Does It Matter How Hypertension Is Controlled?

Moral of the story: The ACCOMPLISH trial showed new outcomes data that is not consistent with previous data, where there were no differences in benefit received as long as the drop in blood pressure was equivalent. It can't hurt to follow the results of the new data, so I would go with that.

Does It Matter How Hypertension Is Controlled?
Aram V. Chobanian, M.D.

Hypertension is one of the most important risk factors for cardiovascular and renal diseases. Currently, approximately 73 million adults in the United States and approximately 1 billion adults worldwide have hypertension, and the prevalence is increasing.¹ Many clinical trials have examined the effects of antihypertensive drugs. Studies comparing the effects of antihypertensive medications with those of placebo have shown consistently that lowering blood pressure is associated with major reductions in the incidence of coronary events, strokes, and congestive heart failure.² These benefits have been observed irrespective of age, sex, severity of the hypertension, presence or absence of associated risk factors or concomitant diseases, or class of antihypertensive drug used. However, the results of trials comparing the effects of different antihypertensive drugs or drug regimens have not been as consistent.

The initial findings from a new drug comparison study, the Avoiding Cardiovascular Events through Combination Therapy in Patients Living with Systolic Hypertension (ACCOMPLISH) trial (ClinicalTrials.gov number, NCT00170950 [ClinicalTrials.gov] ), are reported in this issue of the Journal.³ The ACCOMPLISH trial was a randomized, double-blind, industry-sponsored study involving subjects with hypertension that examined the effects on cardiovascular outcomes of treatment with the angiotensin-converting–enzyme (ACE) inhibitor benazepril combined with either the calcium-channel blocker amlodipine or the diuretic hydrochlorothiazide. Somewhat surprisingly, as compared with the benazepril–hydrochlorothiazide group, the group that was treated with benazepril and amlodipine had a relative risk reduction of approximately 20%, and an absolute risk reduction of 2.2%, in the primary end point, a composite of illness and death from cardiovascular causes. The secondary end point of death from cardiovascular causes and nonfatal myocardial infarction and stroke showed a similar benefit.

The ACCOMPLISH study population was at high risk for cardiovascular diseases. The average age at entry was 68 years, and participants with a history of ischemic heart disease, peripheral vascular disease, stroke, left ventricular hypertrophy, or diabetes (which was present in 60% of the subjects) were included. Because the study design did not include a drug washout period, data on pretreatment blood-pressure levels were unavailable. However, most subjects probably had relatively severe hypertension; at study entry, 38% were receiving three or more antihypertensive drugs, yet only 37% had blood-pressure levels less than 140/90 mm Hg.

Most previous comparison trials have failed to show significant differences in the primary outcomes as long as equivalent decreases in blood pressure were achieved with the different drug regimens. Selected examples include the Swedish Trial in Old Patients with Hypertension-2 (STOP-2) trial, a study that examined treatment with diuretics and beta-blockers as compared with treatment with ACE inhibitors and calcium-channel blockers in elderly subjects with hypertension⁴; the International Verapamil-Trandolapril Study (INVEST) (NCT00133692 [ClinicalTrials.gov] ), a trial in which a regimen of verapamil with or without trandolapril was compared with a regimen of atenolol with or without hydrochlorothiazide among patients with hypertension and coronary heart disease⁵; and the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) (NCT00000542 [ClinicalTrials.gov] ), which compared chlorthalidone, lisinopril, and amlodipine therapies.⁶ In none of these trials did the primary outcomes differ between regimens. In the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT), which compared treatment with the combination of amlodipine and perindopril with treatment with the combination of atenolol and bendroflumethiazide, the primary outcome of fatal coronary heart disease and nonfatal myocardial infarction also did not differ significantly between the two treatment groups; the composite secondary outcomes, which included stroke, were less favorable in the atenolol–bendroflumethiazide group, which also had average blood-pressure levels that were approximately 3 mm Hg systolic and 2 mm Hg diastolic higher than those of subjects in the amlodipine–perindopril group.⁷ In contrast, in the Losartan Intervention for Endpoint Reduction in Hypertension (LIFE) study (NCT00338260 [ClinicalTrials.gov] ), the primary cardiovascular outcomes (particularly stroke) with treatment with the angiotensin-receptor blocker losartan were better than those with atenolol therapy, even though there were similar reductions in blood pressure in the two groups.⁸ In the Second Australian National Blood Pressure Study, ACE-inhibitor therapy was associated with a somewhat lower incidence of cardiovascular events than thiazide-based treatment, although the benefit was observed only in men.⁹

