PRACTICAL POINTERS

 

FOR

 

PRIMARY CARE

 

ABSTRACTED MONTHLY FROM THE JOURNALS

 

 

 

 

JANUARY TO JUNE

 

2005

 

 

 

PRACTICAL POINTS FOR PRACTICE

 

MEDICAL SUBJECT HEADINGS

 

HIGHLIGHTS AND EDITORIAL COMMENTS

 

 

 

 

 

 

JAMA, NEJM, LANCET                                                                    PUBLISHED BY PRACTICAL POINTERS INC.

BRITISH MEDICAL JOURNAL                                                      EDITED BY RICHARD T. JAMES JR

ARCHIVES OF INTERNAL MEDICINE                                              400 AVINGER LANE, SUITE 203

ANNALS OF INTERNAL MEDICINE                                            DAVIDSON NC 2803

               

               

 

WWW.PRACTICALPOINTERS.ORG                                               RJAMES6556@AOL.COM

 

 

 

This document is divided into three parts:

1)  “Practical Points”—one sentence statements of how the articles abstracted during the 6 months may influence primary care practice.

2) Seventy seven medical subject headings (MeSH) from “Absolute Cardiovascular Risks” to “Ximelagatran”.  Each of the medical subject headings is linked to one or more

“Highlights and Editorial Comments” of articles abstracted during the first half of 2005.

3) A “Highlights-Editorial Comments” Section, arranged alphabetically following the list of MESH,  provides a means of recalling to memory, in an  evening or two, what the editor considered new and important for primary care presented in 6 flagship journals over the 6 months.

 

The numbers in the brackets refer to the full abstract.  For example, [6-2] indicates the 2nd abstract published in the June issue.

The indexes and each monthly issue for the past 5 years can be found on the website (www.practicalpointers.org).  HTML links make possible easy and speedy access to the full abstract and the journal reference of all articles abstracted under an individual MeSH.

I hope you find the publication useful and interesting.

 

Richard T. James Jr. M.D.

The editor thanks Whitney Lowell for internet applications and Lois M. James for proofreading.

 

 

PRACTICAL POINTS JANUARY-JUNE 2005

HOW THE ARTICLES ABSTRACTED INFLUENCED MY PRACTICE

·         Consider use of herpes zoster vaccine when it becomes available. [6-1]

·         Consider use of delayed prescriptions for acute lower respiratory infections  [6-2]

·         Encourage patients to consider their abdominal girth a risk factor [6-3]

·         Be cautious in using aspirin for primary protection of CHD in elderly women. [6-5]

·         Care in using antipsychotic drugs in nursing homes [6-6]

·         Consider  a thiazide a first-line treatment in hypertensive diabetics and blacks  [6-8]  [4-1]

·         Use opioids more freely for patients with neuropathic pain [6-9]   Consider use of gabapentin combined with morphine for severe neuropathic pain [3-4]

·         Advise patients that high dose vitamin E is useless in the elderly with memory defects or for reduction of risk of cardiovascular disease and cancer. And it may be toxic [6-10]  [3-10]

·         Advise younger overweight patients that weight loss will prevent later development of hypertension [6-11]

·         Continue to advise vitamin D (800 IU) for primary prevention of osteoporosis and fractures [5-3]

·         For first-line therapy, advise symptomatic treatment for traveler’s diarrhea, not antibiotics. [5-4]

·         For patients with persistent cough, pertussis is a possibility [5-5]

·         Oral vitamin B12 in high dose is effective therapy [5-6]

·         Progesterone, not estrogen, is the risk factor for breast cancer in women receiving HRT [5-7]

·         Inform men about risks of PSA screening as well as benefits. Consider that “most prostate cancers now removed need not be removed”  [5-9]

·         Treat acute  pain of herpes zoster aggressively to lower severity of post-herpetic neuralgia pain [5-10]

·         Stress the benefits of a modified Mediterranean diet which contains poly-unsaturated fats as well as mono-unsaturated fats. [4-4]

·         Consider the “Money needed to treat” as well as the “Number needed to treat needlessly” [4-6]

·         Consult with your cardiologist consultants about availability and advisability of cardiac resynchronization in patients with left bundle-branch-block and heart failure.  [4-10]

·         Consider myasthenia gravis in a patient with fluctuating weakness which improves with rest and application of cold. [4-11]

