2002 THERAPEUTICS REPORT

January/February 2002                         Bruce H. Woolley, Pharm.D., Editor                                        Vol. 9, No. 1
Kenneth J. Hunt, Associate Editor

Expectations for Missionary Physical Examinations:
To Physical/Medical Providers and Local Church Leaders

Recent Presidents of the Church have stressed that by the time of their arrival to their assigned field of labor, newly-called full-time missionaries need to be spiritually, emotionally and physically ready to "hit the ground running".

The Brethren have continually requested that our physical and emotional screening efforts "raise the bar," so that missionaries who are called can in reality fully carry out the work that is expected of them, and that potential missionary candidates who do not fully meet the "raised bar" standard not be called and sent, only to fail and be sent home. It is tragic, both economically and emotionally, when a family encourages a young man or woman to send in their missionary application papers and spends over $1000 to get them outfitted as a missionary, only to be turned down because of emotional or physical problems that preclude effective service. It is even worse to have them return home early because of problems that were well known prior to their call.

It is expected that EVERY missionary be able to work 12 to 16 hours per day, walk 6 to 8 miles a day, or ride a bike up to 15 miles a day. There is no exception to this anywhere. Frequently, we read on the application that the applicant requires a special diet, has to eat every two hours, can only walk a few blocks, needs to rest frequently, etc.

There is NO mission where this type of problem may be accommodated. Joint problems are readily aggravated, excessive weight precludes effective work because the morbidly obese missionary can't fit in a car, walk or ride bikes. Many intestinal distresses are not properly evaluated prior to their leaving, and it creates excessive problems in countries with parasites and bacterial infections.

Rectal bleeding, a varicocoele, plantar warts, pilonidal disease or headaches may not seem to be very important at home, but in the mission field, these problems are very disruptive. Others state that they require special medical treatment, follow up care, medications, etc. that may not be available in many parts of the world.

There are many missionaries in the U.S. who have pre-existing problems that need special care, and it places a tremendous burden on the mission presidents, the missionary's companions, and even the missionary to find that they cannot carry their full load. Elder Richard W. Scott has said that no missionary can expect to be propped up by his companion. Every missionary should be able to take care of him/herself fully.

At present we have over 5% of the total missionary force returning home early because of problems that were improperly evaluated, eradicated, or stabilized prior to their call.

In many cases, the application received at Church Headquarters does not reveal problems that were well known to those at home. Recently a young man was sent home from Mongolia that had been there only 3 days, but whose prior knee injury would not allow him to function in as required as a missionary. Another was assigned to the Russian Novosibirsk Mission who has celiac sprue that was not disclosed in his pre-mission evaluation or history. It would be questionable that he could function consistently enough to be able to serve effectively even if assigned in the United States.

Some physicians report headaches without any workup to explain or alleviate the problem. When the missionary arrives in the field and becomes ill enough to impair the work, they then must see a physician and obtain a thorough work-up. This would be much easier to do at home prior to their leaving, Frequently an asthmatic is not properly controlled. A diabetic rarely reports his A1c Hb on the application. There are many cases to prove the fact that: PROBLEM + STRESS = WORSE PROBLEM

Fortunately, most of the American missionaries go to the MTC in Provo, where, if necessary for a previously-undisclosed problem, they can be further screened prior to entering the field. However, the Church now sends many missionaries directly to an MTC in Brazil and Preston, England, and for some of their training to Lima, Peru and the Dominican Republic. They are expected to be healthy and ready to go when they leave home.

The MTC in Provo issues over 600 shuttle passes a month to those who insist they need further dental, eye or skin care that should have been completed prior to their leaving home. This is not acceptable and should be rectified. Dentists tell us that one can determine if a wisdom tooth needs to be removed by age 15. The dental exam could be completed six months ahead of submission of papers.

A recent survey of those who had to return home from the MTC in Provo in the first six months of 2001, showed that of 51 cases 49 were for emotional problems that couldn't even survive the MTC pressures. Some 37 of those had no mention of the pre-existing problems on their applications. When the problems come to light, the missionary, their family, and their family physicians usually were well aware of them.