No previous outcome trial has compared treatment with a combination of an ACE inhibitor and a calcium-channel blocker with treatment with the combination of an ACE inhibitor and a thiazide-type diuretic. ALLHAT compared chlorthalidone therapy with amlodipine therapy, though not in combination with an ACE inhibitor. The chlorthalidone dose used in ALLHAT and the hydrochlorothiazide dose used in the ACCOMPLISH trial were both in a range of 12.5 to 25.0 mg per day. Chlorthalidone is estimated to have double the potency of hydrochlorothiazide and a much longer duration of effect in this dose range. A recent study used 24-hour ambulatory blood-pressure measurements to study the effects of chlorthalidone (25 mg per day) as compared with hydrochlorothiazide (50 mg per day).¹⁰ Although blood-pressure levels measured during the daytime in the clinician's office were similar, blood-pressure levels measured during the nighttime, and 24-hour average blood pressures, were considerably lower with chlorthalidone than with hydrochlorothiazide. The reported blood-pressure levels measured in the clinician's office in the ACCOMPLISH trial were also relatively similar in the two treatment groups, but the possibility exists that the relatively low dose of hydrochlorothiazide used (averaging 19 mg per day) did not provide 24-hour blood-pressure control that was as effective as that provided by the benazepril–amlodipine regimen. Ambulatory blood-pressure measurements were apparently included in the design of the ACCOMPLISH trial,¹¹ and the data, if available, could address this issue in the future.

Experimental evidence has suggested that ACE inhibitors and calcium-channel blockers can have vasoprotective effects. These agents have been shown to inhibit atherosclerosis in various animal models with hypercholesterolemia and to improve endothelium-dependent vasodilatation in isolated arteries and in patients with vascular disease.^12,13 Diuretics do not share these properties. However, the clinical relevance of these findings is uncertain.

Are the results from the ACCOMPLISH trial applicable to the general population with hypertension? As noted above, the study participants were older and had relatively severe hypertension and a high prevalence of cardiovascular disease and diabetes. Although this group of subjects clearly does not mirror the broader population with hypertension, the same criticism can be applied to the other trials as well. Treatment recommendations should be based on the total available evidence rather than on the results of any single trial.

The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure, published in 2003, included a strong preference for thiazide-type diuretics as the initial therapy for most patients with hypertension in the absence of compelling indications for specific drugs.¹⁴ However, it is time to reexamine these recommendations. The results from the many recent studies, including the ACCOMPLISH trial, when considered together, suggest that greater flexibility is now indicated in the choice of the initial drug. In my opinion, each of the major classes (diuretics, ACE inhibitors, calcium-channel blockers, angiotensin-receptor blockers, and, to a lesser extent, beta-blockers) appears reasonable as first-line therapy. The choice of a drug should depend on criteria such as compelling indications or contraindications, coexisting conditions, adverse effects, race, and the clinician's experience. Nevertheless, increased flexibility in choice should not negate the importance of diuretics, which have been a cornerstone of antihypertensive therapy for the past 50 years. The data from the ACCOMPLISH trial also should not diminish the value of treatment with the combination of an ACE inhibitor and a diuretic, a combination that effectively lowers blood pressure and that was recently shown to produce major reductions in mortality and morbidity in the very old.¹⁵

Many excellent medications are available to control hypertension. These drugs have acceptable side-effect and adverse-event profiles, and many are now available in generic versions, making cost less of an issue in the selection of a drug. Most patients with hypertension will require two or more drugs to control their hypertension, and combination drug formulations may also be useful. Although specific benefits may be provided by a given drug or drug combination, the evidence is overwhelming that the most important aspect of treatment is to reduce blood pressure to goal levels. How this is achieved is less important. Unfortunately, despite the remarkable progress in therapy, blood pressure remains inadequately controlled in almost two thirds of patients with hypertension in the United States. We must do better.

Dr. Chobanian reports serving as chair for the seventh report of the Joint National Committee, which developed guidelines for the management of hypertension, and receiving a lecture fee from Bristol-Myers Squibb of Mexico. No other potential conflict of interest relevant to this article was reported.

Source Information

From the Department of Medicine, Boston University School of Medicine, and the Boston University Medical Center, Boston.

