Women's Health Newsletters 1/15/06 - 6/11/06
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********** Health Newsletter ***********
January 15, 2006
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From BackupMD on the Net
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1. Statin associated muscle problems
2. Uterine artery embolization for fibroids
3. Reader submitted Q&A - Recurrent urine infections
4. Sleep tips
5. Health tip to share - Duct tape and warts
6. Humor is healthy
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1. Statin associated muscle problems
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
Statins are becoming one of the most widely prescribed
class of drugs, used mainly for lowering cholesterol
and for preventing heart attacks in people who have
previously had a cardiovascular problem. In general,
statin drugs lower heart attacks by about 2.5% over 5
years in high risk individuals who have not previously
had a serious cardiovascular event and by 4.8% in
individuals who have already had a major cardiovascular
event. The reduction in both fatal and non fatal heart
attacks is thought to be worth it for individuals to
take the risk of serious side effects such as muscle
dissolving leading to death (rhabdomyolysis) which is
about 1 in 10,000 people or less. Muscle weakness
(myopathy) is also a related side effect of statins and
occurs more commonly than complete muscle destruction
but the data on how often myopathy occurs and what is
the normal course is not readily available.
A recent study from Wisconsin looks at a retrospective
review of cases of statin associated myopathy to see
what the expected course is. They found that the
average duration of statin therapy before muscle
weakness or pain symptom onset was 6.3 months.
Resolution of muscle pain occurred on the average 2.3
months after discontinuation of statin therapy.
Thirteen percent of patients were hospitalized for the
management of rhabdomyolysis; 2 had reversible kidney
dysfunction, and 1 with preexisting kidney
insufficiency subsequently began lifelong dialysis.
Patients who had a myopathy from a statin drug often
received a different statin after an episode of statin-
associated myopathy; 57% reported recurrent muscle
pain, whereas 43% tolerated other statins without
recurrent symptoms.
We still do not have an incidence number for statin
associated myopathy but it is probably in the range of
0.5% or less. Now we at least know that most of the
time the myopathy does regress after stopping the drug
but it is very likely to recur if another statin is
begun.
Statin associated muscle problems
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2. Uterine artery embolization for fibroids
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
Uterine artery embolization (UAE) is a radiological
procedure in which the arteries of the uterus are
injected with a substance to clot off the blood supply
to uterine fibroids. It is an alternative to
hysterectomy. Uterine fibroids are benign muscle
growths that make the uterus enlarged causing a weighty
or pressure feeling as well as sometimes abnormal
menstrual bleeding problems and pain. UAE is not as
effective in getting rid of fibroid symptoms as is
hysterectomy (100%) but it is not as risky as surgery.
It does not require an abdominal incision and patients
may return to work in a week or less.
The long term follow up of UAE has not previously been
determined. A recent study however has looked a a 5
year follow up of women who underwent a uterine artery
embolization to see how successful it is. The
investigators considered the procedure a failure if a
woman subsequently had a hysterectomy or surgical
procedure to remove separate fibroids (myomectomy). It
was also considered a failure if a repeat embolization
had to be done or even if the symptoms had not resolved
without any more treatment.
This study at Georgetown University Hospital in
Washington D.C. found that UAE was 75% successful at
getting rid of fibroid symptoms with only one
treatment.
Uterine artery embolization for fibroids
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3. Reader submitted Q&A - Recurrent urine infections
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"My wife is suffering with urinary tract infections
over the last six years and several times she has taken
antibiotic courses after Urine examination and culture
but they have not worked. One of her urologists did her
TB test and after it was positive by DNA PCR method he
has given her six months course for TB. She remained
fine up to one year and after that same problem with
same frequency occurring. One more thing I want to add
that periodically some blisters develop on her genital
area, sometimes inside or up to her thigh. It starts
very tiny and hard but within two or three days they
become big and blister with pus and pain. She feels
pain with itching in her vagina at the time of
infection and she can't sit or sleep." - sanjiv
You have not posed a question but If you did, I suppose
it would be what is going on and are all these things
related?
