Michele G. Sullivan

Two scores used to measure disease activity in axial psoriatic arthritis are similarly accurate, but the older measure is easier to employ and thus, probably more clinically practical, a study has shown.

A comparative study determined that the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), with its single patient-derived format of six questions, is just as accurate as the newer Ankylosing Spondylitis Disease Activity Score (ASDAS). That measure has four formulas including two that assess both C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR), and two that assess each of the factors separately.

ASDAS was introduced in 2007 because researchers felt the BASDAI had limited face and construct validity, reported Dr. Lihi Eder and colleagues (Ann. Rheum. Dis. 2010 July 13 [doi:10.1136/ard.2010.129726]).

Dr. Eder of Toronto Western Hospital and the coauthors compared the scores’ validity in 201 patients with axial psoriatic arthritis. Their mean age was 53 years; the mean duration of psoriatic arthritis was 18.5 years, with a mean of 9 years since the diagnosis of axial involvement. For each patient, the researchers calculated the BASDAI and ASDAS and correlated those with the patients’ and their physicians’ rating of disease.

The BASDAI includes patient rating of six aspects of disease: fatigue, total back pain, pain and swelling of peripheral joints, pain at entheseal sites, severity of morning stiffness, and duration of morning stiffness. The ASDAS involves only three of those factors: total back pain, pain and swelling of peripheral joints, and duration of morning stiffness. All patients gave a global assessment of their disease activity and were examined by a rheumatologist who gave a global assessment of disease activity as well.

Both the patient and physician global ratings are given on a scale of 0-10 with 10 being the most severe disease. Any patient with either a patient or physician global assessment score on either scale equal to or above 6 was considered to have highly active disease.

Both the BASDAI and ASDAS correlated well with disease activity, which is not surprising given that both consist largely of patient-derived information, the investigators said. Physician global assessment correlated less well with BASDAI and ASDAS.

Both scores were able to discriminate between high and low disease activity, an important function in that the scores are used to guide treatment decisions.

The addition of the CRP and ESR components to the ASDAS score showed poor correlation with both patient and physician ratings of disease activity. "While CRP showed only marginally significant and weakly positive correlation with patient or physician global scores, ESR did not show any significant correlation with either of those scores," the authors noted.

In a logistic regression analysis, both scores discriminated well between high and low disease activity. "As expected, the scores showed better discrimination when the definition of the disease activity was based on patient- rather than physician-derived scores," the authors wrote.

Because the scores are similarly accurate, the authors endorsed the BASDAI score on the basis of its relative simplicity. "The ASDAS score did not improve discriminative ability compared with BASDAI," they wrote. “Therefore, because BASDAI is easier to calculate, it may be more practical for clinical use in patients with axial psoriatic arthritis."

Disclosures: The study was funded by the University of Toronto Psoriatic Arthritis Program. The authors said they had no conflicts of interest.

Two scores used to measure disease activity in axial psoriatic arthritis are similarly accurate, but the older measure is easier to employ and thus, probably more clinically practical, a study has shown.

A comparative study determined that the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), with its single patient-derived format of six questions, is just as accurate as the newer Ankylosing Spondylitis Disease Activity Score (ASDAS). That measure has four formulas including two that assess both C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR), and two that assess each of the factors separately.

ASDAS was introduced in 2007 because researchers felt the BASDAI had limited face and construct validity, reported Dr. Lihi Eder and colleagues (Ann. Rheum. Dis. 2010 July 13 [doi:10.1136/ard.2010.129726]).

Dr. Eder of Toronto Western Hospital and the coauthors compared the scores’ validity in 201 patients with axial psoriatic arthritis. Their mean age was 53 years; the mean duration of psoriatic arthritis was 18.5 years, with a mean of 9 years since the diagnosis of axial involvement. For each patient, the researchers calculated the BASDAI and ASDAS and correlated those with the patients’ and their physicians’ rating of disease.

The BASDAI includes patient rating of six aspects of disease: fatigue, total back pain, pain and swelling of peripheral joints, pain at entheseal sites, severity of morning stiffness, and duration of morning stiffness. The ASDAS involves only three of those factors: total back pain, pain and swelling of peripheral joints, and duration of morning stiffness. All patients gave a global assessment of their disease activity and were examined by a rheumatologist who gave a global assessment of disease activity as well.

Both the patient and physician global ratings are given on a scale of 0-10 with 10 being the most severe disease. Any patient with either a patient or physician global assessment score on either scale equal to or above 6 was considered to have highly active disease.

Both the BASDAI and ASDAS correlated well with disease activity, which is not surprising given that both consist largely of patient-derived information, the investigators said. Physician global assessment correlated less well with BASDAI and ASDAS.

Both scores were able to discriminate between high and low disease activity, an important function in that the scores are used to guide treatment decisions.

The addition of the CRP and ESR components to the ASDAS score showed poor correlation with both patient and physician ratings of disease activity. "While CRP showed only marginally significant and weakly positive correlation with patient or physician global scores, ESR did not show any significant correlation with either of those scores," the authors noted.

In a logistic regression analysis, both scores discriminated well between high and low disease activity. "As expected, the scores showed better discrimination when the definition of the disease activity was based on patient- rather than physician-derived scores," the authors wrote.

Because the scores are similarly accurate, the authors endorsed the BASDAI score on the basis of its relative simplicity. "The ASDAS score did not improve discriminative ability compared with BASDAI," they wrote. “Therefore, because BASDAI is easier to calculate, it may be more practical for clinical use in patients with axial psoriatic arthritis."

Disclosures: The study was funded by the University of Toronto Psoriatic Arthritis Program. The authors said they had no conflicts of interest.

Two scores used to measure disease activity in axial psoriatic arthritis are similarly accurate, but the older measure is easier to employ and thus, probably more clinically practical, a study has shown.

A comparative study determined that the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), with its single patient-derived format of six questions, is just as accurate as the newer Ankylosing Spondylitis Disease Activity Score (ASDAS). That measure has four formulas including two that assess both C-reactive protein (CRP) level and erythrocyte sedimentation rate (ESR), and two that assess each of the factors separately.