References

1. Heart disease and stroke statistics: 2008 update at-a-glance. Dallas: American Heart Association, 2008. (Accessed November 13, 2008, at http://www.americanheart.org/downloadable/heart/1200082005246HS_Stats%202008.final.pdf.)
2. Turnbull F, Neal B, Algert C, et al. Effects of different blood pressure-lowering regimens on major cardiovascular events in individuals with and without diabetes mellitus: results of prospectively designed overviews of randomized trials. Arch Intern Med 2005;165:1410-1419. [Free Full Text]
3. Jamerson K, Weber MA, Bakris GL, et al. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high-risk patients. N Engl J Med 2008;359:2417-2428. [Free Full Text]
4. Hansson L, Lindholm LH, Ekbom T, et al. Randomised trial of old and new antihypertensive drugs in elderly patients: cardiovascular mortality and morbidity the Swedish Trial in Old Patients with Hypertension-2 study. Lancet 1999;354:1751-1756. [CrossRef][ISI][Medline]
5. Pepine CJ, Handberg EM, Cooper-DeHoff RM, et al. A calcium antagonist vs a non-calcium antagonist hypertension treatment strategy for patients with coronary artery disease: the International Verapamil-Trandolapril Study (INVEST): a randomized controlled trial. JAMA 2003;290:2805-2816. [Free Full Text]
6. Major outcomes in high-risk hypertensive patients randomized to angiotensin-converting enzyme inhibitor or calcium channel blocker vs diuretic: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2002;288:2981-2997. [Erratum, JAMA 2003;289:178, 2004;291:2196.] [Free Full Text]
7. Dahlöf B, Sever PS, Poulter NR, et al. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. Lancet 2005;366:895-906. [CrossRef][ISI][Medline]
8. Dahlöf B, Devereux RB, Kjeldsen SE, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet 2002;359:995-1003. [CrossRef][ISI][Medline]
9. Wing LM, Reid CM, Ryan P, et al. A comparison of outcomes with angiotensin-converting-enzyme inhibitors and diuretics for hypertension in the elderly. N Engl J Med 2003;348:583-592. [Free Full Text]
10. Ernst ME, Carter BL, Goerdt CJ, et al. Comparative antihypertensive effects of hydrochlorothiazide and chlorthalidone on ambulatory and office blood pressure. Hypertension 2006;47:352-358. [Free Full Text]
11. Jamerson KA, Bakris GL, Wun CC, et al. Rationale and design of the Avoiding Cardiovascular events through COMbination therapy in Patients LIving with Systolic Hypertension (ACCOMPLISH) trial: the first randomized controlled trial to compare the clinical outcome effects of first-line combination therapies in hypertension. Am J Hypertens 2004;17:793-801. [ISI][Medline]
12. Chobanian AV, Haudenschild CC, Nickerson C, Drago R. Antiatherogenic effect of captopril in the Watanabe heritable hyperlipidemic rabbit. Hypertension 1990;15:327-331. [Free Full Text]
13. Lüscher TF, Wenzel RR, Moreau P, Takase H. Vascular protective effects of ACE inhibitors and calcium antagonists: theoretical basis for a combination therapy in hypertension and other cardiovascular diseases. Cardiovasc Drugs Ther 1995;3:509-523.
14. Chobanian AV, Bakris GL, Black HR, et al. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report. JAMA 2003;289:2560-2572. [Erratum, JAMA 2003;290:197.] [Free Full Text]
15. Beckett NS, Peters R, Fletcher AE, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med 2008;358:1887-1898. [Free Full Text]

Benazepril plus Amlodipine or Hydrochlorothiazide for Hypertension in High-Risk Patients

Moral of the story: it matters what medications you are taking for high blood pressure. Talk to your physician about whether your regimen adheres to the recommendations of the ACCOMPLISH trial.

Benazepril plus Amlodipine or Hydrochlorothiazide for Hypertension in High-Risk Patients

Kenneth Jamerson, M.D., Michael A. Weber, M.D., George L. Bakris, M.D., Björn Dahlöf, M.D., Bertram Pitt, M.D., Victor Shi, M.D., Allen Hester, Ph.D., Jitendra Gupte, M.S., Marjorie Gatlin, M.D., Eric J. Velazquez, M.D., for the ACCOMPLISH Trial Investigators

ABSTRACT

Background The optimal combination drug therapy for hypertension is not established, although current U.S. guidelines recommend inclusion of a diuretic. We hypothesized that treatment with the combination of an angiotensin-converting–enzyme (ACE) inhibitor and a dihydropyridine calcium-channel blocker would be more effective in reducing the rate of cardiovascular events than treatment with an ACE inhibitor plus a thiazide diuretic.

Methods In a randomized, double-blind trial, we assigned 11,506 patients with hypertension who were at high risk for cardiovascular events to receive treatment with either benazepril plus amlodipine or benazepril plus hydrochlorothiazide. The primary end point was the composite of death from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, hospitalization for angina, resuscitation after sudden cardiac arrest, and coronary revascularization.

Results The baseline characteristics of the two groups were similar. The trial was terminated early after a mean follow-up of 36 months, when the boundary of the prespecified stopping rule was exceeded. Mean blood pressures after dose adjustment were 131.6/73.3 mm Hg in the benazepril–amlodipine group and 132.5/74.4 mm Hg in the benazepril–hydrochlorothiazide group. There were 552 primary-outcome events in the benazepril–amlodipine group (9.6%) and 679 in the benazepril–hydrochlorothiazide group (11.8%), representing an absolute risk reduction with benazepril–amlodipine therapy of 2.2% and a relative risk reduction of 19.6% (hazard ratio, 0.80, 95% confidence interval [CI], 0.72 to 0.90; P<0.001).> of death from cardiovascular causes, nonfatal myocardial infarction, and nonfatal stroke, the hazard ratio was 0.79 (95% CI, 0.67 to 0.92; P=0.002). Rates of adverse events were consistent with those observed from clinical experience with the study drugs.

Conclusions The benazepril–amlodipine combination was superior to the benazepril–hydrochlorothiazide combination in reducing cardiovascular events in patients with hypertension who were at high risk for such events. (ClinicalTrials.gov number, NCT00170950 [ClinicalTrials.gov] .)

General and Abdominal Adiposity and Risk of Death in Europe

Moral of the story: Not only does your general BMI and fat percentage matter to your health, but abdominal fat deposits are a separate risk factor. In addition to making sure your BMI falls within the acceptable range for your gender (link here: BMI information and calculator from the CDC) you should make sure your waist size is reasonable. General aerobic exercise is excellent for your health, but spend a little extra time slimming that waist.