When your wife was treated for TB she received
antibiotics that may have prevented urinary tract
infections. Now that she if off of the tuberculosis
medications, she may be regressing to frequent urine
infections again. It is time for her to see her
urologist again. She may need antibiotics on a regular,
preventative basis to ward off the infections.
The other problem of blisters in the genital area that
you describe may not be related to the urinary tract
problem. The gynecology doctor needs to look at them
when they break out and see if they represent a viral
infection such as herpes genitalis. If that is the
case, it will need to be treated differently than a
urinary tract infection.
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4. Sleep tips
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Most people know the importance of adequate sleep. It
helps learning and memory. While you sleep, your brain
commits new information to memory through a process
called memory consolidation. Sleep may also help keep
your weight down since sleep deprivation often is
associated with weight gain. Adequate sleep may also
help prevent falls, traffic accidents or even work
mistakes. Lack of sleep can cause irritability,
impatience, problems with concentration, and moodiness
as well as weaken your immune system.
The National Sleep Foundation has the following
suggestions for people who have sleep problems.
1. Maintain a regular bed and wake time schedule
including weekends.
2. Establish a regular, relaxing bedtime routine such
as soaking in a hot bath or hot tub and then reading a
book or listening to soothing music.
3. Create a sleep-conducive environment that is dark,
quiet, comfortable and cool.
4. Sleep on a comfortable mattress and pillows.
5. Use your bedroom only for sleep and sex.
6. Finish eating at least 2-3 hours before your regular
bedtime.
Sleep tips
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5. Health tip to share - Duct tape and warts
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
"It sounds crazy but I went to a foot doc who charged
me $720 to tell me I need surgery. A friend told me
that he heard about the duct tape on the radio. Put on
a new piece every day. I used it and have gotten rid of
massive warts that had been there 3 years with no
surgery." - Nancy
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6. Humor is healthy
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
"Secrets Of Personal Growth"
1. As I let go of my feelings of guilt, I am in touch
with my inner sociopath.
2. I have the power to channel my imagination into
ever-soaring levels of suspicion and paranoia.
3. I assume full responsibility for my actions, except
the ones that are someone else's fault.
4. I no longer need to punish, deceive, or compromise
myself, unless I want to stay employed.
5. In some cultures what I do would be considered
normal.
6. Having control over myself is almost as good as
having control over others.
7. My intuition nearly makes up for my lack of self-
judgment.
8. I honor my personality flaws for without them I
would have no personality at all.
9. Joan of Arc heard voices too.
10. I am grateful that I am not as judgmental as all
those censorious, self-righteous people around me.
11. I need not suffer in silence while I can still
moan, whimper, and complain.
12. As I learn the innermost secrets of people around
me, they reward me in many ways to keep me quiet.
13. When someone hurts me, I know that forgiveness is
cheaper than a lawsuit, but not nearly as gratifying.
14. The first step is to say nice things about myself.
The second, to do nice things for myself. The third, to
find someone to buy me nice things.
15. As I learn to trust the universe, I no longer need
to carry a gun.
16. All of me is beautiful, even the ugly, stupid and
disgusting parts.
17. I am at one with my duality.
18. Blessed are the flexible, for they can tie
themselves into knots.
19. Only a lack of imagination saves me from
immobilizing myself with imaginary fears.
20. I will strive to live each day as if it were my
69th birthday.
21. I honor and express all facets of my being,
regardless of state and local laws.
22. Today I will gladly share my experience and advice,
for there are no sweeter words than "I told you so!"
23. False hope is better than no hope at all.
24. A good scapegoat is almost as good as a solution.
25. Just for today, I will not sit in my living room
all day in my underwear in the Dream Motel. Instead, I
will move my computer into the bedroom.
26. Who can I blame for my problems? Just give me a
minute. . . . I'll find someone.
27. Why should I waste my time reliving the past when I
can spend it worrying about the future?
28. The complete lack of evidence is the surest sign
that the conspiracy is working.