ASDAS was introduced in 2007 because researchers felt the BASDAI had limited face and construct validity, reported Dr. Lihi Eder and colleagues (Ann. Rheum. Dis. 2010 July 13 [doi:10.1136/ard.2010.129726]).

Dr. Eder of Toronto Western Hospital and the coauthors compared the scores’ validity in 201 patients with axial psoriatic arthritis. Their mean age was 53 years; the mean duration of psoriatic arthritis was 18.5 years, with a mean of 9 years since the diagnosis of axial involvement. For each patient, the researchers calculated the BASDAI and ASDAS and correlated those with the patients’ and their physicians’ rating of disease.

The BASDAI includes patient rating of six aspects of disease: fatigue, total back pain, pain and swelling of peripheral joints, pain at entheseal sites, severity of morning stiffness, and duration of morning stiffness. The ASDAS involves only three of those factors: total back pain, pain and swelling of peripheral joints, and duration of morning stiffness. All patients gave a global assessment of their disease activity and were examined by a rheumatologist who gave a global assessment of disease activity as well.

Both the patient and physician global ratings are given on a scale of 0-10 with 10 being the most severe disease. Any patient with either a patient or physician global assessment score on either scale equal to or above 6 was considered to have highly active disease.

Both the BASDAI and ASDAS correlated well with disease activity, which is not surprising given that both consist largely of patient-derived information, the investigators said. Physician global assessment correlated less well with BASDAI and ASDAS.

Both scores were able to discriminate between high and low disease activity, an important function in that the scores are used to guide treatment decisions.

The addition of the CRP and ESR components to the ASDAS score showed poor correlation with both patient and physician ratings of disease activity. "While CRP showed only marginally significant and weakly positive correlation with patient or physician global scores, ESR did not show any significant correlation with either of those scores," the authors noted.

In a logistic regression analysis, both scores discriminated well between high and low disease activity. "As expected, the scores showed better discrimination when the definition of the disease activity was based on patient- rather than physician-derived scores," the authors wrote.

Because the scores are similarly accurate, the authors endorsed the BASDAI score on the basis of its relative simplicity. "The ASDAS score did not improve discriminative ability compared with BASDAI," they wrote. “Therefore, because BASDAI is easier to calculate, it may be more practical for clinical use in patients with axial psoriatic arthritis."

Disclosures: The study was funded by the University of Toronto Psoriatic Arthritis Program. The authors said they had no conflicts of interest.

CHICAGO – Patients with severe acne are missing out on the skin-clearing benefits of oral contraceptives and need to know that OCs can be prescribed for acne without a pelvic examination by a gynecologist, according to Dr. Bethanee Schlosser.

“When talking to teens and their parents, it’s important to explain that a pelvic exam is not necessary before giving these medications to young women,” she said.

It appears that patients aren’t privy to this information, and are reluctant to ask for oral contraceptives as acne medication.

“That may be the biggest hurdle keeping these patients from getting adequate treatment for their acne,” she said.

In 2004, the World Health Organization released guidelines stating that pelvic exams and Pap smears are no longer required before administering combination oral contraceptives.

Dr. Schlosser noted, however, that she does ask all of her female patients when they had their last full gynecologic exam, Pap smear included, and encourages them to stay current.

Oral Contraceptives

Three combination oral contraceptives are approved for the treatment of acne in women in the United States: ethinyl estradiol and norgestimate (Ortho Tri-Cyclen), ethinyl estradiol and norethindrone (Estrostep), and ethinyl estradiol and drospirenone (Yaz).

Drospironone, an analogue of spironolactone, reduces sebum production and increases sex hormone–binding globulin, thus reducing circulating androgens, Dr. Schlosser said. “Some women will come to me, though, and say that their ob.gyn. has told them they can’t take any pill containing drospirenone or spironolactone,” because of its possible effect on potassium levels, especially in combination with other drugs that increase serum potassium (ACE inhibitors, angiotensin receptor blockers, potassium-sparing diuretics, heparin, aldosterone antagonists, and nonsteroidal anti-inflammatories).

Dr. Schlosser pointed to a 2009 study of 27 women with either severe papular or nodulocystic acne who were treated with a combined oral contraceptive containing 30 mg ethinyl estradiol, 3 mg drospirenone, and 100 mg spironolactone. None of the patients had a significant elevation in serum potassium level; there were no reports of adverse events serious enough to require discontinuation of treatment. At follow up, 85% of subjects were entirely clear of acne lesions or had excellent improvement, 7% were mildly improved, and 7% were not improved (J. Am. Acad. Derm. 2008;58:60-2).

A 2008 study looked only at the risk of hyperkalemia among 22,429 women who used the drospirenone-containing contraceptive compared with 44,858 who used other oral contraceptives (Contraception 2008;78:377-83). There was no significant between-group difference in the incidence of hyperkalemia.

This type of treatment is not an overnight acne cure, Dr. Schlosser stressed. “I tell women you have to allow at least three cycles of use before you start to judge efficacy. Patients can continue to get more benefit from 3-6 months of use, too.”

A 2007 Cochrane review of the three Food and Drug Administration–approved acne-fighting oral contraceptives found no significant differences in effectiveness, she said.

The Role of Androgen Testing

Elevated androgens are a large contributor to acne in women, and both the estradiol and progestins in combination oral contraceptives work to decrease them, said Dr. Schlosser, director of the women’s skin health program at Northwestern University, Chicago. Androgen testing may be appropriate for some women.

“If a woman complains of sudden onset of acne, or acne that is severe or recalcitrant to traditional therapy, I would say testing is a good idea. You might also consider it for women with androgenic features – hirsutism, deep voice, muscular habitus, or androgenic alopecia,” she said.

Because these features can also be symptoms of polycystic ovary syndrome, Dr. Schlosser also suggested checking for acanthosis nigricans, central obesity, irregular menses, and infertility.