The most common problems encountered are the following:

1. Problems that weren't resolved prior to leaving home.

2. Not revealing that a problem exists.

3. Denial by the missionary to him/herself that a problem exists.

4. Expecting a miracle to occur.

5. Stopping needed medications-then crashing.

6. Not being worked up thoroughly for a medical problem.

7. Emotional problems not evaluated or stabilized.

8. Refusing to get required immunizations.

It is hoped that our youth might be aware of pitfalls that become stumbling blocks when they get into the mission field. Some of these make them high risks for survival. It would be wise for bishops and other priesthood leaders to address these pitfalls in the lives of the youth to work them out early, These are the most common pitfalls that might lead to failure in the field:

1. Divorce of parents (especially recent).

2. Dysfunctional families.

3. Parental over-protection.

4. High or unrealistic expectations.

5. Diabolical distractions.

6. Pornography.

7. Improper literature and music.

8. Drugs and alcohol.

9. Bizarre fads.

Youth who, have had to deal with these problems are frequently overcome and crumble from the pressures of the mission. Problems such as depression, obsessive compulsive disorder, acute psychosis, and even suicidal tendencies become magnified in the field away from home and other previously supportive influences.

We would encourage church leaders to focus on better preparation of youth for the rigors of missionary service by doing the following:

1. Give spiritual experiences to build faith.

2. Focus on physical fitness.

3. Train in personal hygiene.

4. Teach good nutrition.

5. Obtain recommended vaccines early.

6. Teaching youth to be self-reliant.

7. Develop good study habits and self-discipline.

8. Recognize and deal with emotional problems.

9. Learn how to deal with stress.

10. Complete dental work six months early.

Many people do net understand the pressures of a mission. They seem to think it is like living in the United States. Consider the world conditions that missionaries are encountering somewhere at any one time:

1. Terrorism

2. Pollution: water, food, air, & etc.

3. Natural disaster: earthquakes, hurricanes, tornadoes, typhoons, floods.

4. Inferior living conditions.

5. Extreme temperatures.

6. Strange diseases.

7. Inferior medical physicians, care and facilitities.

8. Minimal laboratory and medication support.

9. Difficult languages.

Medical costs incurred in the mission field are covered by the Church. Costs for preexisting problems must be borne by the family or their insurance.

Therefore, if possible, it is important for anyone who enters the mission field today to maintain prior insurance coverage.

In times past the missionary physical exam used to be approached much like a WWII military induction exam ("count the arms, legs, eyes, hands, feet, and if there are 2 of each, you're in"). That is no longer adequate or acceptable. A missionary physical exam needs to be thorough and complete and should be performed by an M.D. (medical doctor) or D.O. (doctor of osteopathy). If done by a physician's assistant (P.A.) or nurse practitioner (N.P.), the exam must be reviewed and countersigned by the supervising or consulting physician. Exams by any others are not acceptable. The best person to do the exam is the family doctor who preferably has known and taken care of the candidate for several years. Some youth seek out a medical provider who doesn't know them so they may hide occult problems that may keep them from their goal.

It is important to keep one's immunizations current. There is not enough time to complete the hepatitis A and B series if beginning the series is delayed until after the call is made. Why not give them at age18? Recent military use has taken many of our common vaccines for the troops, which has caused a shortage. This includes diphtheria/tetanus, yellow fever, typhoid, etc. They need to be obtained when they are available. Also, there is a significant movement, seemingly originating in Utah, against immunizations in general. We cannot force anyone to get immunizations, but the missionary refusing them does sign a waiver and is assigned only to the United States. Many countries do not permit entry without Current immunizations. Also, we cannot take chances on assignments to undeveloped countries where the diseases are endemic.

Missionaries, who take medications, such as for epilepsy, emotional problems, diabetes, asthma, etc., must understand the need to continue taking them throughout the mission. Many will stop the medications on their own, leading to a disaster. Almost invariably this results in an early release.

