Diabetes: Death From A Thousand Cuts (7 Sep, 2010)

The cruel cost of ignoring diabetes: Jane lost an arm and two legs to the disease because, like so many, she didn't take it seriously

Last updated at 10:52 PM on 6th September 2010

Six years ago, Jane Knight was just another of Britain's army of multi-tasking women: a devoted wife and mother who frantically balanced looking after her family, including an autistic son, with her work as a complimentary therapist.

But today, the 47 year-old is a triple amputee, having undergone operations to remove both her legs and one arm. She faces the prospect of losing her remaining arm in the near future.

The cause of such devastating physical disability is not an horrific accident or advanced cancer but a condition that affects more than three million of us: diabetes.

Harsh truth: Jane Knight has lost an arm and both legs because she failed to manage her diabetes when she was younger

Furthermore, as Jane acknowledges, her situation could have been avoided had she done more to keep her blood sugar levels under control.

Her story is a harrowing reality check to those who fail to understand how uncontrolled diabetes can cause wide-ranging health complications ranging from loss of sight, damaged kidneys, heart problems and even amputation.

'Diabetes is a condition that has to be respected otherwise the implications are horrendous,' she says. 'It was only when I became pregnant with my son, almost 20 years after first being diagnosed, that I realised how vital it is to keep the condition under strict control. Unfortunately by then the damage had started.

'I don't want anyone to feel sorry for me. I just want people to learn from my situation. When I hear of teenagers skipping diabetic clinics or adults who think that because they feel all right they can just ignore their condition, I want to scream in frustration. I want them to shout: "Look at me and see what diabetes can do. Is this what you want?"'

Alarmingly, Jane's situation is not unique.

It's thought that there are around a million people with undiagnosed diabetes ignoring warning signs such as wounds that fail to heal and tingling sensations in their limbs. And that's aside from the two million or so who have been diagnosed with the condition.

More...

Heart attack risk of diabetes drug: Experts call for Avandia to be withdrawn

Every week in the UK around 100 diabetics lose a limb because poorly managed diabetes leads to nerve damage, a side-effect known as diabetic neuropathy, and also restricts blood flow to the extremities, making it harder for wounds to heal.

Left untreated, within just weeks even a minor foot injury, such as a blister, can lead to infection and gangrene. In many cases this occurs when sufferers simply don't give the condition enough respect labelled by psychologists as diabetic denial.

'One moment sufferers are living an ordinary life and the next they're being told they have a chronic disease that, if not managed properly, could lead to blindness, amputation and many other horrific complications,' says Dr Brian Karet, Chief medical officer for primary care for Diabetes UK.

'But since it has no immediate physical effect, they go into denial.'

There is, he adds, no set demographic for those who react this way.

'I've seen it in young, old, men, women. I've known company directors who run huge organisations and yet ignore the problems diabetes can cause and carry on eating and drinking too much and putting on weight, while ignoring high blood sugar readings. The complications are catastrophic so it needs to be respected.'

At mercy of diabetes: The 47-year-old is living in fear of losing her other arm

Jane was diagnosed with Type 1 diabetes at the age of ten. She had been feeling unwell for several weeks, lost weight and was lethargic, when a urine test confirmed she was diabetic.

Diabetes develops when the pancreas either stops producing insulin or its output drops sharply. Insulin helps mop up excess sugar in the bloodstream. There are two types of diabetes.

Type 1 - which affects 15 per cent of all diabetics - tends to strike young people and happens when the immune system starts to attack healthy tissues such as the insulin-producing cells in the pancreas.

Type 2 diabetes usually happens in later life and is linked with obesity and a sedentary lifestyle - although spiralling rates of obesity in children have led to an unprecedented explosion in this form of the disease, too.

But regardless of the type, the risks and side-effects of both conditions is exactly the same - which is why they both need close monitoring.

After her diagnosis Jane was immediately referred to the Children's Hospital in Bristol where she spent a week learning about injecting insulin - once a day, every day - and how she and her mother could control her diet through regulating carbohydrate and sugar intake.

'One moment I was just a normal kid who loved sport and going to Brownies. The next I was in hospital practising injections on oranges.'

'When I hear of people skipping diabetic clinics, I want to scream in frustration: "Look at me and see what diabetes can do. Is this what you want?"'

Meanwhile she was supposed to keep an eye on her blood sugar levels by putting a special litmus dipstick in a sample of urine - the resulting colour would tell her how high or low her blood sugar was.

Jane says she tried to eat sensibly and her mother made healthy meals but she found her condition hard to control. Normal blood-sugar readings should be between 4 to 8mmol/l - Jane's regularly hit 20.

'I felt the need to prove myself all the time - that I was normal - so I carried on doing ballet, hiking club and badminton with my friends. The problem was that I didn't want to have hypos - when blood sugar plunges and makes you dizzy.

'As a result, Mum and I agreed that if I was doing something strenuous I'd just eat family-sized bars of chocolate. My blood sugar was sky high as a result but since it didn't cause any immediate symptoms we thought it would be OK. With hindsight that's ridiculous, but there was very little information around in those days.'

In fact, managing diabetes like this can lead to catastrophic long-term damage.

'The bottom line is that sugar is toxic to the lining of the blood vessels,' explains Dr Karet. 'It produces nitrous oxide which creates irregularities in the arteries, roughening them up, which in turn attracts plaque. And this is what blocks the blood flow over a period of years. With less blood to nourish tissues, sores and cuts are hard to heal. Just a minor injury can become seriously infected, even leading to gangrene.'

But Jane was blissfully unaware of this. When she finished teacher training college she decided to open a boutique.

She thought running her own business would make it easier to work around her condition but relied on on sugary drinks to keep going.

'I was supposed to keep a record of the results of every blood-sugar test I did so I could show the hospital.

'But often I'd forget to do this and I'd sort of guess them and write them down the night before an appointment. I was young and naive - there's no other excuse for it.'

At 29, Jane met Ian, an IT consultant, on a blind date and became pregnant with Thomas, now 17.

It was when she started on a family, that Jane finally realised the gravity of her condition. Doctors warned that diabetics have to extra vigilant during pregnancy - and for the first time Jane took heed.

Too little, too late: Jane began to take her condition seriously after meeting her husband Ian and starting a family but the damage to her health was already done

From then onwards, and throughout pregnancy with her second son, Alex, now 15, Jane started to monitor diabetes religiously. She went for check ups at a diabetic clinic every six months, and cut down on sugary drinks and chocolates. But it was too little, too late.

In August 2004, Jane noticed a small cut on the ball of her right foot. But because of the damage already done the nerves, she hadn't felt it at first.

To compound the problem, years of diabetes and high blood sugar levels had damaged her blood vessels restricting circulation, which meant the cut would not heal.

'I started to get shooting pains in my right leg. I went to my GP who, because of my condition, referred me vascular surgeon, to check blood flow in my arteries.

'Unfortunately he didn't get that far. They couldn't find a proper pulse in my leg. Then they saw that my little toe was turning black.

'I had thought it was just bruised - but actually it was gangrenous and the tissues were dead. I was then told it would have to be removed,' she remembers.

'I was shocked. I knew that this was a risk of diabetes but I thought it was extremely rare. Of course, it was horrific being told I was going to lose a toe but I had to come to terms with it. I rationalised that at least it was only a toe.

And it was a warning; this was what could happen if I didn't look after myself so I resolved to try even harder to keep up the tight control.'

But this warning came too late. By now the infection was spreading into Jane's foot and up her leg.

'After the toe was removed I developed a big blister on my foot that wouldn't heal. It was agony. I went back and forth to the hospital but there was nothing they could do; the tissue was on its way to turning gangrenous. My consultant told me I would lose my leg.

'Being diabetic comes with a chance of staying healthy. But I'm afraid I learned that lesson too late'

'You'd think I'd have been screaming hysterically but I wasn't. I simply wanted this gut-wrenching pain to stop. I didn't start asking myself what if my control had been better. I had horrific surgery to face and that was all I could think about.'

Surgeons removed the leg up to the knee, and Jane was in hospital for five days. Six weeks later she received a prosthesis, slowly learning how to walk again. Family and friends rallied round to help with her children while Jane continued to meticulously monitor her condition.

Then, two years later, in early 2006 she noticed that her left foot had started to feel numb while her podiatrist noticed a black blotch the size of a 10p piece.

In view of her history, she was referred back to surgeon David Mitchell who broke the news that only amputating my leg could stop the gangrene.

'Ian and my friends were fantastic, and I really pushed myself to do what I could in a wheelchair. Though sometimes I'd find it hard to put on a brave face. I remember going to the beach with the children and having to sit on the promenade in my chair while they scampered across the sand. I so wanted to be with them.'

Carefree: Ignoring her condition when she was young cost her limbs

And there were more challenges ahead. A few months later her kidneys started to fail and she had a kidney transplant last February.

Persistently raised blood-sugar levels can cause damage in the tiny blood vessels, stopping them filtering out toxins. Then, about a year ago - Jane's worst nightmare came about.

She suffered a cat scratch that would not heal on her right hand, despite countless antibiotics. Slowly, the infection spread up her arm and another amputation was required.

'This time it was so much worse than my legs. This was my writing hand. And I loved to paint, sew, play the piano.

'That familiar tingling and numbness has now started in my left hand and my eyesight is also diminishing.

'I know that sometime in the next year I'll lose my hand and that frightens the hell out of me. I'm trying to mentally prepare myself for that. Of losing all my limbs.

'But how do you psyche yourself up for that? I have been controlling to the point of obsessive about my diabetes. If I have a bar of chocolate once a year then that's a splurge for me. But sadly it's not enough to halt the damage.

'People ask how on earth I go on, and the answer is that I simply don't know. In a strange way the demands of being a mother and the fact my boys still need me, in what ever way I can manage, makes a difference.'

Carers help her dress and shower and she has prosthetic aids for her arm to help her do normal things.

'Of course I do think "why me", though in practical terms I know why. Getting Type 1 diabetes was something that happened to me and I had no control over that. But I know now - to my eternal regret - that I shouldn't have waited so long to rein in my diabetes and to take such hard line control. And that tears me up.

'Being diabetic comes with a chance of staying healthy. But I'm afraid I learned that lesson too late.'

Posted by: PV Mayer at 06:00 am 0 comments - Add a Comment

Collagen from Tobacco Plants (3 Sep, 2010)

Put that in your pipe and smoke it! Brilliant work to find a healthy use for the tobacco plant.

CollPlant's Human Collagen Grown From Tobacco One Step Closer to Dressing Your Wounds

Filed under: Medicine , Surgery

The FDA ruled recently that CollPlant's Vergenix product, human recombinant collagen grown from genetically modified tobacco plants, will be treated as a device as opposed to a pharmaceutical. This will make the approval process easier for CollPlant and get them to market quicker.

We reported on CollPlant's collagen expressing tobacco back in 2006 and Vergenix is the company's flagship product. Vegenix will be used as a dressing for acute and chronic wounds to facilitate healing and act as a scaffold for fibroblasts and epithelial cells to bridge wounds.

From the company's website:

Vergenix™ Wound Dressing is an advanced wound care device indicated for the treatment of acute and chronic wounds. Based on Collage rh™ collagen, Vergenix™ Wound Dressing is composed of pure recombinant human collagen type I produced in transgenic tobacco plants. The entire manufacturing process involves no animal-derived or human-derived materials. Therefore, Vergenix™ offers a non-allergenic and a pathogen-free scaffold for a safe and physiologically relevant environment. Vergenix™ Wound Dressing is an excellent choice for safe and successful wound management.

Video and links below the fold:

Limb Salvage in Brazil (30 Aug, 2010)

Research

The effectiveness of educational practice in diabetic foot: a view from Brazil

Maria I Anselmo , Marcia Nery and Maria CR Parisi

Endocrinology Department, Medical School of the State University of Sao Paulo, Sao Paulo, Brazil

author email corresponding author email

Diabetology & Metabolic Syndrome 2010, 2:45doi:10.1186/1758-5996-2-45

The electronic version of this article is the complete one and can be found online at:http://www.dmsjournal.com/content/2/1/45

Received:	19 October 2009
Accepted:	29 June 2010
Published:	29 June 2010

© 2010 Anselmo et al; licensee BioMed Central Ltd.
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

The aim of the present study was to evaluate the prevention and self-inspection behavior of diabetic subjects with foot at ulcer risk, no previous episode, who participated in the routine visits and standardized education provided by the service and who received prescribed footwear. This evaluation was carried out using a questionnaire scoring from 0-10 (high scores reflect worse practice compliance).

Results

60 patients were studied (30 of each sex); mean age was 62 years, mean duration of the disease was 17 years. As for compliance, 90% showed a total score ≤5, only 8.7% regularly wore the footwear supplied; self foot inspection 65%, 28,3% with additional familiar inspection; creaming 77%; proper washing and drying 88%; proper cutting of toe nails 83%; no cuticle cutting 83%; routine shoe inspection 77%; no use of pumice stones or similar abrasive 70%; no barefoot walking 95%.

Conclusion

the planned and multidisciplinary educational approach enabled high compliance of the ulcer prevention care needed in diabetic patients at risk for complications. In contrast, compliance observed for the use of footwear provided was extremely low, demonstrating that the issue of its acceptability should be further and carefully addressed. In countries of such vast dimensions as Brazil multidisciplinary educational approaches can and should be performed by the services providing care for patients with foot at risk for complications according to the reality of local scenarios. Furthermore, every educational program should assess the learning, results obtained and efficacy in the target population by use of an adequate evaluation system.

