Effectiveness of Pharmaton Capsules in
Relieving Fatigue among Internal Medicine
Residents in Tertiary Public Hospitals:
A Randomized Controlled Study
Benjamin G. Abela III
Lizzette R. Caro
Samantha Gail V. Cosalan
Melissa A. Dator
Ricardo M. De Castro
Jay Grace U. Hernandez
Luisa M. Hernandez
Marie P. Ishimura
Rodelia C. Pascua
Agnes Karen B. Que
Public Health Research Proposal
Ateneo School of Medicine and Public Health
March 2011
INTRODUCTION
Background Information
Pursuing a career in medicine is not a job to be taken lightly. An employee in the medical profession
means that an individual must have the nerve to deal with the chronic stress and anxiety brought about by the job
itself. Doctors and nurses are often placed in situations where they will need to make split-second decisions to
save a person’s life; such situations leave no room for hesitation or for errors. Doctors in training are often the
ones most subject to the brutal rigors of the medical career. Medical residents and interns face overwhelming
pressure to succeed and to please their seniors, whereas established doctors, the consultants, find themselves in a
more comfortable position because of their clinical experience and mastery.
According to Dr. Cornelio G. Banaag Jr., chair of the department of Psychiatry at The Medical City,
“Medicine is one of the most stressful careers. A doctor must bring a tremendous amount of knowledge and skills
into practice. It is a lifetime of continuing medical education. That alone is a major source of stress, especially in an
environment where knowledge and skills are constantly changing. Doctors have to always be on their toes.” 1 The
sources of stress for medical practitioners are widely varied and are related to the job itself, to the organization or
hospital where the doctor is training or practicing, doctor’s personality, relationships with other people, and worklife balance.2
Medical residents and interns in the Philippines have varied shift schedules, depending on the hospital
where they are training. A regular shift usually ranges between 12-24 hours, but can be extended up to 36 hours.
Sleep and meal patterns are often erratic and uncoordinated, depending on the patient load and the resident’s or
intern’s designated work activities in the hospital. Sleep deprivation plays an important role in contributing to
increased stress levels in the body. Sleep is vital in carrying out the normal protective bodily functions: body repair,
energy replenishment, thermoregulation, memory consolidation, preservation of neuronal integrity, and
resculpting of synaptic connections in the brain. Chronic lack of sleep results in generalized symptoms of
irritability, frustration, inability to concentrate, memory problems, confusion, mood swings, inability to make good
decisions, emotional outbursts, and an overall feeling of being unable to cope with workplace demands. 6 The
person may find himself pushed to his breaking point. For a doctor, being in a chronic sleep-deprived state result
to unresolved stress and anxiety. The chronic fatigue, emotional problems, and impaired memory function may
severely compromise the doctor’s capacity to properly examine, diagnose, treat, and follow-up his or her patients.6
Not surprisingly, doctors in training often experience a burnout phase because they are unable to cope with the
rigorous demands of their training. The end result is a feeling of chronic, immense fatigue and stress because of
the perception that “their daily routine becomes unbearable and work seems unfulfilling, meaningless, and
endless.”3
Several studies have been published exploring the different causes and rates of burnout or stress in
doctors.
[4],[5],[6]
These studies show that clearly, there is a high prevalence of stress in doctors, with resultant
physical, emotional, and mental consequences, but what is noteworthy here is that these doctors are reluctant to
seek help for themselves.2 This has been attributed to their being perfectionists, their high levels of personal drive,
and altruism. Doctors seem to have difficulty acknowledging their own shortcomings in terms of health and in their
ability to handle stress. Dr. Banaag reiterates this fact when he discussed The Medical City’s stress management
program for both their medical and nonmedical staff, “Those who serve other human beings are very poor at
taking care of themselves. We want to take care of other people, but we forget ourselves. This reflects a very bad
trait in doctors and caregivers”.1 What is worse is that doctors themselves are “poor patients” because they would
rather self-medicate or try to manage their stress on their own, without seeking formal medical consultation even
when they are unable to deal with it.2 They may try to deal with the source of stress, the sleep deprivation and the
workload, by taking psychostimulants. There is no question that caffeine is the most commonly abused substance
in our attempts to stay awake and to complete designated tasks. Excessive intake of coffee and soda will only
provide a person with enough energy for short-term use. Afterwards, the “caffeine rush” may cause the person to
crash, and they end up feeling even more tired and exhausted than before they drank the coffee.
Newer research studies have tried to explore more natural remedies to effectively manage stress and
fatigue in the workplace. These remedies include meditation, self-hypnosis, acupuncture, and use of herbal
medications. One study has tried to correct deficits in cognitive function and mood as a result of fatigue in doctors
working shift patterns through the administration of dietary supplements containing a combination of vitamins,
minerals, and Panax ginseng.25 Ginseng is a group of herbs from the family Araliacae, with 3 major types: Chinese
or Korean ginseng, American ginseng, and Siberian ginseng.7 The herb is believed to have healing properties,
specifically in association with lowering blood sugar and cholesterol levels, increasing resistance to diabetes,
cancer, heart disease, and infections. It is also widely recognized for its use as an “adaptogen” because it enhances
physical and mental performance, resist stress, improve psychologic function, and promote relaxation. 7 It is now
popularly used in combination drugs with other vitamins and nutrients that combat fatigue and exhaustion, such
as the B complex vitamins, vitamin C, nicotinamide adenine dinucleotide (NADH), L-carnitine, magnesium, and bee
pollen. Other herbs have been studied in combination with these substances, such as gingko biloba and maca, but
ginseng has proved to be the most potent energy enhancer and is said to be the most effective in boostering the
body’s natural ability to cope with stress.8
Significance
In other countries, they have rules on the duration of duty hours of residency. This was adopted to
achieve excellent clinical and academic experience and competence of residents.
In July 2003, Accreditation Council for Graduate Medical Education (ACGME) enacted the standards to
limit resident hours. Duty hours must be limited to 80 hours per week, averaged over a four-week period, inclusive
of all in-house call activities. Residents must be provided with one day in seven free from all educational and
clinical responsibilities, averaged over a four-week period, inclusive of call. Adequate time for rest and personal
activities must be provided. This should consist of a 10-hour time period provided between all daily duty periods
and after in-house call.9
In the Philippines, as of the year 2005, the physician patient ratio is approximately 1 in every 20,000 to
30,000 patients.11 This data proves how much workload is given to our resident doctors. The data also implies how
much they should be on the top of their performance ensuring every detail and every decision is the best for the
lives of their patients. With this setting, how can we ensure optimal learning of the residents and safe care of
patients?