Androgen testing is most informative when performed at the onset of menses. “This is because androgen secretion follows the same pattern as estradiol, which peaks in midcycle and falls to a nadir at the beginning of menstruation,” Dr. Schlosser said. “I print out a lab request, and tell the patient to have her blood drawn on the first day of her period.” Morning testing is better, if possible, because of the hormone’s diurnal secretion.

Total testosterone is the most sensitive test for androgen levels in women with acne. However, “it’s important to note that the levels associated with acne can be elevated compared to controls, but still within the normal reference ranges,” she said. Total testosterone level can also be falsely elevated in obese women, “because insulin reduces the liver’s secretion of sex hormone–binding globulin,” she said.

Treatment Risks

There are some contraindications to the use of oral contraceptives for the treatment of acne, Dr. Schlosser noted. Hypercoagulability, a history of venous thromboembolism (VTE), stroke or coronary artery disease, any gynecologic cancer, uncontrolled hypertension, abnormal liver function tests, pregnancy, or abnormal vaginal bleeding should be considered before prescribing.

Oral contraceptives do increase the risk of venous thromboembolism, although that risk is highly dependent on other factors as well, including advancing age and tobacco use. Dr. Schlosser said a concrete, direct link between oral contraceptives and VTE risk has yet to be found, but he hopes an ongoing case-control study of more than 50,000 oral contraceptive users (including up to 5 years of follow-up data) will provide answers.

Finally, Dr. Schlosser added, the single greatest risk of VTE among women is pregnancy and the postpartum period. “So I would say if you’re treating acne in a woman of childbearing age with an oral contraceptive, you are also protecting her from the biggest risk factor she has for thromboembolic events.”

Dr. Schlosser said she had no relevant financial disclosures.

CHICAGO – Patients with severe acne are missing out on the skin-clearing benefits of oral contraceptives and need to know that OCs can be prescribed for acne without a pelvic examination by a gynecologist, according to Dr. Bethanee Schlosser.

“When talking to teens and their parents, it’s important to explain that a pelvic exam is not necessary before giving these medications to young women,” she said.

It appears that patients aren’t privy to this information, and are reluctant to ask for oral contraceptives as acne medication.

“That may be the biggest hurdle keeping these patients from getting adequate treatment for their acne,” she said.

In 2004, the World Health Organization released guidelines stating that pelvic exams and Pap smears are no longer required before administering combination oral contraceptives.

Dr. Schlosser noted, however, that she does ask all of her female patients when they had their last full gynecologic exam, Pap smear included, and encourages them to stay current.

Oral Contraceptives

Three combination oral contraceptives are approved for the treatment of acne in women in the United States: ethinyl estradiol and norgestimate (Ortho Tri-Cyclen), ethinyl estradiol and norethindrone (Estrostep), and ethinyl estradiol and drospirenone (Yaz).

Drospironone, an analogue of spironolactone, reduces sebum production and increases sex hormone–binding globulin, thus reducing circulating androgens, Dr. Schlosser said. “Some women will come to me, though, and say that their ob.gyn. has told them they can’t take any pill containing drospirenone or spironolactone,” because of its possible effect on potassium levels, especially in combination with other drugs that increase serum potassium (ACE inhibitors, angiotensin receptor blockers, potassium-sparing diuretics, heparin, aldosterone antagonists, and nonsteroidal anti-inflammatories).

Dr. Schlosser pointed to a 2009 study of 27 women with either severe papular or nodulocystic acne who were treated with a combined oral contraceptive containing 30 mg ethinyl estradiol, 3 mg drospirenone, and 100 mg spironolactone. None of the patients had a significant elevation in serum potassium level; there were no reports of adverse events serious enough to require discontinuation of treatment. At follow up, 85% of subjects were entirely clear of acne lesions or had excellent improvement, 7% were mildly improved, and 7% were not improved (J. Am. Acad. Derm. 2008;58:60-2).

A 2008 study looked only at the risk of hyperkalemia among 22,429 women who used the drospirenone-containing contraceptive compared with 44,858 who used other oral contraceptives (Contraception 2008;78:377-83). There was no significant between-group difference in the incidence of hyperkalemia.

This type of treatment is not an overnight acne cure, Dr. Schlosser stressed. “I tell women you have to allow at least three cycles of use before you start to judge efficacy. Patients can continue to get more benefit from 3-6 months of use, too.”

A 2007 Cochrane review of the three Food and Drug Administration–approved acne-fighting oral contraceptives found no significant differences in effectiveness, she said.

The Role of Androgen Testing

Elevated androgens are a large contributor to acne in women, and both the estradiol and progestins in combination oral contraceptives work to decrease them, said Dr. Schlosser, director of the women’s skin health program at Northwestern University, Chicago. Androgen testing may be appropriate for some women.

“If a woman complains of sudden onset of acne, or acne that is severe or recalcitrant to traditional therapy, I would say testing is a good idea. You might also consider it for women with androgenic features – hirsutism, deep voice, muscular habitus, or androgenic alopecia,” she said.

Because these features can also be symptoms of polycystic ovary syndrome, Dr. Schlosser also suggested checking for acanthosis nigricans, central obesity, irregular menses, and infertility.

Androgen testing is most informative when performed at the onset of menses. “This is because androgen secretion follows the same pattern as estradiol, which peaks in midcycle and falls to a nadir at the beginning of menstruation,” Dr. Schlosser said. “I print out a lab request, and tell the patient to have her blood drawn on the first day of her period.” Morning testing is better, if possible, because of the hormone’s diurnal secretion.

Total testosterone is the most sensitive test for androgen levels in women with acne. However, “it’s important to note that the levels associated with acne can be elevated compared to controls, but still within the normal reference ranges,” she said. Total testosterone level can also be falsely elevated in obese women, “because insulin reduces the liver’s secretion of sex hormone–binding globulin,” she said.

Treatment Risks

There are some contraindications to the use of oral contraceptives for the treatment of acne, Dr. Schlosser noted. Hypercoagulability, a history of venous thromboembolism (VTE), stroke or coronary artery disease, any gynecologic cancer, uncontrolled hypertension, abnormal liver function tests, pregnancy, or abnormal vaginal bleeding should be considered before prescribing.