The full article can be accessed here

General and Abdominal Adiposity and Risk of Death in Europe
T. Pischon, M.D., M.P.H., H. Boeing, Ph.D., M.S.P.H., K. Hoffmann, Ph.D., M. Bergmann, Ph.D., M.B. Schulze, Dr.P.H., K. Overvad, M.D., Ph.D., Y.T. van der Schouw, Ph.D., E. Spencer, Ph.D., K.G.M. Moons, Ph.D., A. Tjønneland, M.D., Ph.D., Dr.Med.Sci., J. Halkjaer, Ph.D., M.K. Jensen, Ph.D., J. Stegger, M.D., F. Clavel-Chapelon, Ph.D., M.-C. Boutron-Ruault, Ph.D., V. Chajes, Ph.D., J. Linseisen, Ph.D., R. Kaaks, Ph.D., A. Trichopoulou, M.D., Ph.D., D. Trichopoulos, M.D., Ph.D., C. Bamia, Ph.D., S. Sieri, Ph.D., D. Palli, M.D., R. Tumino, M.D., P. Vineis, M.D., M.P.H., S. Panico, M.D., M.Sc., P.H.M. Peeters, M.D., Ph.D., A.M. May, Ph.D., H.B. Bueno-de-Mesquita, M.D., Ph.D., M.P.H., F.J.B. van Duijnhoven, Ph.D., G. Hallmans, M.D., L. Weinehall, M.D., Ph.D., J. Manjer, M.D., Ph.D., B. Hedblad, M.D., Ph.D., E. Lund, M.D., Ph.D., A. Agudo, Ph.D., L. Arriola, Ph.D., A. Barricarte, Ph.D., C. Navarro, M.D., Ph.D., C. Martinez, M.D., J.R. Quirós, M.D., T. Key, D.Phil., S. Bingham, Ph.D., K.T. Khaw, M.B., B.Chir., P. Boffetta, M.D., M.P.H., M. Jenab, Ph.D., P. Ferrari, Ph.D., and E. Riboli, M.D., M.P.H., Sc.M.

ABSTRACT

Background Previous studies have relied predominantly on the body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) to assess the association of adiposity with the risk of death, but few have examined whether the distribution of body fat contributes to the prediction of death.

Methods We examined the association of BMI, waist circumference, and waist-to-hip ratio with the risk of death among 359,387 participants from nine countries in the European Prospective Investigation into Cancer and Nutrition (EPIC). We used a Cox regression analysis, with age as the time variable, and stratified the models according to study center and age at recruitment, with further adjustment for educational level, smoking status, alcohol consumption, physical activity, and height.

Results During a mean follow-up of 9.7 years, 14,723 participants died. The lowest risks of death related to BMI were observed at a BMI of 25.3 for men and 24.3 for women. After adjustment for BMI, waist circumference and waist-to-hip ratio were strongly associated with the risk of death. Relative risks among men and women in the highest quintile of waist circumference were 2.05 (95% confidence interval [CI], 1.80 to 2.33) and 1.78 (95% CI, 1.56 to 2.04), respectively, and in the highest quintile of waist-to-hip ratio, the relative risks were 1.68 (95% CI, 1.53 to 1.84) and 1.51 (95% CI, 1.37 to 1.66), respectively. BMI remained significantly associated with the risk of death in models that included waist circumference or waist-to-hip ratio (P<0.001).

Conclusions These data suggest that both general adiposity and abdominal adiposity are associated with the risk of death and support the use of waist circumference or waist-to-hip ratio in addition to BMI in assessing the risk of death.

Source Information

The authors' affiliations are listed in the Appendix.

Dr. Kurt Hoffmann is deceased.

Address reprint requests to Dr. Tobias Pischon at the Department of Epidemiology, German Institute of Human Nutrition, Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany, or at pischon@dife.de.

Short Sleep Duration and Incident Coronary Artery Calcification

Moral of the story: We have all heard that sleep is good for you, and this is yet another reason that statement is extremely true. Sleeping more will decrease your risk for developing atherosclerosis, plaque development and hardening of the arteries (AHA explanation).

Short Sleep Duration and Incident Coronary Artery Calcification

Christopher Ryan King, BS; Kristen L. Knutson, PhD; Paul J. Rathouz, PhD; Steve Sidney, MD, MPH; Kiang Liu, PhD; Diane S. Lauderdale, PhD

JAMA. 2008;300(24):2859-2866.(http://jama.ama-assn.org/cgi/content/abstract/300/24/2859)

Context Coronary artery calcification is a subclinical predictor of coronary heart disease. Recent studies have found that sleep duration is correlated with established risk factors for calcification including glucose regulation, blood pressure, sex, age, education, and body mass index.

Objective To determine whether objective and subjective measures of sleep duration and quality are associated with incidence of calcification over 5 years and whether calcification risk factors mediate the association.

Design, Setting, and Participants Observational cohort of home monitoring in a healthy middle-aged population of 495 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) cohort Chicago site (black and white men and women aged 35-47 years at year 15 of the study in 2000-2001 with follow-up data at year 20 in 2005-2006). Potential confounders (age, sex, race, education, apnea risk, smoking status) and mediators (lipids, blood pressure, body mass index, diabetes, inflammatory markers, alcohol consumption, depression, hostility, self-reported medical conditions) were measured at both baseline and follow-up. Sleep metrics (wrist actigraphy measured duration and fragmentation, daytime sleepiness, overall quality, self-reported duration) were examined for association with incident calcification. Participants had no detectable calcification at baseline.