Our country does not have laws on regulation of duty hours of medical residents. Despite the number of
malpractice cases filed were attributed to impaired performance of overburdened doctors. At present, we can only
do so much in terms of lobbying for individual hospitals to decide on the optimum time for the residents to work.
A double blind, placebo controlled trial was already done among nurses to determine the effects of a
combination of Panax Ginseng, Vitamins and Minerals on Mental Performance Mood and Fatigue. 24 This current
study is different from the former because it challenges the drug Pharmaton in alleviating fatigue among medical
residents compared to placebo.
Nursing and medical residents have their rightful role to play in the care of the patients but the
researchers believe that on the basis of hours of duty and required skills, medical residents are more overworked
and fatigued compared to nurses. These health professionals are more fit as subjects for the study because it will
really show the effect of the drug in relieving fatigue among cases.
The table below summarizes the many differences among nurses and physicians. 29,30
Job description
Skills required
Hours of duty
Nurse
- Works with physicians to develop
and manage nursing care plans
Instruct patients and families in
proper treatment
- Performs physical assessments of
patients, including triage duties
and more
- Performs
other
procedures
including: vision screening, apply
splints and ice wraps, dressing
changes, throat swabbing for
cultures and collection of body
fluid specimen
- Strong problem solving and
decision making skills
- Considerable
knowledge
of
principles, practices and current
trends in nursing
- Good physical fitness necessary for
frequent
standing,
bending,
reaching, squatting, and moving of
patients and/or equipment
- 8 hours per day31
Physician
- Provides medical patient care by interviewing,
examining and treating of clinical patients in order
to meet their medical needs
- Determines level of urgency of follow-up,
referral/consultation appointments
- Exercises final medical judgment in all issues of
health care
- Prescribes medical treatment and clinical drugs to
patients
- Orders studies, test and ancillary services
- Oversees mid-level medical staff as assigned as well
as nursing clinical staff
- Knowledge of and ability to apply professional
medical principles, procedures, and techniques
- Thorough knowledge of pharmacological agents
used in patient treatment
- Effective verbal and written communication skills
along with proper telephone etiquette
- Performs in a tactful and professional manner
- 24 hours to 36 hours
This study challenges the drug Pharmaton in alleviating fatigue compared to placebo. The researchers
would like to find ways how to relieve exhaustion. This would help overworked medical residents to carry out their
duties of resuscitating, treating and managing patients. This study will also be of significance in terms of stressing
the need of policies to set limits on duty hours of residents and other medical professionals to safeguard patients
from mismanagement and avoid malpractices due to stress.
Statement of the Problem
This study would like to determine the effectiveness of Pharmaton capsules, a multivitamin supplement in
relieving fatigue, physical and mental stress, loss of concentration, rapid tiredness and reduced performance
among internal medicine residents in a public hospital as compared to a placebo.
Limitations
This randomized placebo controlled study has its inherent limitations due to its design and for the
purpose of feasibility. The sample population will be limited to internal medicine residents under the purposively
selected major public hospitals in Metro Manila. The subjects will only be provided with baseline assessment and
tests for the 6th and 12th week of the randomized controlled study. Monitoring of subject’s compliance regarding
their intake of other substances which are prohibited during the trial will not be done.
Assessment tools used in the study will be confined to the Cognitive Drug Research (CDR) Assessment
system, Bond Ladder Visual Analog Scale and Chalder Fatigue scale. No other tests will be employed to the
subjects.
Limitations regarding the study variables are the following:
a.
Hours on duty will be regardless of the type of rotation, whether at the Out Patient Department or at the
Operating Room.
b.
Hours of sleep will be regardless of the individual sleep patterns and the individual’s preference on hours
of sleep required.
c.
Medical error documentation may be limited depending on the existing reporting system of the hospital
under study.
OBJECTIVES
General Objective
The general objective of the study is to determine the effectiveness of Pharmaton capsules, a
multivitamin supplement in relieving fatigue, physical and mental stress, loss of concentration, rapid tiredness and
reduced performance among internal medicine residents in a public hospital as compared to a placebo.
Specific Objectives
1.
To determine the baseline statistics of residents to include number of hours on duty per week, number of
hours of sleep per week, usual agents used to beat fatigue
2.
Obtain a demographic profile of internal medicine residents in tertiary public hospitals in Metro Manila
3.
To determine the usual errors made by surgical residents caused by fatigue or stress
4.
To determine efficacy and relative potency of the drug suitable for medical residents
5.
To determine the possible side effects of the drug
LITERATURE REVIEW
Performance and Fatigue among Medical Professionals
Those who are training for the medical profession are subjected to very rigorous and demanding training
schedules that would require them to be awake and fully functioning at all times including those that would
conflict with their endogenous sleep and circadian physiology. 11 This would lead to chronic sleep deprivation and
chronic fatigue.
Stress and fatigue have been linked to decreased work productivity because of the lack of concentration,
irritability, poor decsision-making skills, reduced hand-eye coordination, reduced visual perception, reduced
vigilance, and slower reaction times. Performance levels continue to drop as work periods become longer and
sleep deprivation increases. Staying awake for 17 hours straight has been found to have the same effect on
performance as having a blood alcohol content of 0.05%, while staying awake for 21 hours straight is equivalent to
a blood alcohol content of 0.1%.27 Being stressed on the job can have a positive effect as well, as some studies have
shown that setting deadlines for work reports can motivate people who seem bored or unmotivated, or when
people experience an adrenaline rush while working. However, these positive effects are often short-term, and
negative effects begin to increase as the level of stress also increases. The relationship between stress and job
performance is described as having an “inverted-U” relationship, as shown by this graph:
Basically, the graph explains that when there is little pressure for people to carry out a specific task, there
is also not enough incentive for them to focus their energy on it. As stress levels increase, people find themselves
devoting more time, energy, and effort in accomplishing that task and making it “perfect”, however as stress and
workload pile up, they eventually succumb to the pressure and easily become tired, unhappy, and irritable with
their work. When under severe stress, an individual’s judgment and decision making skills suffer and they
eventually end up unable to prioritize their work duties, becoming distracted and unproductive or simply
experiencing “burnout”.
