How to start an intravenous glyceryl trinitrate (GTN) infusion

How to start an intravenous glyceryl trinitrate (GTN) infusion

Posted in Emergency, Emergency Dept., Medicine, Michael Tam at 20:20 by Michael Tam

Original article: Michael Tam :: Printer friendly
An understanding of how to start and setup an intravenous infusion of glyceryl trinitrate (GTN) is a rather useful skill. Unfortunately, setting up a GTN infusion is sufficiently complicated that it can’t be worked out in an emergency situation. In a nutshell:

Start with glyceryl trinitrate 5 mcg/min then increase infusion rate by 5 mcg/min every 3-5 minutes if needed when infusion rate is GTN 20 mcg/min or more increase infusion rate by 10 mcg/min every 3-5 minutes if needed

GTN infusions are not trivial. Call for help. It should best be performed under the supervision of someone who has experience with them (e.g., a medical registrar or emergency medicine registrar).


Step One: Indications
GTN infusions can be used in the following (1) (2):

hypertensive emergency / malignant hypertension congestive cardiac failure with acute myocardial infarction treatment of angina pectoris not responding to oral nitrates and/or beta blockers control of perioperative hypertension

In hypertensive encephalopathy, aim to reduce the blood pressure slowly (3). There are substantial risks in reducing it quickly.

• reduce the mean arterial pressure by 10% per hour;
• by no more than 25% of the original value.

mean arterial pressure = diastolic + 1/3 (systolic – diastolic)

Step Two: Contraindications
Avoid in the following (1) (2):

hypotension or uncorrected hypovolaemia raised intracranial pressure or cerebral haemorrhage constrictive pericarditis or pericardial tamponade severe anaemia and arterial hypoxaemia concurrent use of phosphodiesterase-5 inhibitors, i.e., sildenafil (Viagra), tadalafil (Cialis) and vardenafil (Levitra)

Step Three: Initial stabilisation
Remember your “ABCs” of emergency management (3):
Position:

• Comfortably;
• in a monitored bed.

Airway:

• Keep patent.

Breathing:

• Administer high flow (i.e., > 6 L/min) via a Hudson mask or non-rebreather mask;
• consider using CPAP if severe pulmonary oedema is present;
• assess respiratory rate and effort (if inadequate, assist with ventilation, e.g., bag-valve-mask with oxygen).

Circulation:

• Measure pulse rate, blood pressure (both arms if thoracic aortic dissection is suspected) and capillary refill;
• attach cardiac monitoring equipment and correct any immediate life threatening arrhythmia;
• insert intravenous cannulae x 2;
• take bloods (FBC, UEC).

Perform a 12-lead ECG
Disability:

• Measure Glasgow Coma Score (GCS); if less than or equal to 8 then consider endotracheal intubation to protect the airway.

Step Four: Draw up and dilute the GTN
GTN is absorbed into many plastics, especially PVC (2). Hence it is important to minimise the amount of tubing / filters in the giving sets and aim to use a glass bottle for dilution.
In Australia, GTN for injection comes in 50 mg/10 mL ampoules.

glyceryl trinitrate 50 mg in 500 mL of 0.9% NaCl solution (glass infusion bottle)

• This yields a concentration of GTN of 100 mcg/mL;
• a solution of 5% dextrose (D-glucose) can be used as an alternative.

Step Five: Start infusion
The dose of GTN needs to be carefully titrated for the patient according to response. The starting dose is low:

glyceryl trinitrate 5 mcg/min which is 3 mL/h of the dilution (glyceryl trinitrate 100 mcg/mL)

Step Six: Upward titration
Start with small increases up to GTN 20 mcg/mL:

Increase infusion rate by glyceryl trinitrate 5 mcg/min every 3-5 minutes. which is 3 mL/h of the dilution (glyceryl trinitrate 100 mcg/mL) every 3-5 minutes

When the infusion rate of GTN is greater than of equal to 20 mcg/mL (i.e., from the forth upward titration and beyond):

Increase infusion rate by glyceryl trinitrate 10 mcg/min every 3-5 minutes. which is 6 mL/h of the dilution (glyceryl trinitrate 100 mcg/mL) every 3-5 minutes

• There is no real maximum dose and the infusion rate should be adjusted to effect;
• GTN has a wide therapeutic range;
• it is suggested by McCowan and Shapiro (2006) (1) that the maximum rate to be GTN 200 mcg/min.

Step Seven: Arrange for definitive care
Once the patient has been stabilised, definitive care should be arranged. For a patient who requires a GTN infusion, this will be a monitored bed (i.e., a coronary care unit, intensive care unit or at least, a monitored bed).

Discussion

• Beware in severe hypertension following head injury, intracranial bleed or cerebrovascular accident. The hypertension is in part the body’s response to maintain cerebral perfusion.
• Some patients may respond fully to even the starting infusion rate of GTN (5 mcg/min) so careful titration and monitoring is required.
• For patients requiring a high infusion dose of GTN, it can be helpful to increase the concentration of the infusion solution and then use the appropriate rate.

Reference articles
(1) McCowan C., Shapiro N. Hypertensive Emergencies. Emedicine. Last updated 13 April 2006. [Link]
(2) Glyceryl Trinitrate Concentrate Injection (DBL). MIMS Online. Last updated 13 September 2005.
(3) Hypertensive Emergencies, Treatment. Emergency Life Support (ELS) Course Manual. Second Edition. 2002.

Ibuprofen Use Linked to Reduced Parkinson's Disease Risk

 

February 18, 2010 — A new prospective analysis using data on more than 136,000 people participating in the Nurses' Health Study (NHS) and the Health Professionals Follow-up Study (HPFS) suggests that use of ibuprofen, but not other nonsteroidal anti-inflammatory drugs (NSAIDs), is associated with a reduction in Parkinson's disease (PD) risk on the order of 40%.
Neuroinflammation is thought to play a role in PD, said lead author Xiang Gao, MD, from Harvard School of Public Health, Boston, Massachusetts, "but our results showed only ibuprofen and not other agents seems to be protective for PD.
"This suggests that specific effects of ibuprofen not shared by other NSAIDs play a role in this protective effect, but we don't know the exact mechanism at this time," Dr. Gao told Medscape Neurology.
The results were published online February 17 in advance of their presentation at the upcoming American Academy of Neurology 62nd Annual Meeting in Toronto, Ontario, Canada, April 10-17, 2010. The abstract is posted at www.aan.com.
Addressing Neuroinflammation?
Neuroinflammation may contribute to the pathology of Parkinson's disease, the study authors note, and use of NSAIDs in general, and ibuprofen in particular, has previously been linked to reduced risk of the disease. For example, a previous paper presented by Dr. Gao's Harvard School of Public Health colleague Albert Ascherio, MD, using data from the American Cancer Society's Cancer Prevention Study II Nutrition Cohort, showed that ibuprofen users had a reduced PD risk of about 35%.
In the present study, Dr. Gao and colleagues analyzed data on 136,197 men and women included in the prospective cohorts of the NHS of women and the HPFS of men who were free of PD and other diseases at baseline in 1998 for the NHS and 2000 for the HPFS. The use of NSAIDs was assessed by questionnaire.
During 6 years of follow-up, there were 291 incident cases of PD. The study authors report that users of ibuprofen had a significantly lower risk of developing PD than nonusers and, further, that there was a dose-response relationship between the number of tablets taken per week and PD risk (P for trend = .01)
Table 1. Risk for Parkinson's Disease for Ibuprofen Users vs Nonusers

Comparison	Relative Risk (95% CI)	P Value
Ibuprofen use vs nonuse	0.62 (0.42 – 0.92)	.02