Oral contraceptives do increase the risk of venous thromboembolism, although that risk is highly dependent on other factors as well, including advancing age and tobacco use. Dr. Schlosser said a concrete, direct link between oral contraceptives and VTE risk has yet to be found, but he hopes an ongoing case-control study of more than 50,000 oral contraceptive users (including up to 5 years of follow-up data) will provide answers.

Finally, Dr. Schlosser added, the single greatest risk of VTE among women is pregnancy and the postpartum period. “So I would say if you’re treating acne in a woman of childbearing age with an oral contraceptive, you are also protecting her from the biggest risk factor she has for thromboembolic events.”

Dr. Schlosser said she had no relevant financial disclosures.

CHICAGO – Patients with severe acne are missing out on the skin-clearing benefits of oral contraceptives and need to know that OCs can be prescribed for acne without a pelvic examination by a gynecologist, according to Dr. Bethanee Schlosser.

“When talking to teens and their parents, it’s important to explain that a pelvic exam is not necessary before giving these medications to young women,” she said.

It appears that patients aren’t privy to this information, and are reluctant to ask for oral contraceptives as acne medication.

“That may be the biggest hurdle keeping these patients from getting adequate treatment for their acne,” she said.

In 2004, the World Health Organization released guidelines stating that pelvic exams and Pap smears are no longer required before administering combination oral contraceptives.

Dr. Schlosser noted, however, that she does ask all of her female patients when they had their last full gynecologic exam, Pap smear included, and encourages them to stay current.

Oral Contraceptives

Three combination oral contraceptives are approved for the treatment of acne in women in the United States: ethinyl estradiol and norgestimate (Ortho Tri-Cyclen), ethinyl estradiol and norethindrone (Estrostep), and ethinyl estradiol and drospirenone (Yaz).

Drospironone, an analogue of spironolactone, reduces sebum production and increases sex hormone–binding globulin, thus reducing circulating androgens, Dr. Schlosser said. “Some women will come to me, though, and say that their ob.gyn. has told them they can’t take any pill containing drospirenone or spironolactone,” because of its possible effect on potassium levels, especially in combination with other drugs that increase serum potassium (ACE inhibitors, angiotensin receptor blockers, potassium-sparing diuretics, heparin, aldosterone antagonists, and nonsteroidal anti-inflammatories).

Dr. Schlosser pointed to a 2009 study of 27 women with either severe papular or nodulocystic acne who were treated with a combined oral contraceptive containing 30 mg ethinyl estradiol, 3 mg drospirenone, and 100 mg spironolactone. None of the patients had a significant elevation in serum potassium level; there were no reports of adverse events serious enough to require discontinuation of treatment. At follow up, 85% of subjects were entirely clear of acne lesions or had excellent improvement, 7% were mildly improved, and 7% were not improved (J. Am. Acad. Derm. 2008;58:60-2).

A 2008 study looked only at the risk of hyperkalemia among 22,429 women who used the drospirenone-containing contraceptive compared with 44,858 who used other oral contraceptives (Contraception 2008;78:377-83). There was no significant between-group difference in the incidence of hyperkalemia.

This type of treatment is not an overnight acne cure, Dr. Schlosser stressed. “I tell women you have to allow at least three cycles of use before you start to judge efficacy. Patients can continue to get more benefit from 3-6 months of use, too.”

A 2007 Cochrane review of the three Food and Drug Administration–approved acne-fighting oral contraceptives found no significant differences in effectiveness, she said.

The Role of Androgen Testing

Elevated androgens are a large contributor to acne in women, and both the estradiol and progestins in combination oral contraceptives work to decrease them, said Dr. Schlosser, director of the women’s skin health program at Northwestern University, Chicago. Androgen testing may be appropriate for some women.

“If a woman complains of sudden onset of acne, or acne that is severe or recalcitrant to traditional therapy, I would say testing is a good idea. You might also consider it for women with androgenic features – hirsutism, deep voice, muscular habitus, or androgenic alopecia,” she said.

Because these features can also be symptoms of polycystic ovary syndrome, Dr. Schlosser also suggested checking for acanthosis nigricans, central obesity, irregular menses, and infertility.

Androgen testing is most informative when performed at the onset of menses. “This is because androgen secretion follows the same pattern as estradiol, which peaks in midcycle and falls to a nadir at the beginning of menstruation,” Dr. Schlosser said. “I print out a lab request, and tell the patient to have her blood drawn on the first day of her period.” Morning testing is better, if possible, because of the hormone’s diurnal secretion.

Total testosterone is the most sensitive test for androgen levels in women with acne. However, “it’s important to note that the levels associated with acne can be elevated compared to controls, but still within the normal reference ranges,” she said. Total testosterone level can also be falsely elevated in obese women, “because insulin reduces the liver’s secretion of sex hormone–binding globulin,” she said.

Treatment Risks

There are some contraindications to the use of oral contraceptives for the treatment of acne, Dr. Schlosser noted. Hypercoagulability, a history of venous thromboembolism (VTE), stroke or coronary artery disease, any gynecologic cancer, uncontrolled hypertension, abnormal liver function tests, pregnancy, or abnormal vaginal bleeding should be considered before prescribing.

Oral contraceptives do increase the risk of venous thromboembolism, although that risk is highly dependent on other factors as well, including advancing age and tobacco use. Dr. Schlosser said a concrete, direct link between oral contraceptives and VTE risk has yet to be found, but he hopes an ongoing case-control study of more than 50,000 oral contraceptive users (including up to 5 years of follow-up data) will provide answers.

Finally, Dr. Schlosser added, the single greatest risk of VTE among women is pregnancy and the postpartum period. “So I would say if you’re treating acne in a woman of childbearing age with an oral contraceptive, you are also protecting her from the biggest risk factor she has for thromboembolic events.”

Dr. Schlosser said she had no relevant financial disclosures.