29. I am learning that criticism is not nearly as
effective as sabotage.
30. Becoming aware of my character defects leads me
naturally to the next step of blaming my parents.
31. To have a successful relationship I must learn to
make it look like I'm giving as much as I'm getting.
32. I am willing to make the mistakes if someone else
is willing to learn from them.
33. Before I criticize a man, I walk a mile in his
shoes. That way, if he gets angry, he's a mile away and
barefoot.
34. All of the evil that I speak, hear, and see, are
pleasurable to me.
35. The only friend I have...moved to parts unknown.
36. When counting my blessings, I count backwards from
one.
37. They no longer allow me into the confessional.
38. The person I admire the most is Elmer Fudd.
39. I enjoy watching a magazine stand.
40. Experience shows that people who write, can't be
trusted.
41. When I am here I wish I was there....and I am.
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That's it for this time.
Your BACKUPMD on the Net.
Rick
Frederick R. Jelovsek MD
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********** Health Newsletter ***********
February 12, 2006
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From BackupMD on the Net
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1. Breast cancer in women not reduced with low fat diet
2. Eradication of H.Pylori helps dyspepsia
3. Reader submitted Q&A - Celiac disease symptoms
4. Antidepressants (SSRIs) and adverse effect on newborns
5. Health tip to share - Traveller's diarrhea
6. Humor is healthy
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1. Breast cancer in women not reduced with low fat diet
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
On and off over the last decade, some scientists have
suggested that breast cancer was related to the dietary
intake of fat. They never concluded whether fat was a
direct cause or if the cause might have been
carcinogenic substances that were dissolved in the fat
from environmental fertilizers, insecticides and
pesticides. Nevertheless the data was not very
conclusive about dietary fat as a breast cancer cause.
The recent Women's Health Initiative Randomized
Controlled Dietary Modification Trial looked at a total
of 48,835 postmenopausal women, aged 50 to 79 years,
without prior breast cancer, including 18.6% of
minority race/ethnicity. Half of the group was placed
on a low fat diet in which only 20% of the daily
calorie intake was provided by fat. The other half of
the group had a regular diet as they preferred.
The difference between the two groups in change from
baseline for percentage of energy from fat varied from
10.7% at year 1 to 8.1% at year 6. In other words the
low fat group was eating about a third less fat than
the control group. In spite of that, the incidence of
newly occurring breast cancer was 0.42% in the low fat
group and 0.45% in the comparison group. There was no
significant difference in the incidence of breast
cancer according to the amount of dietary fat ingested
over 6 years.
This is not absolutely conclusive about the lack of a
cancer cause by dietary fat since it takes about 6-8
years for a breast cancer to go from a few microscopic
cells to a detectable lump but it is still pretty good
evidence about the lack of a major effect.
Breast cancer in women not reduced with low fat diet
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2. Eradication of H.Pylori helps dyspepsia
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
Dyspepsia is a term meaning pain related to the
digestive tract mainly throat and stomach pain. It
includes peptic ulcer disease as well as
gastroesophageal reflux disease. Peptic ulcer disease
has been found to be caused by an acid-loving bacteria
called helicobacter pylori. Ulcers respond to
antibiotic treatment that eradicates H. pylori but it
is not certain how much gastroesophageal reflux and
other non ulcer dyspepsia can be improved by treatment
of the H. pylori bacteria.
In a British study of over 1500 people who were
infected with H. pylori, half were treated with
antibiotic therapy and half were given placebo. Over
the next two years after treatment, the number of
people who further consulted their doctors for
dyspepsia symptoms was reduced by 35%. The net result,
however is that thirty people with H. pylori would have
to be treated to prevent one person consulting their
doctor for dyspepsia. This is not a very cost effective
ratio. It probably means that most people put up with
the symptoms of dyspepsia and do not visit their doctor
or that the infection may spontaneously subside or go
away.