CI = confidence interval
Conversely, there was no significant relationship between use of aspirin, other NSAIDs, or acetaminophen and PD risk.
Table 2. Risk for Parkinson's Disease Associated With Use of Other Pain Relievers

Pain Reliever	Relative Risk	P Value
Aspirin	0.98	.86
Other NSAIDs	1.26	.24
Acetaminophen	0.87	.39

NSAIDs = nonsteroidal anti-inflammatory drugs
They also performed an additional meta-analysis of 5 prospective studies, Dr. Gao added. "We found similar results," he said. "The use of ibuprofen is associated with around 30% lower risk of PD in this meta-analysis."
Table 3. Meta-Analysis: Risk for PD With Ibuprofen Use vs No Ibuprofen Use

Comparison	Relative Risk (95% CI)	P Value
Ibuprofen use vs nonuse	0.73 (0.63 – 0.85)	< .001

CI = confidence interval
Dr. Gao said it will be important to have these findings confirmed in other independent populations and would like to see whether ibuprofen might also affect disease progression in people who already have PD.
First though, he said, "I think the most important thing is to try and find out the mechanism; why ibuprofen is protective against Parkinson's disease."
Extension of Earlier Studies
Asked for comment on these findings, Kapil Sethi, MD, professor of neurology and director of the Movement Disorders Program at the Medical College of Georgia in Augusta and a member of the Medscape Neurology editorial advisory board, said these findings are an extension of earlier studies documenting an inverse relationship between use of anti-inflammatory drugs and PD.
"However, the reduced risk was associated only with the use of ibuprofen and not the other [NSAIDs], suggesting that it is the drug and not the underlying conditions for which the [NSAIDs] are administered that is responsible for the risk reduction," Dr. Sethi noted.
"The relative number of individuals treated with ibuprofen vs the other agents is not mentioned in the news release," he added, "but we look forward to the complete report."
The study was funded by grants from the National Institutes of Health/National Institute of Neurological Disorders and Stroke. The study authors have disclosed no relevant financial relationships.
American Academy of Neurology (AAN) 62nd Annual Meeting: Abstract 1347. Presented April 10-17, 2010.

North American Menopause Society Issues Guidelines on Hormone Therapy Laurie Barclay, MD

North American Menopause Society Issues Guidelines on Hormone Therapy

Laurie Barclay, MD

February 18, 2010 — The benefit-risk ratio for menopausal hormone therapy (HT) is favorable for women beginning HT close to menopause but decreases in older women and with time since menopause in previously untreated women, according to the latest evidence-based position statement of the North American Menopause Society (NAMS), posted online February 16 and will be published in the March/April issue of Menopause.
"From a clinical perspective, the latest NAMS position statement on HT considers the current best practice of medicine," NAMS Executive Director Margery L. S. Gass, MD, NCMP, said in a news release. "The Panel of world famous authorities clarified a broad spectrum of topics related to HT benefits and risks for postmenopausal women."
Development of the Guidelines
The goal of the latest guidelines was to update clinicians as well as the lay public regarding NAMS' recommendations for menopausal HT for postmenopausal women, considering the therapeutic benefit-risk ratio at various times through and beyond menopause.
An advisory panel of 17 clinicians and researchers with special expertise in HT reviewed each section of the previous position statement, published by NAMS in July 2008, in light of new studies and findings, and reached consensus on recommendations. The NAMS board of trustees then approved the updated official position statement, which highlights recent evidence regarding risks for breast cancer, cognitive dysfunction and decline, dementia, coronary heart disease (CHD), and stroke, as well as new recommendations regarding discontinuing HT.
The updated guidelines also include new sections on HT and ovarian and lung cancer, a listing of areas that vary from the 2008 position statement, and a suggested bibliography of key references published since the last statement.
The American Medical Women's Association, the Asociación Mexicana para el Estudio del Climaterio, the Endocrine Society, Healthy Women (formerly the National Women's Health Resource Center), the National Association of Nurse Practitioners in Women's Health, and the Society of Obstetricians and Gynaecologists of Canada all had representatives participating fully in the editorial process and have endorsed the newest NAMS position statement.
"Current evidence supports a consensus regarding the role of HT in postmenopausal women, when potential therapeutic benefits and risks around the time of menopause are considered," the statement authors write. "Recent data support the initiation of HT around the time of menopause to treat menopause-related symptoms; to treat or reduce the risk of certain disorders, such as osteoporosis or fractures in select postmenopausal women; or both. The benefit-risk ratio for menopausal HT is favorable for women who initiate HT close to menopause but decreases in older women and with time since menopause in previously untreated women."
The Women's Health Initiative (WHI) trial of estrogen therapy (ET) offered evidence of considerable safety for 0.625 mg/day of oral conjugated estrogen, supporting the position that at least for this form of HT, the potential absolute risks are low.
In the WHI trial of combined estrogen-progestogen therapy (EPT), most risks were determined to be rare, using the criteria of the Council for International Organizations of Medical Sciences, except for stroke, which was above the rare category.
"For women younger than age 50 or those at low risk of CHD, stroke, osteoporosis, breast cancer, or colon cancer, the absolute risk or benefit from ET or EPT is likely to be even smaller than that demonstrated in the WHI, although the relative risk at different ages may be similar," the statement authors write. "There is a growing body of evidence that each type of estrogen and progestogen, route of administration, and timing of therapy has distinct beneficial and adverse effects. Further research remains essential."
Cancer and HT
Evidence to date is conflicting regarding the role of HT and risk for ovarian cancer, with no association or a modest increase in most epidemiologic studies, but with an association between HT use and increased ovarian cancer risk based on a relatively large volume of observational trial data. The statement suggests that the association between ovarian cancer and HT beyond 5 years, if any, should be considered as rare or very rare, but that women with a positive family history or other increased risk for ovarian cancer should be counseled about this rare association.
Overall data, including those from WHI analysis, suggest that starting EPT in older women with a positive smoking history may promote the growth of existing lung cancers. In contrast, evidence from the WHI and some case-control and cohort studies suggests that use of HT in women younger than 60 years offers some protection against lung cancer.
Although safety of EPT in survivors of breast cancer is controversial, with observational studies suggesting that it is safe and possibly even protective against recurrence, a randomized controlled trial showed a statistically significant 2.4-fold increase in new breast cancer events. ET use in breast cancer survivors has not been proven to be safe and may be associated with an increased risk for recurrence.
Cognitive Impairment, CHD, and HT
For the sole or main indication of preventing cognitive aging or dementia, the statement does not recommend HT at any age, and HT is actually linked to increased incidence of dementia when started in women age 65 years and older. Available data do not adequately address whether HT started soon after menopause increases or decreases later dementia risk, and limited evidence does not support the use of HT as a treatment of Alzheimer's disease.
In terms of cardiovascular effects, the statement authors note that HT is currently not recommended as a sole or main indication for coronary protection in women of any age. Starting HT by age 50 to 59 years or within 10 years of menopause to treat typical menopausal symptoms does not seem to increase the risk for CHD events, and there is some recent evidence that starting ET in early postmenopause may lower CHD risk.
Findings of observational studies have been inconsistent regarding stroke risk with HT. The Nurses Health Study and WHI showed an increased risk for ischemic stroke, but other studies showed no effect on stroke risk.
Current data suggest that when HT is either tapered or abruptly discontinued, rates of vasomotor symptom recurrence are similar. The statement therefore makes no recommendation concerning how to discontinue therapy.
"When HT is desired by patients, individualization of therapy is key to providing health benefits with minimal risks, thereby enhancing [quality of life]," the statement authors conclude. "Women should be informed of known risks, but it cannot be assumed that benefits and risks of HT apply to all age ranges and durations of therapy. A woman's willingness to accept risks of HT will vary depending on her individual situation, particularly whether HT is being considered to treat existing symptoms or to lower risk for osteoporotic fractures that may or may not occur."