Background

The presence of foot ulcerations in diabetic individuals at risk for complications is a frequent event, with an estimated 15% of all diabetic individuals experiencing an episode of ulceration at some point during their life. Although most of the ulcerations heal, 70% of the cases recur, frequently progressing to unavoidable limb amputation. Several factors are involved in the development of this process which include Peripheral Neuropathy (PN), Peripheral Vascular Disease (PVD), limited joint mobility and repeated trauma from abnormal load distribution on the foot [1,2]. However, this unfavorable progression can be modified provided effective preventive measures are adopted such as adequate guidance regarding: 1- lack of sensitivity and/or presence of peripheral vascular disease and its implications, 2- hygiene and moisturizing practices, 3- use of adequate footwear (when indicated), 4- mandatory daily self-care (self-examination).

These guidelines should be extended to family members and caregivers as many diabetic patients at risk for complications such as obesity are frequently impaired for fulfilling self-examination.

Therefore, preventive and care practices should provide guidance on the correct way to wash, dry and moisturize the feet as well as on how to cut nails and not trim cuticles, or use pumice stones and similar abrasive objects, use appropriate footwear, perform regular foot and footwear inspection and never walk barefoot [3-5].

The aim of the present study was to evaluate the efficacy of an educational practice routinely used at the service and developed to guide diabetic patients at risk for complications.

Patients and Methods

This was a cross sectional study. Sixty consecutive outpatients under treatment at the service and who participated in all routine care and educational guidance, classified according to the criteria from the International Working Group on Diabetic Foot Classification System [6] were studied.

Target population was followed-up for at least two years, had participated in the complete treatment program and for longer than one year in the educational program, besides periodically attending medical visits.

Presence of Neuropathy, Peripheral Vascular Disease and feet deformities were specifically assessed. Neuropathy diagnosis was determined using vibration perception (128 Hz tuning fork) at two sites (hallux pulp and malleolus), point pressure (Semmes-Weinstein 10 g monofilament) at seven sites, and ankle reflexes [6]. Arterial blood supply to the foot was determined by palpation of the dorsalis and posterior tibial foot pulses. For diminished or impalpable pulses ankle brachial pressure index (ABPI) was performed. The presence of callosities, toe deformities (i.e. claw, hallux valgus) or other signs of plantar overload were considered risk deformities.

The full program comprises three steps: 1- Medical visit and examination with diagnosis and detailed explanation of the disease, risk of ulcer progression, risk of amputation and footwear prescription (when indicated); 2- individual visit with a nursing professional directed towards general preventive care and review of the medical prescriptions (15 minutes long in average); 3- educational group, set up by the nursing team, directed to patients and family members and/or caregivers (with the objective of reinforcing self-examination instructions and in average 45 minutes long).

In order to assess the efficacy of the program, daily routine of foot self-examination was analyzed using a simple 10-item questionnaire in which the following parameters where assessed: self foot inspection, additional foot inspection performed by family member, adequate washing and drying, creaming, toe-nail and cuticle cutting, use of proper footwear, routine shoe inspection, no use of pumice stones or similar abrasive objects, no barefoot walking. Each question was awarded a "0/1" score according to the reply, where "0" meant a correct procedure and "1", inadequate. Each patient had a final 0-10 score for the questionnaire, where high scores represented an increased number of inadequate daily practices.

Statistical analysis was performed using SAS statistical software (SAS Institute Inc., Cary, NC) and a p value of 0.05 was considered statistically significant.

Results

Of the 60 studied patients, 30 were male, 30 female. Mean age was 62 years; mean duration of the disease was 17 years (baseline characteristics of studied subjects - Table 1).

Table 1. Baseline characteristics of studied subjects

Patients' performance was: 77% adequate moisturizing, 88% proper washing and drying, 83% proper toe-nail cutting, 83% no cuticle trimming, 77% routine shoe inspection, 70% no use of pumice stones or similar abrasive objects, 95% no barefoot walking, but only 5 patients (8.7%) regularly wore the provided footwear.

There were no score differences observed among the sexes (Table 2). Until the conclusion of this paper, there was no ulcer in the studied population.

Table 2. Patient Score Distribution by Sex

Discussion

The results obtained demonstrate that the multidisciplinary educational program conducted led to constructive attitudes in self-examination. This was previously described by other groups which observed that well-integrated multidisciplinary teams are associated with better clinical outcome [7-10].

It was a striking surprise to verify that 90% of the patients performed all suggested measures; and also that less than 10% of the patients made use of the provided footwear. Although this study was not designed to evaluate compliance of footwear use the finding is important and similar to results published by other authors from reference centers of great expertise in the field [11].

Unfortunately, our evaluation did not focus on questions regarding the poor compliance in use of the footwear. However, critically analyzing the prescribed footwear, which was custom made according to established standards for safe and adequate footwear [12], it was observed that they were far from attractive. Probably the esthetic aspect played a relevant role in the lack of compliance, as has previously been observed [13,14].

In 1994, one of the first studies to evaluate footwear use in patients with severe neuropathy and history of foot ulcerations concluded that differences in age, perception of foot abnormalities and health status, as well as other distressing medical conditions (i.e. renal replacement therapy, previous minor amputations), in addition to cosmetic reasons, may affect the patients' compliance [15].

The esthetic aspect seems to be so important that 10 years later an Editorial states: "Whereas bad shoes cause ulcers and "ugly" shoes are likely to remain in the closet, a major effort is required to demonstrate that the good shoes do actually benefit our high-risk patients"[16].

Another possible reason for such low compliance may be related to what extent the multidisciplinary team routinely and effectively practices footwear prescription. Footwear prescription for diabetic patients at risk for complications is a controversial topic where even the proposed guidelines often leave gaps not addressed. Depending on the healthcare service, most of what is prescribed is based on empirical opinions [17,18].

It therefore seems appropriate, under such considerations, and as per Reiber et al [19], to defend those healthcare professionals should guide patients on identifying footwear characteristics and on choosing footwear adequately. Instruction on footwear characteristics does in fact provide significant information about foot protection and increase in ulceration risk, better enabling patients to choose from available footwear and also recognizing hazardous footwear.

Careful review of the footwear provided at our service and further new analysis of its acceptability are most required.

Finally, we believe that it would be interesting to report this local experience considering that in Brazil educational initiatives involving diabetic patients at risk for complications are still limited. The continental dimensions of our country and social-economic differences among the regions cannot be forgotten. This experience is feasible at centers where family healthcare programs have not yet been implemented as both medical and nursing professionals provide services at any center from the National Health System (SUS-Brazil). In this context, it is our belief that every educational program should be carried out with systematic evaluation of the learning process, results and efficacy in the target population.

Conclusion

A planned and multidisciplinary educational approach enabled high compliance of ulcer prevention care needed in patients at risk for diabetic foot complications. However, compliance for use of provided footwear was extremely low and for reasons only partially understood. Careful review of the footwear provided at our service and further new analysis of its acceptability are most required.

In countries of such vast dimensions as Brazil multidisciplinary educational approaches can and should be performed by the services providing care for diabetic patients at risk for complications, respecting the reality of local scenarios. Furthermore, every educational program should assess the learning, results and efficacy in the target population with an adequate evaluation system.

Competing interests

The authors declare that they have no competing interests.

Authors' contributions

MIA applied the questionnaires used in this paper, collected the used data and participated in the results analyses. MN participated in the design of the study and participated in the drafted the manuscript. MCRP conceived of the study, participated in its coordination and participated in the drafted the manuscript. All authors read and approved the final manuscript.

Acknowledgements

The authors would like to thank to the Endocrinology Department, Medical School of the State University of Sao Paulo, Sao Paulo, Brazil who supported this research.

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Posted by: PV Mayer at 10:37 am 0 comments - Add a Comment Category: Limb Salvage Teams

Ontario Ramping Up Wound Care in Community (30 Aug, 2010)

A great first step towards treating diabetic foot disease.

Article

Nurse Debrah Dell'Angelo changes a dressing for Rick Carroll as he recovered at home recently from a toe amputation and diabetes complications. Carroll is among the patients involved in testing a new model of home care that proponents say will save money while improving home care.

CARLOS OSORIO/TORONTO STAR

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Theresa BoyleHealth Reporter

Malton resident Rick Carroll can’t even venture a guess at the number of at-home nursing visits he’s received over the last 18 months.

“Initially they came every day. Now it’s twice a week,” says the 63-year-old diabetic, whose left foot is still mending after the big toe was amputated in January last year. Visiting nurses change the dressings on his wound and remove dead tissue.

Poor circulation and nerve damage, not uncommon for those with diabetes, also resulted in Carroll’s right leg being amputated below the knee five years ago.

Patients like Carroll are major consumers of health-care resources. The annual bill for treating venous leg ulcers and diabetic foot ulcers in Ontario is $511 million, according to a 2007 study in the journal Wound Care Canada.

“The government has spent more on me in the last few years than it did in the previous 50 years combined,” Carroll acknowledges.

But budget pressures and the exploding diabetes epidemic are forcing Ontario health-care providers to rethink the way these services are provided. There is a growing realization that patients like Carroll could be better served at a lower price, by coordinating services and paying for products that cost more upfront but help speed healing.

The journal study pegged possible savings from improved treatment practices in Ontario at $338 million annually, or a whopping 66 per cent of current spending.

At the same time, the quality of care could be vastly improved. The study suggests patients could experience 33 per cent to 57 per cent fewer infections, fewer lower extremity amputations, increased healing and improved quality of life.

A more conservative savings estimate of $50 million per year was offered earlier this year in a joint report from the Ontario Association of Community Care Access Centres, the Ontario Hospital Association and the Ontario Federation of Community Mental Health and Addiction Programs.

Leading the way in overhauling wound-care treatment is the Central West Community Care Access Centre, one of 14 such organizations in the province that connect patients with community health services.

It began putting theory to practice in April by launching a project in the western GTA aimed at improving care while saving money, with the help of the University of Toronto’s Rotman School of Management.

Dr. Brian Golden, chair of Rotman’s health sector strategy, says the traditional way of offering this kind of home care has served neither patients nor taxpayers well.

“The experience is not as good as it should be,” he said at a breakfast speech at the university, hosted by Longwoods Publishing, in June.

Such care has typically been uncoordinated because it has involved multiple community health-care agencies and multiple health professionals, Golden said. One agency sends a nurse to a patient’s home, another dispatches a personal support worker and another an occupational therapist.

Many of the nurses involved are generalists, not specialists in diabetic foot ulcers, Golden noted. Best practices aren’t always followed. For example, using a certain sandal can take the pressure off wounds, speed up healing and reduce the number of nursing visits needed, but many care providers aren’t aware of that.

More upfront investment can save money long term, Golden said. For instance, “We can invest in more expensive dressings that require only two visits per week to the home and fewer nursing visits (overall).”

He pointed out that neither community care access centres nor the province’s assistive devices program cover the cost of air casts, which can also speed healing of foot wounds. Air casts are $250 boots that encase an injured foot inside an air cushion, in turn encased by a hard shell.

“The idea for this project is to heal the wound faster, quicker, better, and to make sure that everybody in the circle of care is in the communications loop and knows what they are doing so that you look at the person as a whole being,” said Margaret Mottershead, CEO of the Ontario Association of Community Care Access Centres.

To this end, a single agency will be responsible for all aspects of a patient’s care — not only healing the wound, but addressing the causes. In the case of a patient with diabetes, a dietitian could be sent to the home as well as a nurse who specializes in wound care and a chiropodist who specializes in foot care.

“We have to start seeing the full person — from the foot ulcer, to the diabetic, to the full person,” Golden said.

As a result, people like Carroll might even be spared the trauma of amputation.

“If they can save money and spare people from going through what I went through, then they should do it,” he says.

Posted by: PV Mayer at 07:34 am 0 comments - Add a Comment

Obesity is a Deadly Disease (30 Aug, 2010)

We need to start early on in our fight against diabetes.

Obese Men at Age 20 Years Double Death Risk

Men who enter adult life obese face a life-long doubling of the risk of dying prematurely, new research has found. The chance of dying early increased by 10% for each BMI point above the threshold for a healthy weight and this persisted throughout life, with the obese dying about eight years earlier than the non-obese....

In a new study researchers tracked more than 5,000 military conscripts starting at the age of 20 up to the age of 80. They found that at any given age, an obese man was twice as likely to die as a man who was not obese and that obesity at age 20 years had a constant effect on death up to 60 years later. They also found that the chance of dying early increased by 10% for each BMI point above the threshold for a healthy weight and that this persisted throughout life, with the obese dying about eight years earlier than the non-obese.

"As the obesity epidemic is still progressing rapidly, especially among children and adolescents, it is important to find out if obesity in early adulthood has lifelong mortality effects," said the study's leader, Esther Zimmermann, a researcher at the Institute of Preventive Medicine, Copenhagen University Hospital and the Institute of Biomedical Sciences at University of Copenhagen in Denmark. "Previous studies have investigated obesity and mortality in middle-aged populations, which only tells us about the detrimental effects of obesity in middle age. Our study sheds light on how obesity at age 20 years affects obesity throughout adult life. It is the first study with such a long follow-up time and thus the first study to investigate the lifelong effect."