Main Outcome Measure Coronary artery calcification was measured by computed tomography in 2000-2001 and 2005-2006 and incidence of new calcification over that time was the primary outcome.

Results Five-year calcification incidence was 12.3% (n = 61). Longer measured sleep duration was significantly associated with reduced calcification incidence (adjusted odds ratio, 0.67 per hour [95% confidence interval, 0.49-0.91 per hour]; P = .01). No potential mediators appreciably altered the magnitude or significance of sleep (adjusted odds ratio estimates ranged from 0.64 to 0.68 per sleep hour; maximum P = .02). Alternative sleep metrics were not significantly associated with calcification.

Conclusion Longer measured sleep is associated with lower calcification incidence independent of examined potential mediators and confounders.

Author Affiliations: Department of Health Studies, University of Chicago, Chicago, Illinois (Mr King and Drs Knutson, Rathouz, and Lauderdale); Division of Research, Kaiser Permanente, Oakland, California (Dr Sidney); and Department of Preventive Medicine, Northwestern University, Chicago, Illinois (Dr Liu).

Basic Splinting Techniques

Moral of the story: This is an interesting video that presents emergency physician guidelines for splinting, which when adapted could be helpful if you are ever in need of splinting something on your own (not near a hospital for some reason). There are a couple of interesting takeaways concerning indications (fractures, sprains and dislocations), preparation (expose wound, evaluate sensorimotor function, treat superficial wounds, remove jewelry!), techniques (volar, ulnar gutter, long-arm, sugar-tong and posterior-leg (with or without stirrup)) and aftercare (reevaluating sensorimotor function).

Basic Splinting Techniques

Michael T. Fitch, M.D., Ph.D., Bret A. Nicks, M.D., Manoj Pariyadath, M.D., Henderson D. McGinnis, M.D., and David E. Manthey, M.D.

Volume 359:e32 December 25, 2008 Number 26

http://content.nejm.org/cgi/video/359/26/e32/

warning: some graphic pictures

FDA reprimands Coca Cola

Moral of the Story: Soda is never good for you, ever.

Department of Health and Human Services
Public Health Service
Food and Drug Administration

College Park, MD 20740

DEC 10 2008

WARNING LETTER

CERTIFIED MAIL
RETURN RECEIPT REQUESTED

Mr. Muhtar Kent
President and Chief Executive Officer
The Coca-Cola Company
1 Coca Cola Place, NW
Atlanta, GA 30313-2424

Re: CFSAN-OC-09-01

Dear Mr. Kent:

The Food and Drug Administration (FDA) has reviewed the label for your Diet Coke Plus 20 FL OZ (1.25 PT) 591ml. Based on our review, we have concluded that this product is in violation of the Federal Food, Drug, and Cosmetic Act (the Act). Your Diet Coke Plus product is misbranded within the meaning of section 403(r)(1)(A) of the Act [21 USC 343(r)(1)(A)] because the product makes a nutrient content claim but does not meet the criteria to make the claim.

Your product bears the term "Plus" as part of its name, and the principal display panel of the product label also includes the language, "Diet Coke with Vitamins & Minerals." The ingredient list includes the following added vitamins and minerals: magnesium sulfate (declared at 10% of the Daily Value (DV) for magnesium in the Nutrition Facts panel), zinc gluconate (declared at 10% of the DV for zinc), niacinamide (declared at 15% of the DV for niacin), pyridoxine hydrochloride (declared at 15% of the DV for vitamin B6), and cyanocobalamine (declared at 15% of the DV for vitamin B12).

Your product is misbranded within the meaning of section 403(r)(1)(A) of the Act because it bears the nutrient content claim "plus" but does not comply with the regulations governing the use of this claim. The term "plus" in "Diet Coke Plus," read in conjunction with the language "Diet Coke with Vitamins & Minerals," meets the definition of a nutrient content claim because it characterizes the product's level of vitamins and minerals, which are nutrients of the type required to be in nutrition labeling (21 CFR 101.13(b)). The term "plus" is defined in 21 CFR 101.54(e). This term may be used on the label or in labeling of foods to describe the level of nutrients (such as vitamins and minerals) in the food, provided that (1) the food contains at least 10 percent more of the Reference Daily Intake or Daily Reference Value for the nutrient per reference amount customarily consumed than an appropriate reference food, (2) where the claim is based on nutrients that are added to the food, that the fortification is in accordance with the policy on fortification of foods in 21 CFR 104.20, and (3) the claim bears the required information for relative claims as described in 21 CFR 101.13(j)(2) and 101.54(e)(1)(iii).

Your product Diet Coke Plus is a carbonated beverage. The policy on fortification in 21 CFR 104.20(a) states that the FDA does not consider it appropriate to fortify snack foods such as carbonated beverages. Additionally, the label of your product does not state the identity of a reference food and the percentage (or fraction) of the amount of the nutrient in the reference food by which the nutrient in the labeled food differs, as is required for relative claims such as "plus" under 101.13(j)(2). Therefore, the "plus" claim on the label of this product does not meet the requirements of 21 CFR 101.54(e)(1).

