CELLPHONE ALLERGY- OCT 2008

Do you have a child/ grandchild with facial rash ?
Does she use a cell phone ?

Did you ever think why the hell she gets a rash after using cellphone ?

Did you change her telephone two, three times ? But she gets the rash no matter what telephone she uses.

Did you send her to a dermatologist ?
Did you have her use a lot of steroid creams ?

Until it happens to some one close to you, you will not realize how important this is.

I am sure I am not the only MD with some one in the family with cell phone allergy.

I thought I will share my experience with you.

See attached : this was published this year. Almost none of us know about it.



Take one look at the picture and make the diagnosis, please.

So what do you do ?


After investigations we found Nokia phones do not have any nickel in it as it says in table 1. After spending some money on other phones once we found the answer and switched to Nokia phone the facial skin got back to normal.

Thought this will help some one in my 100 MD net work study group. I hope most people in my group benefit from these educational pieces and each of you is better off after reading these, than before reading these.

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CMAJ • January 1, 2008; 178 (1). doi:10.1503/cmaj.071233.
© 2008 Canadian Medical Association or its licensors
All editorial matter in CMAJ represents the opinions of the authors and not necessarily those of the Canadian Medical Association.
This Article
from JOURNAL OF CANADIAN MEDICAL ASSOCIATION- CMAJ JAN 1, 2008

Teaching Case Report

Cellphone contact dermatitis with nickel allergy

Lionel Bercovitch, MD* and John Luo
*Department of Dermatology, Warren Alpert Medical School of Brown University; Liberal Medical Education, Brown University, Providence, Rhode Island

The case: An 18-year-old male presented with pruritic lichenified dermatitis on his lower abdomen and eczematous dermatitis on his extremities, flanks and face that had lasted several weeks. We suspected his belt buckle had led to allergic contact dermatitis with subsequent autoeczematization. Patch testing using the expanded North American Contact Dermatitis Group allergen battery of 65 allergens1 disclosed an edematous and papulovesicular reaction to nickel at 72 hours. The patient had no other positive reactions, nor did he react to other metals tested, including gold, cobalt, chromium, copper and palladium.

The patient suspected that his recurrent facial dermatitis was related to contact with the headset of his cellphone. We spot tested both the antenna and the headset for free nickel. The test of the antenna, which was plastic coated with metallic paint, was negative. The test of the headset was strongly positive for free nickel. The patient began using a cellphone that contained no nickel, and his facial dermatitis cleared. He decided to resume using his old cellphone to confirm that it had caused his dermatitis and the eruption recurred (Figure 1).

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Figure 1: Patches of eczematous dermatitis on patient's face (left) in areas that came into contact with the headset of his cellphone (right).

We performed spot tests for free nickel on 22 different popular models of cellphones from 8 manufacturers and a Bluetooth headset. We used a commercially available kit (Allertest Ni, Allerderm Laboratories, Phoenix, Arizona), in which we applied a drop of dimethylglyoxime and a drop of ammonium hydroxide solution to a cotton-tipped applicator and rubbed it on the part of the equipment being tested (Figure 2, left). A pink colour on the applicator indicates the presence of free nickel. We performed spot tests on the menu button, the headset, the area bordering the screen and any other metallic areas that could come into contact with the skin (Figure 2, right). The results of the nickel spot testing are summarized in Table 1.


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Figure 2: Spot tests for free nickel were performed by adding a dimethylglyoxime and ammonium hydroxide solution to a cotton-tipped applicator and then rubbing the applicator on areas of cellphones likely to have skin contact. A pink colour on the applicator tip indicates the presence of free nickel (left). In some models, the area around the screen and the menu button tested positive for free nickel (right).

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Table 1.


In the last few years, use of wireless devices for basic communication has risen significantly around the world. In December 2006 the Canadian Residential Telephone Service Survey reported that two-thirds of Canadian households had at least 1 cellphone and that 80% of Alberta households had cellphone service.2 In the same year, a news report in the United States indicated that 53% of American adolescents aged 12–17 owned cellphones, up from 39% in 2005 and 33% in 2002.3 Given the widespread use of cellphones, the presence of metal in the exterior casing of these phones and the high prevalence of nickel sensitization in the population, it is not surprising that cellphones can cause allergic contact dermatitis. Recently, facial contact dermatitis from exposure to hexavalent chromium plating4,5 and to nickel6 in cellphones has been reported.

Although cellphone batteries containing nickel have received much attention as an environmental concern, little has been written about the presence of nickel in cellphone cases. Nearly half of the phones we spot tested contained some free nickel. The menu buttons, decorative logos on the headsets and the metallic frames around the liquid crystal display (LCD) screens were the most common sites.

There appears to be a relation between cellphone models and nickel content. Cellphones intended for rugged use, such as the Motorola i series (i580 and i870), often have rubber coating and no surface nickel. Those with more fashionable designs often have metallic accents and are more likely to contain free nickel in their casings.

Cellphone use should be considered in the differential diagnosis of facial and ear contact dermatitis in individuals who are sensitive to nickel. Manufacturers and industrial designers should be aware of the potential for cellphones to cause allergic reactions related to nickel. Before purchasing cellphones, individuals sensitive to nickel should consider spot testing phones for free nickel. Nickel spot-test kits such as the one we used are readily available for consumer use. These tests are sensitive enough to detect the presence of free nickel at a level as low as 10 ppm — a threshold below which only individuals with the most pronounced sensitivity to nickel would experience a reaction. In addition, we recommend that cellphone retailers allow users with a medically documented allergy to metallic parts of their phones to exchange the equipment without penalty.




Footnotes

This article has been peer reviewed.
Competing interests: None declared.




REFERENCES
Top
REFERENCES

Pratt MD, Belsito DV, DeLeo VA, et al. North American Contact Dermatitis Group patch-test results, 2001–2002 study period. Dermatitis 2004;15:176-83.[Medline]
Residential Telephone Service Survey. Ottawa: Statistics Canada. Available: www.statcan.ca/Daily/English/070504/d070504a.htm. (accessed 2007 Oct 31).
Meyerson B. Schools crack down on cellphones. MSNBC; 2006 Available: www.msnbc.msn.com/id/14912068 (accessed 2007 Oct 31).
Seishima M, Oyama Z, Yamanura M. Cellular phone dermatitis. Arch Dermatol 2002;136:272-3.
Seishima M, Oyama Z, Oda M Cellular phone dermatitis with chromate allergy. Dermatology 2003;207:48-50.[CrossRef][Medline]
Wohrl S, Jandl T, Stingl G, et al. Mobile telephone as new source for nickel dermatitis. Contact Dermatitis 2007;56:113.[Medline]

LIST OF POSTINGS

NEW MEDICINE FOR LIVING LONGER HEALTHIER- 5 oz WINE-HEARD OF RESVERATROL?- NOV 2008

ALLERGY TO CELLPHONE- OCT/NOV 2008

SUNSHINE VITAMIN- JULY 2008

CAN YOU POSTPONE YOUR DATE WITH CANCER AND MI- SEPT 2007

ARE YOU TREATING UNCOMPLICATED UTIS CORRECTLY- FEB 2007

ARE YOU STILL USING ATENOLOL FOR HTN? - OCT 2006

VITAMIN D AND YOU- AUG. 2006

LOVENOX AND BLEEDING- JULY 2006

TREATMENT OF HYPOCALCEMIA- JUNE 2006

TRAZODONE AND SLEEP- MAY 2006

QUESTIONS AND ANSWERS ON SUNSHINE VITAMIN

In answer to many of the questions you ask let me bring you
uptodate in the form of questions and answers on sunshine vitamin - Vitamin D

1) Q : How much vitamin D you should I recommend to my patients
?
A: vitamin D ( CVS/ Walgreens /store brand/ ) 1000 units
capsules at least 1000 is needed. This is in addition to the vitamin D you make from sun exposure and vitmain D you may consume and vitamin D in multivitamin pills
you may be taking. ( the other day my wife got me a multivitamin bottle which
says that contains 1000 units vitamin D per capsule, that is an exception,
usually it contains - 200 units plus ./ minus. In older people, nursing home
residents you may need to give 2000 units howeve. So the dose is 1000 units or higher dailyin any case

2) Q: Do I need to do vitamin D level before starting vitamin
D suppliment. ?
A: No, vitamin D level test is $ 100 per test in 2008 -
Not necessary. vitamin D capsule costs 2 cents

3) Q: What if my blood level is OK and if I take extra vitamin
D is there any harm ?
A: No harm at all, vitamin D 3- cholecalciferol, even 10,000 units daily for three months has been studied - no harm at all. Hypervitaminosis D without extra calcium can do no harm as far as we know.

4) Q: If I order vitamin D 1000 units for hospital patients is
that enough ?
A : Commonest mistake : If you order like that they get
the wrong vitamin D, in my opinion. When MDs order vitamin D in hospitals (
at least the ones I know of ) they get vitamin D2- Ergocalciferol, which is not
the vitamin D we are talking about. I see a lot of patients with that order,
every time I see that order I change it to vitamin D3 - cholecalciferol-
"Ergo" in much less potent than "chole" unit for unit 1 to 3 . ie Chole is three times stronger than Ergo.
Vitamin D without further qualification means vitamin
D2 in NSMC. So if you really want to give "vitamin D 1000 units"- you need to
write vitamin D3 or cholecalciferol which is a mouthful and you may forget it,
remember # 3, if you can

5) Q: When patients go to pharmacy OTC and get vitamin D what
do they get ?
A : vitamin D3- cholecalciferol-
vitaminD2 - Ergocalciferol- is prescription and not OTC in USA . I do
not know why. In USA Ergo- vitamin D is prescription only.
6) Q: How much vitamin D2 should patients get on
prescription-
A: 10,000 units a day or 50,000 units a week . If patients does not want to pay for vitamin D and wants to get it on prescription you
should order vitamin D2- Ergocalciferol- 50,000 units weekly or q 2 weeks or at least q monthly for maintenance

7) Q : My patient takes calcium with vitamin D- 200 units BID
May be I should double the dose.?
A : May be but giving extra calcium with vitamin D
increases risk of hyperclacemia and kidney stones. All the new data is on
vitamin D alone. No calcium with it, just vitamin D

8) Q: Patients already has cancer is it any good to give
vitamin D now ?
A : Yes it is , if you take vitamin D even after the
diagnosis of cancer you live longer.

In fact in my opinion all cancer patients of course with a
small number of exceptions should be on extra vitamin D. All oncologists on
board please. Exceptions may be patients with hypercalcemia to begin with, or perhaps calcium oxalate kidney stones, may be some other exceptions too

9) Q: Is it true Vitamin D prevents diabetes and improves
cardiac problems ?
A: Yes. Your cadiac muscle as well as pancreatic cells need
vitamin D . You have a better chance of postponing the DX of MI or diabetes
if you take extra vitamin D (see the last reference -for all the
cardiologists, second reference: for diabetes prevention) All
cardiologists on board please.