·         Consider that all adults have at least one risk factor for cardiovascular disease. All should be considered in each individual patient. Changing life-styles is basic therapy. Many will benefit from  drug therapy  [3-1]   [3-2]

·         Know the drugs available for prophylaxis and treatment of influenza [ 2-1]

·         Never give up encouraging smokers to quit  [ 2-3]

·         For atrial fibrillation, rate control is preferable to rhythm control  [ 2-4]

·         Simple first aid and local wound care the best approach for bites of the brown recluse spider. [ 2-6]

·         Extent of treatment of hypertension and dyslipidemia should depend on the patient’s absolute cardiovascular risk. [1-1]

·         In considering application of results of trials beware of surrogate endpoints, composite outcome measures, underreporting of adverse effects, and reports by pharmaceutical companies. [1-2]

·         Uncertainty is inherent in primary care practice. Evidence helps quantify the uncertainty, but cannot remove it.  [1-4]

·         Know the benefits of a new class of drugs to treat breast cancer (aromatase inhibitors)  [1-5]

·         Fast foods are an ominous public health issue [1-8]

·         For patients with persistent dyspepsia consider testing of H pylori and treating if positive. [1-9]

·         The U. S Preventive Services Task Force recommends one-time screening for abdominal aortic aneurysm in persons who smoke. [1-11]

 

 

 

MEDICAL SUBJECT HEADINGS (MeSH)   JANUARY- JUNE 2005

 

ABSOLUTE CARDIOVASCULAR RISK

ACUTE CORONARY SYNDROMES

ADVERTISING

ALCOHOL

ALLHAT STUDIES    (SEE HYPERTENSION [6-8])

ANEURYSM

ANTIBIOTICS

ANTICOAGULANT THERAPY

ANTIPSYCHOTIC DRUGS

AROMATASE INHIBITOR   (SEE BREAST CANCER [1-5])

ASPIRIN      

 ATKIN’S DIET  (SEE DIET [1-7])

ATRIAL FIBRILLATION

 

BREAST CANCER 

BROWN RECLUSE SPIDER

 

CANCER 

CARDIOVASCULAR DISEASE 

CHOLESTEROL

COGNITIVE DECLINE

COGNITIVE IMPAIRMENT

CONGESTIVE HEART FAILURE   (SEE HEART FAILURE)

CORONARY HEART DISEASE    (SEE ALSO ISCHEMIC HEART DISEASE [5-2])

C-REACTIVE PROTEIN   (SEE STATIN DRUGS [1-13])

 

DIABETES

DIABETIC NEUROPATHY

DIET

DYING

DYSPEPSIA

 

ENDOMETRIAL CANCER

ESTROGEN (SEE HORMONE REPLACEMENT THERAPY)

EVIDENCE-BASED MEDICINE

 

FAST FOOD

FOLIC ACID  (See HOMOCYSTEINE [3-9])

FRACTURE  (SEE VITAMIN D  [5-3])     

GASTRO ESOPHAGEAL REFLUX DISEASE

GESTATIONAL DIABETES MELLITUS

 

HEART FAILURE

HERPES ZOSTER

HOMOCYSTEINE

HORMONE REPLACEMENT THERAPY  

HYPERPARATHYROIDISM

HYPERTENSION

 

INFLUENZA

INSULIN RESISTANCE

INTRACRANIAL STENOSIS.

ISCHEMIC HEART DISEASE

 

MACULAR DEGENERATION

MEDITERRANEAN DIET

“MONEY” NEEDED TO TREAT

MYASTHENIA GRAVIS

MYOCARDIAL INFARCTION

 

 

NEUROPATHIC PAIN

NUMBERS NEEDED TO TREAT (NEEDLESSLY)

 

OBESITY

OPIOID AGONISTS

 

PAIN   (SEE OPIOID AGONISTS [6-9])

PERTUSSIS   (SEE WHOOPING COUGH  [5-5])

PNEUMONIA

POLYPILL (SEE CORONARY HEART DISEASE)

POSTHERPETIC NEURALGIA AND PAIN   (SEE HERPES ZOSTER)

POWER AND AUTHORITY IN MEDICINE

PREMENSTRUAL SYNDROME

PROSTATE CANCER

 

RANDOMIZED CONTROLLED TRIALS

RESPIRATORY INFECTION

 

SENSITIVITY, SPECIFICITY, AND PREDICTIVE VALUES: A REVIEW

SMOKING

STATIN DRUGS

STROKE

       