In the study, the researchers compared mortality in a sample of 1,930 obese male military conscripts with that in a random sample of 3,601 non-obese males. Body mass index (BMI) was measured at the average ages of 20, 35 and 46 years, and the researchers investigated that in relation to death in the next follow-up period. A total of 1,191 men had died during the follow-up period of up to 60 years. The results were adjusted to eliminate any influence on the findings from year of birth, education and smoking.

"At age 70 years, 70% of the men in the comparison group and 50% of those in the obese group were still alive and we estimated that from middle age, the obese were likely to die eight years earlier than those in the comparison group," Zimmermann said. The researchers also investigated the effect of the broad BMI range on mortality from the age of 20 and found the lowest death risk in the men who had a BMI of 25. Underweight men had a slightly elevated risk, and the risk of early death crept up steadily by 10% for each BMI unit above 25 for those men who were overweight or obese.

Zimmermann said it is unclear whether it is being obese at age 20 that conferred the men's increased death risk or whether the lifelong effect is due to obesity often being a lifelong condition for them. She said more research is warranted to find the answer to that question.

"More than 70% of the obese young men were still obese at the follow-up examinations, whereas only 4% of the men in comparison group developed obesity during follow-up. Obesity seems to be a persistent condition and it appears that if it has not occurred in men by the age of 20, the chance of it developing later are quite low. The persistence of obesity may partly explain why obesity at 20 years of age has lifelong mortality effects, but it needs to be proven whether that is the full explanation or whether, by itself, being obese at an early age increases the risk of early death," she said.

Zimmermann said her group plans to study the patterns of ill health that caused the early death in the obese group, in order to determine whether the same diseases are causing death at different ages. Such information may shed some light on the mechanisms through which obesity works at different ages, she said.

Presented at the International Congress on Obesity in Stockholm, July 2010

Posted by: PV Mayer at 06:44 am 0 comments - Add a Comment

Green Vegetables Cut Diabetes Risk (30 Aug, 2010)

More evidence that our mothers were right-veggies are good for you!

Green Leafy Vegetables Cuts The Risk of Diabetes by 14%

A British meta-analysis found that increasing the daily intake of green leafy vegetables can reduce the risk of Type 2 diabetes…

According to Patrice Carter, a PhD student at the University of Leicester, consuming 1.35 servings of these vegetables per day was associated with a 14% reduction in risk compared with consuming only 0.2 servings (HR 0.86, 95% CI 0.77 to 0.96, P=0.01).
A trend also was seen suggesting a benefit for consuming greater quantities of fruits and vegetables overall, although this was not statistically significant.
The incidence of Type 2 diabetes has been rising dramatically during the past two decades, with diet being a major contributor, but evidence thus far has been conflicting as to whether increasing consumption of fruit and vegetables would have an impact.

To sort through this evidence, Carter and colleagues conducted a systematic review and meta-analysis, identifying six studies that met their inclusion criteria.

The studies included a combined population of 223,512 subjects who were 30 to 74 years of age. Length of the studies ranged from 4.6 to 23 years.

Comparisons of the lowest versus highest intake of fruit and vegetables found these hazard ratios for Type 2 diabetes:

Vegetables only, HR 0.91 (95% CI 0.76 to 1.09, P=0.32)
Fruit only, HR 0.93 (95% CI 0.83 to 1.01, P=0.27)
Fruit and vegetables overall, HR 1 (95% CI 0.92 to 1.09, P=0.97)

The researchers found considerable heterogeneity between the studies, so they carried out a sensitivity analysis, examining multiple factors that could be sources of bias.

They found no influence of study location, despite one study having been conducted in China, where the traditional diet is high in fruit and vegetables. Heterogeneity also could result from differences in food group classifications, with some studies defining green leafy vegetables as lettuce, spinach, and kale, while others included Chinese greens.

The researchers pointed out that the food group of green leafy vegetables actually includes brassicas, such as cabbage and cauliflower, Compositae such as lettuce, and herbs such as parsley and dill.

They listed possible reasons why fruit and vegetables might help prevent chronic disease, among them the antioxidant effects of beta-carotene, vitamin C, and polyphenols, as well as the magnesium and polyunsaturated fatty acid content.

However, they noted that the benefits of these compounds are likely to result from consumption in foods rather than as dietary supplements, with disappointing results having been seen in earlier trials of supplements for disease prevention.

The importance of overall nutrition was echoed in an editorial by Jim Mann, PhD, of the University of Otago, in Dunedin, New Zealand, and Dagfinn Aune, BSc, of Imperial College in London, which accompanied the meta-analysis.

"Although some studies have shown associations between individual vegetables and fruits and coronary heart disease, stroke, and some cancers (for example, allium vegetables and stomach and colorectal cancer, tomatoes and prostate cancer), most current recommendations focus on food groups as a whole rather than magic bullets," they wrote.

The editorialists noted that although it may be "reasonable" to draw attention to the potential benefits of green leafy vegetables, the more important message is for increasing fruit and vegetable intake overall.

"The findings are also a useful reminder to clinicians that giving dietary advice may be just as beneficial, if not more so, than prescribing drugs to patients at risk of chronic disease," wrote Mann and Aune.

Practice Pearls:

Consuming 1.35 servings of green leafy vegetables per day was associated with a 14% reduction in risk of Type 2 diabetes compared with consuming only 0.2 servings, according to an analysis of six different studies.
Note that cabbage, cauliflower, lettuce, and herbs such as parsley and dill are also in the "green leafy vegetables" category.

BMJ: Carter P, et al "Fruit and vegetable intake and incidence of Type 2 diabetes mellitus: systematic review and meta-analysis" BMJ 2010; 341: c4229. DOI: 10.1136/bmj.c4229.

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New Hope in the Treatment of Charcot Arthropathy (24 Aug, 2010)

Brilliant work from Dr. Pinzur in Chicago.

Surgeon Reports Successful Treatment of Charcot Foot

Charcot foot can make walking difficult or impossible, and in severe cases can require amputation but a newsurgical technique that secures foot bones with an external frame has enabled more than 90 percent of patients to walk normally again....

Loyola University Health System foot and ankle surgeon Dr. Michael Pinzur, Department of Orthopaedic Surgery and Rehabilitation at the Chicago Stritch School of Medicine, describes the procedure in a current publication.

The device, called a circular external fixator, is a rigid frame made of stainless steel and aircraft-grade aluminum. It contains three rings that surround the foot and lower calf. The rings have stainless-steel pins that extend to the foot and secure the bones after surgery.

The fixator "has been demonstrated to achieve a high potential for enhanced clinical outcomes with a minimal risk for treatment-associated morbidity," Pinzur wrote. Pinzur treats about 75 Charcot patients per year with external fixators, most of whom are diabetics.

Charcot foot can occur in a diabetic who has neuropathy (nerve damage) impairing the ability to feel pain. Charot foot typically occurs following a minor injury, such as a sprain or stress fracture. Because the patient doesn't feel the injury, he or she continues to walk, making the injury worse. Bones fracture, joints collapse and the foot becomes deformed. The patient walks on the side of the foot and develops pressure sores. Bones can become infected.

The obesity epidemic is increasing the incidence of Charcot foot in two ways. The excess weight increases the risk of diabetic neuropathy, as well as the risk that patients with diabetic neuropathy will develop Charcot foot.

There has been an alarming increase in morbid obesity among diabetics. About 62 percent of U.S. adults with Type 2 diabetes now are obese, and 21 percent are morbidly obese, according to a 2009 study by Loyola kidney specialist Dr. Holly Kramer and colleagues published in the Journal of Diabetes and its Complications.

Morbid obesity is defined as having a body mass index (BMI) greater than 40. For example, a person who is 5-foot, 10-inches tall and has a BMI of 40 weighs 278 pounds.

Traditional surgical techniques, in which bones are held in place by internal plates and screws, don't work with a subset of obese Charcot patients. Their bones, already weakened by complications of Charcot foot, could collapse under the patient's heavy weight.

A common treatment in such cases is to put the patient in a cast. But bones can heal in deformed positions. And, it is difficult or impossible for obese patients to walk on one leg when the other leg is in a cast. Patients typically have to use wheelchairs and are confined to the first story of the house for as long as nine months. And after the cast comes off, they must wear a cumbersome leg brace.

By contrast, patients who are treated with an external fixator often are able to walk or at least bear some weight on the treated leg. The device is attached to the leg for only two or three months.

A 2007 study by Pinzur, published in Foot & Ankle International, demonstrated the benefits of the external fixator. Pinzur followed 26 obese, diabetic Charcot foot patients who had an average body mass index of 38.3. After surgery to correct the deformity, the foot bones were held in place by the external fixator. A year or more later, 24 of the 26 patients (92 percent) had no ulcers or bone infections and were able to walk without braces, wearing commercially available shoes designed for diabetics.

journal Hospital Practice, July 2010

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Innovation in Diabetes Care (1 Jul, 2010)

Here's more evidence that nonlinear thinking in the treatment of diabetes, works.

The disease management program took place in one year for a group of patients who were at least age 65 and who opted for a Medicare Advantage health plan with Health Net of Arizona. Because these patients had diabetes and heart disease, they were more likely to need future medical care and hospitalizations, said principal investigator James Rosenzweig, MD, a member of the scientific advisory board for Alere, the care management provider for Health Net of Arizona.

"More than 55 percent of all diabetes-related health care expenditures are for those aged 65 years and older, with Medicare covering much of this financial burden," said Rosenzweig, who is an associate professor of medicine at Boston University School of Medicine. "Appropriate care could mitigate much of the suffering and cost associated with diabetes. However, only about 45 percent of persons with diabetes receive recommended care."

The goal of Alere's disease management program was to close gaps in care, such as lack of patient education, by providing patients with telephone support and information from nurse care managers, according to Rosenzweig. Nurses sent the patients primary care physicians' summary reports before scheduled office visits and alerted them to changes in their patient's health status.

Of the 526 patients whom the researchers contacted to participate in the study, 462 randomly selected patients were offered the disease management program (intervention) and 64 received usual care (control group). The health plan wanted most of its members to receive the intervention, Rosenzweig explained. The researchers analyzed data for all 462 patients they intended to treat, although 356 actually participated in the program.

Compared with controls, the intervention group had a significantly decreased number of inpatient hospital admissions for reasons relating to either diabetes or all causes, the authors reported. The intervention group also had a decline in the number of emergency room visits, but it was not statistically significant, probably because the control group was too small, Rosenzweig said.

Annual medical costs were almost $1,000 lower for each patient who received disease management services and more than $4,500 higher per control. The cost of the contracted disease management program was not included in the analysis, but Rosenzweig said "the savings were still substantial."

Patients receiving the intervention also reported having better results of blood sugar control and cholesterol tests, fewer diabetic complications such as diabetic eye disease and foot ulcers, and better adherence to prescribed medications.

"These clinical measures demonstrate improved health status, which is the likely reason their medical costs and use of hospital services decreased," he said.

Presented at The Endocrine Society's 92nd Annual Meeting in San Diego, June 2010.

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Maggots and other Medical Miracles (29 Jun, 2010)

Leeches and maggots: Doctors' old-fashioned little helpers

Published: Tuesday, June 29, 2010, 8:00 AM Updated: Tuesday, June 29, 2010, 9:17 AM

Evelyn Theiss, The Plain Dealer
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Courtesy of Pam EggersPam Mitchell says she wouldn't be alive today if maggots hadn't saved her feet from amputation 10 years ago. She's had Type I diabetes since she was a child and suffered from deep ulcers on her feet as a result.

Most people's visceral response to leeches and maggots is revulsion. That can change quickly when this old-fashioned medicine saves your finger, your foot or, possibly, your life.

Maggots saved Pam Mitchell's feet and, she's certain, her life 10 years ago. As the Springfield Township woman explains, "Yes, maggot therapy is kind of gross, but what would you do to save your feet from amputation?" Mitchell, who has suffered from diabetes since she was a child, has become an advocate for maggot therapy and gives talks around the country.

Doctors and surgeons at the Cleveland Clinic, University Hospitals and MetroHealth medical centers don't commonly talk about it, but the hospitals do employ leeches and, to a lesser degree, maggots, when medically necessary. They are part of a specialty known as biotherapy.

The U.S. Food and Drug Administration gave official approval for the administration of both creatures in 2004 -- making something old in medical treatment new again.

The FDA considers leeches and maggots "medical devices," so they require a doctor's prescription. To be used medically, they must be "germ-free" maggots and leeches, not the kind you'd scare up yourself in a pond or by the side of a road.

RankL OPG Pathway and Charcot Neuroarthropathy (25 Jun, 2010)

From the clever fellows at SALSA!

Tuesday, June 22, 2010

Overview of the RANKL OPG Pathway

Southern Arizona Limb Salvage Alliance (SALSA)

www.ToeAndFlow.com

Authorship:
Nicholas A. Giovinco
Julia Bernardini
David G. Armstrong

The Receptor Activator for Nuclear Factor kappa B Ligand is believed to be an important molecule of bone metabolism. This is a natural and necessary surface-bound molecule on several types of cells, and serves to activate osteoclasts.