10) Q: How much vitamin D is in there in cow's milk ?
A: Close to zero, my take on that is: even well fed,
well grazing cows, non vitaminD deficient cows will have only as much vitmain D
in mild as it is in cow's blood/ serum may be say 30/ liter. Vitamin D is not
secreted into the milk.
However all milk in cartons have extra vitamin D added
into it, so if you drink extra milk or dairy products you are probably OK but
even there you should not get into problem if you take 1000 units vitamin D3 in addition.

11) Q :Africans , Indians and others who live in the tropics do they need vitamin D, they get plenty of sun. ?
A : They do , melanin pigment works like a sunscreen and
protect the skin but it unfortunatley also block vitmain D production in the
skin from UV-B rays . So even pigmented people need synthetic vitamin D.
Sunscreen used when you go to the beach also shuts off vitamin D production by
the skin.


Did any of your patients tell you 50,000 units is too much ,
give them less ?. One of the medical students said so last year to me. In fact
now it is in milligrams. 1 mg is 40,000 units. So 50,000 units is 1.25 mgs .
thought you should know









Vitamin D helps colorectal cancer patients: studyThu Jun 19 05:28:41 UTC 2008


By Will Dunham
WASHINGTON (Reuters) - Vitamin D may extend the lives of people with colon and
rectal cancer, according to a study published on Wednesday suggesting another
health benefit from the so-called sunshine vitamin.
Previous research has indicated that people with higher levels of vitamin D may
be less likely to develop colon and rectal cancer, also called colorectal
cancer.
The new study led by Dr. Kimmie Ng of Dana-Farber Cancer Institute in Boston
involved 304 men and women diagnosed with colorectal cancer from 1991 to 2002,
to see if higher levels of vitamin D in the patients affected their survival
chances.
In fact, that turned out to be the case.
The researchers in the study, published in the Journal of Clinical Oncology,
used blood samples to determine vitamin D levels of the patients, and they were
tracked for an average of about 6-1/2 years.
Those in the highest 25 percent of vitamin D levels were about 50 percent less
likely to die during the study from their cancer or any other cause compared to
the patients in the lowest 25 percent of vitamin D levels.
During the study, 123 of the patients died, 96 of them from colorectal cancer.
"It's probably premature to say that we should be recommending this as treatment
for colon cancer, but vitamin D should definitely be studied in the setting of a
clinical trial to see if it has any benefit to treating colorectal cancer," Ng
said in a telephone interview.
Ng said a clinical study is being planned to test vitamin D as part of
colorectal cancer treatment. It would involve patients who already have gotten
their cancer surgically removed, with some getting chemotherapy with vitamin D
after surgery and the others getting just the standard chemotherapy.
"Definitive evidence of a benefit of vitamin D in treating colon cancer would
have to come from a clinical trial," Ng said.
The body makes vitamin D when the skin is exposed to sunlight, thus earning its
nickname the "sunshine vitamin." Milk commonly is fortified with it, and it is
found in fatty fish like salmon. But many people do not get enough of it.
Vitamin D helps the body absorb calcium and is considered important for bone
health. In adults, vitamin D deficiency can lead to osteoporosis, and it can
lead to rickets in children.
A number of recent studies have indicated vitamin D also may offer a variety of
other health benefits, including protecting against types of cancer such as
breast cancer, peripheral artery disease and tuberculosis.
According to the American Cancer Society, about 1.2 million new cases of
colorectal cancer are diagnosed a year, and the disease kills about 630,000
people a year, accounting for 8 percent of all cancer deaths.
In addition, a study published on June 9 in the journal Archives of Internal
Medicine found that men with low levels of vitamin D had an elevated risk for a
heart attack.
The American Medical Association, the largest U.S. doctors group, voted this
week to urge the Food and Drug Administration to re-examine recommendations for
vitamin D intake in light of new scientific findings showing its benefits.

------------------------------------------------------------------------------------
Chronic Kidney Disease Expert Column



Vitamin D and the Diabetic Patient


Posted 04/28/2008

Daniel W. Coyne, MD
Author Information


Vitamin D


Vitamin D and its active metabolite, 1,25-di(OH)-vitamin D or calcitriol, have
long been recognized as important regulators of serum calcium and bone health.
Production of calcitriol is dependent on adequate vitamin D. Following
constitutive conversion of vitamin D to 25(OH)-vitamin D by the liver, most
circulating calcitriol (hormonal calcitriol) is made by the highly regulated
1alpha-hydroxylase (CYP27B1) present in the kidneys. Numerous other tissues also
possess 1alpha-hydroxylase and appear to produce calcitriol locally at high
concentrations. The receptor for calcitriol, the vitamin D receptor (VDR), is
expressed in virtually all tissues. Thus, this latter form of calcitriol
production constitutes a classic paracrine-autocrine system. Local production of
calcitriol may even be important in the classic calcitriol target tissues of
bone and the parathyroid gland because investigators have demonstrated the
presence of 1alpha-hydroxylase in bone and parathyroid
cells.[1,2]

Activation of the VDR by hormonal or locally produced calcitriol generally
promotes differentiation of tissues and inhibits proliferation. Some regulatory
actions of VDR are even independent of calcitriol. Scientists have investigated
the relationship of vitamin D deficiency to cancer, cardiovascular disease,
neuromuscular function, and autoimmune diseases.

A large proportion of the population has low vitamin D levels, which are
generally defined as a serum level of 25(OH)-vitamin D less than 20 or 30 ng/mL.
Although sunlight stimulates skin production of vitamin D, many in modern
society are dependent on ingestion of vitamin D in milk or supplements to
maintain normal vitamin D levels, especially during the winter months. Vitamin D
deficiency is particularly common in hospitalized individuals, those with
chronic diseases, and African Americans. Over the past decade, the relationship
of vitamin D deficiency to the risk of developing diabetes mellitus (DM) and the
risk for diabetic complications has been of great interest to scientists.

Dialysis patients have an enormous burden of vitamin D abnormalities, and this
burden also falls on diabetics, who constitute almost 50% of new dialysis
patients. Due to the loss of renal function, dialysis patients are unable to
produce adequate calcitriol. Consequently, these patients have very low hormonal
calcitriol levels. Without supplementation with calcitriol or a calcitriol
analog, they have profoundly diminished activation of the VDR in tissues
throughout the body. Wolf and colleagues examined incident hemodialysis
patients, and found that diabetics were more likely to be severely
25(OH)-vitamin D-deficient (< 10 ng/mL) than nondiabetics (22% vs 17%).[3] Lower
25(OH)-vitamin D levels and lower calcitriol levels strongly correlated with an
increased risk for death during the first 90 days in patients not given
injectable calcitriol or an analog.[3]


Vitamin D and the Risk of Developing DM


Several observational studies have suggested that either low vitamin D levels or
low vitamin D intake may predispose to the development of both type 1 and type 2
DM. The Nurses' Health Study found that vitamin D intake above 800 IU/day and
more than 1200 mg of calcium per day were associated with a 33% reduction in the
risk of developing type 2 DM compared with an intake of < 600 mg of calcium and
< 400 IU of vitamin D.[4] A meta-analysis of largely observational studies
concluded that there was "a relatively consistent association between low
vitamin D status, calcium or dairy intake, and prevalent type 2 DM or metabolic
syndrome.[5]" Evidence from interventional trials suggests that combined vitamin
D and calcium supplementation may help prevent type 2 DM in only some
populations at high risk for diabetes.[5]

Low vitamin D levels, low sun exposure, and low intake of vitamin D have each
been associated with an increased risk for the development of type 1 DM. In
animal models, induction of type 1 DM by streptozocin induces a marked fall in
calcitriol levels, whereas 25(OH)-vitamin D levels remain normal. Treatment with
insulin restores calcitriol levels to normal. Calcitriol has an immunomodulatory
effect. In a nonobese diabetic mouse model, administration of calcitriol or
1alpha-(OH)-vitamin D (a precursor of calcitriol) has been shown to
significantly reduce the likelihood of development of type 1 DM.[6]


Low Vitamin D levels and the Presence of DM or Glucose Intolerance


A report from Martins and colleagues on data from over 15,000 adults in the
Third National Health and Nutrition Examination Survey is perhaps the best
recent evidence on vitamin D and the general population.[7] The 25(OH)-vitamin D
levels were lower in diabetics, women, the elderly, and racial minorities,
groups that are at increased risk of having chronic kidney disease (CKD).[7]
Scragg and colleagues reported in 1995 the association of low 25(OH)-vitamin D
levels with the presence of DM or glucose intolerance.[8] Consistent with these
findings, low vitamin D levels are associated with obesity, as assessed by body
mass index or waist circumference, and weakly with elevated glycated hemoglobin
(A1C) levels.[9]


Vitamin D and Diabetic Complications


Wang and colleagues studied 1739 Framingham offspring participants without prior
cardiovascular disease, and found that low 25(OH)-vitamin D levels (< 15 ng/mL)
were significantly associated with an increased incidence of a first
cardiovascular event during the mean 5.4 years of follow-up.[10] Among diabetics
in this cohort, low 25(OH)-vitamin D levels were significantly more common than
nondiabetics (11% vs 7%), but the association of low vitamin D levels to first
cardiovascular event remained after adjustment for diabetics and other known
risk factors.

Low 25(OH)-vitamin D levels have been shown to correlate with the presence of
cardiovascular disease in diabetics.[11] Similarly, hypovitaminosis D has been
independently associated with carotid artery intimal-medial thickening, a
harbinger of cerebrovascular and cardiovascular events.[12] Suzuki and
colleagues found that microvascular complications were more frequent when
vitamin D levels were low, despite similar duration of disease and other
clinical characteristics compared with control patients without
complications.[13]

These data suggest that diabetic patients are at greater risk of being vitamin
D-deficient and harmed by this deficiency. The presence of CKD will compromise
the production of calcitriol, and potentially further contribute to inadequate
vitamin D signaling. Consistent with this, among 463 diabetics with CKD, low
vitamin D levels were independently associated with the presence of
cardiovascular disease.[14]


VDR Activators and Improved Outcomes in Patients on Dialysis and CKD


Vitamin D receptor activators (VDRAs) are calcitriol or related analogs capable
of binding to the VDR and activating it. Use of a VDRA is common in patients
with CKD and dialysis for the treatment of secondary hyperparathyroidism. In
nephrology, the first suggestion that use of a VDRA may be related to survival
was the sentinel study in 2003 by Teng and colleagues reporting an association
of improved survival in hemodialysis patients given paricalcitol, a VDRA and
analog of calcitriol, compared with native calcitriol.[15] Critics of that study
suggested that either agent may be worse than no VDRA therapy. These critics
noted that both paricalcitol and calcitriol increase serum calcium and
phosphorus, which are associated with lower survival in some observational
studies of the dialysis population.