TRAVELERS’ DIARRHEA

TUBERCULOSIS

 

VITAMIN B12

VITAMIN D

VITAMIN E  

 

WAIST CIRCUMFERENCE

WHOOPING COUGH

 

XIMELAGATRAN

 

HIGHLIGHTS AND EDITORIAL COMMENTS

JANUARY- JUNE 2005

 

ABSOLUTE CARDIOVASCULAR RISK

Treat the Patient, Not the BP, Not the cholesterol

1-1  TREATMENT WITH DRUGS TO LOWER BLOOD PRESSURE AND BLOOD CHOLESTEROL BASED ON  AN INDIVIDUAL’S ABSOLUTE CARDIOVASCULAR RISK.

        Absolute risk of a cardiovascular disease is the probability that an individual patient will have an event over a defined period. It is determined by a synergistic effect of all CVD risk factors present in the individual. It may be true that, in a large group of individuals with a systolic BP of 160, the CVD risk is twice as  high as in a large group with a systolic of 110 (relative risk). In an individual, however, absolute risk depends on much more than a single risk factor. Indeed, absolute differences in risk can vary more than 20-fold in patients with the same BP.

        “Cardiovascular treatment benefit is directly proportional to the pre-treatment absolute risk.”

        A new approach to preventive therapy is to modestly reduce all modifiable risk factors rather than concentrating on reaching “target levels’ of one or two.

        This is a sea change in our approach to lowering risk.

        Please read the full abstract.

 

 

ACUTE CORONARY SYNDROMES

Proposing an ABCDE Memory Device to Simplify Adherence to Guidelines

1-6   A SIMPLIFIED APPROACH TO THE MANAGEMENT OF NON-ST-SEGMENT ELEVATION ACUTE CORONARY SYNDROMES

        The study assembled a comprehensive plan through an “ABCDE” approach. The intention was to provide a

memory device to overview therapies and lifestyle changes that are clinically useful for patients with      NSTE-ACS.

        Elements of the plan:

                A     Antiplatelets; Anticoagulation;  ACE inhibitors;  Angiotensin II blockers.

                B     Beta-blockers; Blood pressure control

                C     Cholesterol management;  Cigarette cessation

                D     Diet;  Diabetes management

                E      Exercise.

        This practical approach allows physicians to more effectively create disease management protocols, define roles and responsibilities for different medical personnel, and ensure implementation of evidence-based short-

and long-term medical and risk-reducing strategies.

        This plan is almost identical to a check list presented in the Archives Int Med July 2004 for secondary prevention of cardiovascular disease. (See Practical Pointers July 2004 [7-8] )

        I believe check lists can be a valuable addition to primary care. In the hurried pace of practice, we all omit (simply forget to consider) aspects of treatment and lifestyle which should be addressed at almost every patient visit. A mneumonic check list is a practical approach.

       

        Some clinicians may make their own. I tried to create a mneumonic check list for diabetes:

                D     Diet; Depression

                I       Insulin

                A     Aspirin; ACE inhibitors

                B     BMI; BP

                E     Exercise

                T      Tests (blood glucose; HbA1c; lipids; microalbuminuria; liver function; ejection fraction)

                E     Eye (retinopathy); Extremities (foot health; foot pulses; peripheral neuropathy)

                S      Sulfonylureas, Statins, and other oral drugs; Smoking 

                Plus (Add others which might be indicated.)

 

 

ADVERTISING

“Ask Your Doctor if X  is Right for You”

4-12   DIRECT-TO-CONSUMER ADVERTISING

A Haphazard Approach to Health Promotion

        DTCA drives sales of newer, more expensive products for symptomatic relief of chronic conditions. The market potential is huge. Erectile dysfunction, arthritis, and allergies are the most common conditions advertised.

        “Relying on emotional appeals, most advertisements provide a minimal amount of health information, describe benefits in vague, qualitative terms, and rarely offer evidence of support claims.”

        The great majority of physicians believe that DTCA does not provide balanced information. The FDA  rarely writes regulatory letters. “Millions of patients are exposed to misleading advertisements.” Nearly 80% of physicians think that DTCA encourages patients to seek treatments they do not need. Less than 10% of physicians consider DTCA a positive trend in health care.

        Is ED a manufactured “disease”? Is drug treatment mainly recreational?