According to the Federal Motor Carrier Safety Administration, which regulates the trucking industry in the
United States, 3 main factors have been identified as causing fatigue in truck drivers. These include circadian
rhythm effects, the biological rhythm of human beings to go through a normal everyday cycle of wakefulness and
sleepiness in 24 hours. When the body is at its low points in this cycle, people are more likely to be sleepy, tired,
inattentive, and basically passive. During the high points, however, people become more active, alert, and efficient
in carrying out assigned tasks. The circadian rhythm has its basis on ambient lighting, which regulates the body’s
production of melatonin, the sleep-inducing hormone, from the pineal gland. Dark environments normally cause
the pineal gland to release more amounts of melatonin to induce sleep, which explains why people who work night
shift have reduced performance levels and job productivity as compared to their daytime counterparts. The effects
of sleep deprivation and having a dysregulated circadian rhythm can vary from person to person. Another factors is
sleep deprivation and cumulative fatigue effects, which describe how individuals who do not get enough sleep at
night (less than 7-8 hours) or who stay awake longer than most people suffer from sleep deficit, which has been
shown to significantly reduce cognitive performance and cause additional fatigue. It often takes 2-3 conventional
sleep cycles for an individual to correct a single sleep deficit and return to their normal performance levels.
Sleep deprivation would reduce cerebral metabolism within the pre-frontal cortex which is responsible for
higher order cognitive processes such as judgment and decision making. 12 This highly threatens one of the most
important principles of health care which is to “first do no harm”. 13 In the United States, 100,000 people die in
hospitals every year due to preventable medical errors. 60-80% of these errors have been linked to fatigue of the
health care workers.14
Health practitioners that are chronically sleep deprived have shown significant decreases in levels of
cognitive dysfunction, depressed mood and a decrease in working memory capacity. Working memory capacity is a
good measure of impaired judgement in medical professionals since this involves the ability to retain and
manipulate information or sensory outputs in complex or stressful settings. 14 Multiple studies have shown
significant effects of sleep deprivation and chronic fatigue to the functional and cognitive capacity of medical
interns and/or residents. It only takes 2 weeks of sleep restriction to markedly impair one’s functional and
cognitive capacity and make one less alert.15 Shifts that would last for 24 hours or more have shown to cause twice
as many errors in reading ECGs and twice as many technical errors in simulated laparoscopic surgical skills. 16
Performance on tests of vigilance and mathematical calculations have also significantly declined within one week
of having only 5-7 hours of sleep. Verbal processing and complex problem solving were also observed to be
impaired in chronic sleep deprivation.17 A study done on the Pediatric Residents of Brown University have shown
that performances on sustained attention, vigilance and simulated driving tasks after a heavy call rotation (90
hours per week; 34-36 hours per overnight call) is significantly comparable to having a 0.04-0.05g % blood alcohol
concentration (which is equivalent to a cocktail drink of 80 proof vodka mixed with tonic water in a 1:5 ratio)
during a light call rotation ( day time clinic rotations; 44 hours per week). 18 Sleep deprivation has also shown to
affect mood, relationship related stresses, cause depression, anxiety and chronic pain.
[14],[19]
The third factor is
industrial or “time-on-task” fatigue, which refers to how fatigue that accumulates during work hours affects
individual performances at different times of the shift. Performance levels decline the longer a person works on a
specific task. Performance levels are found to be lowest during the first few minutes or hours at work and during
the end of a long period at work, as explained by the “inverted-U” graph of stress and performance described
earlier. The decrease in performance levels at the beginning of work is generally attributed to the individual’s
adjustment to the working environment and conditioning of the mind to focus on the task at hand, while the
decreased performance levels at the end of a long work period is due to the chronic buildup of stress and fatigue
on the person’s body and mind.28
To eliminate one preventable cause of medical errors, the Accreditation Council for Graduate Medical
Education in the United States established rules that limited resident hours to less than 80 hours each week,
restricted extended shifts to less than 30 hours and mandated a 10 hour rest period between shifts. 15 Residents
and medical interns should also try to counteract sleepiness by taking naps, trying low dose stimulants and
engaging in physical activity. It has been shown that a 2-8 hour nap prior to a 24 hour sleep loss shift can improve
vigilance and minimize sleepiness. Power naps (15 minutes) can also significantly improve performance if done in
2-3 hour intervals during a 24 hour shift.18 Medical schools and hospitals should also contribute in trying to reduce
fatigue by formulating programs that can enhance the quality of sleep like scheduling maintenance naps for on call
interns, programs that would enhance a sense of teamwork among health professionals and decrease perceived
stress in the hospital environment.20
Panax Ginseng
Panax ginseng (Renshen, Chinese ginseng) is the most researched herb that has been used for physical
performance trials.21 Being a member of the Araliaceae family, the genus Panax comes from the Greek term “allhealing” and consists of around nine species namely, P.ginseng, Panax quinquefolium(Xiyangshen, American
ginseng), Panax notoginseng (Sanqi) and Panax japonicas(Japanese ginseng).22 It is a common dietary and
medicinal practice in many Asian countries especially in China and Korea, which is available in different forms
ranging from whole root, root powder, teas, tinctures, and standardized root extracts containing a specified
amount if ginsenosides, which is known to be the pharmacologically active components of ginseng. 21
For the P. ginseng, there have been more than 13 identified ginsenosides, which are glycosylated steroidal
saponins regarded as the likely active agents in ginseng roots. Preparations of their extracts are taken from roots
that have been harvested after more than 5 years of growth that would approximately have 1-2% ginsenosides.