Weekly Vitamin D3 Improves Vitamin D Insufficiency but Not Neuromuscular Function in Older Adults

 

Laurie Barclay, MD

Authors and Disclosures 

February 18, 2010 — Weekly treatment with 8400 IU of vitamin D₃ raises serum 25-hydroxyvitamin D [25(OH)D] concentrations in elderly, vitamin D–insufficient individuals, according to the results of a randomized controlled, double-blind trial reported online February 3 in the American Journal of Clinical Nutrition.
"Vitamin D insufficiency, which is prevalent in older individuals, is associated with bone and muscle weakness and falls," write Paul Lips, from Vrije Universiteit Medisch Centrum, Amsterdam, Netherlands, and colleagues. "We examined the effects of a weekly dose of 8400 IU vitamin D₃ on postural stability, muscle strength, and safety."
Participants 70 years or older with 25(OH)D concentrations of 20 ng/mL or less but at least 6 ng/mL were randomly assigned to receive a weekly dose of 8400 IU of vitamin D₃ or placebo. The main endpoint of the study was mediolateral body sway with eyes open, measured with use of the AccuSwayPLUS platform (Advanced Medical Technology Inc, Watertown, Massachusetts). The short physical performance battery and serum 25(OH)D concentrations were secondary outcomes. Safety and tolerability were evaluated, and treatments were compared by use of an analysis of covariance model.
Strength of Randomized Study Design
"An increasing number of studies report on significant associations between low serum levels of 25-hydroxyvitamin D (25-(OH)D) and a multitude of extra-skeletal diseases and pathological conditions," Meinrad Peterlik, PhD, MD, professor emeritus of pathophysiology at Medical University Vienna in Vienna, Austria, told Medscape Nutrition when asked for independent comment.
"However, these mostly observational studies are rarely controlled for potential confounders, and interventional trials that would prove a causative relation between a compromised vitamin D status and disease incidence are rare. The main strength of the study by Lips et al. thus lies in the fact that it was designed as a randomized controlled multicenter trial to evaluate the effect of vitamin D₃ supplementation on a well defined neuromuscular functional parameter, i.e., body sway, in a group of elderly people with sub-optimal vitamin D supply."
In patients treated with 8400 IU of vitamin D₃ (n = 114) but not in patients receiving placebo (n = 112), serum 25(OH)D concentrations increased significantly from 13.9 to 26.2 ng/mL (P < .001). Mediolateral sway and short physical performance battery at 16 weeks were not significantly different between treatment groups.
Treatment with 8400 IU of vitamin D₃ was associated with significantly decreased sway vs treatment with placebo (P = .047) in patients with elevated baseline sway but not in patients with normal baseline sway, based on a post hoc analysis of patients subgrouped by baseline sway (≥ 0.46 vs < 0.46 cm).
"Weekly treatment with 8400 IU vitamin D₃ raised 25(OH)D concentrations in elderly, vitamin D–insufficient individuals," the study authors write. "Treatment with 8400 IU vitamin D₃ did not reduce mediolateral sway significantly compared with treatment with placebo in this population, although in post hoc analysis, treatment with 8400 IU vitamin D₃ reduced sway in the subgroup of patients who had elevated sway at baseline. Weekly treatment with 8400 IU vitamin D₃ was well tolerated."
Parathyroid hormone levels decreased significantly in the vitamin D₃ group but not in the placebo group. Both groups had similar adverse events and incidences of hypercalcemia, hypercalciuria, and elevated creatinine levels.
Limitations of the Study
"Although the results are straightforward, their interpretation is hampered by a number of facts, most of which are appropriately addressed by the authors themselves," Dr. Peterlik told Medscape Nutrition. "However, they fail to discuss what impact the optimization of calcium intake in the entire study group could have had on the outcome of the study. It could well be that at high calcium intake levels vitamin D supplementation is only minimally effective. This would not be surprising since a recent study by one of the coauthors (Pfeifer et al., Osteoporosis Int. 20:315-322, 2009) shows a positive effect of combined vitamin D and calcium supplementation on parameters of muscle function in elderly people."
Limitations acknowledged by the study authors include small size and unusually healthy condition of the elderly participants. In addition, a substantial number of participants had mediolateral sway values at baseline that were consistent with participants who did not fall, suggesting that their balance as measured by sway was adequate. There may have been little room for improvement of sway and physical performance with treatment in these patients.
"It is clear that elderly individuals with an increased body sway will benefit from a daily dose of 1200 IU vitamin D₃ in combination with intake of > 1000 mg calcium per day," Dr. Peterlik concluded. "Additional studies with fracture rates as endpoint are necessary to prove that the observed reduction of body sway actually has a substantial impact on the incidence of falls and osteoporotic fractures in elderly people."
Merck & Co Inc supported this study, employs 5 of the study authors, and provided research grants to 4 other study authors. Dr. Peterlik has disclosed no relevant financial relationships.
Am J Clin Nutr. Published online February 3, 2010.

Pandemic H1N1 Virus Should Be Added to 2010-2011 Seasonal Influenza Vaccine, Says WHO

Robert Lowes

Authors and Disclosures 

February 18, 2010 — The World Health Organization (WHO) recommended today that the 2010-2011 seasonal influenza vaccines for the northern hemisphere should include a strain of the "dominant" pandemic A (H1N1) virus, as well as 2 nonpandemic influenza strains.
National public health authorities will decide whether to include a strain of the pandemic virus in the traditional trivalent vaccine or administer it separately as a monovalent vaccine, said Keiji Fukuda, MD, MPH, the special pandemic influenza advisor to the WHO director-general, at a press conference today.
WHO is dropping the older, nonpandemic seasonal A (H1N1) virus strain from its recommended mix because it does not expect this strain to circulate at significant levels.
The decision to replace the nonpandemic A (H1N1) strain with a pandemic strain was based on input from a WHO advisory committee composed of experts mostly from the laboratories and national public health agencies that make up the WHO Global Influenza Surveillance Network.
"In essence, what the scientists said was that in the past year, the overwhelming number of influenza viruses isolated around the world were the pandemic H1N1 virus," said Dr. Fukuda. "The experts believe, based on this information, that these viruses will continue to be one of the dominant viruses in the coming fall and winter season in the northern hemisphere."
Trivalent Vaccine with Pandemic Strain Makes Sense for Countries "That Use a Lot of Seasonal Flu Vaccine"
The 3 influenza strains recommended by WHO for northern hemisphere vaccines are an 

1) A/California/7/2009 (H1N1)–like virus, which is a pandemic strain; an 
2) A/Perth/16/2009 (H3N2)–like virus; and a 
3) B/Brisbane/60/2008-like virus.

In September 2009, WHO recommended these same strains for seasonal influenza vaccines for the southern hemisphere in 2010. WHO issues these recommendations for vaccine composition each September and February for the southern and northern hemispheres, respectively, for the coming influenza season.
If national public health authorities choose to use the pandemic strain for a monovalent vaccine, then the other 2 strains could make up a second vaccine.
Dr. Fukuda said a trivalent vaccine containing the pandemic virus would make sense for countries "that use a lot of seasonal flu vaccine."
Vaccine manufacturers and national governments, he said, would theoretically be able to use their current stockpiles of pandemic vaccines in bulk form for 2010-2011 seasonal vaccines in a trivalent formulation. In contrast, pandemic vaccine already packaged in vials and syringes could not be reused.
Dr. Fukuda emphasized that the recommendation to give seasonal-vaccine status to the pandemic influenza virus does not mean that the current pandemic is over. However, a WHO emergency committee will convene next week to decide whether the pandemic has entered an official "postpeak period," which means the worst is over, although the pandemic virus continues to cause sickness and even cause outbreaks in new regions. As proof, Dr. Fukuda noted that WHO has received new reports this week of communitywide transmission of the pandemic virus in Mauritania, which comes on the heels of outbreaks in neighboring Senegal.