        I confess that advertisements on TV touting a drug in market terms and then asking the listener to “Ask your doctor if the drug is right for you” irritates me. It would require considerable time and patience to educate individual patients about the benefit/harm-cost ratio of a given drug. It may be easier to submit as gracefully as possible.

        I believe claims by drug companies that DTCA is for instruction and benefit of the consumer are specious. The purpose is to market the drug and increase profits.. After all, we live in a capitalistic society.

 

 

ALCOHOL

One or Two Drinks per Day may Reduce Risk of Cognitive Decline

1-12   EFFECTS OF MODERATE ALCOHOL CONSUMPTION ON COGNITIVE FUNCTION IN WOMEN.

        This study asks—What is the effect of moderate consumption of alcohol on cognition? A benefit is plausible considering the strong link between moderate alcohol and decreased risk of cardiovascular disease. Cognitive impairment and cardiovascular disease share common risk factors.

        Compared with abstainers, moderate drinkers (less than 15 g alcohol per day; one drink) had better mean cognitive scores. (Relative risk of impairment = 0.81 based on a global cognitive score.)  Also, compared with abstainers, moderate drinkers (15 to 30 g per day) had a reduced relative risk of cognitive impairment (although slightly less favorable, with wider confidence intervals).

        In older women consumption of one alcoholic drink per day did not impair cognitive function, and may actually decrease risk of cognitive decline.

         Benefits of moderate alcohol consumption have been reported with remarkable consistency over the past 10 years. Indeed, some epidemiologists consider abstinence to be a risk factor for cardiovascular disease.

        As always, we should be cautious about generalizing the conclusions of observational studies.

 

“Almost No Pattern of Drinking (Even Low-To-Moderate) is Entirely Risk Free.”

2-2    ALCOHOL AND PUBLIC HEALTH

        Over the past 30 years, advances in our understanding of drinking problems have been substantial.

        This review considers 3 subtopics:  1) the epidemiology of alcohol’s role in health and illness, 2) treatment of alcohol use disorders as part of public health, and 3) prevention and policy research.

        Alcohol is causally linked to more than 60 different medical conditions—most, but not all, detrimental.

For most diseases there is a dose-response relationship. Not only the volume of consumption, but patterns of drinking (especially binge drinking) determine the burden of disease. Almost no pattern of drinking (even low-to-moderate) is entirely risk free.

                Breast cancer (BC):

Meta-analyses have shown a linear increase in risk of BC associated with increasing average consumption of alcohol.

                Coronary heart disease  (CHD):

Comprehensive meta-analyses reiterate the protective effect of low-to-moderate alcohol intake—a  J-shaped curve.

                Injury (violence)

                        Several pharmacological effects are likely to increase probability of aggressive behavior.

        Alcohol accounts for about as much of the burden of disease globally as tobacco.  Its burden is surpassed only by unsafe sex, high blood pressure, and malnutrition.

        Among heavy drinkers who have no evidence of severe alcohol dependence, an intervention in primary care aimed at reduction of drinking to moderate levels may benefit. Evidence suggests that clinically significant effects on drinking behavior can follow a brief intervention—but not in alcohol-dependent persons.

        Overall, a discouraging report. Primary care clinicians may have some place in prevention of alcohol dependence by early assessment and intervention.

        Many experts have urged screening, especially for patients who are hospitalized for any reason.

        AUDIT and CAGE questionnaires available on Google. Screening in itself may broach the subject and lead patients to self-examination.

        The relation between breast cancer and alcohol has not been well publicized. I believe it prudent to inform women at high risk (family history; breast cancer genes) about the risk.

        No level of alcohol consumption is known to be safe in pregnancy.

 

Associated With A Slight Reduction In Days Of Heavy Drinking

4-13   EFFICACY AND TOLERABILITY OF LONG-ACTING INJECTABLE NALTREXONE FOR ALCOHOL DEPENDENCE

        The opioid antagonist naltrexone has been shown to be effective for treatment of alcohol dependence (AD). The FDA approved naltrexone in 1994 to treat AD after it was shown to reduce drinking frequency and likelihood of relapse to heavy drinking.

However, adherence to daily oral therapy is problematic, as it is with other medications.

        Recently a new formulation of naltrexone has been made available. When given by injection, it releases the drug over a period of one month without daily peaks in concentration.

        A randomized, double-blind, placebo-controlled multicenter trial followed over 400 patients (mean age = 45). All were considered to be AD and almost all were still actively drinking (median heavy drinking days per month = 20). All were seeking treatment for their AD.