On both the history and physical sheets there is a blank space to give details of ALL issues marked "yes," or "abnormal." Details and above all the functional capacity of the missionary regarding the designated problems must be documented. For example, it is not enough to state "asthma." We need to know the frequency of attacks, what provokes them, hospitalizations, ER visits, medications used, dosages, and what limitations are expected because of the problem. The Church Missionary Department wants only for a missionary to be able to succeed, but with two thirds of the missionary force outside of the United States, where medical care may be less than desirable with proper medications possibly not being available, those assigning missionaries' fields of labor must know all the facts up front in order to make proper assignments. Medications cannot be shipped to foreign countries because of current restrictions.

It is important to be sure to include all ancillary and laboratory test results on the application form. Because tuberculosis is running rampant in the world and because of extensive missionary work with ethnic groups in the United States there must be an accurate PPD reading prior to the mission and also at the conclusion of the missionary service. Half of the returning missionaries from some countries may have converted their PPD test. Chest x-rays must be obtained on all candidates exhibiting positive tests.

The bishop, stake president and parents must carefully review the application form. When they sign it, it means that they can verify the health of the missionary, and that he/she is physically and emotionally able to serve well.

Perhaps the most important information to be gleaned from the application is the final evaluation of the functional capacity of the young prospect. Levels A and B are likely to be able to serve without difficulty. Level C is very questionable. It might be appropriate to encourage service locally under the direction of the stake president. Those marked in levels D and E are definitely not candidates according to the current guidelines established by the Brethren.

The First Presidency has instructed our leaders that "full-time missionary service is a privilege, not a right.... They should not submit a recommendation until they are satisfied that the brother or sister is physically, mentally, and emotionally able to serve." To have to come home early may be devastating. Many who do feel that they are a failure. The Church Missionary Department is anxious to avoid this situation.

Many of the above details apply directly to the mature missionaries as well as to the young adults. The need for superb documentation on the applications of ALL missionaries is imperative.

Quinton S. Harris, MD Chairman, Medical Services Divison Missionary Department

Patient Height Inversely Correlates with Mortality Risk from Stroke

According to a recent report from investigators at Tel Aviv University in Israel, shorter men are at an increased risk of death from stroke. Using data collected on more than 10,000 employed Israeli men between the ages of 40 and 65, the researchers investigated the relationship between stature and death from stroke and heart disease. Subjects in the lowest quartile were less than 163 cm (5 feet 4 inches); those in the highest quartile were taller than 172 cm (5 feet 7 inches). Average height in the cohort was 167.1 cm (about 5 feet 6 inches).

The investigators reported in their 23-year follow-up, there were 364 stroke-related deaths in the patient population. Risk of death from stroke was 54% higher for the shortest men compared with the tallest. There was no link between height and risk of death from heart disease. The researchers comment that "short stature is a marker for unfavorable conditions during early life. Better life conditions in infancy, better nutrition in early life contribute to decreased risk of death from stroke later in life.

They also reported that many individuals in the study were immigrants, who tended to be poor and disadvantaged in their early years. Patients of European descent had higher risk of dying from heart disease, while those from North Africa had a higher risk of stroke death. Even given genetic and ethnic variations in groups, "within each area where they were born there were height-influenced differences in stroke risk. Investigations such as these are important in identifying risk factors for common diseases so that appropriate screening and prevention methodologies can be developed.

Opiates Activate Same Neurons as Placebo

A group of Scandinavian investigators report that placebo treatment appears to activate the same part of the brain that is activated by opioid drugs. Researchers in the Cognitive Neurophysiology Research Group in Stockholm compared regional cerebral blood flow measured by positron emission tomography (PET) while inducing pain or a control stimulation in nine subjects. Their findings are reported in the February 7th issue of the online edition of the journal Science, called Sciencexpress.