CHICAGO — A drug that targets metastatic melanoma with mutations in the BRAF oncogene may be the first step on a path to individualized chemotherapy for patients with these formerly untreatable cancers.

“We are rapidly unraveling the molecular underpinnings of these tumors, and discovering the mechanisms by which they drive melanoma growth. These insights allow us to develop and select drugs on the basis of every patient’s individual genome,” Dr. Hensin Tsao said at the American Academy of Dermatology’s 2010 meeting.

Courtesy Bill Truslow/Massachusetts General Hospital

PLX4032 is the first drug to successfully shrink both cutaneous and internal metastases of BRAF-mutated melanomas, said Dr. Tsao, a dermatologist who is director of the Massachusetts General Hospital Melanoma Genetics Program in Boston.

His colleague, Dr. Keith Flaherty, is about to publish data from the drug’s phase II trial of 87 patients; 81% of those with the BRAF-mutated melanoma responded with a 30% or more shrinkage of the targeted lesions.

After a phase I safety and dose-finding trial, investigators settled on an oral dose of 960 mg twice daily for the phase II study. The effect was little short of remarkable, Dr. Flaherty, director of developmental therapeutics at the Massachusetts General Hospital Cancer Center, said in an interview.

“My first responding patient had cutaneous and internal metastases, and the cutaneous metastases were clearly getting better right in front of our eyes,” he said. “We have seen this in some other areas of cancer, but never in melanoma, which before this was a clinical scenario with an unmet need for therapy.”

PLX4032, first engineered by the Berkeley, Calif., company Plexxikon Inc. and being developed in partnership with Roche, is not a foolproof cure, Dr. Tsao said in an interview. “It’s clearly a huge leap forward for the patients who responded so rapidly, yet most are still progressing despite being on the drug. It’s the best stun we’ve ever seen for melanoma, but it’s not a permanent kill.”

Sustained response in the phase I and II trials has varied from only 2 months to up to 2 years, Dr. Flaherty said. He could find no significant predictors of progression or response among the group except for initial tumor number and size. Typically, he said, the patients with the greatest mass of metastatic disease had the shortest duration of response, while those with a smaller tumor burden had a longer duration of response.

“When you have metastatic melanoma, your days are numbered—and numbered in a way we can’t predict when metastatic disease is diagnosed,” Dr. Flaherty said. “What this therapy does is push out the time until the disease worsens. We are not yet smart enough to understand what it is that allows a tumor to work its way around the drug’s activity.”

Chemotherapy-resistant cancers are nothing new, Dr. Tsao noted. What will be new is the full investigation of melanoma’s genetic pathways, and the development of drugs to block them in multiple ways. “The next frontier will be to understand all the ways that melanoma can outsmart treatment. We may have to use multiple therapies to corner it. So a full discovery of all melanoma’s potential vulnerabilities is very important.”

There is already at least a hint that PLX4032 has a very narrow target—only BRAF tumors with the V600E subtype. “There is some laboratory evidence that if you give this drug to a tumor that may be mutated at another gene you may be worsening things,” Dr. Tsao said. “This has yet to be borne out in clinical studies, but bench-side data suggest that you have to be very precise with this drug, because the wrong choice could be potentially deleterious.”

In vitro and in vivo experiments did suggest that PLX4032 was ineffective against non-BRAF melanomas, Dr. Flaherty said. “In a lab, the drug will kill a cancer cell with a BRAF mutation but not with another mutation. Whether it can facilitate the growth of others is an interesting concept supported by some laboratory data, with the observation that this and drugs like it can transiently stimulate other cancer cells with RAS mutations. In these, the drug basically activates the BRAF pathway instead of blocking it. We don’t know the relevance of this finding to humans. It is interesting, but it may have no real clinical impact.”

Discovering the best targets for molecular therapies is typically a long process, Dr. Tsao said, but the race to treat BRAF metastatic melanoma has so far been a fast one. “In 2002, the first BRAF mutation in melanoma was published, and the first drug is already coming to clinical fruition. This is pretty fast for something we’ve been fooling around with ineffectively for 20 years.”

During the 8 years between the mutation’s discovery and Dr. Flaherty’s trial, drug companies have not been idle. “There is now a pipeline of drugs against BRAF. PLX4032 might not be the best or the least toxic, but it’s the first of a host coming down the pike. This is very significant, because now we have a brand-new way of looking at a previously untreatable cancer.”

Roche Pharmaceuticals and Plexxikon sponsored the PLX4032 studies. Dr. Tsao said he had no financial declarations with regard to the drug. Dr. Flaherty has served as a consultant to Roche regarding further development of PLX4032 in melanoma.

CHICAGO — A drug that targets metastatic melanoma with mutations in the BRAF oncogene may be the first step on a path to individualized chemotherapy for patients with these formerly untreatable cancers.

“We are rapidly unraveling the molecular underpinnings of these tumors, and discovering the mechanisms by which they drive melanoma growth. These insights allow us to develop and select drugs on the basis of every patient’s individual genome,” Dr. Hensin Tsao said at the American Academy of Dermatology’s 2010 meeting.

Courtesy Bill Truslow/Massachusetts General Hospital

PLX4032 is the first drug to successfully shrink both cutaneous and internal metastases of BRAF-mutated melanomas, said Dr. Tsao, a dermatologist who is director of the Massachusetts General Hospital Melanoma Genetics Program in Boston.

His colleague, Dr. Keith Flaherty, is about to publish data from the drug’s phase II trial of 87 patients; 81% of those with the BRAF-mutated melanoma responded with a 30% or more shrinkage of the targeted lesions.

After a phase I safety and dose-finding trial, investigators settled on an oral dose of 960 mg twice daily for the phase II study. The effect was little short of remarkable, Dr. Flaherty, director of developmental therapeutics at the Massachusetts General Hospital Cancer Center, said in an interview.

“My first responding patient had cutaneous and internal metastases, and the cutaneous metastases were clearly getting better right in front of our eyes,” he said. “We have seen this in some other areas of cancer, but never in melanoma, which before this was a clinical scenario with an unmet need for therapy.”