        Randomized to: 1) monthly injections of 380 mg long-acting naltrexone, or 2) placebo injections.

        All also received low-intensity psychosocial intervention.

        Follow-up = 6 months.

        Conclusion:  Long-acting naltrexone, given by injection once a month, was associated with a slight reduction in days of heavy drinking.

        Authors (with concurrence from journal editors) persist in reporting efficacy as percentages. (“Naltrexone resulted in a 25% reduction in the event rate of heavy drinking days”).

Results of the trial were not impressive. Dropout rate was high. Women did not benefit. Adverse effects were frequent. “Spin” was evident.

        The most evident benefit shown by the study was in the “placebo” group (motivated patients who received counseling).  At 6 months there was a median reduction in days of heavy drinking per month from about 19 to about 6.  Naltrexone was associated with a further reduction from 6 to 3 days. (My assessment of the figure 2 page 1622). Over the 6 months, in the placebo group there was a median of 56 cumulative days of heavy drinking vs 47 cumulative days in the naltrexone group, a difference of only about 9 days.

        Should primary care clinicians administer long-acting naltrexone by injection?  I believe only in exceptional circumstances. If a patient with AD approaches the primary care clinician for help, the desire to quit must be understood to be strongly motivated. The clinician must be able to provide adequate counseling. Follow-up must be rigid. The clinician and patient must enter a contract to guide compliance. The small added benefit from naltrexone must be made clear.

We await better treatments, perhaps with the addition of two or more pharmacological agents (eg, acamprosate).

        The study was sponsored by Alkermes and Pharmacological Product Development Inc. who collected and monitored the data. Data were managed and analyzed by Alkermes clinical and statistical staff.

 

 

ANEURYSM

The USPSTF Now Recommends One-Time Screening in Select Subsets of Men

1-11   SCREENING FOR ABDOMINAL ANEURYSM

        The U.S. Preventive Services Task Force (USPSTF) now recommends one-time ultrasonographic screening for abdominal aortic aneurysm (AAA) for men ages 65 to 75 who presently smoke or who have smoked in the past.

        The task force makes no recommendation for or against screening men who have never smoked. It recommends against routine screening for women.

        One-time screening is sufficient.

        Is there any medical treatment? Will beta-blockers decrease the rate of expansion by reducing the

stress caused by the steep increase in wall expansion during systole?  Many patients in this age group with AAAs would be candidates for beta-blocker therapy because of an increase in risk factors for CVD, including sub-optimal BP control.

        As always, primary care clinicians must judge benefits vs harms of individual patients. The availability of expert, safe surgery is a major factor influencing the recommendation. 

        Advice for screening carries ethical considerations. Although opportunistic preventive medicine is considered a part of good medical practice, is it always ethically justifiable? Consider a male smoker age 70 who consults for arthritis. Should the primary care clinician at the time of the consultation advise the patient to undergo screening for AAA? Should the primary care clinician advise a prostate specific antigen?

        Physicians who offer a screening test carry a considerable responsibility. They must offer enough information  about risks and benefits in order to enable the patient to give informed consent. Every test carries a chance of a false-positive result leading to interventions that do not benefit the patient, and may cause harm.

        I believe many primary care clinicians would limit screening for AAA to patients who consult for a specific indication—assessment of their general health status. 

 

 

ANTIBIOTICS

Antibiotics Provided Little Advantage Compared With No-Antibiotics.

6-2   INFORMATION LEAFLET AND ANTIBIOTIC PRESCRIBING STRATEGIES FOR ACUTE LOWER RESPIRATORY INFECTION

        Pharyngitis and acute bronchitis are the main causes of excess antibiotic prescribing.

        This pragmatic study assessed the effectiveness of 3 different antibiotic strategies for acute bronchitis.

        Randomized, controlled trial followed over 800 patients presenting to primary care with acute uncomplicated

LRI.  Patients with findings suggestive of pneumonia were excluded—new focal chest signs (focal crepitations or bronchial breathing);  and systemic features (high fever, vomiting, severe diarrhea). Also excluded patients with asthma, other chronic or acute lung diseases, cardiovascular disease, or with previous pneumonia.

        Randomized to:  1) no antibiotic prescribed [control group],   2) delayed prescription [to be picked up later], or 3) immediately prescribed antibiotic. The antibiotic of choice was amoxicillin 250 mg 3 times daily for 10 days, or, if allergic, erythromycin 250 mg 4 times a day for 10 days.