Traditional use of the herbal plant is in the form of powdered roots of about 3-9 g/d either alone or in combination
with other herbs. But standardized preparations are also commercially available such as those of the Swiss GPL
Ginsana products that have around 4% ginsenosides.21
There is a multitude of proposed mechanisms of actions for ginseng. Among these is the traditional use
of the herb to generally restore life energy. Isolation of ginsenosides has also revealed effects on the immune
system, stimulation and depression of the central nervous system, and animal studies that exhibited activation of
anabolic processes for DNA, RNA, and protein synthesis in tissues and antioxidant activity. Nitric oxide production
has also been observed to be activated by ginsenosides in immune system cells, vascular endothelial cells, arteries,
and erectile tissues.21
Unfortunately, these mechanisms have been thoroughly been studied as to their exact mode of action,
especially in terms of their ergogenic effects in humans. Moreover, studies have resulted in results that are not
universal due to the dose-dependent effects of the herb in physical and mental performance. Studies have shown
that administration through a sufficient duration with standard doses enough to exhibit the therapeutic potential
of the drug is necessary to enhance performance in humans.21
Pharmaton (Soft Gelatin Cap)
Pharmaton (Soft Gelatin Cap) consists of vitamins and minerals that are indicated as daily nutritional
supplement for vitamin and mineral deficiencies, fatigue, physical and mental stress, loss of concentration, rapid
tiredness and reduced performance. It may also be used as a prophylaxis and treatment of general symptoms of
aging such as reduced physical and mental efficiency, fatigue and depressive mood. The cap is taken twice daily for
the first 2-3 weeks and then followed by 1 cap daily as maintenance and should be taken with food. Pharmaton
can be bought at the Generics Pharmacy for Php 12.40/tablet. Its Anatomical Therapeutic Chemical (ATC)
classification is A11AA03. This means that the capsule belongs to the class of multivitamins and minerals and is
used as dietary supplements. The table below shows the specific contents of the capsule:23
Ca 90.3mg
Ca pahtothenate 10mg
Copper 1mg
Deanol bitartrate 26mg
Fluorine 0.2mg
Concentrated standardized
ginseng extract G115 40mg
Inositol
Fe 10mg
Lecithin 66mg
Linoleic acid
Mg 10mg
Mangangese 1 mg
Phosphorus 70mg
K 8mg
Rutin 20mg
Vit A 4,000iu
Vit B1 2mg
Vit B12 1mcg
Vit B2 2mg
Vit B3 15mg
Vit B6 1mg
Vit C 60mg
Vit D 400iu
Vit E 10mg
Zn 1mg
The Effects of a Combination of Panax Ginseng, Vitamins and Minerals on Mental Performance, Mood and Physical
Fatigue in Nurses Working Night Shifts: A Double Blind, Placebo Controlled Trial
A study back in 2003 was performed on 32 male and female nurses or nursing auxiliaries working a night
shift were included in this double-blind, randomized, placebo controlled study that spanned a 12 week treatment
period. Exclusion criteria included subjects who were already taking vitamin and mineral supplementation, those
with a history of alcohol, drug abuse, and extensive use of caffeine or nicotine. Subjects were randomized into
treatment groups and were given either a placebo or Pharmaton Caplets. They were instructed to take 1 tablet per
day in the morning during the treatment period.
The study developed a Shift-Work model wherein the nurses were evaluated repeatedly on a variety of
cognitive tests and questionnaires immediately prior to a three night shift and then again afterwards. The
approximated levels of cognitive performance of the nurses were measured using a test developed by the
Cognitive Drug Research (CDR) assessment system, which has been found to be sensitive enough to detect fatiguerelated deficits.24 The study respondents who took the test were evaluated based on the following cognitive
parameters24:
1.
Word presentation - where 15 words, matched for frequency and concreteness, were presented in
sequence for 1.5 seconds each for the subjects to remember.
2.
Immediate word recall - the subject was then given 60 seconds to write down as many of the words they
could remember from (1) and were scored based on the number of words they got correct (%), errors,
and intrusions.
3.
Picture presentation - 20 images were presented in sequence for 2 seconds each for the subject to
remember.
4.
Simple reaction time - subjects were instructed to press the “yes” button as quickly as possible every time
the word “yes” was presented on the monitor. Reaction times were recorded in milliseconds.
5.
Digit vigilance task - a random number was continuously displayed on the right portion of the monitor,
while a series of other numbers was presented in the center of the screen at a rate of 150 numbers per
minute. The subject had to press the “yes” button as quickly as possible every time the number in the
series matched the target number. This task measured accuracy, reaction time in milliseconds, and the
number of false alarms.
6.
Choice reaction time - the words “yes” or “no” were randomly projected on the screen and the subjects
had to press the corresponding button as quickly as possible. This task measured accuracy and reaction
time in milliseconds.
7.
Tracking - the subject had to use a joystick to move an object on the screen in pursuit of a randomly
moving target over 60 seconds. The average distance from the target was measured in millimetres.
8.
Spatial working memory - a picture of a house was presented on screen for 10 seconds with 4 of its 9
windows lit up. The subjects were then instructed to memorize the position of the lit windows. A series of
images of the same house with a differently lit window each time were presented, and the subject had to
decided if that window had been lit in the original image using the yes/no response buttons. This task
measured accuracy of responses and reaction time in milliseconds.
9.
Numeric working memory - 5 numbers were presented in sequence on screen for each subject to
remember. This was followed by a series of 30 random numbers. Subjects had to press the yes/no buttons
if the individual numbers were in the original series. The subjects were then evaluated based on their
ability to identify the previously presented numbers, the ability to reject novel numbers, and reaction
time in milliseconds.
10. Delayed word recall - the subjects were given 60 seconds to write down as many of the words as they
could remember from (1). Scoring was based on number correct, errors, and intrusions.
11. Word recognition - the original words from (1) plus 15 “distractor” words were presented one at a time in
random order. Subjects had to press the yes/no buttons if they recognized the word as being from the
original list. They were evaluated based on their ability to correctly identify the previously presented
words, the ability to reject novel words, and the average reaction time in milliseconds.
12. Picture recognition - the original pictures from (3) plus 20 “distractor” pictures were presented one at a
time in random order. Subjects had to press the yes/no buttons if they recognized as the image as being
from the original list. They were evaluated based on their ability to correctly identify the previously
presented pictures, the ability to reject novel pictures, and the average reaction time in milliseconds.
The following factor scores were used in the present study:
1.
Power of Attention - measured by simple reaction time, choice reaction time, and digit vigilance.
2.
Continuity of Attention - choice reaction time (accuracy), digit vigilance (targets detected and false alarms),
tracking (average distance from target).
3.
Quality of Memory - immediate word recall (words correctly recalled, intrusions & errors), delayed word
recall (words correctly recalled, intrusions, & errors), word recognition (words correctly recalled and
rejected), picture recognition (pictures correctly recalled and rejected).
4.
Speed of Memory - numeric working memory (speed), spatial working memory (speed), word recognition
(speed), picture recognition (speed).
Questionnaires that were used in the study following administration of the cognitive test were the following:
1.
Bond-Ladder Visual Analogue Scales32 – this comprised sixteen 100-mm lines with the end points
anchored with of the following word pairs: alert-drowsy, calm-excited, strong-feeble, muzzy-clearheaded, well
coordinated-clumsy, lethargic-energetic, content-discontented, troubled-tranquil, mentally slow-quick witted,
tense-relaxed, attentive-dreamy, incompetent-proficient, happy-sad, antagonistic-friendly, interested-bored,
withdrawn-sociable. The responses to each scale were combined to form 3 mood factors: “alertness”,
“calmness”, and “contentment”. Each line is scored as millimetres to mark from the negative antonym. These
scales were originally designed to assess the mood effects of anxiolytics and have been used in various
pharmacological, psychological, and medical trials because of their high reliability and validity.