For their study, pain was induced with a heat stimulation of 48 degrees C during 70 seconds on the dorsum of the left hand. A control condition involved application of a 38 C stimulation. The experiments were repeated three times: once without pretreatment; once with pretreatment with intravenous injection of remifentanil 0.5 g/kg; once with pretreatment with saline placebo. In the absence of pretreatment, both stimulations caused increased activity in the contralateral thalamus, bilaterally in the insula, and in the caudal anterior cingulate cortex.

The remifentanil activated the rostral anterior cingulate cortex and the lower brainstem, while attenuating the response in the insula. Saline also activated the anterior cingulate cortex, rostral to the anterior cingulate cortex activation during pain, as well as the orbitofrontal cortex. The orbitofrontal area has been implicated in cognitively driven pain modulation. The increased activity in rostral anterior cingulate cortex during placebo treatment of pain may support its involvement in the analgesic response mechanism during placebo treatment.

The researchers also noticed an association between opioid activation of the rostral anterior cingulate cortex and adjacent areas and how well subjects respond to placebo treatment. "The experience of pain is always subjective," they remark. The placebo effect is influenced by several factors, including a subject's expectations of the treatment and their desire to feel better. By demonstrating that placebo and an opioid agonist activate the same brain regions, the findings suggest that some of these same factors may be involved in triggering the pain relief. This evidence that placebo can affect the brain does not necessarily support the use of placebo alone in treatment of pain. The findings do show, however, that the placebo effect is part of every treatment.

Petrovic et al. February 7 2002; 10.1126/science; http://www.sciencexpress.org

Polio Vaccine Might Still be Necessary After Disease Eradication

Even if polio is effectively eradicated worldwide, many infectious disease and biodefense experts believe polio immunizations should continue. It would be essentially impossible to ensure that polio had been eliminated from the entire world; its potential for use as a biological weapon even after eradication prompts many experts to argue for continuing vaccination indefinitely.

The poliovirus does not seem an ideal choice for biowarfare at present because polio vaccines are still being given routinely throughout the world. However, experts believe that an end to vaccination could make the virus "very attractive" to aspiring bioterrorists. A full report from a research group at the Johns Hopkins Center for Civilian Biodefense Studies in Baltimore, Maryland is in a January edition of Clinical Infectious Disease Journal.

The introduction of the inactivated polio vaccine (IPV) in 1955, followed several years later by the oral polio vaccine (OPV), have sharply cut the number of polio cases worldwide each year. The last polio case in the US occurred in 1979. Children in the United States currently receive the IPV because the oral vaccine contains a live, weakened virus that has been found to cause polio in rare cases. In the developing world, however, the oral vaccine is still used because it is easier to administer and considered more effective. Although IPV prevents infection, it does not prevent the poliovirus from being shed in the feces--a major concern in countries with poor sanitation.

International health officials suggest that polio could be eradicated globally by 2005. However, it will be difficult to ensure that the virus, which usually does not cause symptoms but is nonetheless transmissible, is indeed wiped out in developing nations. There have also been reports of recent small outbreaks of paralytic illness caused by apparently mutated strains of OPV that had been shed by vaccinated individuals and then circulated among others who were not sufficiently protected.

In Hispaniola, which comprises Haiti and the Dominican Republic, a number of paralytic illnesses among children in 2000 were attributed to an OPV strain that had reverted to virulence. Such a scenario has also been blamed for a number of cases in Egypt in the late 1980s and early 1990s.

The potential of the poliovirus as a bioweapon and the possibility of accidental release from a lab are factors that argue strongly for keeping up polio vaccination. Public health officials are currently debating how to handle polio once it is considered eradicated. One tactic might be to replace the oral vaccine with IPV for a while, before eventually stopping polio vaccination.

Clin Infect Dis 2002;34:79-83.

Valproate for Treatment of Acute Migraine

While valproate is known to prevent migraine, its ability to relieve acute migraine has not been established. According to a recent report in the journal Headache, IV valproate appears to be a safe and effective alternative to dihydroergotamine/metoclopramide (DHE/MCLP) for the acute treatment of migraine. Because this drug lacks cardiovascular side effects and does not interact with triptans or ergotamines, valproate could be particularly useful in the acute setting.