PLX4032, first engineered by the Berkeley, Calif., company Plexxikon Inc. and being developed in partnership with Roche, is not a foolproof cure, Dr. Tsao said in an interview. “It’s clearly a huge leap forward for the patients who responded so rapidly, yet most are still progressing despite being on the drug. It’s the best stun we’ve ever seen for melanoma, but it’s not a permanent kill.”

Sustained response in the phase I and II trials has varied from only 2 months to up to 2 years, Dr. Flaherty said. He could find no significant predictors of progression or response among the group except for initial tumor number and size. Typically, he said, the patients with the greatest mass of metastatic disease had the shortest duration of response, while those with a smaller tumor burden had a longer duration of response.

“When you have metastatic melanoma, your days are numbered—and numbered in a way we can’t predict when metastatic disease is diagnosed,” Dr. Flaherty said. “What this therapy does is push out the time until the disease worsens. We are not yet smart enough to understand what it is that allows a tumor to work its way around the drug’s activity.”

Chemotherapy-resistant cancers are nothing new, Dr. Tsao noted. What will be new is the full investigation of melanoma’s genetic pathways, and the development of drugs to block them in multiple ways. “The next frontier will be to understand all the ways that melanoma can outsmart treatment. We may have to use multiple therapies to corner it. So a full discovery of all melanoma’s potential vulnerabilities is very important.”

There is already at least a hint that PLX4032 has a very narrow target—only BRAF tumors with the V600E subtype. “There is some laboratory evidence that if you give this drug to a tumor that may be mutated at another gene you may be worsening things,” Dr. Tsao said. “This has yet to be borne out in clinical studies, but bench-side data suggest that you have to be very precise with this drug, because the wrong choice could be potentially deleterious.”

In vitro and in vivo experiments did suggest that PLX4032 was ineffective against non-BRAF melanomas, Dr. Flaherty said. “In a lab, the drug will kill a cancer cell with a BRAF mutation but not with another mutation. Whether it can facilitate the growth of others is an interesting concept supported by some laboratory data, with the observation that this and drugs like it can transiently stimulate other cancer cells with RAS mutations. In these, the drug basically activates the BRAF pathway instead of blocking it. We don’t know the relevance of this finding to humans. It is interesting, but it may have no real clinical impact.”

Discovering the best targets for molecular therapies is typically a long process, Dr. Tsao said, but the race to treat BRAF metastatic melanoma has so far been a fast one. “In 2002, the first BRAF mutation in melanoma was published, and the first drug is already coming to clinical fruition. This is pretty fast for something we’ve been fooling around with ineffectively for 20 years.”

During the 8 years between the mutation’s discovery and Dr. Flaherty’s trial, drug companies have not been idle. “There is now a pipeline of drugs against BRAF. PLX4032 might not be the best or the least toxic, but it’s the first of a host coming down the pike. This is very significant, because now we have a brand-new way of looking at a previously untreatable cancer.”

Roche Pharmaceuticals and Plexxikon sponsored the PLX4032 studies. Dr. Tsao said he had no financial declarations with regard to the drug. Dr. Flaherty has served as a consultant to Roche regarding further development of PLX4032 in melanoma.

CHICAGO — A drug that targets metastatic melanoma with mutations in the BRAF oncogene may be the first step on a path to individualized chemotherapy for patients with these formerly untreatable cancers.

“We are rapidly unraveling the molecular underpinnings of these tumors, and discovering the mechanisms by which they drive melanoma growth. These insights allow us to develop and select drugs on the basis of every patient’s individual genome,” Dr. Hensin Tsao said at the American Academy of Dermatology’s 2010 meeting.

Courtesy Bill Truslow/Massachusetts General Hospital

PLX4032 is the first drug to successfully shrink both cutaneous and internal metastases of BRAF-mutated melanomas, said Dr. Tsao, a dermatologist who is director of the Massachusetts General Hospital Melanoma Genetics Program in Boston.

His colleague, Dr. Keith Flaherty, is about to publish data from the drug’s phase II trial of 87 patients; 81% of those with the BRAF-mutated melanoma responded with a 30% or more shrinkage of the targeted lesions.

After a phase I safety and dose-finding trial, investigators settled on an oral dose of 960 mg twice daily for the phase II study. The effect was little short of remarkable, Dr. Flaherty, director of developmental therapeutics at the Massachusetts General Hospital Cancer Center, said in an interview.

“My first responding patient had cutaneous and internal metastases, and the cutaneous metastases were clearly getting better right in front of our eyes,” he said. “We have seen this in some other areas of cancer, but never in melanoma, which before this was a clinical scenario with an unmet need for therapy.”

PLX4032, first engineered by the Berkeley, Calif., company Plexxikon Inc. and being developed in partnership with Roche, is not a foolproof cure, Dr. Tsao said in an interview. “It’s clearly a huge leap forward for the patients who responded so rapidly, yet most are still progressing despite being on the drug. It’s the best stun we’ve ever seen for melanoma, but it’s not a permanent kill.”

Sustained response in the phase I and II trials has varied from only 2 months to up to 2 years, Dr. Flaherty said. He could find no significant predictors of progression or response among the group except for initial tumor number and size. Typically, he said, the patients with the greatest mass of metastatic disease had the shortest duration of response, while those with a smaller tumor burden had a longer duration of response.

“When you have metastatic melanoma, your days are numbered—and numbered in a way we can’t predict when metastatic disease is diagnosed,” Dr. Flaherty said. “What this therapy does is push out the time until the disease worsens. We are not yet smart enough to understand what it is that allows a tumor to work its way around the drug’s activity.”

Chemotherapy-resistant cancers are nothing new, Dr. Tsao noted. What will be new is the full investigation of melanoma’s genetic pathways, and the development of drugs to block them in multiple ways. “The next frontier will be to understand all the ways that melanoma can outsmart treatment. We may have to use multiple therapies to corner it. So a full discovery of all melanoma’s potential vulnerabilities is very important.”