A subsequent observational study by Teng and colleagues found that use of either
paricalcitol or calcitriol in dialysis patients was associated with improved
survival compared with no VDRA therapy.[16] The strength and consistency of the
association of VDRA use with improved survival has increased over the succeeding
years, with diverse studies of CKD and dialysis populations confirming the
associations.[17-19]


Diabetes, Vitamin D, and Future Research

Most of the data outlined above show associations of vitamin D, calcitriol, or
calcitriol analogs with cardiovascular burden and survival in diabetic patients.
The potential mechanisms by which treatment of vitamin D and calcitriol
deficiency can lead to improved survival and lower cardiovascular events reflect
the diverse actions of vitamin D in the body. Studies are ongoing to determine
through randomized trials whether use of vitamin D can lower inflammation,
moderate cardiac and vascular disease, and lower proteinuria. Significant work
is still required to determine whether this decade of associating vitamin D
deficiency with diabetics and their complications will be followed by results
showing that treatment can mitigate those complications, and even lower the
prevalence of diabetes.

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Lack Of Vitamin D May Increase Heart Disease Risk


ScienceDaily (Jan. 8, 2008) - The same vitamin D deficiency that can result in
weak bones now has been associated with an increased risk of cardiovascular
disease, Framingham Heart Study researchers report in Circulation: Journal of
the American Heart Association.

*
*

"Vitamin D deficiency is associated with increased cardiovascular risk, above
and beyond established cardiovascular risk factors," said Thomas J. Wang, M.D.,
assistant professor of medicine at Harvard Medical School in Boston, Mass. "The
higher risk associated with vitamin D deficiency was particularly evident among
individuals with high blood pressure."

In a study of 1,739 offspring from Framingham Heart Study participants (average
age 59, all Caucasian), researchers found that those with blood levels of
vitamin D below15 nanograms per milliliter (ng/mL) had twice the risk of a
cardiovascular event such as a heart attack, heart failure or stroke in the next
five years compared to those with higher levels of vitamin D.

When researchers adjusted for traditional cardiovascular risk factors such as
high cholesterol, diabetes and high blood pressure, the risk remained
significant with a 62 percent higher risk of a cardiovascular event in
participants with low levels of vitamin D compared to those with higher levels.

Researchers observed the highest rate of cardiovascular disease events in subset
analyses dividing 688 participants according to high blood pressure status.
After researchers adjusted for conventional cardiovascular risk factors,
participants with hypertension and a vitamin D deficiency had about 2 times the
risk of having a cardiovascular disease event in five years.

Researchers also found an increase in cardiovascular risk with each level of
vitamin D deficiency.

"We found that people with low vitamin D levels had a higher rate of
cardiovascular events over the five-year follow-up period," Wang said. "These
results are intriguing and suggestive but need to be followed up with further
study."

Study participants had no prior cardiovascular disease and were tested for
vitamin D status and then followed for an average of 5.4 years.

The participants attended the offspring examinations between 1996 and 2001.
Researchers obtained medical history, physical examinations and laboratory
assessments of vascular risk factors. They also obtained medical records related
to cardiovascular disease.

Overall, 28 percent of individuals had levels of vitamin D below15 ng/mL and 9
percent had levels below10 ng/mL. Although levels above 30 ng/mL are considered
optimal for bone metabolism, only 10 percent of the study sample had levels in
this range, researchers said.

During follow-up:

* 120 participants developed a first cardiovascular event including fatal
and nonfatal coronary heart disease;
* 28 participants had fatal or nonfatal cerebrovascular events such as
nonhemorrhagic stroke;
* 19 participants were diagnosed with heart failure; and
* 8 had occurrences of claudication, fatigue in the legs during activity.

"Low levels of vitamin D are highly prevalent in the United States, especially
in areas without much sunshine," Wang said. "Twenty to 30 percent of the
population in many areas has moderate to severe vitamin D deficiency."

Most of this is attributed to lack of sun exposure, pigmented skin that prevents
penetration of the sun's rays and inadequate dietary intake of vitamin D
enriched foods, researchers said.

"A growing body of evidence suggests that low levels of vitamin D may adversely
affect the cardiovascular system," Wang said. "Vitamin D receptors have a broad
tissue distribution that includes vascular smooth muscle and endothelium, the
inner lining of the body's vessels. Our data raise the possibility that treating
vitamin D deficiency, via supplementation or lifestyle measures, could reduce
cardiovascular risk.

"What hasn't been proven yet is that vitamin D deficiency actually causes
increased risk of cardiovascular disease. This would require a large randomized
trial to show whether correcting the vitamin D deficiency would result in a
reduction in cardiovascular risk."

Therfore, Wang doesn't recommend physicians check for vitamin D deficiency or
that those with a known vitamin D deficiency be treated to prevent heart disease
at this time.

During the past decade, researchers have studied several other vitamins that
initially showed promise in reducing heart disease. But the vitamins didn't
reduce heart disease in subsequent large randomized trials.

"On the flip side, just because other vitamins haven't succeeded doesn't
preclude the possibility of finding vitamins that might prevent cardiovascular
disease," Wang said. "This is always an area of great interest. Vitamins are
easy to administer and in general have few toxic effects."

The American Heart Association recommends that healthy people get adequate
nutrients by eating a variety of foods in moderation, rather than by taking
supplements. Food sources of vitamin D include milk, salmon, mackerel, sardines,
cod liver oil and some fortified cereals. Vitamin or mineral supplements aren't
a substitute for a balanced, nutritious diet that limits excess calories,
saturated fat, trans fat, sodium and dietary cholesterol. This dietary approach
has been shown to reduce coronary heart disease risk in healthy people and those
with coronary disease.

Co-authors are: Michael J. Pencina, Ph.D.; Sarah L. Booth, Ph.D.; Paul F.
Jacques, D.Sc.; Erik Ingelsson, M.D., Ph.D.; Katherine Lanier, B.S.; Emelia J.
Benjamin, M.D.; Ralph B. D'Agostino, Ph.D.; Myles Wolf, M.D.; and Ramachandran
S. Vasan, M.D. The National Institute of Health, U.S. Department of Agriculture
and American Heart Association funded the study.

CAN YOU POSTPONE YOUR DATE WITH CANCER AND MI

Do you have prostate cancer ? Will you get prostate cancer ? Do you have colon cancer ? Or get one sooner or later ? What about breast cancer ?

Even when you develop cancer excess vitamin D increases apoptosis and you survive longer. Not debatable.

Every one of your patients and ourselves and our spouses should be on vitamin D 2000 units a say for ever. There is no down side to it. Mind you I said vitamin D, not vitamin D with calcium.

Vitamin D decreases the incidence of all kind of cancers further all cancer patients should be on vitamin D also. Even after the diagnosis is made vitamin D increases the life span and it increases apoptosis. Remember there is no down side to vitamin D ingestion at that dose or even multiples of that dose, below may be a dose of 10,000 units a day
.

Milk from even well fed cows , how much vitamin D is there ? Zilch, zero- point is milk has no vitamin D unless you add it to milk. How many of you know that ?


Did you know that if you live in Atlanta , SanAntonio you have less chance of getting all kinds of cancers than in Boston .

FROM NEJM Volume 357:266-281 July 19, 2007 Number 3

Vitamin D Deficiency

Michael F. Holick, M.D., Ph.D.


Once foods were fortified with vitamin D and rickets appeared to have been conquered, many health care professionals thought the major health problems resulting from vitamin D deficiency had been resolved. However, rickets can be considered the tip of the vitamin D–deficiency iceberg. In fact, vitamin D deficiency remains common in children and adults. In utero and during childhood, vitamin D deficiency can cause growth retardation and skeletal deformities and may increase the risk of hip fracture later in life. Vitamin D deficiency in adults can precipitate or exacerbate osteopenia and osteoporosis, cause osteomalacia and muscle weakness, and increase the risk of fracture.

The discovery that most tissues and cells in the body have a vitamin D receptor and that several possess the enzymatic machinery to convert the primary circulating form of vitamin D, 25-hydroxyvitamin D, to the active form, 1,25-dihydroxyvitamin D, has provided new insights into the function of this vitamin. Of great interest is the role it can play in decreasing the risk of many chronic illnesses, including common cancers, autoimmune diseases, infectious diseases, and cardiovascular disease. In this review I consider the nature of vitamin D deficiency, discuss its role in skeletal and nonskeletal health, and suggest strategies for its prevention and treatment.

Sources and Metabolism of Vitamin D

Humans get vitamin D from exposure to sunlight, from their diet, and from dietary supplements. A diet high in oily fish prevents vitamin D deficiency. Solar ultraviolet B radiation (wavelength, 290 to 315 nm) penetrates the skin and converts 7-dehydrocholesterol to previtamin D3, which is rapidly converted to vitamin D 3 (Figure 1). 1 Because any excess previtamin D3 or vitamin D3 is destroyed by sunlight ( Figure 1), excessive exposure to sunlight does not cause vitamin D 3 intoxication.


During exposure to solar ultraviolet B (UVB) radiation, 7-dehydrocholesterol in the skin is converted to previtamin D3, which is immediately converted to vitamin D3 in a heat-dependent process. Excessive exposure to sunlight degrades previtamin D 3 and vitamin D3 into inactive photoproducts. Vitamin D2 and vitamin D3 from dietary sources are incorporated into chylomicrons and transported by the lymphatic system into the venous circulation. Vitamin D (hereafter "D" represents D 2 or D3) made in the skin or ingested in the diet can be stored in and then released from fat cells. Vitamin D in the circulation is bound to the vitamin D–binding protein, which transports it to the liver, where vitamin D is converted by vitamin D-25-hydroxylase to 25-hydroxyvitamin D [25(OH)D]. This is the major circulating form of vitamin D that is used by clinicians to determine vitamin D status. ..................

Few foods naturally contain or are fortified with vitamin D. The "D" represents D2 or D3 ( Figure 1). Vitamin D2 is manufactured through the ultraviolet irradiation of ergosterol from yeast, and vitamin D3 through the ultraviolet irradiation of 7-dehydrocholesterol from lanolin. Both are used in over-the-counter vitamin D supplements, but the form available by prescription in the United States is vitamin D2.

Vitamin D from the skin and diet is metabolized in the liver to 25-hydroxyvitamin D ( Figure 1), which is used to determine a patient's vitamin D status. 25-hydroxyvitamin D is metabolized in the kidneys by the enzyme 25-hydroxyvitamin D-1 -hydroxylase (CYP27B1) to its active form, 1,25-dihydroxyvitamin D. The renal production of 1,25-dihydroxyvitamin D is tightly regulated by plasma parathyroid hormone levels and serum calcium and phosphorus levels. Fibroblast growth factor 23, secreted from the bone, causes the sodium–phosphate cotransporter to be internalized by the cells of the kidney and small intestine and also suppresses 1,25-dihydroxyvitamin D synthesis. The efficiency of the absorption of renal calcium and of intestinal calcium and phosphorus is increased in the presence of 1,25-dihydroxyvitamin D It also induces the expression of the enzyme 25-hydroxyvitamin D-24-hydroxylase (CYP24), which catabolizes both 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D into biologically inactive, water-soluble calcitroic acid.