Overproduction of RANKL is implicated in a variety of degenerative diseases. In patients with neuropathy, the RANKL/OPG pathway is thought to mediate the development of Neuropathic Osteoarthropathy or "Charcot Joint"

An illustrative depiction of the RANKL pathway is as follows:

Cellular stress or injury may result in expression of RANK Ligand on the surface of activated ostoblasts and T cells. In this example, an activated T cell is contacting a pre-osteoclast. Because this RANKL presenting cell is in an activated form, RANKL will become expressed, thus activate an uninhibited RANK receptor on the Surface of an Osteoclast.

What is important to note, is that osteoprotegerin is a natural inhibitor of RANK and is thought to mediate a protective balance. Denosumab, and several other drugs, are being studied for their effects in preventing further transduction on the RANKL pathway and could prove to be useful in preventing disease progression.

As the transduction cascade continues, IkB kinase is activated and subsequently phosphorylates the Inhibitor of kappa B, leaving Nuclear Factor kappa B free to diffuse uninhibited. Upon entering the nuclear membrane, Nuclear Factor kappa B will serve as a rapid-acting transcription factor, and will contribute to a variety of changes in gene expression.

This gene expression, is correlated with the progression of Preosteoclastic species in becoming activated as osteoclasts. When the overproduction and/or expression of RANKL is seen, increased osteoclastogenesis will arise. Osteoclastogenesis is one of the fundamental elements in normal bone development and maturation.

However, in Neuropathic Osteoarthropathy, over abundance of osteoclastic activity will result in osteopenia or bone wasting. With compromised bone strength, osteolysis and fragmentation will be observed.

In addition to osseous destruction, the RANKL pathway has been correlated with macroangiopathic disfunction. The RANKL signaling pathway serves a regulatory role in the expression of bone matrix proteins in Vascular smooth muscle cells. A phenomenon that is naturally observed in many patients with Charcot joint destruction is vascular smooth muscle calcification. This presentation is often referred to as Monckeberg's arteriosclerosis.

One important note is that neuropathic osteoarthropathy or "Charcot Foot" is seen in nearly every sort of disease that results in peripheral neuropathy. The exact mechanisms of this correlation are still not entirely understood, but neuropathic degeneration itself serves a presumable teleological role in permitting both an increase in blood flow and vascular permeability into the bone as well as a decreased sensation and detection of boney destruction in patients.

When considering the supporting evidence of these two factors, the emergence of the indpendent, Neurovascular (French theory) and the Neurotraumatic (German theory), may possibly hold a similar etiology which is reflective of a common underlying cause. Because of the varying causes of peripheral neuropathy, the specific role the RANKL signal pathway merits more investigation at this time, and is needed to fully understand the process of neuropathic osteoarthropathy.

When observing Charcot foot on a macro anatomic level, evidence of destruction may be visualized on plain film xray. Vascular calcification is reported in nearly 90% of all diabetics with Charcot foot, and is often seen prior to joint or bone involvement. As Charcot joint progresses through the acute phase, destruction and dislocation will be observed with severe osteopenia. Although this phase will eventually subside, resulting in a coalescence of fragments and overall stability of architecture, the foot is often permanently deformed.

Deformations such as these, when accompanied by peripheral neuropathy and possible microangiopathological status, are often what lead to ulceration and infection. Although Neuropathic Osteoarthropathy is not directly responsible for the loss of limb or even death, the "Stairway to Amputation" is a perilous progression that must be curbed in all patients afflicted with this condition.

References:

Jeffcoate W. Vascular calcification and osteolysis in diabetic neuropathy-is RANK-L the missing link? Diabetologia. Sep 2004;47(9):1488-1492.
Lam J, Nelson CA, Ross FP, Teitelbaum SL, Fremont DH. Crystal structure of the TRANCE/RANKL cytokine reveals determinants of receptor-ligand specificity. J Clin Invest. Oct 2001;108(7):971-979.
Whyte MP. The long and the short of bone therapy. N Engl J Med. Feb 23 2006;354(8):860-863.
Buckley KA, Fraser WD. Receptor activator for nuclear factor kappaB ligand and osteoprotegerin: regulators of bone physiology and immune responses/potential therapeutic agents and biochemical markers. Ann Clin Biochem. Nov 2002;39(Pt 6):551-556.
Collin-Osdoby P. Regulation of vascular calcification by osteoclast regulatory factors RANKL and osteoprotegerin. Circ Res. Nov 26 2004;95(11):1046-1057.
Anandarajah AP, Schwarz EM. Anti-RANKL therapy for inflammatory bone disorders: Mechanisms and potential clinical applications. J Cell Biochem. Feb 1 2006;97(2):226-232.
Baud'huin M, Duplomb L, Ruiz Velasco C, Fortun Y, Heymann D, Padrines M. Key roles of the OPG-RANK-RANKL system in bone oncology. Expert Rev Anticancer Ther. Feb 2007;7(2):221-232.
Boyce BF, Xing L. Biology of RANK, RANKL, and osteoprotegerin. Arthritis Res Ther. 2007;9 Suppl 1:S1.
McClung M. Role of RANKL inhibition in osteoporosis. Arthritis Res Ther. 2007;9 Suppl 1:S3.
Yogo K, Ishida-Kitagawa N, Takeya T. Negative autoregulation of RANKL and c-Src signaling in osteoclasts. J Bone Miner Metab. 2007;25(4):205-210.

Posted by: PV Mayer at 11:08 am 0 comments - Add a Comment Category: Charcot

iPhone 4 for Wound Care? (25 Jun, 2010)

From Medgadget, another spectacular use of Tech. Could this be the way we monitor our patient's diabetic wounds in the future? We hope so!

iPhone 4 FaceTime video conferencing feature can help your doctor

June 23, 2010

The highlight of the recent Steve Jobs keynote where he unveiled iPhone 4 was the video telephony feature that Apple named FaceTime. This is classic Apple, taking an existing technology – video chat, think Skype – and recasting it as a brand new invention.

Predictably, many commentators scoffed that FaceTime is nothing more than marketing fluff, rather than a real innovation. But, on the other hand, if one considers the implications of a zero-configuration feature that allows you to instantly share what you are seeing with a simple phone call, it may turn out to be quite profound – especially for medicine and the patient physician relationship.

Not surprisingly, the advertisement for FaceTime shows heart warming scenes of babies learning to walk, birthday parties, and graduations. But for technicians and repairmen, the ability to instantly show the problem to a distant expert could prove to be very handy.

For physicians, the ability to see a patient’s face as they answer a question is invaluable. So much is conveyed in patients’ body language that sometimes it can appear we are watching more carefully than listening. Thus, being able to see as well as talk to a patient remotely can be a dramatically useful tool for physicians.

For surgeons in particular, the ability to see the condition of a healing incision or the appearance of a limb can alleviate the anxiety of the Friday evening patient phone call, when the only alternative is sending the patient to the emergency room.

We are told that FaceTime currently only works on WiFI until the carriers allow it on cellular, and certainly for now only a minority of patients and physicians will have an iPhone 4.

Apple has submitted the communication protocol used for the FaceTime video conferencing feature to standards bodies so other software and hardware companies can technically communicate with the iPhone 4. The end result being any phone with the correct protocols could video conference with the iPhone 4. Until that happens, it is a brilliant sales tactic by Apple since families and technicians will want to buy two iPhones instead of one.

Posted by: PV Mayer at 07:35 am 0 comments - Add a Comment

Insulin Pills to be Studied (17 Jun, 2010)

Yet another weapon in the battle against diabetes.

I

Insulin Pills Finally in Clinical Trials

After years of research and anticipation, insulin pills that could make it easier for millions of patients worldwide to manage their diabetes are moving ahead in clinical trials....

Drug manufacturers have tried for years to develop oral insulin without much success. Insulin is a peptide hormone that people with diabetes currently take by injection to bring their blood sugar to within normal levels. But doing so requires uncomfortable, inconvenient injections that can make patients reluctant to use the drug frequently enough to adequately control their blood sugar. An oral form of insulin could help solve this problem. However, stomach acids and enzymes easily destroy insulin and other protein-based drugs. Scientists have had difficulty finding an effective way to eliminate this problem.

They've responded to this challenge by developing special coatings for insulin pills that prevent stomach acids from destroying them. Scientists also are using additives that make it easier for the intestine to absorb large molecules like insulin. After years of setbacks, signs of success may be at hand. Several insulin pills are now in various stages of clinical trials, and proof of concept may allow them to move into late-stage and more rigorous clinical testing. Only time will tell, however, whether these much-anticipated pills will make it to the market.

Among developers, India's Biocon is the furthest along, with a technology acquired in 2006 from now-defunct Nobex. In scientific publications, Biocon scientists have described the firm's candidate, IN-105, as an insulin molecule conjugated to a short-chain polyethylene glycol derivative.

Put in a tablet, IN-105 retains similar activity to insulin alone, withstands degradation, and is consistently absorbed, according to Biocon. Results from a Phase III clinical trial in India are expected in September. In late 2009, Biocon applied to the U.S. Food & Drug Administration to allow it to start clinical trials.

Solid oral forms could have efficacy and safety advantages, too. Insulin delivered this way, unlike injected forms that circulate systemically, is believed to behave more like the body's own. Natural insulin is secreted by the pancreas and taken up by the liver, which stores and metes it out when needed. Engineered for release in parts of the small intestine just past the stomach, solid oral insulin can be taken up from there by the portal vein and delivered to the liver.

Getting the insulin through the stomach via an enterically coated tablet or capsule, which is stable under acidic conditions, is the relatively easy first step. The drug isn't released until the pill reaches the small intestine and starts to dissolve at higher pH. Sometimes enzyme inhibitors are added to stave off digestion. The overall goal is keeping as much insulin as possible intact for eventual absorption.

The harder second step is getting a large, hydrophilic protein past the intestinal walls. Although proteins find it hard to diffuse across the hydrophobic lipid membrane or through epithelial cells in the wall, they can conceivably be squeezed between cells. To wedge open tight intercellular junctions, developers add permeability or absorption enhancers to formulations.

Enhancers include oils, fatty acids, surfactants, and mucoadhesive or other polymers. Formulators are loath to give specifics, but they will disclose that the materials are typically off-the-shelf and already approved for use as food additives or in drug formulations. Using physical blends of enhancers with a known drug means that the safety profiles of the components are unchanged for regulatory purposes. In contrast, any chemical modifications create new entities that have to be tested.

With products moving into clinical trials, among the unanswered questions are ones about the long-term effects of insulin and the accompanying materials. Insulin induces cell division, and researchers are concerned that it might be associated with an increased risk of certain cancers. Companies working in this area generally believe that nothing but the drug and enhancers pass through the intestine.

Results from studies with oral insulins will be presented at the American Diabetes Association's 70th Scientific Sessions in Orlando, Florida later this month.

Chemical & Engineering News June 2010

Posted by: PV Mayer at 06:07 am 0 comments - Add a Comment

DoxyCycline as an Antii-inflamatory Agent (16 Jun, 2010)

Outstanding Research from Dr. Glass out of SALSA

Video Learning - Investigation of Doxycycline as an Agent for "Wound Chemotherapy"

Doxycycline is a semi-synthetic tetracycline compound. Classically, this drug is used in podiatry and wound care for its properties of antibiosis and antisepsis. There have, however, been some investigations of doxycycline and other chemically modified tetracycline species (CMTS), which demonstrate its potential as an inflammatory modulator. These qualities may prove useful within a wound environment. This is particularly so, as an inhibitor of nitric oxide (NO) production, matrix metalloprotease (MMP) activity, and tissue necrosis factor alpha converting enzyme (TACE).

MMP activity has been identified as a key player in the environment of chronic wounds as well. Although MMP's are part of the normal breakdown and remodeling of tissues within the human body, non-healing ulcers are particularly less governed by regulatory mechanisms and therefore see an overabundance of MMP activity, and consequently lead to the persistence of inflammation and degradation of the epithelial matrix in situ. The chemical structure of doxycycline has been investigated, and demonstrates satisfactory results as an inhibitor of such zinc catalyzed protease activity. By inhibiting the activity of various MMP species in a wound bed, the breakdown of wound matrix may be prevented.

Similar to MMP inhibition, TACE (otherwise known as ADAM17) is a member of the same metalloprotease superfamily and thus inhibition works by zinc binding as well. As a surface bound enzymatic protein, TACE degrades pre-TNF-a, thereby converting it to a biologically active form. Doxycycline has demonstrated convincing results in lowering the conversion of pre-TNF-a to its active form. Because TNF-a has long been known as a powerful member of the entourage of inflammatory cytokines of chronic wounds, the ability to suppress its expression could potentially be to the patient's advantage.

Next, the presence of Nitric Oxide within a wound environment is made possible by its production via the iNOS enzyme. The mRNA molecule which codes for iNOS is expressed during times of cytokine and inflammatory stimulation. This mRNA molecule has a relatively short half life, which is presumed to be for regulatory purposes, and is stabilized by the presence of p38 MAPK binding to one of several 'AUUA' motifs. When Doxycycline prevents p38 MAPK from stabilizing iNOS mRNA, via competitive binding to metallic ions, subsequent degradation of the iNOS mRNA molecule takes place and therefore acts to decrease the concentration of Nitric Oxide within the wound environment.

Although further investigation is needed to ascertain the true beneficial value of Doxycycline as a wound chemotherapeutic agent, laboratory data is highly suggestive of this possibility.