        Compared with no antibiotics [control group], the other strategies did not significantly alter cough

duration: Delayed prescription shortened duration by 0.75 days;  immediate prescription by 0.11 days.  Treatment group had no effect on duration of other symptoms.

        “Compared with immediate antibiotics, a strategy of either no offer of antibiotics or a delayed prescription was associated with little difference in duration or severity of  symptoms.” Overall, antibiotics probably do provide modest symptomatic relief. If a benefit is present, it represents a shortening of only one day in a relatively long history.  “It is difficult to justify widespread antibiotic prescribing for uncomplicated lower respiratory infection on this basis, given the dangers of antibiotic resistance.”

        I was somewhat surprised at the duration of cough symptoms in this group of patients—a mean total of 3 weeks. However, I believe most patients would experience a gradual improvement over this period. We are admonished to consider pertussis in patient with LRI when the cough lasts 3 weeks or more. I presume in pertussis the cough continues unabated.

        I believe advising patients that antibiotics may be associated with serious adverse effects (eg, colitis) will do more to tilt them toward accepting only symptomatic therapy than would advising them of the danger of antibiotic resistance in the community.

        I have had success in prescribing delayed prescriptions of patients with uncomplicated lower respiratory infections. The great majority never fills the prescription. This may be an acceptable means of satisfying a demanding patient.

        In the US, It is likely that many patients presenting after a week or more of cough and sputum production will receive a cheat X-ray.

        The decision by primary care clinicians to prescribe or not prescribe, I believe, will often depend on how “sick” the patient appears.    

 

 

ANTICOAGULANT THERAPY

Potentially A Less Intimidating Alternative to Warfarin.  Concerns about Hepatotoxicity

2-7   XIMELAGATRAN—Promises and Concerns

        Melagatran is a highly-specific direct thrombin inhibitor, an analogue of hirudin, the thrombin  inhibitor found in the medicinal leech. It is a small dipeptide which binds reversibly to the active site of thrombin. It inhibits clot-bound thrombin as well as free thrombin. Ximelagatran is a prodrug form of melagatran. It is rapidly absorbed from the GI tract. When given orally it is rapidly converted to melagatran. Its antithrombin activity is immediate. Peak blood levels are attained in 3 hours. It is cleared entirely by renal excretion in 12 hours.

        Since the effect is predictable at a fixed dose, monitoring is not necessary.

         This is not yet a practical point for primary care since the drug is not yet approved by the FDA.   Many attributes of the drug make it a very attractive anticoagulant:  immediate action when given orally;  a fixed dose without need for monitoring; rapid renal clearance;  no food or drug interactions;  active against clot-bound as well as free thrombin;  reversible binding to thrombin.

        If the risk of hepatotoxicity can be controlled by monitoring, I believe it will be a major therapeutic advance.

 

Warfarin Provided No Benefit Over Aspirin. Was Associated With More Adverse Effects.

3-7   COMPARISON OF WARFARIN AND ASPIRIN FOR SYMPTOMATIC INTRACRANIAL STENOSIS.

Randomized, double-blind multicenter (59 sites) trial entered over 550 patients (mean age 63). All

had experienced a TIA or a non-disabling stroke caused by angiographically verified 50% to 99% stenosis of a major intracranial artery (internal carotid, middle cerebral,  vertebral, or basilar).

Randomized to:  1) warfarin—target INR of 2.0 to 3.0, or 2) aspirin 650 mg twice daily.

Warfarin provided no benefit over aspirin. It was associated with significantly higher rates of adverse events. “Aspirin should be used in preference to warfarin for patients with intracranial arterial stenosis.”

This is a good example of a pragmatic (real world of practice) trial. Difficulty in control of warfarin dosage may have been the cause of its lack of benefit.

 

 

ANTIPSYCHOTIC DRUGS

“Our Most Important Finding Was The High Level Of Antipsychotic Prescribing In NHs.”

6-6   THE QUALITY OF ANTIPSYCHOTIC DRUG PRESCRIBING IN NURSING HOMES

Antipsychotic drug prescribing in nursing homes (NHs) has been rising.

Federal statutes are in effect to protect NH residents from receiving inappropriate antipsychotics. They may be appropriately prescribed for delirium and dementia only if psychotic features or dangerous behaviors are present. Guidelines also stipulate maximum daily doses.