Definition and Prevalence of Vitamin D Deficiency

Although there is no consensus on optimal levels of 25-hydroxyvitamin D as measured in serum, vitamin D deficiency is defined by most experts as a 25-hydroxyvitamin D level of less than 20 ng per milliliter (50 nmol per liter).
Hydroxyvitamin D levels are inversely associated with parathyroid hormone levels until the former reach 30 to 40 ng per milliliter (75 to 100 nmol per liter), at which point parathyroid hormone levels begin to level off (at their nadir). Furthermore, intestinal calcium transport increased by 45 to 65% in women when 25-hydroxyvitamin D levels were increased from an average of 20 to 32 ng per milliliter (50 to 80 nmol per liter). 13 Given such data, a level of 25-hydroxyvitamin D of 21 to 29 ng per milliliter (52 to 72 nmol per liter) can be considered to indicate a relative insufficiency of vitamin D, and a level of 30 ng per milliliter or greater can be considered to indicate sufficient vitamin D. 14 Vitamin D intoxication is observed when serum levels of 25-hydroxyvitamin D are greater than 150 ng per milliliter (374 nmol per liter).

With the use of such definitions, it has been estimated that 1 billion people worldwide have vitamin D deficiency or insufficiency. According to several studies, 40 to 100% of U.S. and European elderly men and women still living in the community (not in nursing homes) are deficient in vitamin D. More than 50% of postmenopausal women taking medication for osteoporosis had suboptimal levels of 25-hydroxyvitamin D — below 30 ng per milliliter (75 nmol per liter).

Children and young adults are also potentially at high risk for vitamin D deficiency. For example, 52% of Hispanic and black adolescents in a study in Boston 23 and 48% of white preadolescent girls in a study in Maine 24 had 25-hydroxyvitamin D levels below 20 ng per milliliter. In other studies, at the end of the winter, 42% of 15- to 49-year-old black girls and women throughout the United States had 25-hydroxyvitamin D levels below 20 ng per milliliter, 25 and 32% of healthy students, physicians, and residents at a Boston hospital were found to be vitamin D–deficient, despite drinking a glass of milk and taking a multivitamin daily and eating salmon at least once a week.

In Europe, where very few foods are fortified with vitamin D, children and adults would appear to be at especially high risk. People living near the equator who are exposed to sunlight without sun protection have robust levels of 25-hydroxyvitamin D — above 30 ng per milliliter. However, even in the sunniest areas, vitamin D deficiency is common when most of the skin is shielded from the sun. In studies in Saudi Arabia, the United Arab Emirates, Australia, Turkey, India, and Lebanon, 30 to

50% of children and adults had 25-hydroxyvitamin D levels under 20 ng per milliliter. Also at risk were pregnant and lactating women who were thought to be immune to vitamin D deficiency since they took a daily prenatal multivitamin containing 400 IU of vitamin D (70% took a prenatal vitamin, 90% ate fish, and 93% drank approximately 2.3 glasses of milk per day) .73% of the women and 80% of their infants were vitamin D–deficient (25-hydroxyvitamin D level, <20 ng per milliliter) at the time of birth.

Calcium, Phosphorus, and Bone Metabolism

Without vitamin D, only 10 to 15% of dietary calcium and about 60% of phosphorus is absorbed. The interaction of 1,25-dihydroxyvitamin D with the vitamin D receptor increases the efficiency of intestinal calcium absorption to 30 to 40% and phosphorus absorption to approximately 80%

In one study, serum levels of 25-hydroxyvitamin D were directly related to bone mineral density in white, black, and Mexican-American men and women, with a maximum density achieved when the 25-hydroxyvitamin D level reached 40 ng per milliliter or more.8 When the level was 30 ng per milliliter or less, there was a significant decrease in intestinal calcium absorption 13 that was associated with increased parathyroid hormone. Parathyroid hormone enhances the tubular reabsorption of calcium and stimulates the kidneys to produce 1,25-dihydroxyvitamin D. Parathyroid hormone also activates osteoblasts, which stimulate the transformation of preosteoclasts into mature osteoclasts (Figure 1). Osteoclasts dissolve the mineralized collagen matrix in bone, causing osteopenia and osteoporosis and increasing the risk of fracture.

Deficiencies of calcium and vitamin D in utero and in childhood may prevent the maximum deposition of calcium in the skeleton. As vitamin D deficiency progresses, the parathyroid glands are maximally stimulated, causing secondary hyperparathyroidism. Hypomagnesemia blunts this response, which means that parathyroid hormone levels are often normal when 25-hydroxyvitamin D levels fall below 20 ng per milliliter. Parathyroid hormone increases the metabolism of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D, which further exacerbates the vitamin D deficiency. Parathyroid hormone also causes phosphaturia, resulting in a low-normal or low serum phosphorus level. Without an adequate calcium–phosphorus product (the value for calcium times the value for serum phosphorus), mineralization of the collagen matrix is diminished, leading to classic signs of rickets in children and osteomalacia in adults.

Whereas osteoporosis is unassociated with bone pain, osteomalacia has been associated with isolated or generalized bone pain. The cause is thought to be hydration of the demineralized gelatin matrix beneath the periosteum; the hydrated matrix pushes outward on the periosteum, causing throbbing, aching pain. Osteomalacia can often be diagnosed by using moderate force to press the thumb on the sternum or anterior tibia, which can elicit bone pain. One study showed that 93% of persons 10 to 65 years of age who were admitted to a hospital emergency department with muscle aches and bone pain and who had a wide variety of diagnoses, including fibromyalgia, chronic fatigue syndrome, and depression, were deficient in vitamin D.

Osteoporosis and Fracture

Approximately 33% of women 60 to 70 years of age and 66% of those 80 years of age or older have osteoporosis. It is estimated that 47% of women and 22% of men 50 years of age or older will sustain an osteoporotic fracture in their remaining lifetime. Chapuy et al. reported that among 3270 elderly French women given 1200 mg of calcium and 800 IU of vitamin D3 daily for 3 years, the risk of hip fracture was reduced by 43%, and the risk of nonvertebral fracture by 32%. A 58% reduction in nonvertebral fractures was observed in 389 men and women over the age of 65 years who were receiving 700 IU of vitamin D3 and 500 mg of calcium per day.

A meta-analysis of seven randomized clinical trials that evaluated the risk of fracture in older persons given 400 IU of vitamin D3 per day revealed little benefit with respect to the risk of either nonvertebral or hip fractures (pooled relative risk of hip fracture, 1.15; 95% confidence interval [CI], 0.88 to 1.50; pooled relative risk of nonvertebral fracture, 1.03; 95% CI, 0.86 to 1.24). In studies using doses of 700 to 800 IU of vitamin D3 per day, the relative risk of hip fracture was reduced by 26% (pooled relative risk, 0.74; 95% CI, 0.61 to 0.88 ), and the relative risk of nonvertebral fracture by 23% (pooled relative risk, 0.77; 95% CI, 0.68 to 0.87) with vitamin D3 as compared with calcium or placebo. 8 A Women's Health Initiative study that compared the effects of 400 IU of vitamin D3 plus 1000 mg of calcium per day with placebo in more than 36,000 postmenopausal women confirmed these results, reporting an increased risk of kidney stones but no benefit with respect to the risk of hip fracture.

The Women's Health Initiative study also showed that serum levels of 25-hydroxyvitamin D had little effect on the risk of fracture when levels were 26 ng per milliliter (65 nmol per liter) or less. However, women who were most consistent in taking calcium and vitamin D3 had a 29% reduction in hip fracture. 43 Optimal prevention of both nonvertebral and hip fracture occurred only in trials providing 700 to 800 IU of vitamin D3 per day in patients whose baseline concentration of 25-hydroxyvitamin D was less than 17 ng per milliliter (42 nmol per liter) and whose mean concentration of 25-hydroxyvitamin D then rose to approximately 40 ng per milliliter.

Evaluation of the exclusive use of calcium or vitamin D3 (RECORD trial) showed no antifracture efficacy for patients receiving 800 IU of vitamin D3 per day. However, the mean concentration of 25-hydroxyvitamin D increased from 15.2 ng per milliliter to just 24.8 ng per milliliter (37.9 to 61.9 nmol per liter), which was below the threshold thought to provide antifracture efficacy.8 Porthouse and colleagues, 45 who evaluated the effect of 800 IU of vitamin D3 per day on fracture prevention, did not report concentrations of 25-hydroxyvitamin D. Their study had an open design in which participants could have been ingesting an adequate amount of calcium and vitamin D separate from the intervention. This called into question the conclusion that vitamin D supplementation had no antifracture benefit. 8

Muscle Strength and Falls

Vitamin D deficiency causes muscle weakness.Skeletal muscles have a vitamin D receptor and may require vitamin D for maximum function.

Performance speed and proximal muscle strength were markedly improved when 25-hydroxyvitamin D levels increased from 4 to 16 ng per milliliter (10 to 40 nmol per liter) and continued to improve as the levels increased to more than 40 ng per milliliter (100 nmol per liter).8 A meta-analysis of five randomized clinical trials (with a total of 1237 subjects) revealed that increased vitamin D intake reduced the risk of falls by 22% (pooled corrected odds ratio, 0.78; 95% CI, 0.64 to 0.92) as compared with only calcium or placebo. 8 The same meta-analysis examined the frequency of falls and suggested that 400 IU of vitamin D3 per day was not effective in preventing falls, whereas 800 IU of vitamin D3 per day plus calcium reduced the risk of falls (corrected pooled odds ratio, 0.65; 95% CI, 0.4 to 1.0).8 In a randomized controlled trial conducted over a 5-month period, nursing home residents receiving 800 IU of vitamin D2 per day plus calcium had a 72% reduction in the risk of falls as compared with the placebo group (adjusted rate ratio, 0.28%; 95% CI, 0.11 to 0.75).

Nonskeletal Actions of Vitamin D

Brain, prostate, breast, and colon tissues, among others, as well as immune cells have a vitamin D receptor and respond to 1,25-dihydroxyvitamin D, the active form of vitamin D. In addition, some of these tissues and cells express the enzyme 25-hydroxyvitamin D-1 -hydroxylase.