Still if you are a person suffering from stomach or
esophageal pain you should consider being tested for H.
pylori. Home
tests
are available over the Internet.
http://bmj.bmjjournals.com/cgi/content/full/bmj;332/7535/199
Eradication of H.Pylori helps dyspepsia
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3. Reader submitted Q&A - Celiac disease symptoms
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
"Can you tell me the symptoms of celiac disease. I am
45 years old who has had a hysterectomy about 7 years
ago. I had my gall bladder removed in September.
Since my surgery, my digestive system has been out of
whack. My doctor seems to think that I may have celiac
disease." - Vetti
Statistically, the odds are that you have
gastrointestinal problems common in about 1/3 of
patients after having their gall bladder removed. This
is called post cholecystectomy syndrome. However celiac
disease is not as uncommon as one thinks.
Celiac disease is a condition of diarrhea, weight
loss and malnutrition among other symptoms that is
caused by a genetic sensitivity to gluten in the
diet that destroys cells that line the bowel
tract. Gluten is found in barley, oat, rye, wheat
and other grains. In people with celiac disease,
gluten sets off an autoimmune reaction that
attacks the body's own gastrointestinal lining
cells.
While once thought to be a rare disease, recent studies
show it is more common than doctors expect. The test
for celiac disease is a blood test that looks for
IgA/IgG/IgM tissue Transglutaminase (tTG) which is
found in the bowel lining and IgA Gliadin. It is
important to understand that people can have a food
intolerance to gluten but not necessarily have celiac
disease. If you have a food
allergy test that is positive for glutens, you
should then have a specific test for celiac disease.
Celiac disease test kit
A study reported in the Archives of Internal Medicine
looked at different groups of people across the U.S. to
see how common this disease is. They found:
in individuals who are having bowel symptoms, the
risk is 1 in 56
in individuals who are asymptomatic and do not
have a family history of celiac disease, the
risk is 1 in 133.
in individuals who have a parent, sibling or child
with celiac disease, the risk was 1 in 22
in individuals who have an aunt, uncle,
grandparent, niece or nephew with celiac
disease, the risk was 1 in 39
This prevalence is more frequent than most doctors
have previously thought and it turns this
condition from a rare one to something that should be
looked for more commonly. If you or someone you know is
suffering from frequent bowel problems or has
gastrointestinal intolerance to pasta, breads, cereals
and so forth, you may want to seek out testing for
celiac disease.
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4. Antidepressants (SSRIs) and adverse effect on newborns
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
There has been some suggestive evidence recently that
the anti-depression medications Paxil(R), Prozac(R),
Zoloft(R) and other drugs belonging to the selective
serotonin reuptake inhibitors (SSRIs) cause problems in
newborns if mom takes them during pregnancy.
Originally, SSRIs have been thought to be safe during
pregnancy.
A study from San Diego looked at newborns who developed
what is called persistent pulmonary hypertension
(PPHN). This is a serious condition that can result in
death of the newborn, difficulty breathing and low
oxygen levels. The investigators looked at this because
previous studies had suggested, but not proven, that
SSRIs taken in the last half of pregnancy resulted in
more PPHN.
The study found a 6-fold increase in persistent
pulmonary hypertension of the newborn in women who used
SSRIs after the 20th week of pregnancy. In contrast,
neither the use of SSRIs before the 20th week of
gestation nor the use of non-SSRI antidepressant drugs
at any time during pregnancy was associated with an
increased risk of PPHN.
The net result of this study is that women taking SSRIs
during pregnancy should definitely discontinue them
even if the depression becomes worse.
Antidepressants (SSRIs) and adverse effect on newborns
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5. Health tip to share - Traveller's diarrhea
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
Giardia intestinalis is a parasite that can cause long
term diarrhea, gas and nausea symptoms. These symptoms
start 1-2 weeks after exposure and may last 2-6 weeks.
Visitors to foreign countries as well as backpackers
and hikers in the U.S. are more likely to pick up this
parasite. Actually anyone who ingests water from
pools, spas, lakes and rivers can get this. While tests
of water for Giardia are expensive (see your public
health department) you can inexpensively check your
water for coliform bacteria (Bacteria
water test kit). If positive that means fecal
contamination and increases the likelihood of giardia
infestation.