The above violations are not meant to be an all-inclusive list of deficiencies in your products or their labeling. It is your responsibility to ensure that all of your products are in compliance with the laws and regulations enforced by FDA. You should take prompt action to correct the violations. Failure to promptly correct these violations may result in regulatory actions without further notice, such as seizure and/or injunction.

You should take prompt action to correct these violations. Please respond to this letter within 15 days from receipt with the actions you plan to take in response to this letter, including an explanation of each step being taken to correct the current violations and prevent similar violations. Include any documentation necessary to show that correction has been achieved. If you cannot complete corrective action within fifteen working days, state the reason for the delay and the time within which you will complete the correction.

You should direct your written reply to Felicia B. Williams, Food and Drug Administration, Center for Food Safety and Applied Nutrition, 5100 Paint Branch Parkway, Office of Compliance (HFS-608), Division of Enforcement, College Park, Maryland 20740-3835.

Sincerely,

/S/

Roberta F. Wagner
Director
Office of Compliance
Center for Food Safety
And Applied Nutrition

Adults Need Vaccines

Moral of the story: Adults need vaccinations as well. In fact, 95% of vaccine preventable diseases occur in adults as between 30-70% of adults do not receive the vaccines they are indicated for. It is important to talk to your physician about which of these vaccines you should have: influenza, pneumococcal, tetanus-diptheria-pertussis, hepatitis A, hepatitis B, measles-mumps-rubella, chickenpox (varicella), meningococcal, human papillomavirus, and shingles (zoster). I will post more information on the HPV vaccine later, there are two new papers that are very interesting.

FOR IMMEDIATE RELEASE

ACP Media Contact: Steve Majewski American College of Physicians smajewski@acponline.org or 215-351-2514 IDSA Media Contact: Diana Olson Infectious Diseases Society of America dolson@idsociety.org or 703-299-0201

Medical Societies: Adults Need Vaccines

Many adults areunaware of the potential risks of vaccine-preventable diseases, the need for booster doses to maintain maximum protection, and the availability of newer vaccines

Philadelphia, November 19, 2008 – The American College of Physicians (ACP) and the Infectious Diseases Society of America (IDSA) have released a joint statement on the importance of adult vaccination against an increasing number of vaccine-preventable diseases. The statement has been endorsed by 17 other medical societies representing a range of practice areas.

According to the Centers for Disease Control and Prevention, 95 percent of vaccine-preventable diseases occur in adults and more than 46,000 adults die of vaccine-preventable diseases or their complications.

“It is crucial for physicians – internists, family physicians, and subspecialists who provide primary and preventive care services for patients, especially those with chronic diseases – to discuss and review their adult patients’ vaccination status and either vaccinate them or provide a referral for recommended vaccines,” said Jeffrey P. Harris, MD, FACP, president of ACP. “We believe that the Patient-Centered Medical Home model of care – which in coordination with the other components of the health care delivery system is the future of health care – will help to increase immunization rates among adults.“

“Thanks to immunization, most children never suffer from vaccine-preventable diseases but that’s not true for their parents or grandparents,” said William Schaffner, MD, FIDSA, MACP, chair of IDSA’s Immunization Work Group. “Every year, hundreds of thousands of adults get sick, miss work, and are hospitalized. Many adults die because of vaccine-preventable diseases or their complications. Costs associated with treatment run in the billions.”

Adult vaccination rates range from 26 to 69 percent, depending on the vaccine and specific target group. ACP and IDSA plan to work with the other medical societies toward facilitating access to tools and resources to help physicians encourage adult immunization amongst their patients.

The joint statement includes the following five proposals:

• Primary and subspecialty physicians should conduct an immunization review at appropriate adult medical visits to educate patients about the benefits of vaccination and to assess whether the patient’s vaccination status is current, referring to the Advisory Committee on Immunization Practices Adult Immunization Schedule.
• When appropriate, physicians should provide or refer patients for recommended immunizations.
• Physicians who administer vaccines should ensure appropriate documentation in the medical record. In addition, documentation of vaccination in other settings, patient refusal and any contraindications is advisable. The use of immunization registries and electronic data systems facilitates access to accurate and complete immunization data.
• Physicians who refer patients for vaccination also should review and document the vaccination status of their patients whenever possible.
• Consistent with the CDC Advisory Committee on Immunization Practices and multiple subspecialty organizations, physicians and their staff should be immunized consistent with CDC recommendations, with particular attention to annual influenza immunization.

The list of vaccines that adults should discuss with their physicians includes influenza, pneumococcal, tetanus-diptheria-pertussis, hepatitis A, hepatitis B, measles-mumps-rubella, chickenpox (varicella), meningococcal, human papillomavirus, and shingles (zoster). Specific recommendations vary depending on age and other factors.

For more information, visit the ACP and IDSA Web sites.

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About the American College of Physicians
The American College of Physicians is the largest medical specialty organization and the second-largest physician group in the United States. ACP members include 126,000 internal medicine physicians (internists), related subspecialists, and medical students. Internists specialize in the prevention, detection, and treatment of illness in adults.