For residents with dementia, behavioral assessments must also show evidence of verbal or physical aggression or delusions or hallucinations.

Impaired memory, wandering, restlessness, unsociability, uncooperativeness, and indifference to surroundings are NOT indications.

Use of antipsychotic drugs in NHs was widespread. Most atypicals were prescribed outside the prescribing guidelines with doses, and for indications without strong clinical evidence of benefit. About 1 in 4 received doses exceeding recommended. About 2/3 of use was appropriate—dementia with aggressive behavior; dementia with delusions; psychotic disorder. About 1/3 received the drugs inappropriately—impaired memory;  depression without psychotic features;  indifference to surroundings; insomnia;  anxiety;  wandering; restlessness;  uncooperativeness; unsociability.

The study failed to detect positive relationships between behavioral symptoms and antipsychotic therapy.

“This study raises questions about the current uses of antipsychotics in NHs.”

These are powerful drugs. Elderly patients are subject to more adverse effects. They require a lower dose because of impaired renal function and concomitant illness. The PDR reiterates that schizophrenia is the only indication. There is no mention of use in nursing homes. Few studies have concerned patients over age 65.

I believe the most appropriate question to ask when contemplating use of antipsychotics in NHs is...

Am I prescribing this drug to benefit the patient, or the nursing staff and the family? This can be a most difficult decision to make. If they are prescribed, individual- patient’s response must be carefully monitored.

 

 

ASPIRIN

The NNT to Prevent One Stroke is Very High

3-6   RANDOMIZED TRIAL OF LOW-DOSE ASPIRIN IN THE PRIMARY PREVENTION OF CARDIOVASCULAR DISEASE IN WOMEN.

Use of aspirin in primary prevention in women is controversial. The current recommendations for use of aspirin in primary prevention in women are based on limited data.

The Women’s Health Study was a large, randomized, double-blind placebo-controlled trial of low-dose aspirin in the primary prevention of cardiovascular disease among over 39 000 apparently healthy women followed for a mean of 10 years for major cardiovascular events.

For the entire group of women over age 45, aspirin reduced risk of ischemic stroke. It did not protect against myocardial infarction and death from cardiovascular causes until after age 65.

Women taking aspirin experienced significantly more GI hemorrhages (RR = 1.40)

By my calculation, between 500 and 900 individuals would need to be treated for 10 years to prevent one ischemic stroke. Is this clinically significant?—especially when the increased risk of hemorrhage is considered.   RTJ)

Thus far, studies indicate that, in men, the prophylactic benefit against first occurrence of myocardial infarction is much greater than in women. But in men, aspirin does not provide primary protection against stroke.

 

“No Indication Of A Net Benefit.”

6-5   EPIDEMIOLOGICAL MODELLING OF ROUTINE USE OF LOW-DOSE ASPIRIN FOR THE PRIMARY PREVENTION OF CORONARY HEART DISEASE AND STROKE IN THOSE AGE > 70

Current US guidelines recommend the use of low-dose aspirin for people with a 5-year absolute risk of coronary heart disease (CH D) of > 3%, or a 10-year absolute risk of > 10%.

“Prophylactic use of a potentially toxic agent can be problematic, particularly in people in whom comorbidity and polypharmacy are common.” In a prospective observational study in two large UK general hospitals, aspirin use was the causal agent in 18% of all admissions for adverse drug effects, and was implicated in 61% of all associated deaths. Older females are the most vulnerable.

This epidemiological modeling study was conducted in a hypothetical population (10 000 men and 10 000 women) selected from a reference population from a state in Australia. All were age 70-74. None had known cardiovascular disease.

Proportional benefit gained from aspirin in prevention of MI and ischemic stroke vs excess hemorrhage from age 70-74 to age 100 or to death:

Benefit in preventing                                   Men (n = 10 000) Women (n = 10 000)

Myocardial infarction                          - 389                                - 321

Ischemic stroke                                    - 19                                  - 35

Harm

Excess GI hemorrhage                         + 499                               + 572

Excess hemorrhagic stroke                 + 76                         + 54

When comparing net harms vs net benefits of aspirin, the effects on length and quality of life were equivocal. 

“Despite sound evidence for efficacy, the temptation to blindly implement low-dose aspirin treatment for the primary prevention of cardiovascular disease in elderly people must be resisted.”  Benefits may be offset by harms.

I believe low