An alcohol extract of the cooking herb oregano is a
natural therapy found to be effective against
giardiasis. Antibiotic therapy to treat this from a
doctor is often metronidazole or tinidazole.
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6. Humor is healthy
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"Swiss Chocolate"
A man from Switzerland is walking down the beach and
comes across an old bottle. He picks it up, pulls out
the cork and out pops a genie.
The genie says, "Thank you for freeing me from the
bottle. In return I will grant you three wishes."
The man says "Great! I always dreamed of this and I
know exactly what I want. First, I want one billion
dollars in a Swiss bank account." Poof! There is a
flash of light and a piece of paper with account
numbers appears in his hand.
He continues, "Next, I want a brand new red Ferrari
right here." Poof! There is a flash of light and a
bright red brand-new Ferrari appears right next to him.
He continues, "Finally, I want to be irresistible
to women."
Poof! There is a flash of light and he turns into a box
of chocolates.
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That's it for this time.
Your BACKUPMD on the Net.
Rick
Frederick R. Jelovsek MD
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********** Health Newsletter ***********
March 12, 2006
~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
From BackupMD on the Net
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1. Prediction of death from physical impairment
2. Melatonin ineffective for secondary sleep problems
3. Reader submitted Q&A - Facial itching and tearing
4. Tendency to develop blood clots
5. Health tip to share - Cocoa intake and heart health
6. Humor is healthy
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1. Prediction of death from daily activities
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You have probably already heard about a risk scoring
system that is predictive of how likely one is to die
in the short term future. I think it is worthwhile to
look at the independent risk factors that the
investigators found in this Journal of the American
Medical Association article. Basically the
investigators examined individuals over 50 years of
age.
They found that the risk of dying in the next four
years according to risk score was:
Risk score Risk of dying
in next 4 years
0-5 points less than 4%
6-9 points 15%
10-13 points 42%
14+ points 64%
The key knowledge, however is what they found the risk points to be:
Factor Risk points
Age 60-64 1
Age 65-69 2
Age 70-74 3
Age 75-79 4
Age 80-84 5
Age 85+ 7
Gender male 2
diabetes 1
cancer 2
lung disease 2
heart failure 2
tobacco use 2
body mass index <25 1
bathing difficulties 2
difficulty walking
several blocks 2
difficulty managing
money 2
difficulty pushing
large objects 1
As you can see, physical limitations are just as predictive of death in the near term future as are medical problems such as heart failure or diabetes. Prediction of death from daily activities ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ 2. Melatonin ineffective for secondary sleep problems ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Sleep disorders are a widespread problem and may affect as many as 20% of people at a given time. Sleep problems can be primary like unexplained insomnia or they may be secondary to other conditions such as sleep apnea, shift work, jet lag, medicines, mental health problems etc. Because sleeping pills are fairly sedating and can produce side effects even after awaking from sleep, many people look to alternative medical therapies that may be safer. Since melatonin is a natural hormone that is low during awake hours and elevated during sleeping hours, investigators have used melatonin to try to aid in going to sleep faster in people who have trouble getting to sleep. Melatonin has also been used for jet lag and for people who work evening and night shifts to see if they will benefit from taking it. Some studies have implied that melatonin may be effective but when you look at all of the studies that have evaluated melatonin for secondary sleep disorders they do not seem to show any significant benefit to melatonin use. Melatonin ineffective for secondary sleep problems ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ 3. Reader submitted Q&A - Facial itching and tearing ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ "Two years ago, at age 42, I suffered a mild stroke. Since then, I have had periods of weeks at a time in which the left side of my face itches terribly, and my eye tears up. My doctor said it is an allergy and suggested an antihistamine. I never had an "allergy" before. The neurologist did not seem interested in it if it is not a "pre-stroke" symptom. Any suggestions why I have these periods now?" - MEH What you describe has been reported after strokes but it is not a very common post stroke complication. Most itching (pruritus) is due to a histamine release in the skin due to skin trauma, rashes, bacterial, yeast or fungal infections or skin conditions such as