About the Infectious Diseases Society of America
IDSA is an organization of physicians, scientists, and other health care professionals dedicated to promoting health through excellence in infectious diseases research, education, prevention, and patient care. The Society, which has more than 8,000 members, was founded in 1963 and is based in Arlington, VA.

ACIP Provisional Recommendations for Use of Pneumococcal Vaccines

Moral of the story: Do you smoke? Are you asthmatic? Then get this vaccine! Smokers have been added to those who the CDC will recommend receive the vaccine to guard against a certain type of pneumonia.

• smokers (19 and older)
  
• asthmatics (19 and older)
  
• People without a functioning spleen
• Adults 65 and older
  
• Anyone 2 and older with a weakened immune system (HIV, cancer
  
• Anyone 2 and older with a chronic disease (diabetes, COPD, emphysema, sickle cell anemia, or any other heart, lung, kidney, or liver disease including alcoholics)
  

The vaccine is 23-valent pneumococcal polysaccharide vacine (PPSV23). It protects against 23 types of Streptococcus pneumoniae that cause a sever type of pneumonia that has a mortality rate near 20%. ACIP is the CDC's Advisory Committee on Immunization Practices - the CDC usually adopts their recommendations.

Provisional Recommendations for Use of Pneumococcal Vaccines

http://www.cdc.gov/vaccines/recs/provisional/downloads/pneumo-oct-2008-508.pdf

Date of ACIP vote: October 22, 2008
Date of posting of provisional recommendations: December 8, 2008
On October 22, 2008, the ACIP voted on new and revised recommendations for the use of 23-valent pneumococcal polysaccharide vaccine (PPSV23) for the prevention of invasive pneumococcal disease. The new provisional recommendations are as follows:

1. Recommendation for use of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) among adult cigarette smokers:
Adults who smoke cigarettes are at substantially increased risk for invasive pneumococcal disease. The ACIP recommends that cigarette smoking should be added to the list of indications for PPSV23 in adults aged 19 through 64 years. Proposed wording of the revised recommendation: Persons aged 19 through 64 years who smoke cigarettes should receive a single dose of PPSV23 and smoking cessation counseling.

2. Recommendation for use of PPSV23 among adults who have asthma:
Asthma is an independent risk factor for invasive pneumococcal disease. The ACIP recommends that asthma should be included among the chronic pulmonary diseases (such as COPD and emphysema) that are indications for PPSV23 in adults aged 19 through 64 years. Proposed wording of the revised recommendation: “Persons aged 19 through 64 years who have asthma should receive a single dose of PPSV23.”

Preadmission use of statins and outcomes after hospitalization with pneumonia: population-based cohort study of 29,900 patients.

Moral of the story: Have a cholesterol problem? Taking Lipitor? Well, if you also happen to develop pneumonia your cholesterol meds will help you fight the disease. While there are clearly benefits to taking statins while you have pneumonia, you must be taking them from the start of the disease to see the benefit. There are many side effects to taking statins so there is probably no point in using this in a prophylactic manner (and they don't add statins to the drinking water, yet). However, one day you may be given statins on admission for pneumonia.

Preadmission use of statins and outcomes after hospitalization with pneumonia: population-based cohort study of 29,900 patients.
Thomsen RW, Riis A, Kornum JB, Christensen S, Johnsen SP, Sørensen HT.

Department of Clinical Epidemiology, Aarhus University and Aalborg Hospital, Forskningens Hus, Aalborg, Denmark. r.thomsen@rn.dk

BACKGROUND: While some experimental and clinical research suggests that statins improve outcomes after severe infections, the evidence for pneumonia is conflicting. We examined whether preadmission statin use decreased risk of death, bacteremia, and pulmonary complications after pneumonia.

METHODS: We conducted a population-based cohort study of 29,900 adults hospitalized with pneumonia for the first time between January 1, 1997, and December 31, 2004 in northern Denmark. Data on statin and other medication use, comorbidities, socioeconomic markers, laboratory findings, bacteremia, pulmonary complications, and death were obtained from medical databases. We used regression analyses to compute adjusted mortality rate ratios within 90 days and relative risks of bacteremia and pulmonary complications after hospitalization in both statin users and nonusers.

RESULTS: Of patients with pneumonia, 1371 (4.6%) were current statin users. Mortality among statin users was lower than among nonusers: 10.3% vs 15.7% after 30 days and 16.8% vs 22.4% after 90 days, corresponding to adjusted 30- and 90-day mortality rate ratios of 0.69 (95% confidence interval, 0.58-0.82) and 0.75 (0.65-0.86). Decreased mortality associated with statin use remained robust in various subanalyses and in a supplementary analysis using propensity score matching. In contrast, former use of statins and current use of other prophylactic cardiovascular drugs were not associated with decreased mortality from pneumonia. In statin users, adjusted relative risk for bacteremia was 1.07 (95% confidence interval, 0.69-1.67) and for pulmonary complications was 0.69 (0.42-1.14).

CONCLUSION: The use of statins is associated with decreased mortality after hospitalization with pneumonia.