Directly or indirectly, 1,25-dihydroxyvitamin D controls more than 200 genes, including genes responsible for the regulation of cellular proliferation, differentiation, apoptosis, and angiogenesis. It decreases cellular proliferation of both normal cells and cancer cells and induces their terminal differentiation. One practical application is the use of 1,25-dihydroxyvitamin D3 and its active analogues for the treatment of psoriasis.

1,25-Dihydroxyvitamin D is also a potent immunomodulator.

Latitude, Vitamin D Deficiency, and Chronic Diseases

Cancer ---LET ME HIGHLIGHT SOME OF THE POINTS AGAIN

People living at higher latitudes are at increased risk for Hodgkin's lymphoma as well as colon, pancreatic, prostate, ovarian, breast, and other cancers and are more likely to die from these cancers, as compared with people living at lower latitudes.

More than 50% of postmenopausal women taking medication for osteoporosis had suboptimal levels of 25-hydroxyvitamin D — below 30 ng per milliliter (75 nmol per liter).
-............healthy students, physicians, and residents at a Boston hospital were found to be vitamin D–deficient, despite drinking a glass of milk and taking a multivitamin daily and eating salmon at least once a week.
Also at risk were pregnant and lactating women who were thought to be immune to vitamin D deficiency since they took a daily prenatal multivitamin containing 400 IU of vitamin D
Directly or indirectly, 1,25-dihydroxyvitamin D controls more than 200 genes, including genes responsible for the regulation of cellular proliferation, differentiation, apoptosis, and angiogenesis.It decreases cellular proliferation of both normal cells and cancer cells and induces their terminal differentiation."

Is 30- 50% higher incidence of cancer good enough to convince us to take more vitamin D ?

"People living at higher latitudes are at increased risk for Hodgkin's lymphoma as well as colon, pancreatic, prostate, ovarian, breast, and other cancers and are more likely to die from these cancers, as compared with people living at lower latitudes.Both prospective and retrospective epidemiologic studies indicate that levels of 25-hydroxyvitamin D below 20 ng per milliliter are associated with a 30 to 50% increased risk of incident colon, prostate, and breast cancer,
along with higher mortality from these cancers.

In a study of men with prostate cancer, the disease developed 3 to 5 years later in the men who worked outdoors than in those who worked indoors. Pooled data for 980 women showed that the highest vitamin D intake, as compared with the lowest, correlated with a 50% lower risk of breast cancer . Children and young adults who are exposed to the most sunlight have a 40% reduced risk of non-Hodgkin's lymphoma 65 and a reduced risk of death from malignant melanoma once it develops , as compared with those who have the least exposure to sunlight.

To answer your question what is the dose needed to prevent cancer my answer is whtever it takes to bring the blood 25 OH D3 level to 30 or higher. That is the scientific answer.

""Cardiovascular Disease
Living at higher latitudes increases the risk of hypertension and cardiovascular disease . In a study of patients with hypertension who were exposed to ultraviolet B radiation three times a week for 3 months, 25-hydroxyvitamin D levels increased by approximately 180%, and blood pressure became normal (both systolic and diastolic blood pressure reduced by 6 mm Hg). Vitamin D deficiency is associated with congestive heart failure 54 and blood levels of inflammatory factors, including C-reactive protein and interleukin-

ARE YOU TREATING UNCOMPLICATED UTIs CORRECTLY ?

I support this paper's conclusions and recommendations.

Main points.

This is for outpatients, or clinic patients, not inpatients, not for nosocomial infections.
It is scientific and evidence based in 2007 not to order urine culture and sensitivity for suspected uncomplicated UTIs, if people dispute you remember this article.
Three days is the duration of treatment not seven days not fourteen says- I have seen all these being done.
The medication is Bactrim DS for below the age of say 60 and single strength BID for older folks in my opinion . In renal insufficiency do not use Bactrim at all.

In sulfa allergic patients use Cipro.

Amoxicillin or Keflex is not the right choice as it kills too many other bacteria also which causes other problems, like vaginitis etc etc. Nitrofurnatoin may be.

But do not lose the focus, the treatment of choice is Bactrim for three days. For uncomplicated UTIs. You need a urine dipstck in all cases at least in this paper unless you know the patient from before and has had previous UTI. You can debate that point but do not lose the focus

The treatment is for three days not 10- 14 days.

It is perfectly kosher to order three days treatment any thing more is an over kill, and too expensive and is for no scientific reason. It is our job to highlight the right answer. Probably no one has seen the reference #1 given below

KK










ORIGINAL ARTICLE

Assessing Adherence to Evidence-Based Guidelines for the Diagnosis and Management of Uncomplicated Urinary Tract Infection
MICHAEL L. GROVER, DO; JESSE D. BRACAMONTE, DO; ANUP K. KANODIA, MD; MICHAEL J. BRYAN, MD; SEAN P. DONAHUE, DO; ANNE-MARIE WARNER, MD; FREDERICK D. EDWARDS, MD; AMY L. WEAVER, MS
From the Department of Family Medicine, Mayo Clinic College of Medicine, Scottsdale, Ariz (M.L.G., J.D.B., A.K.K., M.J.B., S.P.D., A.-M.W., F.D.E.); and Division of Biostatistics, Mayo Clinic College of Medicine, Rochester, Minn ( A.L.W.). Dr Kanodia is now with Osher Institute, Harvard Medical School, Boston, Mass. Dr Bryan is in private practice in Prescott, Ariz. Dr Donahue is now with the Stanford University, Stanford, Calif. Dr Warner is now with Maricopa Integrated Health Systems and Medpro Associates, Phoenix, Ariz.




Abstract


OBJECTIVE: To assess adherence to evidence-based guidelines for the diagnosis and management of uncomplicated urinary tract infection (UTI) in a family medicine residency clinic setting.

PATIENTS AND METHODS: We retrospectively reviewed the medical records of female patients seen in 2005 at the Mayo Clinic Family Medicine Center in Scottsdale, Ariz, who were identified by International Classification of Diseases, Ninth Revision code 599.0 (UTI). We assessed documentation rates, use of diagnostic studies, and antibiotic treatments. Antibiotic sensitivity patterns from outpatient urine culture and sensitivity analyses were determined.

RESULTS: Of 228 patients, 68 (30%) had uncomplicated UTI. Our physicians recorded essential history and examination findings for most patients. Documentation of the risk of sexually transmitted disease differed between residents and attending physicians and was affected by patient age. Urine dipstick and urine culture and sensitivity analyses were ordered in 57 (84%) and 52 (76%) patients, respectively. Eighty percent of patients with positive results on urine dipstick analyses also had urine culture and sensitivity analyses. Sulfamethoxazole-trimethoprim (SMX-TMP) was used as initial therapy in 26 patients (38%). Sixty-one percent of SMX-TMP and ciprofloxacin prescriptions were appropriately provided for 3 days. Escherichia coli was sensitive to SMX-TMP in 33 (94%) of 35 cultures. Treatment was not changed in any patient with an uncomplicated UTI because of results of urine culture and sensitivity analyses. Antibiotic sensitivity patterns for outpatients were significantly different from those for inpatients.

CONCLUSION: Only 30% of our patients had uncomplicated UTI, making their management within clinical guidelines appropriate. However, of those patients with uncomplicated UTI, less than 25% received empirical treatment as suggested. Urine culture and sensitivity analyses were performed frequently, even in patients who already had positive results on a urine dip-stick analysis. Although SMX-TMP is effective, it is underused. On the basis of these findings, we hope to provide interventions to increase SMX-TMP prescription, decrease use of urine culture and sensitivity analyses, and increase the frequency of 3-day antibiotic treatments at our institution.

Mayo Clin Proc. 2007;82(2):181-185


EMR=electronic medical record; SMX-TMP=sulfamethoxazole-trimethoprim; STD=sexually transmitted disease; UTI=urinary tract infection



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Urinary tract infection (UTI) is a common chief complaint at primary care offices, accounting for approximately 8.3 million physician visits per year. 1 Because UTI is a common illness, its diagnosis and treatment have important implications for patient health, development of antibiotic resistance, and health care costs. Several evidence-based guidelines and reviews have provided diagnostic and management strategies. 2-5 These guidelines argue against performance of urine culture and sensitivity analyses in patients with classic signs and symptoms of uncomplicated UTI. Furthermore, sulfamethoxazole-trimethoprim (SMX-TMP) for 3 days is advocated as the antibiotic of choice because of its low cost and efficacy.

With this information available, it would seem logical that physician practice would conform to published practice guidelines. However, the reality is that many physicians continue to practice largely independent of these recommendations. 6-11 One study in 1999 of more than 2100 physicians found great variability in UTI management. 6 Many physicians continued to obtain urine cultures. Nearly 30% did not use SMX-TMP as the first-line agent, and almost half of obstetrician-gynecologists used nitrofurantoin as their antibiotic of choice in nonpregnant, low-risk patients. Only about half of physicians treated patients with antibiotics for the recommended 3-day duration. In 2003, a study analyzing more than 10,000 insurance claims found that physicians generally did not use SMX-TMP as the first-line agent, and the duration of treatment was often much longer than the recommended 3 days. 7 Studies have shown that urologists appear to have the best adherence to guidelines. 9 Nonadherence can profoundly affect health care costs.10

We hypothesized that a similar gap between national guidelines and physician practice patterns existed at our primary care practice. Thus, we retrospectively reviewed medical records to evaluate our physicians' practices for diagnosing uncomplicated UTI in female patients. The objectives of this study were to determine (1) the frequency of appropriate documentation of patient histories and essential physical examination findings, (2) the frequency of urine culture and sensitivity analysis being used as a diagnostic tool, (3) the efficacy of SMX-TMP as empirical treatment in this population of patients, and (4) the frequency of short-course (3-day) antibiotic treatments.


PATIENTS AND METHODS


We selected a cohort of women who were patients of the Mayo Clinic Scottsdale Family Medicine Center in Arizona in 2005. Patients were identified by using the diagnosis of UTI (International Classification of Diseases, Ninth Revision code 599.0). We reviewed medical charts and evaluated the first visit of the year in which a UTI was diagnosed. The visit was included for further analysis if the patient was seen in the physician's office for evaluation of symptomatic complaints. Visits were not included for further analysis if patients were being seen at follow-up for a previous evaluation performed elsewhere, were managed by telephone contact, or had urine testing performed for screening or other asymptomatic purposes. Patients with complicated UTI, as defined by the Institute for Clinical Systems Improvement guidelines, 3 were excluded. Exclusion criteria included age younger than 18 years and older than 65 years, symptoms for more than 7 days, documented or reported fever (temperature ≥38.3°C), nausea or vomiting, concomitant symptoms or diagnosis of vaginitis, reported or reproduced flank pain, a history of 4 UTIs in the past 12 months, or failure of SMX-TMP treatment of a UTI in the preceding 4 weeks. Pregnant women, nursing home residents, and individuals with functional or anatomical abnormality (polycystic renal disease, nephrolithiasis, neurogenic bladder, diabetes mellitus, immunosuppression, indwelling Foley catheter, or recent urinary tract instrumentation) were not included in this study. Therefore, patients who were not excluded on the basis of these criteria were considered to have had an uncomplicated UTI (ie, no signs or symptoms of upper urinary tract disease or markers of medical complications).