Transdermal Nicotine for 24 Weeks vs 8 Weeks May Improve Abstinence CME/CE

 

February 2, 2010 — Transdermal nicotine for 24 weeks compared with 8 weeks is more effective in achieving and maintaining abstinence and reduces the risk for lapses in smoking, according to the results of a parallel randomized, double-blinded, placebo-controlled trial reported in the February 2 issue of the Annals of Internal Medicine.
"Tobacco dependence is a chronic, relapsing condition that may require extended treatment," write Robert A. Schnoll, PhD, from the University of Pennsylvania in Philadelphia, and colleagues. "We evaluated the relative efficacy of extended (24 weeks) versus standard (8 weeks) transdermal nicotine therapy for promoting biochemically confirmed point-prevalence abstinence at weeks 24 and 52 among adult smokers."
From September 2004 to February 2008, a total of 568 adult smokers seen at an academic center were randomly assigned to standard therapy (Nicoderm CQ [GlaxoSmithKline, Research Triangle Park, North Carolina], 21 mg, for 8 weeks and placebo for 16 weeks) or extended therapy (Nicoderm CQ, 21 mg, for 24 weeks), with use of an unstratified small block–randomization scheme.
The main endpoint of the study was biochemically confirmed point-prevalence abstinence at weeks 24 and 52, and secondary endpoints were continuous and prolonged abstinence, lapse and recovery events, cost per additional quitter, adverse effects, and adherence.
Compared with standard therapy, extended therapy was associated with higher rates at week 24 of point-prevalence abstinence (31.6% vs 20.3%; odds ratio [OR], 1.81; 95% confidence interval [CI], 1.23 - 2.66; P = .002), prolonged abstinence (41.5% vs 26.9%; OR, 1.97; CI, 1.38 - 2.82; P = .001), and continuous abstinence (19.2% vs 12.6%; OR, 1.64; CI, 1.04 - 2.60; P = .032). The extended therapy group also had lower risk for lapse (hazard ratio [HR], 0.77; 95% CI, 0.63 - 0.95; P = .013), higher likelihood of recovery from lapses (HR, 1.47; 95% CI, 1.17 - 1.84; P = .001), and slower time to relapse (HR, 0.50; 95% CI, 0.35 - 0.73; P < .001).
However, at week 52, extended therapy was associated with higher quit rates only for prolonged abstinence (P = .027). The extended-treatment evaluation revealed no between-group differences in adverse effects and adverse events.
"Transdermal nicotine for 24 weeks increased biochemically confirmed point-prevalence abstinence and continuous abstinence at week 24, reduced the risk for smoking lapses, and increased the likelihood of recovery to abstinence after a lapse compared with 8 weeks of transdermal nicotine therapy," the study authors write. "Additional research on the optimal duration of therapy and the possible addition of other treatment components (for example, more intensive counseling, precessation use of nicotine patches) from an efficacy, patient acceptance, and cost perspective should be a priority."
Limitations of this study include low generalizability because participants were smokers without medical comorbid conditions who were seeking treatment, and also there were differences in adherence between treatment groups.
"Some participants did not provide complete abstinence data," the editors write. "Extended therapy with transdermal nicotine helps some adults quit smoking, but benefits may persist only while treatment is maintained."
The National Cancer Institute and the National Institute on Drug Abuse, National Institutes of Health, supported this study. The senior study author (Caryn Lerman, PhD) has disclosed various financial relationships with GlaxoSmithKline, AstraZeneca, Pfizer, and Novartis.
Ann Intern Med. 2010;152:144-151.
Additional Resources
Futher information on tobacco cessation programs for healthcare professionals to access and for clinicians to distribute to patients is available online.

Clinical Context

Transdermal nicotine therapy has been demonstrated to help cigarette smokers quit, and current guidelines recommend 8 weeks of treatment for patients attempting smoking cessation. The authors of the current research hypothesize that a longer duration of treatment with transdermal nicotine therapy might improve smoking cessation outcomes, although a previous trial comparing 8 weeks vs 22 weeks of transdermal nicotine therapy found no difference in the rate of continuous abstinence from smoking between groups.
The current study compares transdermal nicotine therapy for 8 weeks vs a treatment duration of 24 weeks, and it features a dosing methodology as well as outcome assessment that differs from the previous trial.

Study Highlights

• Study subjects were recruited at 1 academic center among adults between the ages of 18 and 65 years who smoked at least 10 cigarettes daily for the last year. Patients with significant medical or psychiatric illness were excluded from the study protocol.
• Participants were randomly assigned to receive 21-mg transdermal nicotine patches for 24 weeks, or 8 weeks of active patches plus 16 weeks of placebo patches. The patches were changed every 24 hours, and there was no tapering at the end of treatment.
• All participants received 8 behavioral counseling visits to stop smoking. Transdermal nicotine therapy was initiated on a prearranged quit date.
• The primary study outcome was 7-day point prevalence abstinence from smoking at study weeks 24 and 52, which was verified with exhaled carbon monoxide levels. Researchers also followed rates of continuous abstinence and time to relapse.
• 568 smokers provided data for study analysis. The mean age of participants was 44.8 years, and 44.7% of the study cohort consisted of women. The mean number of cigarettes smoked per day was 21.2.
• Study completion rates were higher at 24 weeks in comparing the extended therapy group vs the standard therapy group (91% vs 83%, respectively) but were similar at week 52. Adherence to study patches at 24 weeks was 25% and 40% in the standard and extended therapy groups, respectively.
• Point-prevalence abstinence rates at week 24 favored extended treatment vs standard therapy (31.6% vs 20.3%, respectively), whereas this outcome was similar between groups at week 52 (14.5% and 14.3%, respectively).
• Rates of abstinence from the quit date to week 24 (continuous abstinence) were also higher in the extended treatment group, but this result did not remain valid at week 52. Prolonged abstinence between study groups between weeks 2 and 52 was superior in the extended therapy group vs the standard treatment group.
• Extended nicotine therapy was also associated with a longer time to relapse between weeks 9 to 24 and increased speed of recovery from relapse during this period.
• There were 3 serious adverse events in the extended therapy group and 1 serious adverse event in the standard therapy group. All of these events occurred before 8 weeks. Rates of other adverse events were generally similar between randomized groups.
• The incremental cost of extended vs standard therapy was $2482 for each additional quitter gained through a longer duration of treatment.

Clinical Implications

• The current recommended treatment duration of transdermal nicotine therapy for smoking cessation is 8 weeks.
• In the current study, extended treatment with transdermal nicotine therapy for 24 weeks was associated with improved point-prevalence abstinence and continuous abstinence rates vs standard therapy at 24 weeks, but not at 52 weeks. Extended therapy also improved the time to relapse during active treatment vs placebo.

CME Test

Questions answered incorrectly will be highlighted.

What is the current recommended duration of transdermal nicotine therapy for smoking cessation?