Southern Arizona Limb Salvage Alliance

www.ToeAndFlow.com

Dr. Glass DPM Podcast

www.DrGlass.org

References:

Scimeca CL, Bharara M, Fisher TK, Giovinco N, Armstrong DG. Novel Use of Doxycycline in Continuous-Instillation Negative Pressure Wound Therapy as "Wound Chemotherapy". Foot Ankle Spec. Jun 8.
Hanemaaijer R, Visser H, Koolwijk P, et al. Inhibition of MMP synthesis by doxycycline and chemically modified tetracyclines (CMTs) in human endothelial cells. Adv Dent Res. Nov 1998;12(2):114-118.
De Paiva CS, Corrales RM, Villarreal AL, et al. Corticosteroid and doxycycline suppress MMP-9 and inflammatory cytokine expression, MAPK activation in the corneal epithelium in experimental dry eye. Exp Eye Res. Sep 2006;83(3):526-535.
Winzen R, Kracht M, Ritter B, et al. The p38 MAP kinase pathway signals for cytokine-induced mRNA stabilization via MAP kinase-activated protein kinase 2 and an AU-rich region-targeted mechanism. EMBO J. Sep 15 1999;18(18):4969-4980.
Hoyt JC, Ballering J, Numanami H, Hayden JM, Robbins RA. Doxycycline modulates nitric oxide production in murine lung epithelial cells. J Immunol. Jan 1 2006;176(1):567-572.
Abdul-Hussien H, Hanemaaijer R, Verheijen JH, van Bockel JH, Geelkerken RH, Lindeman JH. Doxycycline therapy for abdominal aneurysm: Improved proteolytic balance through reduced neutrophil content. J Vasc Surg. Mar 2009;49(3):741-749.
Hanemaaijer R, Sorsa T, Konttinen YT, et al. Matrix metalloproteinase-8 is expressed in rheumatoid synovial fibroblasts and endothelial cells. Regulation by tumor necrosis factor-alpha and doxycycline. J Biol Chem. Dec 12 1997;272(50):31504-31509.

Posted by: PV Mayer at 04:36 am 0 comments - Add a Comment

Clean Teeth Prevents more than Bad Breath (11 Jun, 2010)

Our Mothers Were Right After All!

Clean Teeth Prevents Heart Disease by 70%

Individuals who do not brush their teeth twice a day have an increased risk of heart disease, a new study shows. Regular toothbrushing could help stave off cardiovascular disease by 70% according to a nationally-representative study....

Individuals who rarely or never brushed were 70% more likely to have a heart attack or other cardiovascular disease event (P<0.001) even after controlling for many other factors, found researchers led by Richard Watt, MSc, PhD, of University College London.

Even brushing once a day rather than twice a day was associated with a significant 30% increase in the risk of these fatal or nonfatal events.

Low-grade inflammation appeared to be playing a role, although whether it is a causal role remains uncertain, Watt's group reported online inBMJ. These increases in risk could have a "profound public health impact," they wrote in the study.

Nearly 40% of the population has some degree of periodontal disease, a complex chronic inflammatory condition largely caused by poor oral hygiene, the investigators noted. Its link to cardiovascular disease has been extensively studied with results affirmed and strengthened by the new population-level data.

The researchers used self-reported frequency of tooth brushing as a proxy for periodontal disease, which wouldn't have been feasible for a large-scale population study, they said.

The analysis included 11,869 men and women ages 35 and older (mean 50) who retained their natural teeth and were without preexisting cardiovascular disease in the 1995, 1998, and 2003 iterations of the Scottish Health Survey of the general population. Overall, their oral health was good. Regular visits to a dentist at least every six months were reported by 62% of respondents and 71% reported brushing twice a day.

Hazard ratio for cardiovascular events (fatal and nonfatal) relative to how often teeth are brushed each day

Frequency of toothbrushing	HR* (95% CI)
Twice a day	1.0
Once a day	1.3 (1.0-1.5)
Less than once a day	1.7 (1.3-2.3)
p for trend	0.001

More frequent tooth brushing appeared to be dose-dependently protective against cardiovascular disease events -- fatal or nonfatal, including cardiovascular disease-related hospitalization, acute MI, coronary artery bypass surgery, percutaneous coronary angioplasty, stroke, and heart failure.

In the analysis adjusted only for age and sex, the risk of a fatal or nonfatal event was 40% greater for those who brushed once rather than twice a day and 2.3-fold higher for those who brushed less than once a day (P=0.001 for trend).

Further adjustment for socioeconomic status, smoking, physical activity, and visits to the dentist attenuated the link. Additional controls for body mass index, family history of cardiovascular disease, hypertension, and physician-diagnosed diabetes also reduced the relationship but not to the point where significance was lost.

For cardiovascular disease-related death alone, similar trends were seen with a 10% elevated risk with once-a-day brushing and 50% elevated risk with less than once-a-day brushing compared with twice daily. However, this relationship lost significance with multivariate adjustment.

The other independent predictors of fatal and nonfatal cardiovascular disease events combined included:

Smoking (hazard ratio 2.4, 95% confidence interval 1.9 to 2.9)
Hypertension (HR 1.7, 95% CI 1.4 to 2.0)
Diabetes (HR 1.9, 95% CI 1.4 to 2.7)

A subgroup of 4,830 study participants gave blood samples from which markers of inflammation (C reactive protein) and coagulation (fibrinogen) were measured. Among them, less frequent tooth brushing appeared to have an effect that remained significant after multiple adjustments (P=0.46 for trend in C reactive protein levels and P=0.015 for trend in fibrinogen levels). Inclusion of inflammatory markers partly attenuated the point estimates for the link between tooth brushing and cardiovascular disease "thus suggesting a possible mediating role," Watt's group wrote in BMJ.

They add: "Our study suggests a possible role of poor oral hygiene in the risk of cardiovascular disease via systemic inflammation. Raised inflammatory and homoeostatic responses as well as lipid metabolism disturbance caused by periodontal infection might be possible pathways underlying the observed association between periodontal disease and the increased risk for cardiovascular disease."Even though the study could not prove that inflammation from poor dental hygiene was causing the increase in cardiovascular events, Watt and colleagues concluded that "educating patients in improving personal oral hygiene is beneficial to their oral health regardless of the relation with systemic disease."

de Oliveira C, et al "Tooth brushing, inflammation, and risk of cardiovascular disease: Results from Scottish Health Survey" BMJ 2010; 340: c2451 Diabetes Care June.33(6): 1206-12

Posted by: PV Mayer at 04:52 pm 0 comments - Add a Comment

ChemoVAC: Diabetic Wound Care SALSAtized! (21 May, 2010)

From the clever fellows at SALSA.

ChemoVac Dressing Assembly Video Tutorial

As a followup to an older post. There have been many requests to demonstrate this process. This was a little something put together by some members of the SALSA ToeAndFlow team. Enjoy!

For a link to the original post on Chemovac Dressing Assembly: http://diabeticfootonline.blogspot.com/2010/04/step-wise-discussion-of-chemovac.html

Chemotherapy is classically defined as the treatment of disease by use of chemicals. In addition to microbial management of a wound environment, this term has recently become adopted in the field of wound healing for several additional purposes. Wound chemotherapy is best seen as an enabling factor, which further extends the clinicians ability to manipulate a wound environment on a biochemical level.

The benefits of maintaining cleanliness, regular lavage, irrigation, and drainage of open wounds and compound fractures has long been appreciated in medicine. In recent decades, the advent and application of Negative Pressure Wound Therapy (NPWT) has been further augmented with the instillation of chemotherapeutic agents.

Stepwise Technique which has been Shown to Provide Sufficient Results at the Southern Arizona Limb Salvage Alliance:

As one might imagine, the use of chemotherapeutic modalities is generally easy to perform. Topical applications and traditional dressing modifications are, in many instances, technically unchanged from standard practice. Our experience with the application of chemovac dressings has underscored the importance of careful technique for optimal results. Many of these techniques are listed in the product instructions and have been previously discussed in various literary mediums. We have found that they are useful in order to avoid the potential for complications from dressing adherance, leakage, durability, and subsequent maceration.

We therefore recommend that the wound area be thoroughly cleaned and dried between dressing changes. Adhesive tinctures such as benzoin or mastisol are useful in increasing the ability for the plastic dressing to hold a tighter and more rigorous seal.

It has also proven useful to 'Window' the wound edges with smaller strips of dressing seal in order to create more exact boundaries. This is helpful for wounds with irregular borders, the need for bridging two or more wound beds, and to prevent excessive contact between viable surrounding skin with the foam sponge. In addition, we recomend precise trimming of the foam sponge with shears or even a scalpel blade. This further prevents the potential for maceration of surrounding skin.

When the top cover is place over the sponge, it is important to do so in a manner which allows a flat and uniform contact across the sponge and skin. By preventing wrinkles, tracks, or 'Cigar Rolls' one can minimize leakage and non-uniform distribution of negative pressure.

The next step will depend on the type of negative pressure device and dressing being used. The dual port dressings such as ITI Sved units contain both ingress and egress interfaces, which are simply applied in the same manner as one would expect. However, when modifying or augmenting a standard VAC dressing with a make-shift ingress port, it is important to utilize IV tubing which can be inserted directly into the dressing. For this, we recomend a minimal incision. Additional seal or Tegaderm dressing material must then be used to seal this interface, and thus decrease leakage or loss of pressurization.

To our knowledge, the specific arrangement of the ingress and egress ports is of little importance. By this, we have not experienced any notable effects from gravity or direction of flow. It appears that the chemotherapeutic agent perfuses the sponge and is thus 'delivered' to the entire wound bed without prejudice. Therefore, merely spacing a reasonable difference between the two interfaces is more than sufficient at achieving satisfactory distribution.

At this point, negative pressure should be initiated. It is important to identify and eliminate any breaks in seal and loss of pressure. Once a satisfactory seal has been established, the chemotherapeutic input should be initiated. By initiating the negative pressure component PRIOR to chemotherapeutic input, one can ensure a consistent and predictable rate of infusion. In our experience, most dressing configurations merit this process as a 'Best Practice' in avoidance of leakage and maceration, due to a compromised dressing assembly.

Many hospital and care facilities possess automated IV infusion apparatuses. These devices allow for programmable infusion cycles to be administered. This is undoubtedly a convenience to care providers, but is not necessary to deliver infusion. A manual regulator is capable delivering a consistent and reliable infusion rate. Depending on several factors, typical rates of infusion range from 1-3 drops per 10 second interval, or a total of 25 cc's per hour.

One notable observation about the use of foam dressings with infusion ports, both modified as well as designed, is the increased reliance on patient compliance. This is seen, more so, with the use of such chemovac devices outside of hospital and specialized care facilities, where strict adherence to therapeutic instructions, weight bearing status, and foam dressing application is not always satisfied. In this event, the discontinuation of chemovac therapy may need to be considered, in favor of standard dressings or negative pressure wound therapy. After all, wounds have been healed for many years, long before vacuums.

Posted by: PV Mayer at 09:23 am 1 comment - Add a Comment

The Foot as a Health Indicator (20 May, 2010)

A great article from Dr Boberg, DPM in St Louis.

Foot problems may be warning of heart attack, stroke

By Jeffery Boberg, D.P.M

Maybe it’s because of my medical specialty — podiatry, the diagnosis and treatment of foot, ankle and lower leg disorders — but it seems everyone I talk to knows someone who has lost a toe, foot or leg to diabetes.

In reality, only a small percentage of diabetics lose part of a limb. Diabetes reduces blood circulation and causes nerve damage throughout the entire body. The foot, however, is the earliest marker — the “canary in the cage” warning — of vascular disease and nerve damage in the body.

Diabetics with peripheral arterial disease (PAD) of their foot are much more likely to suffer a heart attack or stroke — and that risk is significant! It’s an early warning that you need to have your blood pressure and cholesterol levels carefully monitored to prevent complications that can damage your heart or brain.

When no pain can be a real pain

Your blood vessels are smallest at their furthest point from the heart — in your foot. The excess sugar in a diabetic’s bloodstream results in micro-vascular injury to these small blood vessels that supply the nerves, damaging nerve fibers. We call this condition neuropathy. The body’s electrical wiring system is breaking down, causing numbness, or a burning, “shooting” or stabbing pain.

Everybody describes the symptoms of neuropathy differently. While it may sound contradictory, the neuropathy pain you feel actually reduces your foot’s ability to feel the pain that counts. After you lose natural feeling, you may not realize that your foot has been injured, and you tend to ignore it.

Take, for instance, when you know your shoes are too tight. Painful blisters form on your feet, which you immediately try to help heal.

If the diabetic doesn’t feel that pressure wound, his or her shoe will eventually rub a hole (ulcer) through the skin. This ulcer becomes the portal for infection. Bacteria now have an entry site. And remember, diabetics don’t respond as well to infection; their body’s resistance is compromised compared to non-diabetics.

The bones in the foot are right under the skin, so a skin infection can quickly lead to an infection of a bone in the foot or leg. When all else fails, when antibiotics can’t control the bone infection, the only cure becomes amputation.

Foot care programs can decrease the incidence of lower-extremity ulcers and amputations by 44 to 85 percent. Most ulcers that lead to amputation can be prevented through daily foot inspection and care, and regular visits to your physician and podiatrist.