Data Collection

History and Physical Examination. We recorded the presence or absence of documentation from our electronic medical record (EMR) regarding potential signs and symptoms of uncomplicated UTI (dysuria, frequency, urgency, and hematuria). We collected data on the exclusion of upper urinary tract disease (patient denied fever and flank pain and the absence of fever or flank tenderness on examination) and vaginitis (absence of vaginal discharge or irritability symptoms and sexually transmitted disease [STD] risks). Whether physicians used an available documentation tool within our EMR for recording UTI patient visits was assessed. We also determined whether care was provided by a resident or an attending physician.

Diagnostic Studies. We collected information about performance and results of urine dipstick analyses, microscopic urinalyses, and urine culture and sensitivity analyses.

Treatment. Data collection on treatment included the antimicrobial prescribed and duration of therapy.

Statistical Analyses

We developed a data collection sheet on which to record information from our medical chart review. Data from these sheets were entered into an Excel database and analyzed using the SAS software package (Version 8.2, SAS Institute Inc, Cary, NC).

We used descriptive statistics to present frequencies, percentages, means, SDs, and ranges. We used the 2-sided χ2 test and the Fisher exact test to compare documentation rates, test utilization, and treatments provided between groups (eg, did vs did not use EMR documentation tool, attending physicians vs residents). We determined the antibiotic sensitivity patterns of Escherichia coli bacteria to SMX-TMP based on available urine culture and sensitivity analyses. A 2-sided 1-sample binomial test was used to compare the observed urine culture sensitivities for patients with uncomplicated UTI in the outpatient setting with rates reported for inpatients. All calculated P values were 2-sided, and P<.05 was considered statistically significant. This study was approved by the Mayo Foundation Institutional Review Board.


RESULTS


We identified 332 female patients who had a UTI diagnosis recorded in 2005. Of these 332 patients, 104 were excluded because they did not have an office visit for evaluation of symptomatic complaints (ie, they had initial evaluations elsewhere, were managed by telephone contact, or had testing performed for screening or other asymptomatic reasons). Thus, 228 patients met inclusion criteria, and their initial UTI visits were evaluated for exclusion criteria to determine whether their infections were uncomplicated or complicated. Sixty-eight patients (30%) had uncomplicated UTI ( Figure 1). The remaining 160 patients (70%) were determined to have complicated UTI and were excluded from further analysis.

The reasons for exclusion are listed in Table 1. The most common reason for exclusion was patient age older than 65 years (106/160 patients [66%]). The mean (SD) age of the 68 patients with an uncomplicated UTI was 41.2 (14.7) years, with a median age of 44.5 years and an interquartile range of 28 to 54 years. Forty-six patients (68%) were seen by a resident and 22 (32%) by an attending physician.

Documentation of History and Physical Examination Findings

Our physicians recorded essential history and examination findings for most patients (Table 2). For instance, the presence or absence of dysuria was documented in 64 (94%) of the 68 medical records. However, absence of vaginal discharge or irritation and absence of STD risks were documented less often (51% and 24%, respectively).


FIGURE 1. Inclusion and exclusion criteria. UA=urinalysis; UTI=urinary tract infection.





Use of our EMR documentation tool improved documentation rates for some aspects of the UTI history. Documentation of absence of vaginal irritation increased from 41% in the 53 encounters in which this tool was not used to 87% in the 15 encounters in which this tool was used ( P=.003). Residents were more likely to use this tool than were attending physicians (28% vs 9%, respectively; P=.12).

Residents documented some of the history and physical examination findings more often than did attending physicians. Residents were more likely to document absence of STD risks (30% vs 9%; P=.07), absence of flank tenderness (87% vs 55%; P=.006), and presence of suprapubic tenderness (96% vs 73%; P=.01).

Documentation of STD risk was affected by patient age. In the 14 patients who were 25 years of age or younger, a history of STD risk was documented in 6 (43%). However, in the 54 patients older than 25 years, this information was documented only in 10 (19%). Although this appears to be a clinically important difference, it was not statistically significant ( P=.08), most likely because of the small number of young patients.

Diagnostic Testing

We analyzed the performance and results of urine dipstick analyses, microscopic urinalyses, and urine culture and sensitivity analyses. In 57 (84%) of 68 patients with uncomplicated UTI, urine dipstick tests were ordered. Of these 57 patients, 41 (72%) had positive results on dipstick analyses for either leukocyte esterase or nitrites. Of the patients with positive results on urine dipstick analyses, 8 (20%) also had formal microscopic urinalyses performed in our laboratory, and 33 (80%) also had a urine culture performed.

Of 68 patients with uncomplicated UTI, 52 (76%) had a culture ordered during their office visits. Thirty-eight (73%) of the 52 cultures grew pathogens; 10 cultures had mixed flora (ie, were contaminated), and 4 had no growth. Thirty-five of the 38 urine cultures that grew pathogens were positive for E coli (ie, 92% of positive cultures had E coli). Nearly all E coli bacteria in our patients with uncomplicated UTI were sensitive to SMX-TMP (33/35 [94% sensitive]). In these patients with uncomplicated UTI, no E coli resistance was found to nitrofurantoin, ciprofloxacin, or cephalexin. E coli was sensitive to ampicillin-amoxicillin in only 25 (71%) of the 35 cultures. No study patient with uncomplicated UTI had treatment changed because of bacterial resistance found on her urine culture.



TABLE 1. Reasons for Exclusion as a Function of Patient Age*
Exclusion criteria
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TABLE 2. Documentation of UTI History and Physical Examination Findings in the 68 Patients With Uncomplicated UTI*
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Antibiotic Treatment

All 68 patients received antibiotic treatment. Twenty-six patients (38%) were prescribed SMX-TMP, and 36 patients received ciprofloxacin (53%). The mean treatment duration was 3.5 days with SMX-TMP and 4.3 days with ciprofloxacin. Sixty-one percent of SMX-TMP and ciprofloxacin prescriptions (38/62) were appropriately provided for 3 days. A similar proportion of attending physicians and residents prescribed the recommended 3-day course of antibiotics (13/22 [59%] and 26/46 [57%], respectively). There was a statistically significant difference between residents and attending physicians in the type of antibiotic used. Attending physicians prescribed ciprofloxacin for most of the patients they treated (14 [64%]) of the 22 prescriptions they wrote), whereas residents prescribed either SMZ-TMP or ciprofloxacin with equal frequency (22 [48%] of the prescriptions for each antibiotic) ( P=.01).

Comparing Outpatient to Inpatient Urine Culture and Sensitivity Patterns

We determined that urine culture sensitivity patterns for uncomplicated UTI in outpatients were significantly different from those of inpatients. E coli bacteria were sensitive to SMX-TMP in 94% of outpatient cultures, whereas they were sensitive in only 76% of inpatient cultures ( P=.01). E coli was also significantly more sensitive to other antibiotics for outpatient cultures (ciprofloxacin, 100% vs 81%; P=.001; cephalexin, 100% vs 90%; P=.05). Ampicillin-amoxicillin was a poor treatment choice for E coli UTI because of high rates of resistance. Sensitivity patterns between outpatients and inpatients were not significantly different (71% vs 59%; P=.18).


DISCUSSION


Evaluating and treating patients with UTI symptoms is a common situation for primary care physicians. National guidelines have advocated identification of patients with uncomplicated UTI through risk stratification and empirical therapy with SMX-TMP if resistance rates to E coli are low.2,3 Only 30% of our patients had uncomplicated UTI, making their management within clinical guidelines appropriate. However, of those patients with uncomplicated UTI, less than 25% received empirical treatment as suggested. Our patient population is older, with many having complicating medical problems. Most patients in our practice require office-based evaluation and confirmation of effectiveness of the chosen antibiotic based on urine culture and sensitivity results.

For patients with uncomplicated UTI, our documentation of essential history and physical examination findings appeared adequate. For example, the documentation rates of dysuria and frequency symptoms were good. Residents performed slightly better in some aspects of providing documentation in patient medical records compared with attending physicians; those using our EMR documentation tool performed best. We suggest use of a prompted or formatted guide for medical record documentation or dictation.

Consistent with physician behaviors seen in prior studies,5- 7 our attending physicians were not judicious in ordering urine dipstick analyses, formal urine analyses, or urine cultures. Many dipstick tests were ordered for patients who, based on history and examination, already had a 90% probability of UTI. 5 Despite the high probability of disease evident from positive results on urine dipstick testing, physicians frequently ordered urine culture and sensitivity testing. Furthermore, despite the associated cost, time, and effort, urine culture results did not necessitate change in treatment for any of our patients with uncomplicated UTI.

Treatment with SMX-TMP was not provided for most of our patients even though this has been recommended as the first-line antimicrobial agent by multiple guidelines. For example, the Infectious Diseases Society of America recommends that SMX-TMP is the treatment of choice in areas where the rate of E coli sensitivity is 80% or greater.2 Our results were similar to those of McEwen et al, 7 who reported that 37% of physicians prescribe SMX-TMP for uncomplicated UTI. We not only underprescribed SMX-TMP but also overprescribed fluoroquinolones. This was especially true among our attending physicians.

Our prescribed duration of therapy was often longer than the recommended 3 days. Of the 62 patients treated with SMX-TMP or ciprofloxacin, 24 (39%) were given antibiotic courses for more than 3 days. Kahan et al 11 reported that, even when physicians choose an appropriate antibiotic, duration of therapy was incorrect a vast majority of the time.

Physicians may be using sensitivity data from their hospitalized patients to guide empirical treatment of their outpatients with UTI. Although we have seen increasing resistance of E coli to SMX-TMP in the inpatient setting, our findings in the outpatient setting for uncomplicated UTI were significantly different. It has been recommended that physicians monitor resistance patterns in their own patient populations to determine whether SMX-TMP is an appropriate choice in their setting. 8,12

Simple changes in our practice environment may decrease costs and simplify care. Having the ability to order a formal urinalysis with completion of culture only when the number of epithelial cells seen on microscopy is small would be helpful (ie, a urinalysis with reflex culture). Eleven (21%) of 52 cultures in this low-risk patient group had mixed flora, indicating contamination.

Limitations

Our physicians ordered urine cultures frequently and did not prescribe SMX-TMP appropriately. These behaviors may be explained by the fact that our patient population is older and medically complicated. It appears that we often treat patients with uncomplicated UTI in a manner advocated for complicated UTI. Our rate of SMX-TMP use may be artificially low due to the fact that we did not account for the presence of medication allergies, intolerances, or contraindications. We did not account for the effect of patient preferences or past experiences in the decision about treatment options. One hundred percent compliance with all aspects of clinical guidelines may not be a reasonable or even desirable goal.