2 weeks

4 weeks

6 weeks

8 weeks

All of the following outcomes were improved with extended duration vs standard transdermal nicotine therapy in the current study by Schnoll and colleagues except:

Point-prevalence abstinence at 24 weeks

Point-prevalence abstinence at 52 weeks

Continuous abstinence at 24 weeks

Slower time to relapse from 9 to 24 weeks

 

Management of Acute Poisoning From Medication Ingestion Reviewed CME/CE

Target Audience

This article is intended for primary care clinicians, emergency medicine specialists, and other specialists who provide care to adults and children after acute medication poisoning.

Goal

The goal of this activity is to provide medical news to primary care clinicians and other healthcare professionals in order to enhance patient care.
...

February 8, 2010 — Family physicians should be familiar with treatment of accidental and intentional medication ingestions, according to a review of the management of acute poisoning caused by medication ingestion published in the February 1 issue of American Family Physician.
"Poisoning from medications can happen for a variety of reasons, including intentional overdose, inadvertently taking an extra dose, dispensing or measuring errors, and exposure through breast milk," write Ivar L. Frithsen, MD, and William M. Simpson, Jr, MD, from Medical University of South Carolina in Charleston.
"The most common medication poisonings in adults (in order of prevalence) include analgesics; sedatives, hypnotics, and antipsychotics; antidepressants; cardiovascular drugs; anticonvulsants; antihistamines; hormones and hormone antagonists; antimicrobials; stimulants and illicit drugs; cough and cold preparations; muscle relaxants; topical preparations; gastrointestinal preparations; and miscellaneous drugs," Drs. Frithsen and Simpson write. "The most common medication poisonings in children (in order of prevalence) include analgesics; topical preparations; cough and cold preparations; vitamins; antihistamines; gastrointestinal preparations; antimicrobials; hormones and hormone antagonists; electrolytes and minerals; cardiovascular drugs; dietary supplements, herbal medications, and homeopathic medications; asthma therapies; antidepressants; and sedatives, hypnotics, and antipsychotics."
In the United States, several million episodes of poisoning are reported each year, causing significant morbidity and mortality rates. Nearly one half of all poisonings reported in the United States are attributed to acute medication poisonings, which should be considered in patients with an acute change in mental status.
Steps in Treatment of Poisoning
The first steps in treatment of a patient who has been poisoned are to evaluate the airway, breathing, and circulation, and to perform a complete history. Poisoning with drugs from certain classes, notably anticholinergics, cholinergics, opioids, and sympathomimetics, are associated with constellations of symptoms known as toxidromes. For example, anticholinergic poisoning is associated with delirium; hyperthermia; ileus; mydriasis; tachycardia; urinary retention; and warm and dry skin.
For identification of electrolyte imbalances and/or impairment of liver and renal function, basic laboratory studies, such as a complete metabolic profile, are an important part of the workup for possible medication poisonings. Clinical presentation and history should help determine what other laboratory studies are indicated.
Unless a specific antidote is available, management is supportive in most cases, because less than 1% of poisonings are fatal. Although single-dose activated charcoal is the preferred modality of gastrointestinal tract decontamination, it should not be used in all patients. The review includes specific therapies for acute medication poisoning based on the type of drug ingested.
For unstable patients who have ingested toxic medications, ongoing treatment should aim to correct hypoxia and acidosis and to maintain adequate circulation. Even when these patients appear to be compensating, their mental or hemodynamic status may deteriorate rapidly. Children are particularly susceptible to profound effects from even small amounts of medication.
Multiple factors, including pharmacokinetics of the ingested substance and the ability to be monitored in the home environment, must be considered in the disposition of a person who has been poisoned. Longer monitoring is required for patients with signs or symptoms of toxicity. For patients who have attempted suicide, psychiatric evaluation and often psychiatric hospitalization are indicated. Counseling referral is recommended for patients with evidence of substance abuse.
Key Recommendations
Specific key clinical recommendations for practice, and their accompanying level of evidence rating, are as follows:

• For most medication ingestions, single-dose activated charcoal is the modality of choice for gastrointestinal decontamination. This treatment can generally be used up to 1 hour after ingestion of a potentially toxic amount of medication (level of evidence, C).
• There is no indication for using ipecac syrup in a healthcare setting (level of evidence, C).

"For unstable patients, admission to an intensive care unit is appropriate, and transfer to a tertiary care facility should be considered, especially with children," the review authors conclude. "For stable patients, the amount of observation time is based on the half-life of a medication, the amount ingested, and the formulation. Any patient who develops signs or symptoms of toxicity that do not reverse during the observation period should be admitted for further observation."
The review authors have disclosed no relevant financial relationships.
Am Fam Physician. 2010;81:316-323. Abstract
Additional Resource
emedicineHealth provides clinicians with further information about drug overdose.

Clinical Context

According to the American Association of Poison Control Centers' report by Bronstein and colleagues in the December 2007 issue of Clinical Toxicology, more than 2.4 million poisoning exposures were reported in the United States in 2006. Almost half of poisoning exposures were from prescription and over-the-counter medications.
This summary addresses the management of acute poisoning from medication ingestion.

Study Highlights

• The poison control center can assist with management on the telephone, at the office, or in the hospital.
• Mortality rate is less than 1% from acute poisoning.
• In patients with acute change in mental status, medication poisoning should be suspected based on acute behavioral changes, concern of others, and evidence of ingestion.
• Initial approach includes assessment of airway, breathing, circulation; thorough history; and inspection for transdermal patches.
• Important information includes time, identification, and amount of medication.
• The gastrointestinal decontamination method of choice in most cases is activated charcoal within 1 hour of ingestion except in cases of decreased level of consciousness, low affinity of ingested medication for binding charcoal, and increased risk of gastrointestinal bleeding or perforation.
• Other methods of gastrointestinal decontamination (in order of most to least used) are gastric lavage, cathartics, and whole-bowel irrigation.
• Ipecac syrup has no role in the healthcare or home setting.
• Basic symptom management includes Trendelenburg position and fluid resuscitation for hypotension, stimulation for apnea or lethargy, warming measures for hypothermia, and cooling measures for hyperthermia.
• Complete metabolic profile can assess electrolytes and liver and renal function.
• General toxicology screen is not helpful in immediate treatment.
• Quantitative drug levels should be ordered based on history and signs and symptoms of ingestion of acetaminophen, carbamazepine, digoxin, ethanol, iron, lithium, phenobarbital, phenytoin, salicylates, theophylline, and valproate.
• Serum N-acetyl-para-aminophenol levels should be checked in all unknown ingestions.
• Arterial or venous blood gas analysis can identify acidosis and hypoxia.
• Electrocardiography can assess arrhythmias.
• Chest radiography can assess pulmonary edema.
• Medications associated with certain signs and symptoms are acetaminophen, benzodiazepines, beta-blockers, calcium channel antagonists, clonidine, opioids, salicylates, sulfonylureas, and tricyclic antidepressants.
• Specific medications have toxidromes or certain types of symptoms:
  
  
  • Anticholinergic symptoms: delirium, hyperthermia, ileus, tachycardia, urinary retention, warm and dry skin
  • Cholinergic, muscarinic symptoms: bradycardia, bronchorrhea, meiosis, wheezing
  • Cholinergic, nicotinic symptoms: abdominal pain, fasciculations, hypertension, paresis, tachycardia
  • Opioid symptoms: hypotension, hypothermia, hypoventilation, meiosis, sedation
  • Sympathomimetic symptoms: agitation, diaphoresis, hypertension, hyperthermia, mydriasis, psychosis, seizures, tachycardia
• Certain medications have specific therapies:
  
  
  • Acetaminophen: N-acetylcysteine
  • Benzodiazepines: flumazenil unless contraindicated
  • Beta-blockers: glucagon, calcium gluconate, epinephrine, insulin plus dextrose, sodium bicarbonate
  • Calcium channel antagonists: glucagon, calcium gluconate, epinephrine, insulin euglycemia therapy, or sodium bicarbonate
  • Clonidine: naloxone, atropine, dopamine
  • Opioids: naloxone
  • Salicylates: urine alkalinization, possible hemodialysis
  • Sulfonylureas: dextrose, octreotide, glucagon
  • Tricyclic antidepressants: benzodiazepines, sodium bicarbonate, and dopamine or norepinephrine
• Children have different treatment doses and are affected by smaller ingestions.
• Disposition to intensive care unit, tertiary care facility, home, or psychiatric care depends on patient's stability, medication half-life, amount ingested, formulation, persistent signs and symptoms, home situation, suicidal attempt, and substance abuse.