Foot exam determines risk for other problems

Amputation prevention only partially answers why diabetics must come in for regular foot examinations.

During an exam, the podiatrist will take a soft piece of plastic film and push it up against the foot until the plastic bends from 10 grams of pressure. Patients who cannot feel the plastic have sustained “loss of preventive sensation” or LOPS.

The podiatrist will notify the patient’s primary care physician if the diagnosis is poor foot circulation — peripheral artery disease. In response, the primary care physician will often alter a diabetic’s medication.

Even though blood tests may indicate the diabetic’s cholesterol is under control, cholesterol-lowering drugs called statins will be prescribed. The patient’s blood pressure, even if not particularly high, will be treated more aggressively. These are proven to reduce the incidence of heart attack and stroke in diabetics.

An overreaction to a foot problem? Hardly. Forty percent of diabetics who develop an ulcer on their foot will die within five years — not from the ulcer, but from a heart attack or stroke. That’s a higher mortality rate than for some cancers.

Here are a few podiatric suggestions for diabetics:

• Examine your feet every day. • Wear white socks to see blood and drainage from your foot that you might not feel.

• Keep your feet moisturized; diabetics are more prone to dry skin.

• However, do not use moisturizer in between toes, which might promote athlete’s foot.

• Do not soak feet that have lost feeling. You may burn your foot in water that is too hot; diabetics with PAD can burn their feet even at slightly higher water temperatures.

• Wear a custom-designed diabetic shoe — a wide, soft shoe that most insurers cover for diabetic patients with PAD.

• If a foot is red or swollen, have it checked by a physician immediately.

In general: A diabetic with good circulation needs to see a foot care specialist at least once a year. One with poor circulation should visit a podiatrist every three to six months and if you have any deformity in your feet along with PAD you should have your feet looked at every 2-4 months. Those who have had a history of a diabetic ulcer need to be seen at least every 4 weeks, for the rest of your lives!

Posted by: PV Mayer at 06:54 am 0 comments - Add a Comment Category: Diabetes Education

Insulin is Good for YOU (19 May, 2010)

More evidence that aggressive approach to gylcemic control using insulin has beneficial effects outside the blood sugar control.

Insulin Protects Against Artery Damage

Long suspected of worsening artery damage in patients with diabetes, insulin instead protects blood vessels, a new study by Joslin Diabetes Center scientists indicates....

For decades, medical researchers have debated whether insulin can promote atherosclerosis, the buildup of cholesterol in blood vessels that causes coronary artery disease and stroke. This was no theoretical argument for those patients with Type 2 diabetes who need insulin injections to control their blood glucose.

But now, Joslin researchers have produced clear evidence that insulin protects arteries. "These results are definitive, at least in animals," says George L. King, M.D., Joslin's Chief Scientific Officer and senior author on a paper reporting the study.

Dr. King, who heads Joslin's Dianne Nunnally Hoppes Laboratory for Diabetes Complications and is a Professor of Medicine at Harvard Medical School, suggests that extrapolating the findings to humans would suggest that physicians should not be so wary of prescribing insulin to patients with diabetes.

"It also raises the exciting possibility of designing special insulins that interact directly with blood vessels, potentially slowing atherosclerosis in these patients." Dr. King speculates.

The study focuses on endothelial cells, the cells lining the inside of blood vessels in which atherosclerotic plaques develop. The scientists began with a line of mice, originally developed, in which the gene for the insulin receptor has been knocked out in endothelial cells only. In these mice, endothelial cells are unresponsive to insulin.

"Mice don't get atherosclerosis unless their normal cholesterol metabolism is changed," notes Christian Rask-Madsen, M.D., Ph.D., a research associate in the Nunnally Hoppes lab and lead author on the paper. So the insulin-receptor knockout mice were crossed with another line of mice, known as ApoE mice, which has elevated cholesterol levels in the blood. Dr. Rask-Madsen and his colleagues then compared how atherosclerosis developed in these mice compared to standard ApoE mice.

The two groups of mice showed similar levels of other factors known to promote cardiovascular disease, including blood pressure, glucose metabolism and the levels of lipids in the blood. But the scientists found that the insulin-receptor knockout mice were on a fast track to atherosclerosis. The insulin-receptor knockout mice developed cholesterol plaques that were more than twice the size of those found in the control animals.

The researchers also found a reason for the increased rate of artery damage. The endothelial cells in insulin-receptor knockout mice expressed more of the VCAM-1 adhesion molecule that helps white blood cells grab onto the growing plaques, and blood vessels gathered four times as many white blood cells. This condition was reversed when a VCAM-1 antibody was administered.

Taken altogether, the evidence "suggests that if you can improve insulin action in endothelial cells, you may be able to slow or prevent atherosclerosis," Dr. Rask-Madsen notes.

In recent years, research at Joslin and elsewhere has shown that insulin resistance may work differently in different cell types. "It's important not just to study its effect on glucose metabolism," Dr. Rask-Madsen adds. "In Type 1 diabetes, controlling blood glucose has been shown to be the main way to control late-stage complications. But we've had much less success improving long-term outcomes with Type 2 diabetes. If we understand the special features of insulin resistance in endothelial cells, we may be able to find more effective treatments against artery damage and cardiovascular disease in people with diabetes."

Roman Abramov, I-Hsien Wu, Kai Chen, Junko Yamamoto-Hiraoka, Cell Metabolism online, May 5, 2010.

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More on ACCORD (19 May, 2010)

Another angle on gylcemic control and mortality.

Low HbA1c not linked to mortality in new ACCORD analysis

An analysis of mortality in the Action to Control Cardiovascular Disease in Diabetes, or ACCORD, study found that rapidly lowering glucose and maintaining near-normal glucose levels by using an intensive control strategy did not cause higher death rates compared with a standard control strategy, according to a new study in Diabetes Care.

“Our findings show that neither a rapid early reduction of glucose, and thus HbA1c, nor a sustained near-normal level of HbA1c were associated with the excess mortality accompanying intensive glycemic treatment,” Matthew C. Riddle, MD, professor of medicine at Oregon Health and Science University, toldEndocrine Today. “Instead, findings show that the excess risk occurred among participants who could not reduce HbA1c very much despite vigorous efforts to do so.”

The ACCORD glucose control clinical trial investigated whether an intensive strategy targeting HbA1c levels of less than 6% would reduce the risk for cardiovascular disease in patients with type 2 diabetes at high risk for CVD. Researchers randomly assigned 10,251 patients to a standard strategy (target HbA1c, 7% to 7.9%) or an intensive strategy (target HbA1c, <6%). The data and safety monitoring board advised stopping intensive glycemic treatment in ACCORD in February 2008 after 3.4 years because of increased mortality in the intensive treatment arm (257 deaths vs. 203 deaths).

Data presented at the American Diabetes Association’s 69th Scientific Sessions in June revealed that lower HbA1c levels were associated with lower mortality in patients assigned to both strategies. Each 1% higher HbA1c level was associated with a statistically significant 66% higher RR for mortality in the intensive group and a trend in the same direction in the standard group. In addition, patients who rapidly lowered their HbA1c levels during the first year of treatment appeared to have a lower risk for death. Excess mortality in the intensive control group occurred among those who were unsuccessful in reaching a target goal at or near 6%.

New analysis of ACCORD data

The current analysis “explored whether on-treatment HbA1c itself had an independent relationship with mortality.” The researchers analyzed data obtained during 3.4 years of follow-up before the intensive arm was halted.

According to the researchers, “these analyses implicate factors associated with persisting higher HbA1c levels, rather than low HbA1c per se, as likely contributors to the increased mortality risk associated with the intensive glycemic treatment strategy in ACCORD.”

The increased risk started to emerge within one to two years after the strategy began to aggressively lower the participants’ blood glucose levels. According to the researchers, a higher average on-treatment HbA1c was a stronger predictor of mortality than HbA1c for the last interval of follow-up or the decrease of HbA1c in the first year. Further, higher average HbA1c was associated with a greater mortality risk.

The analysis suggested that mortality risk with the intensive strategy increased linearly from 6% to 9% HbA1c and appeared to be greater with the intensive strategy compared with the standard strategy only when average HbA1c was less than 7%.

“Targeting 7% HbA1c or lower continues to be an evidence-based goal of treatment in type 2 diabetes in general, but ACCORD suggested that a subgroup of patients should seek less ambitious HbA1c goals. Our findings support the view that we will have to consider different HbA1c targets and perhaps different treatment strategies for different groups of patients,” Riddle said in the interview.

Questions remain

The most recent analysis of ACCORD data appear to answer the question of whether rapidly reducing HbA1c levels, or achieving low HbA1c levels, can be seriously harmful, but it does not provide answers as to what caused the excess mortality, Riddle said.

“We still don’t know why more patients in the intensive group died. We wish we knew what it was about this group that caused the additional risk, but we don’t,” Riddle said in a press release. One practical question for future analyses is how to identify the people for whom an intensive regimen may be risky, he told Endocrine Today.

Riddle said his team will continue to investigate potential causes of the increased mortality, including the role of weight gain during the study. The researchers “still need to understand whether changes of weight or use of specific drugs may be associated with either greater or lesser risk during use of the intensive treatment strategy,” he said.

Another question that remains is whether hypoglycemia contributed to the risk. Although analyses to date do not show a link between severe hypoglycemia and higher mortality with an intensive strategy, the data “do not entirely rule out the possibility that repeated mild or moderate hypoglycemia was related to risk in some way,” Riddle said.

In an accompanying editorial, Edward J. Boyko, MD, MPH, professor of medicine, University of Washington, and chief of the general internal medicine section, VA Puget Sound Health Care System, said another possible clue may be the higher mortality associated with resistance to glucose control.

“Whether continuing to pursue intensive treatment in patients in whom no improvement in glucose control leads to more harm than good should be pursued as a possible explanation for the puzzling findings of ACCORD,” Boyko wrote. – by Katie Kalvaitis

Boyko EJ. Diabetes Care. 2010;33:1149.

Riddle MC. Diabetes Care. 2010;33:983-990.

Posted by: PV Mayer at 04:28 pm 0 comments - Add a Comment Category: Diabetes Management

ACCORD Results revisited (12 May, 2010)

Tight control still RULES! We must not lose sight of the fact that UKPDS, DCCT and HOPE trials all show strong evidence that tight gylcemic control reduces microvascular damage. We now must be a bit more gentle in our treatment of resistant diabetics.

Epidemiologic Relationships Between A1C and All-Cause Mortality During a Median 3.4-Year Follow-up of Glycemic Treatment in the ACCORD Trial

Matthew C. Riddle, MD¹,
Walter T. Ambrosius, PHD²,
David J. Brillon, MD³,
John B. Buse, MD, PHD⁴,
Robert P. Byington, MPH, PHD²,
Robert M. Cohen, MD⁵,
David C. Goff Jr., MD, PHD²,
Saul Malozowski, MD, PHD⁶,
Karen L. Margolis, MD, MPH⁷,
Jeffrey L. Probstfield, MD⁸,
Adrian Schnall, MD⁹,
Elizabeth R. Seaquist, MD¹⁰ and
for the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Investigators*

+Author Affiliations

¹Division of Endocrinology, Diabetes, and Clinical Nutrition, Oregon Health and Science University, Portland, Oregon;
²Wake Forest University School of Medicine, Winston-Salem, North Carolina;
³Weill Cornell Medical College of Cornell University, New York, New York;
⁴University of North Carolina School of Medicine, Chapel Hill, North Carolina;
⁵University of Cincinnati College of Medicine, Cincinnati, Ohio;
⁶National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland;
⁷Health Partners Research Foundation, Minneapolis, Minnesota;
⁸University of Washington School of Medicine, Seattle, Washington;
⁹Case Western Reserve University School of Medicine, Cleveland, Ohio;
¹⁰University of Minnesota School of Medicine, Minneapolis, Minnesota.

Corresponding author: Matthew C. Riddle, riddlem@ohsu.edu.

Abstract

OBJECTIVE Randomized treatment comparing an intensive glycemic treatment strategy with a standard strategy in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) trial was ended early because of an unexpected excess of mortality in the intensive arm. As part of ongoing post hoc analyses of potential mechanisms for this finding, we explored whether on-treatment A1C itself had an independent relationship with mortality.

RESEARCH DESIGN AND METHODS Participants with type 2 diabetes (n = 10,251 with mean age 62 years, median duration of diabetes 10 years, and median A1C 8.1%) were randomly assigned to treatment strategies targeting either A1C <6.0% (intensive) or A1C 7.0–7.9% (standard). Data obtained during 3.4 (median) years of follow-up before cessation of intensive treatment were analyzed using several multivariable models.

RESULTS Various characteristics of the participants and the study sites at baseline had significant associations with the risk of mortality. Before and after adjustment for these covariates, a higher average on-treatment A1C was a stronger predictor of mortality than the A1C for the last interval of follow-up or the decrease of A1C in the first year. Higher average A1C was associated with greater risk of death. The risk of death with the intensive strategy increased approximately linearly from 6–9% A1C and appeared to be greater with the intensive than with the standard strategy only when average A1C was >7%.

CONCLUSIONS These analyses implicate factors associated with persisting higher A1C levels, rather than low A1C per se, as likely contributors to the increased mortality risk associated with the intensive glycemic treatment strategy in ACCORD.