Some practice guidelines also allow for the use of telephone triage and empirical treatment of uncomplicated UTI without a clinical visit. 3,13 We excluded these interactions from this analysis and believe that this was an infrequent occurrence in our practice.

Future Research

Now that we have determined our baseline behaviors, we plan to provide educational interventions in hopes of seeing changes in our physicians' practice patterns. We hope to be able to decrease the frequency with which urine culture and sensitivity analysis is being used as a diagnostic tool in uncomplicated UTI and increase the frequency of 3-day treatment with SMX-TMP. Also, we plan to evaluate our management of patients older then 65 years as they account for nearly half of our patients with UTI. Determining whether antibiotic resistance on urine culture and sensitivity analysis is a function purely of age or instead is due to the medical complications of a specific patient would be helpful in making decisions about the utility of diagnostic testing.


CONCLUSION


Discrepancies exist between physician practice behaviors and published guidelines. Using these evidence-based algorithms for the diagnosis and management of UTI can be helpful only when one carefully assesses patients for complicating factors. Only 30% of our patients had uncomplicated UTI, making their management within clinical guidelines appropriate. However, of those patients with uncomplicated UTI, less than 25% received empirical treatment as suggested. Urine culture and sensitivity analyses were performed frequently, even in patients who already had positive results on a urine dipstick analysis. Although SMX-TMP is effective, it is underused. We hope to improve adherence to published guidelines through education and practice support. We suggest that medical groups review their own patient populations and practice behaviors through similar quality improvement processes.

REFERENCES

Centers for Disease Control and Prevention, US Department of Health and Human Services. Ambulatory Care Visits to Physician Offices, Hospital Outpatient Departments, and Emergency Departments: United States, 1999-2000. Available at: www.cdc.gov/nchs/data/series/sr_13/sr13_157.pdf. Accessed December 21, 2006.


Warren JW, Abrutyn E, Hebel JR, Johnson JR, Schaeffer AJ, Stamm WE. Guidelines for antimicrobial treatment of uncomplicated acute bacterial cystitis and acute pyelonephritis in women: Infectious Diseases Society of America (IDSA). Clin Infect Dis. 1999;29:745-758.


Kasten MJ, Gravley E, Olson D, et al. ICSI Health Care Guideline: Uncomplicated Urinary Tract Infection in Women. Bloomington, MN: Institute for Clinical Systems Improvement. Available from: www.icsi.org/knowledge/detail.asp?catID=29&itemID=200 . Accessed December 21, 2006.


Mehnert-Kay SA. Diagnosis and management of uncomplicated urinary tract infections. Am Fam Physician. 2005;72:451-456.


Bent S, Nallamothu BK, Simel DL, Fihn SD, Saint S. Does this woman have an acute uncomplicated urinary tract infection? JAMA. 2002;287:2701-2710.


Wigton RS, Longenecker JC, Bryan TJ, Parenti C, Flash SD, Tape TG. Variation by specialty in the treatment of urinary tract infection in women. J Gen Intern Med. 1999;14:491-494.


McEwen LN, Farjo R, Foxman B. Antibiotic prescribing for cystitis: how well does it match published guidelines? Ann Epidemiol. 2003;13:479-483.


Raz R, Chazan B, Kennes Y, et al, Israeli Urinary Tract Infection Group. Empiric use of trimethoprim-sulfamethoxazole (TMP-SMX) in the treatment of women with uncomplicated urinary tract infections, in a geographical area with high prevalence of TMP-SMX-resistant uropathogens. Clin Infect Dis. 2002 May 1;34:1165-1169. Epub 2002 Apr 4.


Kahan NR, Friedman NL, Lomnicky Y, et al. Physician specialty and adherence to guidelines for the treatment of unsubstantiated uncomplicated urinary tract infection among women. Pharmacoepidemiol Drug Saf. 2005;14:357-361.


Kahan NR, Chinitz DP, Waitman DA, Kahan E. Empiric treatment of uncomplicated UTI in women: wasting money when more is not better. J Clin Pharmacol Ther. 2004;29:437-441.


Kahan NR, Chinitz DP, Kahan E. Physician adherence to recommendations for duration of empiric antibiotic treatment for uncomplicated urinary tract infection in women: a national drug utilization analysis. Pharmacoepidemiol Drug Saf. 2004;13:239-242.


Ansbach RK, Dybus K, Bergeson R. Uncomplicated E. coli urinary tract infection in college women: a follow-up study of E. coli sensitivities to commonly prescribed antibiotics. J Am Coll Health. 2005;54:81-84.


Saint S, Scholes D, Fihn SD, Farrell RG, Stamm WE. The effectiveness of a clinical practice guideline for the management of uncomplicated urinary tract infection in women. Am J Med. 1999;106:636-641.

ARE YOU STILL USING ATENOLOL FOR HTN?.HOPE NOT

ORIGINALLY PUT IN THIS BLOG IN APRIL,2006

At 6:49 PM, North Shore Boston MD Free Forum said...
DID YOU KNOW THIS ? about ATENOLOL :

CAFE study in Circulation MARCH 7 2006 confirmed what LIFE study and ASCOT study had already shown. ATENOLOL is only slightly better than a placebo in cardiovascular outcome and lives saved. !!!!!!!

Atenolol decreases the BP but it does not decrease cardiovascular events

It does decrease brachial blood pressure but not intra-aortic blood pressure.

Vital organs including brain, heart and kidney respond to the intra-aortic BP and not brachial BP !!!!

It is now indisputable. Let me say this again ATENOLOL does not improve the outcome though it may improve the brachial BP.

Read on

ASCOT study- an Anglo-Scandinavian study of 20,000 people- was stopped prematurely because of the higher mortality in the ATENOLOL branch of the study- LANCET- 2005, 366: 895-906

Read on

All BP medications except ATENOLOL decreases brachial BP as much as intra-aortic BP. But not ATENOLOL. So this is not true of all beta blockers it is not a class action

In fact we think: if we knew , what we now know about ATENOLOL. it would not have been cleared for BP control at all. (the LANCET FEB 25, 2006 )

Mind you every thing I said above is for ATENOLOL and hypertension. ATENOLOL is still a good cardiac specific anti anginal drug.

Bottom line ATENOLOL is not a good BP medication at all though it decreases brachial BP( oxymoron) it does not save any lives.

This is specific comment on ATENOLOL ,not for all beta blockers. It still is a good cardiac medication. My challenge to you: how many of your patients are on ATENOLOL for hypertension, are you on it yourselves ?

KK

VITAMIN D AND YOU- what you may not know

One of my patients had 1,25 vitamin D ordered by one of our respected specialists whom I both like and respect. Let me make use of this opportunity to share with you what I know about vitamin D.

There is no place to order vitamin D -1,25 level. The test to order no matter what you are looking for high or low is--- 25 OH vitamin D. WHY?

What is not commonly known is even in renal failure we should not order 1,25 OH Vitamin D level, WHY NOT ?

In vitamin D deficiency -blood 1, 25 D level could be normal, high or low (Dr.Holick,) Why in the world is it high?? Vitamin D deficiency increases PTH level which stimulates 1-25 conversion and the lab report may look normal while the patient is still vitamin D deficient.)

TRIVIA

What is vitamin D 2-? What is vitaminD3- ? for most of us this is all a blurrrrrr..
Vitamin D 2 is from plant source-
Vitamin D 3 is from animal source like fish oils etc.

MORE TRIVIA ABOUT VITAMIN D

Did you know natural milk, mother’s milk or cows milk does not contain vitamin D, even if the mother is not vitamin D deficient !!!!!!!
Therefore the vitamin D is actually added to cows' milk. If babies live on mothers milk alone for too long then.....you fill in the gap yourself.

MORE

Think about nursing home patients or your parents, grand parents exposed to less sunlight than you are. .


When you go to the beach think about this or think about your grand mother sitting in the sun .

Sunscreen shut off UV B (not UV A.) It is UV-B which converts vitamin D on the skin,( UV A does not help with vitamin D synthesis ) MAYO CLINIC PROCEEDINGS p.364 March 2006.

So people using sunscreens on the beach shutting off UV-B may also get less vitamin D conversion in the skin .
Did you know blacks need more vitamin D than fair skinned people in cold climates. Even 50 times more- Melanin is a great sunscreen shutting off UV -B - Makes sense.

DID you know in patients who had gastric surgery or has achlorhydria, TUMS ( Ca CO3) is not a good Calcium source? WHY NOT ?

CACO3 needs gastric HCL for absorption. So in perhaps in old people or people with gastric resection you should use Calcium citrate not CA CO3 for osteoporosis. Is your grand mother on TUMS for osteoporosis, then use this information for her sake.
WHAT IS THE RELATIONSHIP BETWEEN CANCER AND VITAMIN D.?

FACTS- Women living in warmer climates like Atlanta and San Antonio have fewer cancer of the breast than women in northern climates.
People living in warm climates have fewer cancer of the colon.
Dr.William Grant of NASA reported that people who live in sunny climates have lower death rates (once you have cancer) in cancer of breast, colon, prostate ovary, bladder, uterus, esophagus rectum and stomach- New York Times June 17, 2003 section D7
A Scandinavian study linked low levels of Vitamin D with an increased risk of developing cancer of prostate. I do not have this reference in my PDA. In the prostate, Vitamin D hormone is known to be a powerful inhibitor of abnormal cell growth.

These are the facts . Will you extrapolate and say all cancer patients should be getting extra doses of vitamin D ? You decide yourself.
Will you tell patients to get extra sun light without sun screen ?( see what NASA says above) You decide.

SHOULD THEY ALL MOVE TO FLORIDA ????

HOW MUCH VITAMIN D FOR YOU AND YOUR FAMILY AND PATIENTS ?
Michael Hollick in NEJM May 25,2006 p.2287 says " it is generally agreed that 1000 units of vitamin D3 a day is needed....to increase intestinal absorption of calcium and prevention of CANCER" CAN you believe that? Do people know that ? Do MDs know that.
This is different from previous recommendations that stated 800 units a day is enough.

I hope you can use this information to help your family members and patients and those you with prostate cancer and other cancers.

LOVENOX and risk of BLEEDING

LEARN FROM SOMEONE ELSE'S MISTAKE PLEASE.

I had a recent case of intracerebal bleed on a patient I took care of in the North Shore. I go to 3-4 hospitals in greater Boston area and the name of the hospital is not important.
If this happened to me who had been jumping up and down on this particular subject, shame on me. So I will share the incidence with the rest of the world.

76 yrs old lady with mild disorientation had normal CT scan head in June. Because of atrial fibrillation she had been on warfarin and Lovenox. She came to us on Lovenox 60 mg bid. We decreased the dose to 40 mgs qd. She weighed, say , 110 lbs.