Investigators from the Western New England Pain and Headache Center in Bennington, Vermont, randomized 40 patients with migraines of 24 to 96 hours' duration to receive IV valproate or IM DHE/MCLP. At 2, 4, and 24 hours following treatment, 60% of valproate-treated patients reported headache improvement. The improvement rates were similar in the DHE/MCLP group, although 90% of patients reported improvement at the 24-hour time point with DHE/MCLP. The groups did not differ significantly in the percentages of patients experiencing nausea, photophobia, and phonophobia.

While no drug-related side effects were reported with valproate therapy, 15% of DHE/MCLP-treated patients experienced nausea and diarrhea within the first 4 hours of treatment. These results suggest that IV valproate is as safe and effective as IM DHE/MCLP for the acute treatment of prolonged migraine headache. However, headache relief was less likely to be sustained at 24 hours with valproate than with DHE/MCLP. Further studies of IV valproate for acute migraine are called for the further investigate this treatment.

Headache 2001;41:976-980.

Many Patients Have Allergic response to Echinacea

As many as 1 in 5 atopic subjects who have never taken echinacea may show positive skin prick tests to the herbal product according to a report in the Annals of Allergy, Asthma, and Immunology. Echinacea is used worldwide to treat the symptoms of the common cold, and many patients use echinacea to treat allergic symptoms. Adverse reactions to echinacea have been recorded in several international databases.

Researchers from two major Australian medical centers investigated the nature of adverse reactions to this popular herbal remedy. They evaluated 5 patients referred after adverse reactions to echinacea and reviewed additional reports. The five patients were evaluated after they experienced symptoms ranging from a maculopapular rash to acute anaphylaxis after taking echinacea. Two of the patients developed wheals after skin prick testing with an aqueous echinacea solution.

The Australian Adverse Drug Reactions Advisory Committee databases contained 41 reports between January 1979 and March 2000 in which echinacea was the sole trigger substance. The authors considered 26 of these reports to be consistent with IgE-mediated hypersensitivity. Among these 26 cases, 4 patients required hospitalization for treatment of their allergic reaction.

The researchers conducted skin prick testing on an additional 100 atopic patients, 97 of whom had never taken echinacea. Twenty patients developed wheals at least 2 mm greater than the negative control in response to aqueous or glycerinated extracts of echinacea.

Given the number of reports to adverse reactions to echinacea, allergic patients should be cautioned about using this substance. It is further advisable to use caution with other "natural" treatments as most have not been studied for effectiveness, side effects, and long-term outcomes. Natural does not always mean safe; there are too many examples proving the opposite.

Ann Allergy Asthma Immunol 2002;88:42-51.

Patterns of Medication Use in the Adult Population

With rapidly increasing health care costs, many are concerned about the risks and benefits of the wide range of prescription and OTC medications. Significant increases in the use of herbal and "natural" supplements have prompted concerns about these products as well. The public health implications for these issues are limited by the absence of comprehensive information on the full range of medications and supplements in the general population.

A research group from the Boston University School of Public Health recently reported interim results of their ongoing telephone survey of U.S. adults, called the Slone survey. Their goals are to provide population-based information on use of all medications, including prescription and over-the-counter drugs, vitamins and minerals, and herbal preparations/natural supplements in the United States.

Their report in a recent issue of JAMA included 2590 participants aged at least 18 years. Among those patients, 81% used at least 1 medication in the preceding week; 50% took at least 1 prescription drug; and 7% took 5 or more. Herbals/supplements were taken by 14% of the population. Among prescription drug users, 16% also took an herbal/supplement.

In any given week, most US adults take at least 1 medication, and many take multiple agents. The substantial overlap between use of prescription medications and herbals/supplements raises concern about unintended interactions. Documentation of usage patterns can provide a basis for improving the safety of medication use.

JAMA. 2002;287:337-344

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