Arch Intern Med. 2008 Oct 27;168(19):2081-7

Association of Alcohol Consumption With Brain Volume in the Framingham Study

Moral of the story: You have probably heard about the myth that drinking kills brain cells. Well, thanks to a very large heart study in Framinghman, MA that started back in 1948 we now know that drinking copious amounts of alcohol over an extended period of time will shrink the size of your brain. Thats right, the more you drink the smaller your brain will be (especially if you are female). The good news is that with limited amounts of alcohol your heart will be loving life, even if your brain isn't as lucky. However, there is also evidence that large quantities of alcohol are bad for your heart.

Association of Alcohol Consumption With Brain Volume in the Framingham Study
Carol Ann Paul, MS; Rhoda Au, PhD; Lisa Fredman, PhD; Joseph M. Massaro, PhD; Sudha Seshadri, MD; Charles DeCarli, MD; Philip A. Wolf, MD
Arch Neurol. 2008;65(10):1363-1367.
Background While adults who drink low to moderate amounts of alcohol have lower rates of cardiovascular disease than other adults, the effect of alcohol on the brain is less clear. There is evidence that drinking large amounts of alcohol is related to brain atrophy. It is uncertain what the effects of low to moderate consumption might be.
Objective To determine whether consumption of smaller amounts of alcohol negatively affects brain volume or is protective in reducing the well-documented age-related decline in brain volume.
Design Total cerebral brain volume (TCBV) was computed, correcting for head size. Multivariate linear regression models were used to evaluate the association between 5 categories of alcohol consumption (abstainers, former drinkers, low, moderate, high) and TCBV, adjusting for age, sex, education, height, body mass index (calculated as weight in kilograms divided by height in meters squared), and the Framingham Stroke Risk Profile. Pairwise comparisons were also conducted between the alcohol consumption groups.
Participants A total of 1839 subjects from the Framingham Offspring Study who had magnetic resonance imaging of the brain between 1999 and 2001.
Results Most participants reported low alcohol consumption, and men were more likely than women to be moderate or heavy drinkers. There was a significant negative linear relationship between alcohol consumption and TCBV (r = –0.25; P < .001). This relationship was modified by sex, with alcohol consumption having a stronger association with TCBV in women than in men (r = –0.29 vs –0.20). Conclusions In contrast to studies on cardiovascular disease, this study found that moderate alcohol consumption was not protective against normal age-related differences in total brain volume. Rather, the more alcohol consumed, the smaller the total brain volume.

Author Affiliations: Neuroscience Program, Wellesley College, Wellesley, Massachusetts (Ms Paul); Departments of Neurology (Drs Au, Seshadri, and Wolf), Epidemiology (Ms Paul and Dr Fredman), and Biostatistics, Boston University School of Public Health, Boston, Massachusetts (Dr Massaro); Department of Mathematics & Statistics, Boston University, Boston, Massachusetts (Dr Massaro); Framingham Heart Study, Framingham, Massachusetts (Drs Au, Massaro, Seshadri, and Wolf); and Department of Neurology and Center for Neuroscience, University of California, Davis, California (Dr DeCarli).

Caffeinated Cocktails: Energy Drink Consumption, High-risk Drinking, and Alcohol-related Consequences among College Students

Moral of the story: If you mix booze and energy drinks, as with a red bull and vodka, you are more likely to do something stupid and get hurt.

Caffeinated Cocktails: Energy Drink Consumption, High-risk Drinking, and Alcohol-related Consequences among College Students
Mary Claire O'Brien, MD, Thomas P. McCoy, MS, Scott D. Rhodes, PhD, Ashley Wagoner, BS, Mark Wolfson, PhD
From the Departments of Emergency Medicine (MCO), Social Sciences and Health Policy (MCO, SDR, AW, MW), Biostatistical Sciences (TPM), and Pediatrics (MW), Wake Forest University School of Medicine, Winston-Salem, NC.
Correspondence to Mary Claire O'Brien, MD; e-mail: mobrien@wfubmc.edu.

Objectives: The consumption of alcohol mixed with energy drinks (AmED) is popular on college campuses in the United States. Limited research suggests that energy drink consumption lessens subjective intoxication in persons who also have consumed alcohol. This study examines the relationship between energy drink use, high-risk drinking behavior, and alcohol-related consequences.
Methods: In Fall 2006, a Web-based survey was conducted in a stratified random sample of 4,271 college students from 10 universities in North Carolina.
Results: A total of 697 students (24% of past 30-day drinkers) reported consuming AmED in the past 30 days. Students who were male, white, intramural athletes, fraternity or sorority members or pledges, and younger were significantly more likely to consume AmED. In multivariable analyses, consumption of AmED was associated with increased heavy episodic drinking (6.4 days vs. 3.4 days on average; p < p =" 0.027).">Conclusions: Almost one-quarter of college student current drinkers reported mixing alcohol with energy drinks. These students are at increased risk for alcohol-related consequences, even after adjusting for the amount of alcohol consumed. Further research is necessary to understand this association and to develop targeted interventions to reduce risk.
Academic Emergency Medicine: Volume 15, Issue 5, Pages 453-460.