Her INR ranged between 1.7 and 2.9 most of the time .On two episodes her INR was 4.8, 5.2. She was on daily PT/INR. She had one dose of Vitamin K 5 mgs which improved INR.

She continued to get more and more confused. She had no observed fall or head trauma
Repeat Ct scan head two weeks later showed posterior fossa subdural hematoma.

Looking back her serum creatinine was 1.2 on admission then improved to 0.8 e GFR was 49 initially then 54 and later 60.

My take on this is: Lovenox is risky on patients old people.
Whatever you definition of old is I have no problem with.
Maybe the mechanism is renal insufficiency after all.
All old people have renal insifficiency. No matter what their serum creatinine is.
No matter what the eGFR is they may have renal insifficiency.

Most people do not know eGFR is the GFR of an Ideal American- 5'6" tall weighing 140 lbs. for any particualr age.

The patient in front of you may be 100 lbs , 4'10" or 180 lbs 6 feet tall But the eGFR is the same if they have the same age, sex and race ( white or black). So both serum creatinine and eGFR are misleadingly better than the real renal function .

So I am going to take a position when you are old ? over 60 ? over 70 or whatever you should not use Lovenox at all or use a smaller dose than usual.

The generally accepted Lovenox adjustment of using 30 mgs once a day and no more in renal insufficiency ( defined as GFR less than 30 ml, not eGFR but real GFR) is misleading and does not offer protection in many cases in "old age".

So save some lives please in old age think twice before you use Lovenox.

You would notice I am talking about only Lovenox not all low molecular heparins, as my experience is mostly with Lovenox , by its brand name.

Do not miss the point I am not saying Lovenox is worse than this or that. That is what MDs have to decide themselves. My point is it is not easy to measure Factor Xa or any other labs for Lovenox over dose. Neither serum creatinine nor eGFR gives the real renal function in old people.So we are DOUBLY HANDICAPPED.
YOU DO NOT HAVE TO LEARN THE HARD WAY , LEARN FROM SOME ELSE'S MISTAKE.
Related Thrombosis
General Dosing Guidelines
A. Initial treatment of acute thrombosis:
Enoxaparin 1mg/kg SQ q12h until minimum course of 5 days has been completed and INR is greater than 2.0 (1.5mg/kg q24h may also be used in pts who are not obese [BMI > 27] and who do not have malignancy).
B. Initial anticoagulation in patients with atrial fibrillation, heart valve replacement, LV thrombus, or other cardiovascular indications for anticoagulation:
Enoxaparin 1mg/kg SQ q12h.
C. Bridge therapy during prolonged periods of under anticoagulation:
Enoxaparin 1mg/kg SQ q12h until INR > lower limit of therapeutic range (1.5mg/kg q24h may also be used in patients whose indication for anticoagulation is DVT/PE or other non-cardiovascular indication for anticoagulation, including patients with malignancy).
D. Bridge therapy before and after invasive or dental procedures:
Enoxaparin 1mg/kg SQ q12h initiated when INR <> lower limit of therapeutic range (1.5mg/kg q24h may also be used in patients whose indication for anticoagulation is DVT/PE or other non-cardiovascular indication for anticoagulation, including patients with malignancy).
E. Long term use in place of warfarin:
Enoxaparin 1mg/kg q12h (1.5mg/kg q24h may also be used in patients whose indication for anticoagulation is DVT/PE or other acute non-cardiovascular indication for warfarin, including patients with malignancy).
II. Dosage Adjustments in Obesity
A. Use Total Body Weight (TBW) up to 190kg.
B. If > 190kg:
AntiXa level monitoring available:
Use TBW and adjust dose downward if necessary based on antiXa levels
AntiXa level monitoring NOT available
Use TBW and adjust dose downward if necessary if bleeding occurs
III. Dosing in Renal Impairment
A. If no antiXa monitoring available: Avoid use if CrCl < 30 ml>B. If antiXa monitoring is available, consider the following initial dosing and adjust as necessary based on peak antiXa activity levels:
Clcr > 60: 1mg/kg q12h
Clcr 30-60: 0.85mg/kg q12h
Clcr <> 2.0
Until antiXa level < name="Anchor-Short-37516">IV. Short Term Monitoring Guidelines
A. Platelet count: Every 2 to 3 days during first 14 days of therapy.
B. Peak antiXa activity:
3 to 4 hrs after dose in patients with:
renal impairment (Clcr<> 190kg)
unexpected hemorrhage.
Check after 3rd dose and again if adjustment required.
Goal:
0.5-1.0 U/mL for bid dosing
1.0-2.0 U/mL for qd dosing
C. Trough antiXa activity:
At end of dosing interval
Check before 4th dose and again if adjustment required
Goal: < name="Anchor-Long-23522">V. Long Term Monitoring Guidelines
A. Peak antiXa activity: Check at 7 days, then once monthly.
B. Trough antiXa activity: Check at 7 days, then check once monthly.
C. Scr: Once monthly (routine labs acceptable).
D. Clcr: Calculate monthly (adjust dose as necessary).
E. Patient weight: Check monthly (adjust dose as necessary)
F. Platelets: Once monthly (routine labs acceptable)
G: Hct: Once monthly (routine labs acceptable)
Questions & Comments© 2006, University of Washington Anticoagulation Services.All Rights Reserved.

DEPT OF ERROR

The patient whose hypocalcaemia worsened after prompt
intravenous calcium replacement therapy
Piero Stratta, Giorgio Soragna, Veronica Morellini, Massimo Gai, Daria Motta,Elisa Lazzarich, Maddalena Brustia, Marco Quaglia,Caterina Canavese
LANCET JAN. 21, 2006
As a junior in the emergency department, I saw a 30-year-old man with severe numbness, tingling in the fingers and toes and perioral area, muscle cramps, and tetany; he had chronic hypoparathyroidism, due to thyroidectomy, which was being treated with oral replacement of thyroid hormones, calcium, and vitamin D. He had been unable to take his regular treatment over the past few weeks because of gastroenteritis.

Blood tests showed a low total calcium of 1·125 mmol/L ( ie equal to 4.4 mg/dl in American terms: kk) (free ionised portion 0·51 mmol/L), phosphate 1·8 mmol/L,creatinine 88·4 mol/L, urea 3·57 mmol/L, sodium139 mmol/L, potassium 4·5 mmol/L, blood bicarbonate29 mmol/L, and pH 7·4.

Because of the severe hypocalcaemia, I chose intravenous calcium replacement according to the formula: 1–2 mg/kg per h (body-weight 50 kg) of calcium. Using ampoules of 10 mL10% calcium gluconate, I assumed that each ampoule contained 1 g (1000 mg) of calcium. I diluted the 10 mL ampoule into 500 mL 5% dextrose, calculating that each mL of this solution contained almost 2 mg of calcium(1000 mg in 510 mL=1·96 mg/mL). The infusion was scheduled at 50 mL/h for the next 10 h, delivering 98 mgof calcium per h (1·96 mg/mL at 50 mL/h); this schedule met the requirement of 1–2 mg/kg per h, as the patient weighed 50 kg.

3 h later, my consultant took me to the patient’s bedside; the young man had complained of carpopedal spasm, laryngeal spasm, and bronchospasm, and 1 h earlier he had had other typical signs of hypocal-caemia—namely, a focal seizure, arrhythmia, and prolongation of the Q-T interval. His ionised calcium concentration had decreased further to 0·49 mmol/L.

Unfortunately, my calculation of calcium replacement had been incorrect: the replacement assumed that calcium gluconate was constituted only by elemental calcium; in the formula the replacement therapy is expressed as mg of elemental calcium and not mg of calcium salt. Calcium gluconate is the calcium salt of gluconic acid, and contains only 9 mg/mL elemental calcium (table). Therefore, each ampoule of 10%calcium gluconate contained 1000 mg of calcium gluconate, but only 90 mg of elemental calcium.

100–360 mg of elemental calcium should be given over5–10 min in cases of life-threatening hypocalcaemia(free ionised calcium 0·59 mmol/L), followed by a1–2 mg/kg per h of elemental calcium. This means that one to four 10 mL ampoules of 10% calcium gluconate should have been used in our patient, as this dose raises the concentration of ionised calcium by 0·5 mmol/L. We applied this dosing-schedule to our patient, followed by an infusion of 50 mL (five ampoules) of 10% calcium gluconate diluted in 500 mL 5% dextrose (450 mg elemental calcium); the 550 mL solution contained0·8 mg of elemental calcium per mL of solution.Therefore, an infusion of 100 mL/h provided 80 mg/h of elemental calcium—equivalent to 1·6 mg/h of elemental calcium for each kg of bodyweight. IE: five ampoules in 500 ml to run 100 cc an hour that is how you treat life threatening hypocalcemia- kk- The patient’s condition gradually improved over 24 h.

Of note, calcium chloride salt is second line choice for treatment of hypocalcaemia, unless there is severe alka-losis, as it causes more tissue necrosis if extravasated.

My mistake will haunt me for the rest of my professional life. When replacing electrolytes, it is important to bear in mind the absolute need to understand basic chemistry, calculate replacement in Standard International Units, replace element and not salts, and to refer to the hospital formulary when in doubt. Lancet 2006; 367: 273

Nephrology andTransplantation, Departmentof Nephro-Urology, AmedeoAvogadro University, OspedaleMaggiore della Carità, CorsoMazzini 18, 28100 Novara,Italy (Prof P Stratta,V Morellini MD,E Lazzarich MD,M Brustia MD, M Quaglia MD,C Canavese MD); andDepartment of InternalMedicine, Section ofNephrology, University ofTorino, Molinette Hospital,Corso Bramante 88, 10126Torino (G Soragna MD, M Gai MD,D Motta MD)Correspondence to:Prof P Stratta strattanefro@hotmail.comThe patient whose hypocalcaemia worsened after promptintravenous calcium replacement therapyPiero Stratta, Giorgio Soragna, Veronica Morellini, Massimo Gai, Daria Motta,Elisa Lazzarich, Maddalena Brustia, Marco Quaglia,Caterina Canavese

Calcium salt Formula Molecular Elemental calcium Elemental Calcium weight(Ca2) mg(Ca2) mmol

Calcium gluconate C12H22CaO14430·3890 mg per2·3 mmol per10% injection 10 mL10 mL10 mL ampouleampouleampoule(1000 mg per 10 mL)/ but only 90 mg per ampoule
Calcium chlorideCaCl2110·98270 mg per6·8 mmol per10% anhydrous injection 10 mL 10 mL10 mL ampoule(1000 mg per 10 mL) but
rino, Molinette Hospital,Corso Bramante 88, 10126Torino (G Soragna MD, M Gai MD,D Motta MD)Correspondence to:Prof P Stratta strattanefro@hotmail.com
7:11 AM