Clinical Implications

• The initial evaluation of acute medication poisoning includes assessment of airway, breathing, and circulation; thorough history; and determination of the presence of transdermal patches.
• In most cases of medication poisoning, the gastrointestinal decontamination modality of choice is single-dose activated charcoal, which can be given up to 1 hour after ingestion. Ipecac syrup use is not indicated.

CME/CE Test

Questions answered incorrectly will be highlighted.

In a patient who is suspected of ingesting a toxic amount of medication, assessment of which of the following is most likely to be useful in the initial evaluation of acute poisoning?

Skin

Airway

History

Circulation

All of the above

A 40-year-old patient presenting in the emergency department for medication poisoning needs gastrointestinal decontamination. Which of the following forms is most likely to be recommended?

Ipecac syrup

Activated charcoal

Gastric lavage

Whole-bowel irrigation

All of the above

ARBs May Reduce Incidence of Alzheimer's Over ACE Inhibitors, but Combination May Be Best CME

February 3, 2010 — A new study shows a significant reduction in the incidence of Alzheimer's disease (AD) and dementia among subjects taking angiotensin receptor blockers (ARBs) compared with those taking angiotensin-converting enzyme (ACE) inhibitors or other cardiovascular drugs.
Further, there appeared to be a reduction in rates of disease progression, indicated by the time to admission to a nursing home or death, among those taking ARBs, the study authors note.
"We also saw that the people who did the best appeared to be those who were taking ARBs together with ACE inhibitors, " senior author Benjamin Wolozin, MD, PhD, from Boston University School of Medicine in Massachusetts and the Center for Health Quality Outcomes and Economic Research, Veterans Affairs Medical Center, Bedford, Massachusetts, told Medscape Neurology.
"There, the data actually gets very striking; we saw a 55% lower incidence of Alzheimer's or dementia, and a 70% decrease in nursing home admissions," Dr. Wolozin added.
Their report was published online January 12 in the BMJ.
Protective Effect
ARBs selectively inhibit the AT1 receptor, and although slightly less effective at lowering blood pressure than ACE inhibitors, they have been shown in an increasing number of studies to be related to preservation of cognitive function through a mechanism independent of their antihypertensive action, the study authors write.
In this study, Dr. Wolozin and colleagues used data from the US Veterans Affairs administrative database to look at time to incident AD or dementia during a 4-year period in 3 prospective cohorts. Participants were predominantly male and 65 years and older, with a diagnosis of cardiovascular disease. One group included subjects taking an ARB, a second included those taking the ACE inhibitor lisinopril, and a third comparator group were taking other cardiovascular drugs, excluding ARBs, ACE inhibitors, and statins.
Among those with a previous diagnosis of AD or dementia, disease progression was defined for these purposes as the time to admission to a nursing home or death.
After adjustment for age, diabetes, stroke and cardiovascular disease, incident AD, and particularly incident dementia were reduced with the ARB vs both the ACE inhibitor and the cardiovascular comparator group.
Table 1. Risk for Incident Alzheimer's Disease and Dementia With ARB Treatment vs Lisinopril and a Cardiovascular Comparator

Outcome	Hazard Ratio (95% CI)	P Value
Incident Alzheimer's disease
ARB vs lisinopril	0.81 (0.68 – 0.96)	.016
ARB vs cardiovascular comparator
Incident dementia	0.84 (0.71 – 1.00)	.045
ARB vs lisinopril	0.81 (0.73 – 0.90)	<.001
ARB vs cardiovascular comparator	0.76 (0.69 – 0.84)	<.001

ARB = angiotensin receptor blocker; CI = confidence interval
Among those who already had AD, treatment with an ARB was associated with a significantly lower risk of admission to a nursing home or death during the follow-up period.
"Angiotensin receptor blockers exhibited a dose response as well as additive effects in combination with angiotensin-converting enzyme inhibitors," the study authors note. Compared with the ACE inhibitor alone, the combination was associated with a significantly reduced risk of incident AD and dementia and admission to a nursing home.
Table 2. Risk for Dementia and Nursing Home Admission With Combined ARB and ACE Inhibitors vs ACE Inhibitor Alone

Outcome	Hazard Ratio (95% CI)	P Value
Incident Alzheimer's disease	0.45 (0.41 – 0.50)	<.001
Incident dementia	0.54 (0.51 – 0.57)	<.001
Nursing home admission	0.33 (0.22 – 0.49)	<.001

ACE = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker; CI = confidence interval
"I actually find that nursing home finding very striking because you can imagine the big impact if you could avoid going to a nursing home," Dr. Wolozin told Medscape Neurology. Still, other factors play a role in this decision, including caregivers' situations and financial resources, he added.
The investigators point out that stroke was consistently ranked the most important covariate in this data set, suggesting the importance of vascular factors in the progression of cognitive loss. ARBs also have been shown to be effective in preventing vascular damage induced by amyloid-β that accumulates in AD, they note.
"Because vascular dysfunction and stroke are associated with cognitive decline, our data raise the possibility that combined use of angiotensin receptor blockers and angiotensin-converting enzyme inhibitors might confer superior protection against cognitive decline (compared with other cardiovascular drugs) by reducing neuronal damage associated with stroke and vascular dysfunction," the study authors speculate.
Complex Mechanisms
In an editorial appearing with the paper, Colleen J. Maxwell and David B. Hogan, both from the University of Calgary, Alberta, point out that the reason that ARBs may be superior to ACE inhibitors is that the AT1 and AT2 receptors have "complex and nonidentical mechanisms of action."
"Stimulation of type 1 receptors causes vasoconstriction, whereas stimulation of type 2 receptors reportedly leads to vasodilatation, neuronal differentiation, apoptosis, and axonal regeneration," they write. ARBs selectively inhibit the type 1 receptors, which might translate to improved cerebral blood flow and enhanced neuroprotective effect.
Still, they point out that the randomized clinical trials SCOPE (Study on Cognition and Prognosis in the Elderly) and PRoFESS (PReventiOn regimen For Effectively avoiding Second Strokes) showed no significant effect on either the rate of cognitive decline or incident dementia with an ARB.
Limitations of the study include the nonrandomized allocation of treatment, which they call a "serious problem" because racial disparities have been reported in the use of antihypertensives, such as ARBs, among American veterans and the ethnic origin of most subjects was not reported.
"The public health implications of finding an effective way of preventing dementia are immense, but further work is needed to verify the usefulness of antihypertensives in general and angiotensin receptor blockers in particular," they conclude.
The study was supported by a grant to Dr. Wolozin from the Retirement Research Foundation and a donation from the Casten Foundation. Dr. Wolozin reports having received these grants as disclosure of competing interests in the paper. The editorialists have disclosed no relevant financial relationships.
BMJ. Published online January 12, 2010 .