2.
Chalder Fatigue Scale - this test was designed to measure both physical and mental aspects of fatigue. It is
commonly used in practice because of its relative ease of administration, excellent psychometric properties,
and its applicability to both hospital and community populations. 33 It contains 14 items, 8 of which measure
physical fatigue and 6 of which measure mental fatigue. The subject can choose from 4 possible answers to
each question: (0) - better than usual, or no more than usual, or (1) - worse than usual or much worse than
usual. With this bimodal method of scoring, scores can range from 0 to 14, with higher scores indicating greater
levels of fatigue.
Results of the tests and questionnaires showed that after a three night shift, there were significant declines in
speed and accuracy of attention, and the ability to store and retrieve information from memory. After the
treatment period, results showed that Pharmaton significantly reduced the deficits on the Quality of Memory
among the nurses and also reduced the self-reported decline in calmness as well as the self-reported fatigue.
In conclusion, “The results of the study suggest that a combination of Ginseng, vitamins and minerals is
useful in counteracting not only self-reported increases in fatigue and decreases in calmness resulting from shiftwork but also deficits on objective tests of the ability to store and retrieve information in memory.”24
A Double Blind Comparison of the Effect on Quality of Life of a Combination of Vital Substances Including
Standardized Ginseng G115 and Placebo
A 12 week double blind study among 390 subjects was done and compared the effect on the quality of life
of a placebo versus Ginseng G115. Quality of life was evaluated through two standard, self-administered
questionnaires: Psychological General Well Being Index and the Sleep Dysfunction Scale. Participants were divided
into the placebo group (185) and the combination group (205).
Results of the study showed that there was improvement in both placebo and combination groups,
however there was a more pronounced improvement from baseline levels in the combination group. Therefore,
the study concluded that the combination treatment had a significant advantage over the placebo therapy. 25
Pharmaton Capsules in the Treatment of Functional Fatigue: A Double Blind Study vs. Placebo Evaluated by a New
Methodology
A comparative, double blind clinical study of Pharmaton capsules versus a placebo was done on 232
patients who complained of functional fatigue. A Fatigue Score was calculated for each patient from the 1 st day,
the 21st day and the 42nd day of treatment. Results of the study showed that there was a statistically significant
difference in favour of the Pharmaton group. Pharmaton capsules proved their effectiveness in the improvement
of the complaints of fatigue that patients experienced.26
METHODOLOGY
Research Design
The study is a randomized, double blind, placebo controlled trial that is designed to assess and determine
the effectiveness of Pharmaton capsules, a multivitamin supplement in relieving fatigue, physical and mental
stress, loss of concentration, rapid tiredness and reduced performance among internal medicine residents in
tertiary public hospitals located in Metro Manila.
Data Collection Techniques
A questionnaire will be provided to each randomly selected internal medicine residents to obtain their
general profile. Questions regarding the selection criteria will also be included in the same questionnaire to limit
confounding factors of stress. A standard questionnaire is an efficient way to determine which of the residents will
qualify for the study.
The study will run over a 12-week treatment period, with the selected residents being randomly assigned
to treatment or control groups. Their cognitive performance will be assessed throughout the trial using the
Cognitive Drug Research (CDR) Assessment System. Assessment of fatigue levels will also be done using two
standard questionnaires, Bond-Ladder Visual Analogue Scale and Chalder Fatigue Scale.
By conducting these assessment tools, the researchers can gain direct knowledge regarding the condition
of the study subjects and the effect of Pharmaton on their performance throughout the process.
Selection of Study Subjects
Sampling
The target population for this study will be the Internal Medicine (IM) residents of tertiary public hospitals
in the Philippines. The sample population is composed of 394 IM residents from tertiary public hospitals in Metro
Manila.
The
sample
size
was
computed
using
OpenEpi
(http://www.openepi.com/OE2.3/Menu/OpenEpiMenu.htm). The IM residents would be randomly selected from
the hospitals until the sample population is reached.
The sample size was obtained using a power of 70% and a risk ratio of 2.4. Both the power and risk ratio
were used to adjust the sample size according to the development of phase II clinical trials (therapeutic
exploratory), which are small-scale trials designed to evaluate a drug’s preliminary efficacy and side-effect profile
in a sample population of 100 to 250 patients (http://www.pacificbiolabs.com/drug_stages.asp).
All residents would then be assigned to either the treatment group or the placebo group with the use of a
random number generator (accessible via: http://stattrek.com/Ta bles/Random.aspx). This program would allocate
a minimum value of 1 (for treatment group) and maximum value of 2 (for placebo group) to the 394 generated
random numbers, and since the residents would be subjected to the same treatment and placebo, duplication of
entries would be allowed. All residents would then be assigned their randomly generated numbers to determine
whether they would be put into the treatment or placebo group.
Criteria

Inclusion Criteria
o
He/she should be currently a resident of the Internal Medicine Department at a tertiary public
hospital
o
He/she should be completing full rotations at the Department of Internal Medicine, either in the
ward, operating room or out-patient department

Exclusion Criteria
o
He/she should not be taking caffeine supplements, stimulants or energy drinks
o
He/she should not have any chronic medical conditions that may affect performances such as
pregnancy, hypertension, anemia, asthma and other cardiac conditions
Plan for Data Collection
The investigators must first obtain a list of tertiary public hospitals in Metro Manila and from there
calculate the amount of Internal Medicine residents that are found in each hospital. From there, the investigator
will purposely select the public hospitals that will be used in the study. A request letter will be sent to the different
hospital administrators asking for their participation in the study. The investigators will then seek permission or
consent from the residents who are willing to take part in the 12 week study. The number of residents will then be
filtered taking into consideration the inclusion and exclusion criteria.
The three questionnaires (CDR, Bond Lader and Chalder) will be administered to the residents prior to
randomization into groups and at weeks 6 and 12 of the study period.
