manipulate group. In a randomize clinical trial, Liu et alabama 8 found that participants with high blood pressure taking pine bark press out ( 100 mg/d ) required lower doses of nifedipine to obtain normal rake coerce but did not test the effect of ache bark extract in the absence of conventional medications. In the largest randomize clinical trial to date focused on pine bark infusion and lineage coerce, we found that this append did not lower rake pressure among fleshy and corpulent participants with prehypertension or with stage 1 high blood pressure.
Trials of ache bark extract have shown decreases in LDL-C level, 6, 23 while equal numbers of trials, including ours, reported no significant benefits of ache bark excerpt on LDL-C flat. 12, 14 Devaraj et aluminum 6 observed an increase in HDL-C level with ache bark extract but no effect on triglycerides level. Two early studies 12, 14 showed no effect of pine bark extract on HDL-C level. Our subgroup analyses of individuals with elevated railway service line glucose and plasma lipid levels provide extra tell that the pine bark educe evaluated herein does not improve these CVD hazard factors.
Our study has respective strengths. It is the largest study to date of pine bark extract and CVD gamble factors. It used a rigorous randomized controlled trial method, while most other studies of pine bark extract were unfold tag and lacked clear data collection techniques. Our study controlled for life style effects by instructing participants to maintain their baseline dietary and physical activity patterns and by assessing these electric potential confounders at service line and at the end of the cogitation. In addition, although there were no previous base hit concerns about pine bark excerpt, this discipline contributes to tell about the guard of ache bark extract, including its effect on liver-colored function.
There are respective limitations of the study. While the percentage of OPCs in the pine bark extract evaluated herein is comparable to that of other commercially available pine bark extracts, there are variations in monomer, dimer, and trimer chemical components of pine bark extracts with similar percentages of OPCs. This may account for variations in physiologic effects among different pine bark extract preparations and among antioxidants in general. 24 Hence, study findings about this ache bark press out ( at 200 mg/d ) may not be fully applicable to other ache bark extracts or to antioxidant dietary supplements in general. This study exemplifies the challenge faced by researchers studying dietary supplements with chemical constituents that are not well standardized.
furthermore, past studies 8, 15 have shown decreases in CVD risk factors when pine bark extract was tested as an adjunct to conventional pharmacological treatment. In contrast, we evaluated the effects of ache bark excerpt as a alone therapy, a design more likely to isolate the effect of pine bark press out. In addition, we recognize that a hearty part of our cogitation population had baseline lipid panel and lipoprotein profile values within a normal range or an satisfactory range. Nevertheless, we placid would have expected improvement in CVD risk factors given the putative biological mechanism of antioxidants. exploratory analyses of subgroups with promote risk factor values besides failed to reveal any CVD risk component improvement.
In ending, the pine bark distill ( 200 mg/d ) tested in this study for 12 weeks among an fleshy and corpulent population with elevated blood pressure and other CVD risk factors was safe but did not improve lineage pressure or versatile other CVD risk factors. In addition, no profit was noted for subpopulations with service line values higher than medial risk. Although a unlike dose or formulation might produce different results, our findings argue against recommending this pine bark press out to improve CVD risk factors.
Correspondence: Randall S. Stafford, MD, PhD, Program on Prevention Outcomes and Practices, Stanford Prevention Research Center, Stanford University School of Medicine, Stanford, CA 94305-5411 ( rstafford @ stanford.edu ).
Accepted for Publication: February 9, 2010.
Author Contributions: Study concept and design : Drieling, Gardner, Ma, and Stafford. Acquisition of data : Drieling and Stafford. Analysis and interpretation of data : Drieling, Gardner, Ma, Ahn, and Stafford. Drafting of the manuscript : Drieling and Stafford. Critical revision of the manuscript for important intellectual content : Drieling, Gardner, Ma, Ahn, and Stafford. Statistical analysis : Ma, Ahn, and Stafford. Obtained funding : Drieling, Ma, and Stafford. Administrative, technical, and material support : Drieling and Stafford. Study supervision : Drieling and Stafford. Clinical and safety oversight : Stafford.
Financial Disclosure: none reported.
Funding/Support: This research was supported by a research grant from Toyo Shinyaku Co, Ltd, Saga, Japan. Toyo Shinyaku Co, Ltd provided study tablets ( Toyo-FVG ache bark extract and placebo ).
Role of the Sponsor: Toyo Shinyaku Co, Ltd was not responsible for the study blueprint, data psychoanalysis, data rendition, or cooking or content of the publication.
Additional Contributions: Alexis Fields, BA, and Heather Klaftenegger, BS, provided inquiry aid and corroborate, and Diane Castle, BA, managed survey funds.
This article was corrected on-line for typographic errors on 9/27/2010.
References