psoriasis or eczema. This histamine release is a "peripheral" cause of pruritus. Itching can also be caused centrally in the brain. In your case this is what is going on. It is thought to be a "sensitization" of the pain fibers in the brain rather than histamine release in the skin of the affected area. Because a stroke usually affects only one half of the brain (right or left), central causes of pruritus do not involve histamine release in the skin and thus do not respond to antihistamine medications. Since the itching is on the left side of the face and you have tearing on the left, this would indicate that the mini-stroke affected some brain cells on the right side of the brain in the area of the facial nerve. They probably made the cells supersensitive to any stimulus so that the itching is brought on by minor things that you may not even be aware of. I suspect your neurologist is aware that this can be a post stroke symptom but just does not have any medicines to treat the problem with. I am not sure whether any anti-epileptic medications might lessen these attacks like they do with aberrant electrical irritation that causes seizures. I could not find any suggestions for treatment in a review of articles on Pub Med. If the symptoms present a major problem for you so that they interfere with your daily activities, I would suggest you go to a major medical center that has some neurologists who are very experienced with mini-strokes and who might be willing to work with you trying some different types of medications. ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ 4. Tendency to develop blood clots ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Blood clots are an uncommon occurrence. Many times blood clots are associated with trauma or surgery that injures the blood vessels, but they can also be associated with various conditions and diseases. Many are unaware that most of the people who develop spontaneous blood clots unassociated with trauma or surgery have either a disease or genetic tendency to form these clots. Such conditions might be: Deficiencies of natural anticoagulants: anti thrombin, protein C and protein S Genetic alterations: Factor V Leiden or Factor II Increased clotting factors such as high Factor VIII level Immune problems like antiphospholipid antibody syndrome (APS) Any of these clot producing conditions make a person at more risk of having a blood clot associated with hormone use (birth control pills, hormonal replacement), pregnancy or any trauma or surgery. The magnitude of risk has not been well described. In looking at one condition, Antiphospholipid antibody syndrome (APS), investigators in Canada looking at the worlds' medical literature found the following risk of blood clots: Among patients with APSs, the absolute risk of developing new thrombosis (blood clots) is low (less than 1% per year) in otherwise healthy patients without prior thrombotic events. The risk may be moderately increased (up to 10% per year) in women with recurrent fetal loss without prior thrombosis, and is highest (>10% in the first year) in patients with a history of venous thrombosis who have discontinued anticoagulant drugs within 6 months. They also found that aspirin appears to be as effective as moderate-intensity warfarin anticoagulant (Coumadin(R)) for preventing recurrent stroke in APS patients with a history of prior stroke. Tendency to develop blood clots ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ 5. Health tip to share - Cocoa intake and heart health ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ Cocoa intake may be healthy for your heart. At least that's what one study of elderly men found. As with all food studies there may be other factors responsible for an outcome rather than the food that was measured but in a Dutch study of elderly men followed for 15 years, those who had the highest cocoa intake calculated from all the food they regularly ate and drank, had half the death rate from cardiovascular disease compared to men who had almost zero cocoa intake. Their blood pressures were also less. This suggests that chocolate may be heart healthy. - FRJ ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ 6. Humor is healthy ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ An 80 year old man was arrested for shop lifting. When he went before the judge, the judge asked him, "What did you steal?" He replied: "a can of peaches." The judge asked him why he had stolen them and he replied that he was hungry. The judge then asked him how many peaches were in the can.? He replied 6. The judge then said, "I will give you 6 days in jail." Before the judge could actually pronounce the punishment the man's wife spoke up and asked the judge if she could say something. He said, "What is it?" The wife said "He also stole a can of peas." ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~ That's it for this time. Your BACKUPMD on the Net. Rick Frederick R. Jelovsek MD ~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
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