Clinical Context

Previous research has found a link between cardiovascular disease and the risk for AD. A study by Luchsinger and colleagues of 1138 older adults with normal cognition examined the association between cardiovascular risk factors and the risk for incident AD. Their results, which were published in the August 23, 2005, issue of Neurology, found that diabetes, hypertension, heart disease, and current smoking were all independently associated with a higher risk for AD, with diabetes and smoking associated with the highest risk. In addition, the risk for AD increased with the incremental addition of more cardiovascular risk factors.
Inhibitors of the renin-angiotensin system may improve cardiovascular outcomes in selected patients, and there is some evidence that angiotensin may help promote some of the changes associated with dementia. The current trial examines whether renin-angiotensin inhibitors can reduce the risk for incident dementia among a cohort of older men with preexisting cardiovascular disease.

Study Highlights

• Study subjects were members of the Veterans Affairs health system who were at least 65 years old in 2002. All included individuals had not previously received a diagnosis code for AD or dementia.
• Based on records from their health database, study patients were divided into 1 of 3 groups: patients receiving ARBs, patients receiving the ACE inhibitor lisinopril, and patients receiving other cardiovascular medications excluding renin-angiotensin inhibitors and statins (cardiovascular comparator group).
• The main outcome of the study was the effect of ARBs on the risk for incident AD and dementia during 4 years of follow-up. Researchers also examined the treatment effect on the progression of dementia, which was defined by admission to a nursing home or death.
• Researchers focused on patients with similar health profiles to try to reduce bias. Their analyses accounted for disease factors that could promote dementia.
• 819,491 patients provided data for the study analysis of incident AD. 98% of subjects were men, and the average age of the study cohort was 74 years.
• The prevalence of cardiovascular disease and stroke was lower in the ARB and lisinopril groups vs the cardiovascular comparator group, but patients receiving ARBs and lisinopril had higher rates of diabetes. Blood pressure levels were similar between medication groups.
• ARBs were significantly superior to both lisinopril and cardiovascular comparators in reducing the incidence of AD (hazard rate vs each respective treatment: 0.81 and 0.84).
• The hazard rate for any dementia in comparing ARBs vs lisinopril was significant at 0.81, as was the comparison between ARBs and the cardiovascular comparator (0.76).
• ARBs were also superior in reducing the risks for nursing home admission or death vs the cardiovascular comparator among patients with AD.
• Higher doses of ARBs were associated with progressively lower risks for dementia.
• Changing to an ARB from an ACE inhibitor was associated with a lower risk for incident dementia, whereas the converse was not true.
• The combination of ARB plus an ACE inhibitor reduced the risk for incident AD and dementia to a greater degree than the use of either medication alone.

Clinical Implications

• A previous study found that diabetes, hypertension, heart disease, and current smoking were all independently associated with a higher risk for AD, with diabetes and smoking associated with the highest risk. In addition, the risk for AD increased with the incremental addition of more cardiovascular risk factors.
• The current study demonstrates that ARBs may reduce the risk for incident dementia and AD among older men with cardiovascular disease. There was a dose-response effect of ARBs in reducing dementia, and the combination of ARB plus an ACE inhibitor was even more effective in reducing the risk for dementia. ARBs were also associated with reducing the risk for progression of AD.

CME Test

Questions answered incorrectly will be highlighted.

Which of the following was a finding of the previous study by Luchsinger and colleagues examining the association between cardiovascular risk factors and AD?

Heart disease was associated with a higher risk for AD, but hypertension was not

Heart disease was the factor most associated with a higher risk for AD

Current smoking was associated with a lower risk for AD

The risk for AD increased with a higher number of cardiovascular risk factors

Which of the following statements was a finding of the current study of dementia among older men by Wolozin and colleagues?

Only ACE inhibitors were associated with a lower risk for AD

ARBs were associated with lower risks for both incident AD and the progression of AD

The dose of ARB did not affect study outcomes

Combining an ACE inhibitor with an ARB nullified any beneficial effect

Influenza Vaccination Successfully Increased Vaccination Rates

 

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Medscape Medical News

Mandatory Influenza Vaccination Successfully Increased Vaccination Rates

Laurie Barclay, MD

February 11, 2010 — A mandatory influenza vaccination campaign at a large healthcare organization successfully increased vaccination rates, according to a report in the February 15 issue of Clinical Infectious Diseases.
"Influenza vaccination of health care workers has been recommended since 1984," write Hilary M. Babcock, MD, MPH, assistant professor of medicine at Washington University School of Medicine and medical director of occupational health (infectious diseases) at Barnes-Jewish and St. Louis Children's Hospitals in St. Louis, Missouri, and colleagues. "Multiple strategies to enhance vaccination rates have been suggested, but national rates have remained low."
At BJC HealthCare, a large Midwestern healthcare organization with approximately 26,000 employees, organizational vaccination rates remained below target levels. In 2008, therefore, influenza vaccination was made a condition of employment for all employees, although medical or religious exemptions could be requested.
"As a patient safety initiative, we knew the flu shot was safe and effective, and the best way to protect patients was to be sure that employees were vaccinated," Dr. Babcock said in a news release.
Occupational health nurses and their medical directors reviewed medical exemption requests; predetermined medical contraindications included hypersensitivity to eggs, previous hypersensitivity reaction to influenza vaccine, and history of Guillain-Barré syndrome.
Employees who were neither exempted nor vaccinated by December 15, 2008, were not scheduled for work, and those still unvaccinated and not exempted by January 15, 2009, were terminated. Of 25,980 active employees, 25,561 (98.4%) were vaccinated, 90 (0.3%) received religious exemptions, 321 (1.2%) received medical exemptions, and 8 employees (0.03%) were neither vaccinated nor exempted.
Of the medical exemptions, 107 employees (33%) were allergic to eggs, 83 (26%) had a previous allergic reaction or allergy to other vaccine component, 15 (5%) had a history of Guillain-Barré syndrome, and 116 employees (36%) had other medical exemptions, including 14 who were pregnant.
Smooth Execution, Fears Allayed
"Some of the requests for medical exemptions reflected misinformation about the vaccine and influenza," Dr. Babcock said. "Overall, the program went very smoothly, [and] we were able to talk with the people who had concerns about the vaccine and allay their fears. A large number of employees were really glad that we had made it mandatory and that coworkers were being vaccinated."
The study authors note that the experience at BJC HealthCare may not be completely generalizable, that economic factors at the time of the study may have limited the number of employees willing to lose their jobs, and that not all physicians affiliated with BJC HealthCare are employed by the organization and, therefore, were not covered by the policy.
"A mandatory influenza vaccination campaign successfully increased vaccination rates," the study authors conclude. "Fewer employees sought medical or religious exemptions than had signed declination statements during the previous year. A standardized medical exemption request form would simplify the request and review process for employees, their physicians, and occupational health and will be used next year."
In an accompanying editorial commentary, Andrew T. Pavia, from the University of Utah, Salt Lake City, notes that of all the strategies to improve vaccination rates, the policy of mandatory vaccination has generated the most controversy.
"The policy pits the ethical principle of normalfeasance against individual autonomy," Dr. Pavia writes. "Mandatory vaccination policies have been endorsed by several organizations, including the New York State Department of Health, the Infectious Diseases Society of America, the American College of Physicians, the Association for Professionals in Infection Control and Epidemiology, and the National Foundation for Patient Safety.... Mandatory vaccination has also generated vigorous debate and opposition, including legal challenges."
The study authors have disclosed no relevant financial relationships.
Clin Infect Dis. 2010;50:459-464, 465-467.