Methodology Flow Chart
Target Population: Internal Medicine residents working in
Tertiary Public Hospitals in Metro Manila
Purposive Sampling: Selection of the hospitals that will be used
in the study
Obtain permission from hospital directors and obtain consent
from Internal Medicine residents
Administration of baseline survey questionnaire to residents
Obtain baseline functional level of residents using the three questionnaires
before and after a three day shift:
CDR and Bond Lader Mood Alertness Scales – 8am, 12noon, 2pm and 4pm
Chalder Scale – 6pm
Simple Random Sampling: Internal Medicine Residents will be
randomly assigned to either a treatment or placebo group
Pharmaton capsules and the placebo will be placed in identical
looking boxes, each containing two bottles with 50 tablets each
Participants will be required to take 1 tablet per day in the
morning throughout the treatment period
Administration of the three questionnaires again at week 6 and
week 12 of the treatment period using the same time schedule
Data Analysis
Presentation of Study Results
Variables and Operational Definitions

Independent Variables
1.
Hours on duty – defined as the average number of hours on duty per week during the 6-12 week
trial. This will be regardless of the type of rotation, whether at the Out Patient Department or at
the Operating Room.
2.
Hours of sleep – defined as the average number of hours of sleep per week during the 6-12week
trial. This will be regardless of the individual sleep patterns and the individual’s preference on
hours of sleep required.

Dependent Variables
1.
Medical errors – defined as the medical errors done during the 6-12week trial to include errors in
procedures, prescription and patient care. This variable may be limited by under reporting and
lack of documentation of the errors.
2.
Cognitive – defined as the fatigue related deficits in cognition to be measured by the Cognitive
Drug Research Assessment System. This will measure the following factors in cognition:
a.
Power of Attention – this will be measured by simple reaction time, choice reaction time
and digit vigilance.
b.
Continuity of Attention – this will be measured by choice reaction time (accuracy), digit
vigilance (targets detected and false alarms) and tracking (average distance from
target).
c.
Quality of Memory – this will be measured by the immediate word recall, delayed word
recall, word recognition and picture recognition.
d.
Speed of Memory –this will be measured by the numeric working memory, spatial
working memory, word recognition and picture recognition
3.
Mood – defined as the quality or state of a feeling at a particular time. This will be measured by
the Bond Ladder Visual Analog Scale and would rank the subject’s moods in terms of (1)
alertness, (2) calmness and (3) contentment.
4.
Fatigue – defined as the level of fatigue experienced by the subjects during each day of the trial.
This will be measured by the Chalder Fatigue Scale. All scores will be tallied to form a total score
at the end of the trial.
Potential Biases
Confounding factors appear to be a major source of bias in this study because they have a significant
effect on the outcome measure (improved cognitive performance and decreased fatigue levels) being explored.
Subjects who may be taking other supplements such as caffeinated drinks and multivitamins may have
improvement in work performance because of the effect of the supplements, not because of the therapeutic
intervention being tested. Because most individuals have different ways of coping with stress, some subjects may
also be less susceptible to the effects of fatigue and stress as opposed to those who do not have effective coping
mechanisms. To minimize this bias, baseline questionnaires will be given to all potential study participants prior to
the start of the actual study. The baseline questionnaire establishes exclusion criteria in the form of taking
caffeinated drinks, energy drinks, multivitamins, and coping mechanisms that minimize the effects of chronic
stress. This will ensure that the outcome measures seen in the study will be a direct result of the therapeutic
intervention being tested.
Selection bias may also prove to be a problem for this study, as only selected tertiary government
hospitals in Metro Manila will be used to obtain the sample population needed. Some hospitals have to deal with
more patients and more difficult cases than others. Some hospitals may be considered tertiary but still lack the
necessary equipment needed to treat difficult cases. With that scenario, subjects randomly sampled from one
hospital may report increased work performance with the use of Pharmaton while subjects from another hospital
may report that they did not experience any benefits with the drug. This discrepancy may be simply explained by
the fact that one hospital has more patients to deal with than the other, thus the positive outcome seen with the
use of the drug was not actually an effect of it therapeutic actions, but was the result of a disparity in selecting the
sample population. The effects of the drug may not also be generalizable because the study population being
examined is not representative of all internal medicine residents in all tertiary government hospitals in the
country.
Ethical Considerations
In any clinical trial, the major ethical issue raised is the safety of the drug or intervention being tested on
human subjects. Pharmaton is a nutritional supplement that is generally regarded to be safe for use as long as a
person is relatively healthy and as long as the drug is taken only in the right dosage. Because most drug control
trials are experimental, it is difficult to determine if a drug has potentially lethal side effects that may or may not
be seen in the majority of the population who take the drug. Side effects from Pharmaton use are minimal, but
have been reported to include nausea, hypersensitivity to some components of the drug, and some reported drug
interaction with anticoagulants (decreased effect) because of the ginseng component. 34 In addition, no clinical
studies have been done to show that Pharmaton is completely safe for pregnant women. 34
Another ethical issue that may be raised is the inclusion criteria for the study, which requires individuals
who are regular coffee drinkers, those who take other supplements and energy drinks, and those who regularly
engage in some form of stress relief exercise, to refrain from doing so the week prior to the start of data collection
to minimize the effect of possible confounding factors on the results. The study participants may experience
difficulty coping with caffeine withdrawal symptoms, such as irritability, palpitations, and subjective feelings of
being overly tired or sleepy because of lack of coffee. These symptoms might interfere with work performance and
result in the participants making more medical errors while on duty, putting patients at risk of possible harm.
The use of a placebo drug also raises ethical issues, because it is widely considered unethical for a control
group to receive a placebo drug for a particular condition when an accepted and effective treatment already
exists.35 This may not be much of an issue in this study because it has not been scientifically proven that
Pharmaton actually relieves stress and fatigue and improves mood and cognitive performance.
PLAN FOR DATA PROCESSING AND ANALYSIS
Data Processing
A. Hypothesis testing
The null hypothesis is that there is no association between the consumption of the treatment
verum and relief of fatigue, physical and mental stress, loss of concentration, rapid tiredness, and reduced
performance among medical residents in public hospitals. The alternative hypothesis states that there is
an association between the two variables. The null hypothesis will be rejected if the computed p-value is
less than α = 0.05. Otherwise, t the null hypothesis will be accepted. A CI (confidence interval) greater
than 1 means there is a positive correlation; CI < 1 indicates a negative correlation.
B.
Two-tailed test
Two-tailed testing would be performed on all variables to accept or reject the null hypothesis.
C.