Posted by: PV Mayer at 08:00 am 0 comments - Add a Comment Category: Diabetes Management

High Mortality Rate in Diabetics with Charcot Neuroarthropathy (7 May, 2010)

Remember the old adage "You can't make the diagnosis, unless you think about it". We need to think about Charcot always when treating our diabetic patient's feet.

Mortality associated with acute charcot foot and neuropathic foot ulceration.

van Baal J, Hubbard R, Game F, Jeffcoate W.

Foot Ulcer Trials Unit, Nottingham University Hospitals Trust, City Hospital Campus, Nottingham, UK.

Abstract

OBJECTIVE: To compare the mortality of patients with an acute Charcot foot with a matched population with uninfected neuropathic foot ulcers (NFUs). RESEARCH DESIGN AND METHODS: Data were extracted from a specialist departmental database, supplemented by hospital records. The findings were compared with the results of earlier populations with Charcot foot and uninfected NFUs managed from 1980. Finally, the results of all patients with acute Charcot foot and all control subjects managed between 1980 and 2007 were compared with normative mortality data for the U.K. population. RESULTS: A total of 70 patients presented with an acute Charcot foot (mean age 57.4 +/- 12.0 years; 48 male [68.6%]) between 2001 and 2007; there were 66 matched control subjects. By 1 October 2008, 13 (eight male; 18.6%) patients with a Charcot foot had died, after a median of 2.1 years (interquartile range 1.1-3.3). Twenty-two (20 male; 33.3%) control subjects had also died after a median of 1.3 years (0.6-2.5). There was no difference in survival between the two groups (log-rank P > 0.05). Median survival of all 117 patients with acute Charcot foot managed between 1980 and 2007 was 7.88 years (4.0-15.4) and was not significantly different from the control NFU patients (8.43 years [3.4-15.8]). When compared with normative U.K. population data, life expectancy in the two groups was reduced by 14.4 and 13.9 years, respectively. CONCLUSIONS: These data confirm that the mortality in patients presenting to our unit with either an acute Charcot foot and an uninfected neuropathic ulcer was unexpectedly high.

Posted by: PV Mayer at 06:38 am 0 comments - Add a Comment Category: Charcot

Arterial Disease in Diabetes (6 May, 2010)

This is our most troubling complication and the one that ultimately claims our patient's limbs. We need to work harder for a better solution to our medical system's problem with access to quality vascular reconstruction and diabetic limb salvage..

Understanding The Effects Of PAD On The Diabetic Foot

VOLUME: 23 PUBLICATION DATE: May 01 2010

Issue Number:

5 May 2010

Author(s):

Nicholas J. Bevilacqua, DPM, Lee C. Rogers, DPM, and George Andros, MD

The presence of peripheral arterial disease (PAD) in patients with diabetes can result in devastating complications. Multidisciplinary care is critical for these patients. Accordingly, these authors review the current literature and offer pertinent diagnostic insights and keys to effective treatment.

With diabetes affecting 5 to 10 percent of the U.S. population, effective management of diabetes-related complications is imperative both socially and fiscally.

Foot ulcers develop in approximately 15 percent of patients with diabetes with an annual incidence of foot ulceration of slightly more than 2 percent among all people with diabetes and between 5 and 7.5 percent among people with diabetes and peripheral neuropathy.¹ Singh and colleagues have estimated that there is a 25 percent lifetime risk for someone with diabetes to develop a foot ulceration during his or her lifetime.²

Foot ulcers are a harbinger of amputation and they precede 85 percent of lower limb amputations.³This statistic highlights the importance of ulcer prevention and appropriate management of foot ulcers that are already present.

There are a number of contributing factors that interact and as they aggregate, they may lead to a foot ulceration.⁴ Reiber and colleagues established a causal pathway to foot ulceration in people with diabetes. Based on an analysis of 146 patients with foot ulcers, these researchers found that the triad of peripheral neuropathy, trauma and deformity were present in almost two-thirds of the patients with foot ulcers.⁵

However, this study occurred in an outpatient diabetic foot clinic and may have excluded those patients admitted to the hospital or those with limb ischemia requiring surgical intervention. Therefore, the study may have underestimated the level of infection and peripheral arterial disease (PAD) that others have reported.⁶

The prevalence of PAD in people with diabetic foot ulcers ranges wildly from 10 to 60 percent.⁶ This large variation may be the result of using different criteria for defining PAD among different centers.

A Closer Look At The Literature On PAD

The European Study Group on Diabetes and the Lower Extremity (Eurodiale), which is a collaborative network of 14 European centers, conducted a large multicenter study to obtain data on clinical outcomes in patients presenting with a foot ulcer.⁷ This multidisciplinary group initiated a prospective data collection study for 1,229 consecutive patients presenting with a new foot ulcer. Peripheral arterial disease was present in 49 percent of patients but the incidence varied from 22 to 73 percent among the different participating centers.

This variation may be related to the differences in the prevalence of PAD but it more likely highlights the differences in the criteria used to define PAD. In patients without diabetes, the ankle brachial index (ABI) is the method of choice to screen for PAD. However, given the reduced compliance of blood vessels in diabetes secondary to arterial calcification, the pressures may not be accurate and the results may be misleading.

The researchers also found that the presence of PAD is a strong predictor of a non-healing foot ulcer.⁷ In addition, patients with diabetes had more severe disease in the distal arteries in comparison to those without diabetes. The study also found a relatively high prevalence of infection with 58 percent of all ulcers infected at initial presentation.

Previous studies have demonstrated that the combination of infection and PAD results in the worst outcome. Armstrong and colleagues noted that patients presenting with a combination of infection and ischemia were 90 times more likely to undergo amputation than those without infection and ischemia.⁸ Ischemia in extremities with open wounds prolongs or prevents healing, and is a risk factor for amputation. Peripheral vascular disease and impaired distal perfusion associated with diabetes affect the delivery of immune cells and antimicrobials to the target site. The metabolic demands of an infection may cause a limb with severe ischemia to develop local necrosis or gangrene.

Mastering The Crucial Diagnostic Elements

Peripheral arterial disease is a component cause that may lead to foot ulcerations and therefore is an important element of the history exam.1 Symptoms of PAD may include claudication, rest pain or a non-healing ulcer.

One should question all patients about ambulatory calf, thigh and buttock pain.⁴Exercise-induced muscular cramps can, indeed, occur with diabetes but patients infrequently complain because they often have a self-imposed limitation to sustained walking. It is worth noting that the neuropathic patient may not have classic claudication and instead may present with lower extremity fatigue upon exertion that relieves after rest. Important risk factors include hypertension, dyslipidemia and smoking.

Do not discount the importance of a thorough physical exam. One should palpate femoral, popliteal and pedal pulses on both limbs and note the quality. Weak or absent pulses point to occlusion, stenosis or calcification proximal to the abnormal findings.⁶ However, the presence of pedal pulses does not always indicate adequate circulation.

Andros and colleagues reported on a group of five patients with diabetes who had worsening gangrene or failed limited amputations, and palpable pedal pulses.⁹ The authors performed arteriography and noted occlusion of all three infrapopliteal arteries. Collateral blood flow may maintain a palpable pulse but may not offer enough blood flow to heal an ulcer. As a result, Andros and colleagues recommend performing arteriography if gangrene is present, irrespective of palpable pedal pulses.⁹ One may also evaluate arterial flow by Doppler and grade it as monophasic, biphasic or triphasic.

The American Diabetes Association recommends that all patients with diabetes over 50 have ABI measurements and that one perform this examination in younger patients with multiple PAD risk factors.⁴ Traditionally, the method of choice to screen for PAD has been the ABI. As previously noted, arterial non-compressibility may occur in as many as 40 percent of patients with diabetes, rendering the ABI findings spurious.

Arterial calcification will result in falsely elevated values and values greater than 1.3 are associated with an increased risk for amputation. An ABI value of less than 0.9 is considered indicative of PAD although this number is currently being reassessed. Values between 0.9 and 1.3 are generally considered normal. Values less than 0.5 indicate severe obstruction.

The toe brachial index (TBI) may be a better measure of peripheral pressure since the smaller vessels in the toes are generally spared from calcification. Low TBI values are generally associated with a greater risk of amputation.¹⁰

One can use the history, clinical exam and imaging to make the diagnosis. Patients presenting with intermittent claudication and/or rest pain should get referrals to a vascular surgeon. For those patients presenting with a non-healing wound, one must rule out infection and ischemia, and also ensure appropriate pressure reduction.

Physicians can assess the periwound perfusion and oxygenation levels with newer available technologies. A laser Doppler measures skin perfusion pressure (SPP), which may aid in predicting healing. Values greater than 30 mmHg are generally predictive of wound healing. Hyperspectral imaging can measure tissue oxygenation and deoxygenation, and is under current investigation as a healing predictor.

A thorough exam and the results of non-invasive vascular studies will help determine the need for a vascular surgery consultation. Obtain the exam and vascular studies early in the patient’s course so consultation is not needlessly delayed. A patient with a lower extremity wound and contributing peripheral ischemia should have a consult for vascular intervention. Although distal bypass is the “gold standard” for limb revascularization, an endovascular procedure may restore enough flow to the limb to allow the wound to heal, achieving the desired endpoint.

Salient Insights On PAD Treatment

The general principles of proper management of the diabetic foot ulcer include proper wound care, ensuring adequate limb perfusion, appropriate treatment of infection and initiation of a strict offloading plan.

One should aggressively debride infected wounds with prompt drainage of pus. Choose antibiotics based on suspected organisms. Appropriately obtained deep tissue cultures will help guide the antibiotic course. When there is extensive necrotic tissue with fluctuance and pus, as well as gas in the tissues visible on plain radiographs, emergent surgical debridement must take precedence. In these situations, the debridement trumps thoughts of reconstruction and must precede revascularization.

When one diagnoses limb ischemia, referral to a vascular surgeon is necessary to determine if the patient is a candidate for revascularization either by angioplasty or open bypass. Advances in distal lower extremity revascularization have revolutionized limb salvage and continue to be a necessary component in the overall treatment of ischemic ulcers.¹¹

The goal of any revascularization procedure is to restore pulsatile blood flow to the foot. The important occlusive lesions are generally present in the infrapopliteal arteries of the calf. In most cases, a successful bypass from the popliteal artery to an artery of the ankle or foot is possible, and will provide enough perfusion to heal a neuroischemic ulcer. Most often, the circulation is satisfactory to the popliteal artery, thereby making a long graft originating in the femoral artery unnecessary. Clinically, the presence of a good popliteal pulse and a non-palpable pedal pulse is a favorable finding for a distal pedal bypass.

When it comes to the patient with a great deal of ischemia and tibial artery occlusion, angioplasty generally does not establish adequate and durable circulation so a bypass is the preferred procedure in moderate to severe occlusive lesions. An autogenous vein from the leg or the arm will be durable as the five-year patency of a pedal bypass is comparable to a femoral to popliteal bypass. Pomposelli and colleagues reviewed outcomes in more than 1,000 patients who had a dorsalis pedis artery bypass. They found the bypass to be durable with a high likelihood of limb salvage.¹²

Most often, one can determine the choice of target artery for bypass by the quality of the recipient artery. The dorsalis pedis artery is the most common arterial “target” for distal bypass. However, if that artery is occluded and unavailable, the surgeon may use the posterior tibial or plantar arteries.

Although there are many factors to consider in choosing the target artery for revascularization, Neville and colleagues support consideration for revascularization of the artery directly feeding the ischemic angiosome.¹¹ In their retrospective analysis, Neville and colleagues reported higher rates of ulcer healing in ischemic wounds after direct revascularization bypass to a specific angiosome. However, if the only artery available does not provide direct flow to the affected angiosome, revascularization remains indicated as the increased pressures will result in increased perfusion to the ischemic area and assist in ulcer healing.

In Conclusion

The causative factors and effective practices to deal with the acute and chronic ulceration and gangrene are well known. However, the failure of limb salvage lies in our collective inability to implement a team approach to managing these difficult problems.

A multidisciplinary team, a group of highly trained specialists, is best suited to treat these conditions. The podiatric surgeon must work in close collaboration with the vascular surgeon. The neuroischemic foot ulcer is associated with increased morbidity and requires a specialized team. Collaboration between podiatric and vascular surgeons is emerging as the most effective alliance for achieving successful outcomes.

Dr. Bevilacqua is an Associate Medical Director of the Amputation Prevention Center at Valley Presbyterian Hospital in Los Angeles. He is a Fellow of the American College of Foot and Ankle Surgeons.

Dr. Rogers is an Associate Medical Director of the Amputation Prevention Center at Valley Presbyterian Hospital in Los Angeles. He is a Fellow of the American College of Foot and Ankle Orthopaedics and Medicine.

Dr. Andros is the Medical Director of the Amputation Prevention Center at Valley Presbyterian Hospital in Los Angeles. He is a board certified vascular surgeon and is Co-Chairman of the Diabetic Foot Global Conference (DFCon).