There is already at least a hint that PLX4032 has a very narrow target—only BRAF tumors with the V600E subtype. “There is some laboratory evidence that if you give this drug to a tumor that may be mutated at another gene you may be worsening things,” Dr. Tsao said. “This has yet to be borne out in clinical studies, but bench-side data suggest that you have to be very precise with this drug, because the wrong choice could be potentially deleterious.”

In vitro and in vivo experiments did suggest that PLX4032 was ineffective against non-BRAF melanomas, Dr. Flaherty said. “In a lab, the drug will kill a cancer cell with a BRAF mutation but not with another mutation. Whether it can facilitate the growth of others is an interesting concept supported by some laboratory data, with the observation that this and drugs like it can transiently stimulate other cancer cells with RAS mutations. In these, the drug basically activates the BRAF pathway instead of blocking it. We don’t know the relevance of this finding to humans. It is interesting, but it may have no real clinical impact.”

Discovering the best targets for molecular therapies is typically a long process, Dr. Tsao said, but the race to treat BRAF metastatic melanoma has so far been a fast one. “In 2002, the first BRAF mutation in melanoma was published, and the first drug is already coming to clinical fruition. This is pretty fast for something we’ve been fooling around with ineffectively for 20 years.”

During the 8 years between the mutation’s discovery and Dr. Flaherty’s trial, drug companies have not been idle. “There is now a pipeline of drugs against BRAF. PLX4032 might not be the best or the least toxic, but it’s the first of a host coming down the pike. This is very significant, because now we have a brand-new way of looking at a previously untreatable cancer.”

Roche Pharmaceuticals and Plexxikon sponsored the PLX4032 studies. Dr. Tsao said he had no financial declarations with regard to the drug. Dr. Flaherty has served as a consultant to Roche regarding further development of PLX4032 in melanoma.

There is no shortage of clinical guidelines describing the risk factors for deep vein thrombosis and pulmonary embolism and how to effectively treat and prevent them. What is lacking, a national work group has concluded, is any way to track whether those guidelines are being implemented.

Also missing is information about how such guidelines might affect the incidence of venous thromboembolism (VTE). These questions can be answered only through collection of data by a national surveillance program, according to Gary E. Raskob, Ph.D., and his colleagues.

The work group, convened by the Centers for Disease Control and Prevention and the American Society of Hematology, consisted of physicians, epidemiologists, and health care policy experts. Following a 1-day workshop, the group summarized the literature on the clinical impact of deep vein thrombosis (DVT) and pulmonary embolism (PE) in several areas of medicine, wrote Dr. Raskob, of the University of Oklahoma Health Sciences Center, Oklahoma City, and his coauthors (Am. J. Prev. Med. 2010; 38:S502-9).

The available information on the clinical and economic burden of VTE “has been based on two population-based epidemiologic studies and on limited data from hospital discharge surveys or analysis of healthcare provider claims databases,” the work group wrote.

Each year, about 900,000 cases of VTE occur in the United States. The risk of VTE increases with age, and is somewhat higher for men than for women (114 vs. 105/100,000). There are few data on whether DVT incidence varies by ethnic group, and available studies vary widely in methodology and conclusions. A California patient discharge review that spanned 1991-1994 found an annual incidence among whites of 230/1 million population, compared with 293/1 million for blacks, 139/1 million for Hispanics, and 60/1 million for Asian/Pacific Islanders.

Most VTEs are associated with a recent hospitalization; therefore, the work group said, hospitalization is an opportune time to institute prevention measures and to educate patients on the risks of blood clots.

Among its recommendations, the work group suggested that the CDC:

• Establish a demographic picture of DVT and PE in the United States.

• Determine whether there are incidence differences among minorities, compared with white populations.

• Further define risk factors among various patient groups (pregnant patients, surgical patients, children, residents of long-term care facilities, and patients with a family history of VTE).

• Evaluate whether evidence-based preventive measures are being appropriately applied.

• Detect changes in the incidence of DVT and PE and relate these changes to any increase in the use of preventive measures.

The group also recommended that the CDC initiate a two-pronged national public awareness campaign, focusing on increasing overall understanding of the disorder and its risk factors, and encouraging patients who are about to undergo surgery or hospitalization to discuss the subject with their physicians.

Dr. Raskob disclosed that he has received consulting fees from Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Pfizer, GlaxoSmithKline, Johnson & Johnson, Daiichi Sankyo, Sanofi-Aventis, and Takeda.☐

There is no shortage of clinical guidelines describing the risk factors for deep vein thrombosis and pulmonary embolism and how to effectively treat and prevent them. What is lacking, a national work group has concluded, is any way to track whether those guidelines are being implemented.

Also missing is information about how such guidelines might affect the incidence of venous thromboembolism (VTE). These questions can be answered only through collection of data by a national surveillance program, according to Gary E. Raskob, Ph.D., and his colleagues.

The work group, convened by the Centers for Disease Control and Prevention and the American Society of Hematology, consisted of physicians, epidemiologists, and health care policy experts. Following a 1-day workshop, the group summarized the literature on the clinical impact of deep vein thrombosis (DVT) and pulmonary embolism (PE) in several areas of medicine, wrote Dr. Raskob, of the University of Oklahoma Health Sciences Center, Oklahoma City, and his coauthors (Am. J. Prev. Med. 2010; 38:S502-9).

The available information on the clinical and economic burden of VTE “has been based on two population-based epidemiologic studies and on limited data from hospital discharge surveys or analysis of healthcare provider claims databases,” the work group wrote.

Each year, about 900,000 cases of VTE occur in the United States. The risk of VTE increases with age, and is somewhat higher for men than for women (114 vs. 105/100,000). There are few data on whether DVT incidence varies by ethnic group, and available studies vary widely in methodology and conclusions. A California patient discharge review that spanned 1991-1994 found an annual incidence among whites of 230/1 million population, compared with 293/1 million for blacks, 139/1 million for Hispanics, and 60/1 million for Asian/Pacific Islanders.