Risk Ratio (OR)
Odds ratio is the risk developing a disease relative to the exposure being studied. It is a ratio of
the probability that, in this study, fatigue and the other dependent variables being investigated would
occur in the exposed (treatment) as opposed to the non-exposed (placebo) group. Using the following 2x2
frequency table with the formula: AD/BC:
Risk
Treatment Verum (Panax
ginseng) Group
Placebo Group
Disease Status (Fatigue, Cognitive, Mood, Medical Errors)
Present
Absent
A
B
C
D
To interpret the value, < 1 means the independent variables (Hours of duty and Hours of sleep)
are a protective factors for the dependent variables (Medical Errors, Cognitive, Mood, and Fatigue). The
value equal to 1 means there is no association between the two variables being compared; and > 1 means
that the independent variable was not a protective factor for the effective health emergency response.
Two-tailed testing would be used to determine the association of the variables. Confidence level is set at
95% and α = 0.05.
D. Linear Regression
Linear regression will be used to determine the association of more than two independent
variables to the dependent variables. In the study, the samples (treatment and placebo) will be divided
according to a continuous variable: example, level of fatigue; physical and mental stress; etc.
All statistical computations will be done and will be analysed using SPSS 17.
Coding Manual
Number
1
Variable Name
Hours on Duty
2
Hours of Sleep
3
Medical Errors
4
Mood
5
Fatigue
Variable Description
average number of hours on
duty per week during the 6-12
week trial.
average number of hours of
sleep per week during the 612week trial
Number of medical errors done
during the 6-12week trial to
include errors in procedures,
prescription and patient care
quality or state of a feeling at a
particular time. This will be
measured by the Bond Ladder
Visual Analog Scale. This will be
measured in millimeters on the
line graph. Average
measurements will be done for
(1) alertness, (2) calmness, (3)
Contentedness
the level of fatigue experienced
by the subjects during each day
of the trial. This will be
measured by the Chalder
Fatigue Scale
Codes and Instructions
Code as is
Code as is
Code as is
Code as is
Code as is (min 0, max 14)
Dummy Tables: Tables for Frequency Distribution
Table 1. Distribution of IM Residents According to Age
Frequency
<25
Frequency %
25-30
31-35
35-40
>40
Table 2. Distribution of IM Residents According to Civil Status
Cumulative Frequency
Frequency
Frequency %
Cumulative Frequency
Single
Married
Separated
Widowed
Uncertain
Table 3. Distribution of IM Residents According to Average Working Hours per Week
Frequency
Frequency %
<24
24-48
48-96
>96
Table 4. Distribution of IM Residents According to Average Hours of Sleep per Week
Frequency
Frequency %
<10
11-20
21-30
31-40
41-50
>50
Table 5. Distribution of IM Residents According to Coffee/Softdrinks / Tea Consumption
Frequency
Frequency %
None
Once/day
Twice/day
Thrice/day
>3x/day
Table 6. Distribution of IM Residents According to Caffeine Supplements Consumption
Frequency
Frequency %
None
Once/day
Twice/day
Thrice/day
>3x/day
Table 7. Distribution of IM Residents According to Stimulants/Medications Consumption
Frequency
Frequency %
None
Once/day
Twice/day
Thrice/day
>3x/day
Table 8. Distribution of IM Residents According to Energy Drinks Consumption
Frequency
Frequency %
None
Once/day
Twice/day
Thrice/day
>3x/day
Cumulative Frequency
Cumulative Frequency
Cumulative Frequency
Cumulative Frequency
Cumulative Frequency
Cumulative Frequency
Table 9. Distribution of IM Residents According to Stress Relieving Activities
Frequency
Frequency %
None
Yoga
Cumulative Frequency
Meditation
Exercise
Others
Table 10. Distribution of IM Residents According to Chronic Medical Conditions
Frequency
Frequency %
None
Hypertension
Cumulative Frequency
Diabetes
Pregnancy
Psychiatric
Others
PLAN FOR THE DISSEMINATION OF THE RESULTS OF THE STUDY
Workplan
Activity
Random sampling of hospitals that
will be included in the study
Duration
1 week (1st week of
April)
Random sampling of residents that
will be included in the study
1 week (1st week of
May)
Execution of study
Analysis of Data Results
Final research paper writing
Finalization of research paper
12 weeks (June, July,
August)
2 weeks (September)
2 weeks (October)
1 week
Activity
Random sampling of hospitals that will be
included in the study
Random sampling of residents that will
be included in the study
Execution of study
Analysis of Data Results
Final research paper writing
Finalization of research paper
April
May
Pre-requisites
Obtain information on the number of tertiary
public hospitals in the Philippines and their
corresponding number of IM residents
Obtain permission from hospital administration
Obtain consents from residents who are willing
to participate in the study
Random sampling of hospitals and residents
Completed data collection
Completed data collection and analysis
Research paper complete
June
July
Aug
Sept
Oct
Budget
Item
Pharmaton Soft Gelatin
Capsules
A4 Bond Paper
Ink cartridge
Quantity
33,096 capsules
Unit Cost
Php 23.00
Total Cost
Php 761,208.00
1,000 pages
2
50 cents
Php 500.00
Php 500.00
Php 1,000.00
Nov
Photocopy Expenses:
Questionnaire
Travel Expenses: Gasoline
Token for hospital
administrators
TOTAL
1,000 pages
50 cents
Php 500.00
120L
̴25
Php 40.00
Php 100.00
Php 4,800.00
Php 2,500.00
Php 770,508
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APPENDIX
APPENDIX A: Letter of Permission to Hospitals
ATENEO SCHOOL OF MEDICINE AND PUBLIC HEALTH
DON EUGENIO LOPEZ SR. COMPLEX, ORTIGAS AVENUE, PASIG CITY
TEL.NO. ____ EMAIL ADDRESS _____
Hospital Administrator/Medical Director
The Medical City
Dear Sir/Madame,
Greetings! We are 3rd year medical students from the Ateneo School of Medicine and Public Health
(ASMPH) conducting a randomized controlled research trial entitled, “Effectiveness of Pharmaton Capsules in
Relieving Fatigue among Internal Medical Residents in Tertiary Public Hospitals: A Randomized Controlled Trial” as
part of the curriculum for completion of our Doctor of Medicine/Master in Business Administration (MD-MBA)
degree. This study seeks to explore the effects of the nutritional supplement, Pharmaton, in relieving stress and
fatigue and in improving mood and enhancing cognitive performance. This study is primarily based on another
drug trial previously done in Switzerland entitled, “The effects of a combination of panax ginseng, vitamins and
minerals on mental performance, mood and physical fatigue in nurses working night shifts: A double-blind, placebo
controlled trial”. Attached to this letter is a copy of the above mentioned study for your reference.