 

• H1N1 Influenza A (Swine Flu) Alert Center

Medscape Medical News

WHO to Consider Whether H1N1 Pandemic Has Peaked

Robert Lowes

February 11, 2010 — An emergency advisory committee of the World Health Organization (WHO), meeting later this month, will consider making it official what WHO has indicated for weeks — that the H1N1 influenza pandemic, although still active in many parts of the world, is winding down.
However, at a press conference today, Keiji Fukuda, MD, MPH, the special pandemic influenza advisor to the WHO director-general, cited a recent outbreak of H1N1 infection in Senegal as proof that the pandemic has not run its full course.
"We are seeing an overall declining pattern in the Northern Hemisphere, but it's very clear the virus hasn't disappeared," said Dr. Fukuda. "It's continuing to cause disease and death in many parts of the world."
Dr. Fukuda said WHO has received its first reports of communitywide infection in Senegal, where there have been 42 mild cases of pandemic H1N1 influenza, but no deaths. "Western Africa is one part of the world where we haven't seen much activity," he said. "We may be seeing a general decline, but in some places community outbreaks can [still] be expected."
The emergency committee, formed under the International Health Regulations approved by WHO member states, will review epidemiologic data and then recommend whether WHO should classify the pandemic as having entered a postpeak, or transition, phase, said Dr. Fukuda.
The postpeak phase is part of a pandemic classification system used by WHO that immediately follows phase 6, which marks a full-blown pandemic. In a postpeak period, according to WHO's Web site, "pandemic activity appears to be decreasing; however, it is uncertain if additional waves will occur and countries will need to be prepared for a second wave." Official designation of the postpeak period will help national public health authorities plan for the future, Dr. Fukuda said.
The final stage in the WHO spectrum is the postpandemic period. Here, influenza disease activity returns to "levels normally seen for seasonal influenza."
Dr. Fukuda said he expects the emergency committee to meet during the last week of February, although an exact date has not yet been set.
H1N1 Could Be Component of Next Seasonal Flu Vaccine for Northern Hemisphere
Dr. Fukuda also announced that WHO will convene its annual meeting of experts next week to begin deliberating on which influenza virus strains should make up the 2010-2011 seasonal influenza vaccine for the Northern Hemisphere. These experts hail from national public health agencies and laboratories that make up the WHO Global Influenza Surveillance Network. Dr. Fukuda said that this group will likely consider including the pandemic H1N1 virus as 1 of the 3 strains normally constituting the seasonal influenza vaccine.
"I don't want to second-guess what the expert advisors will recommend," said Dr. Fukuda. "But it's fair to point out that the current pandemic virus is by far the most common virus that's been isolated around the world. It's a good bet we'll see it around for quite a while."
Each September, WHO convenes the same experts to recommend the composition of the next year's seasonal influenza vaccine for the southern hemisphere. At their meeting in September 2009, they included a strain of the pandemic H1N1 virus — specifically, an A/California/7/2009 (H1N1)-like virus — as 1 of the 3 strains for 2010. The other recommended strains were an A/Perth/16/2009 (H3N2)-like virus and a B/Brisbane/60/2008-like virus.
Another WHO advisory group, the Strategic Advisory Group of Experts on Immunization, recommended last year that nations ordering vaccines should have the option of either including a pandemic H1N1 virus in the traditional trivalent vaccine for seasonal influenza or making it a separate monovalent vaccine, with the other 2 recommended strains in a second vaccine.
"This Is a True Pandemic"
Dr. Fukuda continued to defend WHO against charges issued by European critics that profit-minded vaccine manufacturers swayed the agency to exaggerate the severity of the H1N1 outbreak. "Our position is very clear," he said. "This is a true pandemic."
WHO, he said, is currently assessing how WHO and other national public health agencies performed in responding to the pandemic so they can "do it better the next time." However, this investigation is not based on allegations by any particular individuals, he added.

Medscape Medical News from the:

• American Academy of Neurology (AAN) 62nd Annual Meeting
  

This coverage is not sanctioned by, nor a part of, the American Academy of Neurology.

Medscape Medical News

Chocolate Linked to Lower Stroke and Stroke Mortality Risk

Susan Jeffrey

February 12, 2010 — Just in time for Valentine's Day, a new systematic review from Canadian researchers suggests higher chocolate consumption may be associated with a lower risk for incident stroke and stroke-related mortality.
Results of 2 prospective cohort studies showed, respectively, a 22% reduction in stroke risk for those who had 1 serving of chocolate per week and a 46% reduction in stroke mortality from weekly consumption of flavonoids in 50 g of chocolate vs no consumption. A third study showed no association between chocolate intake and stroke or death.
However, the number of studies looking at this relationship was small, senior author Gustavo Saposnik, MD, from St. Michael's Hospital and the University of Toronto, Canada, told Medscape Neurology. "We need more prospective studies that specifically identify the type of chocolate and the amount, including the amount of flavonoids included in the composition of the chocolate, to make more valid conclusions," he said.
The results were released February 11 in advance of their planned presentation at the upcoming American Academy of Neurology 62nd Annual Meeting in April. The abstract will post to http://www.aan.com on February 17.
Varying Effects
Chocolate contains cocoa butter, flavonoids, carbohydrates, and vitamins. Previous studies, most of them epidemiological, have shown varying effects of chocolate consumption on the risk for cardiovascular disease, the researchers, with first author Sarah Sahib, BScCA, from McMaster University in Hamilton, Ontario, Canada, write. "Less is known about the risk of stroke in association with flavonoid intake," they note.
To examine this association, the authors carried out a systematic review of studies published between 2001 and 2009, using search terms including flavonoids, flavanols, isoflavones, and anthocyanidins, as well as stroke and mortality.
"We found 88 publications, among them 3 prospective studies, and another retrospective study providing some information on the effect of chocolate consumption on the incident risk of stroke," Dr. Saposnik said. "Two of these studies show a reduction in the incident risk of stroke, and the other 2 didn't show any substantial difference."
For example, of the 3 prospective studies, 1 found no association between flavonoid intake and the risk for stroke or death when 3% of catechin intake came from chocolate (relative risk [RR], 0.92; 95% confidence interval [CI], 0.51 - 1.68).
However, a second study found a reduction in incident stroke for chocolate consumption once per week vs no consumption (RR, 0.78; 95% CI, 0.65 - 0.94).
The third study looked at the association between flavonoid intake and stroke mortality and found a suggestion of protection against stroke mortality from 50 g of chocolate (hazard ratio, 0.54; 95% CI, 0.30 - 0.96).
The authors conclude that further prospective studies are needed "to assess whether the benefit of chocolate-based flavonoid consumption truly lowers stroke risk, or whether the apparent benefit is biased by a healthy user effect."
Investigation a Challenge
However, although more data on this link would be helpful, Dr. Saposnik pointed to several challenges to doing these kinds of studies. First, it is important to document the actual content of flavonoids or other substances thought to be active in the chocolate being consumed.
"There are some studies that compare the content of flavonoids for different food elements and antioxidant capacity," he said. Dark chocolate is one with the highest flavonoids and procyanidins, which have been associated with lower cardiovascular risk, and in addition, dark chocolate has the highest antioxidant capacity.
Still, there are varying types of chocolate, and the amounts that are required to affect stroke risk may bring a load of sugar and fats that may work counter to the beneficial effects. "50g of chocolate per day is a significant amount," Dr. Saposnik notes.
Finally, large longitudinal studies are also expensive, and funding for them scarce, which may explain why much of the evidence is coming from epidemiologic studies, he added. One alternative may be to conduct smaller studies, looking the effects of consuming controlled amounts of chocolate on some intermediate biomarker of stroke risk.
The study received no commercial support. The authors have disclosed no relevant financial relationships.
American Academy of Neurology 62nd Annual Meeting. April 10-17, 2010. Published online February 11, 2009.