References:

1. Boulton AJ, Kirsner RS, Vileikyte L. Clinical practice. Neuropathic diabetic foot ulcers. N Engl J Med.Jul 1 2004; 351(1):48-55.
2. Singh N, Armstrong DG, Lipsky BA. Preventing foot ulcers in patients with diabetes. JAMA Jan 12 2005; 293(2):217-228.
3. Palumbo PJ, Melton LJ. Peripheral vascular disease and diabetes. In Harris MI, Hamman RF (ed.):Diabetes In America. National Institutes of Health, Bethesda, Md., 1985, pp. 1-21.
4. Boulton AJ, Armstrong DG, Albert SF, et al. Comprehensive foot examination and risk assessment: a report of the task force of the foot care interest group of the American Diabetes Association, with endorsement by the American Association of Clinical Endocrinologists. Diabetes Care. Aug 2008; 31(8):1679-1685.
5. Reiber GE, Vileikyte L, Boyko EJ, et al. Causal pathways for incident lower-extremity ulcers in patients with diabetes from two settings. Diabetes Care. 1999;22(1):157-162.
6. Ndip A, Jude EB. Emerging evidence for neuroischemic diabetic foot ulcers: model of care and how to adapt practice. Int J Low Extrem Wounds. Jun 2009; 8(2):82-94.
7. Prompers L, Schaper N, Apelqvist J, et al. Prediction of outcome in individuals with diabetic foot ulcers: focus on the differences between individuals with and without peripheral arterial disease. The EURODIALE Study. Diabetologia. May 2008; 51(5):747-755.
8. Armstrong DG, Lavery LA, Harkless LB. Validation of a diabetic wound classification system. The contribution of depth, infection, and ischemia to risk of amputation [see comments]. Diabetes Care.1998; 21(5):855-859.
9. Andros G, Harris RW, Dulawa LB, Oblath RW, Salles-Cunha SX. The need for arteriography in diabetic patients with gangrene and palpable foot pulses. Arch Surg. 1984; 119(11):1260-1263.
10. Varatharajan N, Pillay S, Hitos K, Fletcher JP. Implications of low great toe pressures in clinical practice. ANZ J Surg. Apr 2006; 76(4):218-221.
11. Neville RF, Attinger CE, Bulan EJ, Ducic I, Thomassen M, Sidawy AN. Revascularization of a specific angiosome for limb salvage: does the target artery matter? Ann Vasc Surg. May-Jun 2009; 23(3):367-373.
12. Pomposelli FB, Kansal N, Hamdan AD, et al. A decade of experience with dorsalis pedis artery bypass: analysis of outcome in more than 1,000 cases. J Vasc Surg. Feb 2003; 37(2):307-315.

Posted by: PV Mayer at 10:17 am 0 comments - Add a Comment

Failure to Launch (28 Apr, 2010)

We need to deliver a persistent, aggressive and understandable message to our patients about insulin so that they may overcome their misconceptions about this life saving treatment.

Why Physicians Do Not Initiate Insulin Earlier

In a current study it was found that there are certain barriers for physicians that prevent them prescribing insulin much earlier in the treatment of diabetes....

Reasons for failing to initiate prescribed insulin (primary nonadherence) are poorly understood. So, this study set out to understand the barriers.

Researchers surveyed insulin-naïve patients with poorly controlled Type 2 diabetes, already treated with two or more oral agents who were recently prescribed insulin. They compared responses for respondents prescribed, but never initiating, insulin (n = 69) with those dispensed insulin (n = 100).

The results showed that the subjects failing to initiate prescribed insulin commonly reported misconceptions regarding insulin risk (35% believed that insulin causes blindness, renal failure, amputations, heart attacks, strokes, or early death), plans to instead work harder on behavioral goals, sense of personal failure, low self-efficacy, injection phobia, hypoglycemia concerns, negative impact on social life and job, inadequate health literacy, health care provider inadequately explaining risks/benefits, and limited insulin self-management training.

From the results it was concluded that among poorly controlled patients with Type 2 diabetes newly prescribed insulin, the major predictors of insulin nonadherence included plans to improve health behaviors in lieu of starting insulin, negative impact on social and work life, injection phobia, and concerns about side effects or hypoglycemia.

Nonadherent patients often blamed themselves, believing prior poor self-management caused the current need for insulin and erroneously conceptualized insulin as itself the cause of future complications. These patient-level findings are consistent with previous studies of attitudes about insulin. Not previously reported is the finding that nonadherent patients frequently felt their provider had not adequately explained the risks and benefits of insulin.

The importance of provider communication is underscored by the association between insulin initiation and health literacy. Primary nonadherence likely also reflects inadequate shared decision making or lack of self-management training. Interventions for PIR need to address both provider- and system-level factors.

Diabetes CareApril 2010 vol. 33 no. 4 733-735

Posted by: PV Mayer at 07:41 am 0 comments - Add a Comment

Diabetic Wound Centre Opens in Turkey (28 Apr, 2010)

Dr Warren Joseph's very learned take on the development of Diabetic Foot Centres around the world.

Diabetic Foot Infections in Turkey

April 11th, 2010 by Warren S. Joseph, DPM, FIDSA

I just returned from a lecture trip to Turkey where I had the privilege of giving 5 talks, one in the Mediterranean resort city of Antalya at a nationwide Hospital Infection Congress and 4 to the faculties at various medical universities throughout the country. Before getting into details about specifics dealing with lower extremity infections I first wanted to say that, if you have never visited, and this was my first time, Turkey is an unbelievable country with warm, welcoming people, incredible history, scenery and great food. Istanbul, a bustling metropolis of over 12 million people, has to be one of the great cities of Europe.

A Diabetic Foot Infection in Malatya, Turkey

In preparation for my talks I was asked to concentrate on the importance of a team approach to amputation prevention. Having just returned from DFCON I was up to date with the latest published data and reports from around the world about the successes that true amputation prevention teams have achieved in reducing the rates of “major” amputation. I have always found it amazing, if not a bit troubling, that smaller, less developed nations can codify a network of diabetic foot centers throughout their countries more than we have accomplished here in the United States. Even Pakistan and Kosovo, as discussed at this year’s DFCON, are able to reduce amputation rates by starting these centers. Turkey has made some progress towards the goal of developing amputation prevention teams. Just last year Yesil, et al from Dokuz Eylul University Medical Center in Izmir (a facility, unfortunately, I did not have a chance to visit) reported a reduction of major amputations after starting such a team. (Yesil S. et.al. Exp Clin Endocrinol Diabetes, 2009). In Istanbul I was honored to meet Dr. N. Saltoglu at Cerrahpasa Medical School, Istanbul University, when I gave one of my lectures to their Infectious Diseases faculty. Dr. Saltoglu has just recently started a multidisciplinary diabetic foot team at this large institution of >1800 beds. They are already beginning to see positive outcomes.

During my trip I also lectured to the infectious disease faculties at Universities in the cities of Malatya and Kayseri both in the Eastern Provinces of the country. They were very interested in the concept of starting comprehensive diabetic foot teams but were stymied by much the same turf battles and, dare I say, ego issues that we find here in the US. Patients are treated by their local primary physicians for protracted periods before being sent to the hospital specialists. Once admitted they are shuttled between various services including endocrinology, vascular surgery, orthopedic surgery and internal medicine with each passing the patient off to another service once their particular part of the job is completed with little coordination of effort. The ID physicians, in particular, play a very primary role in the treatment of DFI and expressed frustration that, by the time they see the patient, it is often very late in the progression of the disease and they are dealing with infections that have received multiple, often inadequate antibiotics and now present with multi drug resistant pathogens. The universal regret, oft expressed at DFCON, about the patient being seen too late in the progression of the disease was repeated time and time again. It just goes to show that you can travel 5000 miles from home to a totally different culture, yet some issues are universal!

A few other thoughts and interesting findings about lower extremity infections in Turkey:

1. MRSA is not the problem we have here. In fact, in most hospitals the rates have been decreasing the past 5 years. Furthermore, they do not differentiate MRSA into HA- vs. CA- strains. The common thinking is that CA-MRSA is not a widespread problem and they just do not worry about it. This is a huge difference from here where I need to treat everybody as if they have CA-MRSA until proven otherwise.

2. There are different antibiotics. Whereas we use so much vancomycin for our MRSA in-patient soft tissue infections, their drug of first choice is teicoplanin. This is another glycopeptides that, although widely used in other parts of the world, never received its US approval. Like vancomycin, teicoplanin presents its own set of problems with dosing including having to give adequate loading dose, measuring troughs and the potential for liver toxicity. There may also be “MIC Creep” issues with MRSA and teicoplanin. Another unique antibiotics is cefoperazone/sulbactam a β-lactamase inhibitor combination I remember reading about 20 years ago when it was thought that it might be brought into the US. Other drugs are the same including piperacillin/tazobactam, ertapenem and imipenem.

3. ESBLs are a major problem. Whereas we are just now beginning to see extended spectrum β-lactamase (ESBL) producing gram negative rods here in our US diabetic foot infections, Turkey has had them for years. In fact, there are enzymes found in Turkey that you would be hard pressed to find anywhere else in the world. Surveillance surveys have found gram negative resistance rates to cephalosporins and even quinolones in the 50-60% range. It is felt that some of this may be caused by the long term, inadequate antibiotic therapy that is often started by primary physicians or even pharmacists before the patient is seen by the ID specialists. And, of course, the universal overuse of the flouroquinolones is thought to contribute.

4. Acinetobacter, especially multi-drug resistant strains, is a problem. I found this particularly interesting given the well documented outbreak of Acinetobacter infections that has been reported in our troops returning from the current Middle Eastern conflict. When in some of these Eastern sections of Turkey one is not far from Iraq and Syria. Perhaps there is something in the environment or the locale that propagates this organism.

With Dr. Bayindir, Director of Infectious Diseases, University Hospital, Malatya, Turkey

Posted by: PV Mayer at 06:25 am 0 comments - Add a Comment

Pay For Performance: The Ultimate Edition (5 Apr, 2010)

This is government using its head instead of its backside, to treat diabetes.

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Diabetes: Death From A Thousand Cuts (7 Sep, 2010)

The cruel cost of ignoring diabetes: Jane lost an arm and two legs to the disease because, like so many, she didn't take it seriously

More...

Collagen from Tobacco Plants (3 Sep, 2010)

CollPlant's Human Collagen Grown From Tobacco One Step Closer to Dressing Your Wounds

Limb Salvage in Brazil (30 Aug, 2010)

The effectiveness of educational practice in diabetic foot: a view from Brazil

Abstract

Background

Results

Conclusion

Background

Patients and Methods

Results

Discussion

Conclusion

Competing interests

Authors' contributions

Acknowledgements

References

Ontario Ramping Up Wound Care in Community (30 Aug, 2010)

Obesity is a Deadly Disease (30 Aug, 2010)

Obese Men at Age 20 Years Double Death Risk

Green Vegetables Cut Diabetes Risk (30 Aug, 2010)

Green Leafy Vegetables Cuts The Risk of Diabetes by 14%

The incidence of Type 2 diabetes has been rising dramatically during the past two decades, with diet being a major contributor, but evidence thus far has been conflicting as to whether increasing consumption of fruit and vegetables would have an impact.

New Hope in the Treatment of Charcot Arthropathy (24 Aug, 2010)

Surgeon Reports Successful Treatment of Charcot Foot

Innovation in Diabetes Care (1 Jul, 2010)

Maggots and other Medical Miracles (29 Jun, 2010)

Leeches and maggots: Doctors' old-fashioned little helpers

Published: Tuesday, June 29, 2010, 8:00 AM Updated: Tuesday, June 29, 2010, 9:17 AM

RankL OPG Pathway and Charcot Neuroarthropathy (25 Jun, 2010)

Tuesday, June 22, 2010

Overview of the RANKL OPG Pathway

iPhone 4 for Wound Care? (25 Jun, 2010)

iPhone 4 FaceTime video conferencing feature can help your doctor

Insulin Pills to be Studied (17 Jun, 2010)

I

Insulin Pills Finally in Clinical Trials

DoxyCycline as an Antii-inflamatory Agent (16 Jun, 2010)

Video Learning - Investigation of Doxycycline as an Agent for "Wound Chemotherapy"

Clean Teeth Prevents more than Bad Breath (11 Jun, 2010)

Clean Teeth Prevents Heart Disease by 70%

ChemoVAC: Diabetic Wound Care SALSAtized! (21 May, 2010)

ChemoVac Dressing Assembly Video Tutorial

The Foot as a Health Indicator (20 May, 2010)

Insulin is Good for YOU (19 May, 2010)

Insulin Protects Against Artery Damage

More on ACCORD (19 May, 2010)

Low HbA1c not linked to mortality in new ACCORD analysis

ACCORD Results revisited (12 May, 2010)

Epidemiologic Relationships Between A1C and All-Cause Mortality During a Median 3.4-Year Follow-up of Glycemic Treatment in the ACCORD Trial

Abstract

High Mortality Rate in Diabetics with Charcot Neuroarthropathy (7 May, 2010)

Mortality associated with acute charcot foot and neuropathic foot ulceration.

Abstract

Arterial Disease in Diabetes (6 May, 2010)

Understanding The Effects Of PAD On The Diabetic Foot

A Closer Look At The Literature On PAD

Mastering The Crucial Diagnostic Elements

Salient Insights On PAD Treatment

In Conclusion

Failure to Launch (28 Apr, 2010)

Why Physicians Do Not Initiate Insulin Earlier

Diabetic Wound Centre Opens in Turkey (28 Apr, 2010)

Diabetic Foot Infections in Turkey

Pay For Performance: The Ultimate Edition (5 Apr, 2010)

Rudd's sweetener for GPs to treat diabetics