In that study, panax ginseng was found to have a positive effect in relieving fatigue and stress and in
enhancing mood and cognitive performance in nurses. As no study of this kind has been performed in our local
setting, we wish to perform a similar study which focuses on the effects of Pharmaton, which contains ginseng as
its active ingredient, on internal medicine residents from tertiary government hospitals in the Philippines. The
results of this study may be used as basis for future drug trials for other nutritional supplements or vitamins.
In line with this, we would like to ask if you are willing to allow your hospital’s internal medicine residents
to participate in our study. This research proposal has been reviewed by an authorized ethics committee from
Ateneo de Manila University and from the Department of Health and has been found to have met all the
appropriate standards for conducting a randomized controlled trial in the Philippines.
Hoping for your kind consideration,
_____________________
Samantha Gail V. Cosalan
Research Team Leader
Noted,
_________________
May Agno, MD
Research Adviser
APPENDIX B: Consent Form
Title of Research
Effectiveness of Pharmaton Capsules in Relieving Fatigue among Internal Medical Residents in Tertiary
Public Hospitals: A Randomized Controlled Trial
Investigators
Abela, Caro, Cosalan, Dator, De Castro, Hernandez Jay, Hernandez Luisa, Ishimura, Pascua, Que Agnes
Supported By
Ateneo School of Medicine and Public Health
Explanation of Procedures
This research study will test how well a nutritional supplement, Pharmaton, relieves stress and fatigue
levels and enhances mood and cognitive performance. Pharmaton is a relatively safe drug that is approved by the
Bureau of Food and Drug (BFAD) for use in the Philippines. The drug is also widely used in other countries abroad.
If you choose to take part in this study, you will first need to answer a baseline questionnaire asking
details about your current intake of caffeinated drinks, energy drinks, vitamins and other supplements, and if you
regularly engage in activities or exercises (ex. yoga, jogging, aerobics, etc.) that help with stress relief. If you drink
any of these substances or engage in any of these activities, you will be requested to stop for 1 week prior to the
start of the actual study.
If you qualify for the study, you will be randomized to one of two treatment groups. The treatment period
will last for a span of 12 weeks. During this period, you will be given either Pharmaton or a placebo drug,
depending on the group you are randomized to. A placebo does not contain any active chemical components, so it
is not detrimental to your health nor will it induce any side effects. The drug will be taken orally every morning
once a day. At weeks 6 and 12 of your 3 day shift, the three questionnaires (Cognitive Drug Reasearch Assessment
Test, Bond-Lader Visual Analogue Scale and Chalder Fatigue Scale) will be administered in order to assess your
measure of fatigue and mood.
Risks and Discomforts
You may have some side effects from taking Pharmaton. Though uncommon, side effects can range from
nausea and hypersensitivity reactions to some components of the drug. There is also a slight risk of drug
interaction in patients currently taking anticoagulants (blood thinners), causing the latter to have a decreased
effect. There may also be risks that are yet unknown at this time.
Confidentiality
The identity of the participant/s and any information obtained about them for use in this study will be
kept confidential to the extent allowed by Philippine law. The results of the treatment, however, may be published
for scientific and research purposes.
Refusal or Withdrawal without Penalty
There will be no penalty if you decide not to participate in the study. If you decide not to participate, you
will not lose any benefits you are otherwise owed by the institution you practice in. Your choice to not participate
or to drop out of the study will not affect your relationship with this institution.
Cost of Participation
There will be no cost to you for taking part in this study. The drug will be provided free of charge. If you
suffer from any side effects or medical concerns that are a direct result of the drug being tested, you will be given
appropriate medical treatment also free of charge.
Significant New Findings
You will be told by your doctor or the study staff if new information becomes available and might affect
your choice to stay in the study.
Questions
If you have any questions, concerns, or complaints about the research or a research- related injury
including available treatments, please contact _______ at ______. We will be glad to address any concerns you
may have.
Legal Rights
You are not waiving any of your legal rights by signing this informed consent document
Signatures
Your signature below indicates that you agree to participate in this study. You will receive a copy of this
signed document
_________________________________________________________
Signature of Participant, Date
Reviewed by:
_________________________________________________________
Signature of Principal Investigator Reviewing Consent Document, Date
***Sample consent form template adapted from www.uab.edu/irb/forms/sample-consent-form.doc.
APPENDIX C: Baseline Questionnaire
Demographics
Name:
Sex:
Age:
Birthdate:
Address
Religion:
Civil Status:
Number of Children:
Other Questions
1. What is your number of average working hours per day? Per week?
2. What is the average number of hours do you sleep per day? Per week?
3. Are you currently taking caffeine supplements, stimulants/medication or energy drinks (Cobra, Red
Bull)? If yes, please fill out the table below:
( ) Coffee / softdrinks / tea
___ 1x/day
___2x/day
___3x/day
___>3x/day
( )Caffeine supplements
___ 1x/day
___2x/day
___3x/day
___>3x/day
( ) Stimulants or medications
___ 1x/day
___2x/day
___3x/day
___>3x/day
( ) Energy drinks
___ 1x/day
___2x/day
___3x/day
___>3x/day
4. Do you engage in other activities that help you relax or relieve stress? (ex. Yoga, exercise)
5. Do you have any chronic medical conditions?
( ) Hypertension
( ) Diabetes
( ) Pregnancy
( ) Psychiatric conditions
( ) Others, please specify ___________________________________
APPENDIX D: Bond-Lader Visual Analogue Mood Scale
Alertness
a) Alert
b) Attentive
c) Lethargic
d) Muzzy
e) Well-coordinated
f) Mentally slow
g) Strong
h) Interested
i) Incompetent
Calmness
a) Calm
b) Tense
Contentedness
a) Contented
b) Troubled
c) Happy
d) Antagonistic
e) Withdrawn
Drowsy
Dreamy
Energetic
Clear-headed
Clumsy
Quick-witted
Feeble
Bored
Proficient
Excited
Relaxed
Discontented
Tranquil
Sad
Friendly
Sociable
APPENDIX E: Chalder Fatigue Scale
Physical Symptoms
1) Do you have problems with tiredness?
2) Do you need to rest more?
3) Do you feel sleepy or drowsy?
4) Do you have problems starting things?
5) Do you start things without difficulty but get weak as you go on?
6) Are you lacking in energy?
7) Do have less strength in your muscles?
8) Do you feel weak?
Mental Symptoms
9) Do you have difficulty concentrating?
10) Do you have problems thinking clearly?
11) Do you make slips of the tongue when speaking?
12) Do you find it more difficult to find the correct word?
13) How is your memory?
14) Have you lost interest in the things you used to do?