Most VTEs are associated with a recent hospitalization; therefore, the work group said, hospitalization is an opportune time to institute prevention measures and to educate patients on the risks of blood clots.

Among its recommendations, the work group suggested that the CDC:

• Establish a demographic picture of DVT and PE in the United States.

• Determine whether there are incidence differences among minorities, compared with white populations.

• Further define risk factors among various patient groups (pregnant patients, surgical patients, children, residents of long-term care facilities, and patients with a family history of VTE).

• Evaluate whether evidence-based preventive measures are being appropriately applied.

• Detect changes in the incidence of DVT and PE and relate these changes to any increase in the use of preventive measures.

The group also recommended that the CDC initiate a two-pronged national public awareness campaign, focusing on increasing overall understanding of the disorder and its risk factors, and encouraging patients who are about to undergo surgery or hospitalization to discuss the subject with their physicians.

Dr. Raskob disclosed that he has received consulting fees from Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Pfizer, GlaxoSmithKline, Johnson & Johnson, Daiichi Sankyo, Sanofi-Aventis, and Takeda.☐

There is no shortage of clinical guidelines describing the risk factors for deep vein thrombosis and pulmonary embolism and how to effectively treat and prevent them. What is lacking, a national work group has concluded, is any way to track whether those guidelines are being implemented.

Also missing is information about how such guidelines might affect the incidence of venous thromboembolism (VTE). These questions can be answered only through collection of data by a national surveillance program, according to Gary E. Raskob, Ph.D., and his colleagues.

The work group, convened by the Centers for Disease Control and Prevention and the American Society of Hematology, consisted of physicians, epidemiologists, and health care policy experts. Following a 1-day workshop, the group summarized the literature on the clinical impact of deep vein thrombosis (DVT) and pulmonary embolism (PE) in several areas of medicine, wrote Dr. Raskob, of the University of Oklahoma Health Sciences Center, Oklahoma City, and his coauthors (Am. J. Prev. Med. 2010; 38:S502-9).

The available information on the clinical and economic burden of VTE “has been based on two population-based epidemiologic studies and on limited data from hospital discharge surveys or analysis of healthcare provider claims databases,” the work group wrote.

Each year, about 900,000 cases of VTE occur in the United States. The risk of VTE increases with age, and is somewhat higher for men than for women (114 vs. 105/100,000). There are few data on whether DVT incidence varies by ethnic group, and available studies vary widely in methodology and conclusions. A California patient discharge review that spanned 1991-1994 found an annual incidence among whites of 230/1 million population, compared with 293/1 million for blacks, 139/1 million for Hispanics, and 60/1 million for Asian/Pacific Islanders.

Most VTEs are associated with a recent hospitalization; therefore, the work group said, hospitalization is an opportune time to institute prevention measures and to educate patients on the risks of blood clots.

Among its recommendations, the work group suggested that the CDC:

• Establish a demographic picture of DVT and PE in the United States.

• Determine whether there are incidence differences among minorities, compared with white populations.

• Further define risk factors among various patient groups (pregnant patients, surgical patients, children, residents of long-term care facilities, and patients with a family history of VTE).

• Evaluate whether evidence-based preventive measures are being appropriately applied.

• Detect changes in the incidence of DVT and PE and relate these changes to any increase in the use of preventive measures.

The group also recommended that the CDC initiate a two-pronged national public awareness campaign, focusing on increasing overall understanding of the disorder and its risk factors, and encouraging patients who are about to undergo surgery or hospitalization to discuss the subject with their physicians.

Dr. Raskob disclosed that he has received consulting fees from Bayer, Bristol-Myers Squibb, Boehringer Ingelheim, Pfizer, GlaxoSmithKline, Johnson & Johnson, Daiichi Sankyo, Sanofi-Aventis, and Takeda.☐

Major Finding: Patients with childhood-onset type 1 diabetes are living longer than they did 40 years ago, but still face a sevenfold increase in the risk of death, compared with those without the disease.

Data Source: The Allegheny County Type 1 Diabetes Registry consisting of 1,075 subjects diagnosed from 1965 to 1979. Compared with the standardized background mortality rate, women were 13 times more likely to die, and men were 5 times more likely to die.

Disclosures: The National Institutes of Health sponsored the study. Neither Dr. Orchard nor Mr. Secrest reported any financial conflicts.

ORLANDO — Despite a steadily improving mortality picture, patients with childhood-onset type 1 diabetes still faced significantly increased mortality risks in a 40-year prospective follow-up study.

Women were particularly at risk, with a 13-fold greater risk of death than women in the same Pennsylvania community who were free of the disease, Dr. Trevor J. Orchard said at the meeting.

However, the follow-up study did show improving survival rates. After 30 years, the death rate among those diagnosed in the earliest cohort (1965-1969) was 22%. That dropped to 19% in the 1970-1974 cohort, and to 15% in the 1975-1979 cohort.

“We believe this reflects better care, resulting in fewer deaths early in diagnosis and—more recently—lower rates of diabetes complications,” Dr. Orchard, professor of epidemiology at the University of Pittsburgh, said in an interview.

“A lot of patients and the public feel that individuals with childhood-onset type 1 have lower life expectancy. These data firmly support that this is rapidly changing, and most people with type 1 diabetes can look forward to a normal life span if they keep their blood glucose and other risk factors under control,” he added.

Dr. Orchard presented data collected by his colleague, Aaron Secrest, who is a Ph.D. candidate at the university.

Mr. Secrest used the Allegheny County Type 1 Diabetes Registry as the basis of his analysis. The registry is one of the largest population-based registries of the disease. “It has been used in a number of studies as a representative cohort of the United States,” Dr. Orchard noted.

The analysis included a total of 1,075 residents of Allegheny County, Pa., who were diagnosed with childhood-onset type 1 diabetes in 1965-1979. The population was stratified into three time cohorts: those diagnosed in 1965-1969, in 1970-1974, and in 1975-1979, with about one-third of the cohort included in each time period. In all, 48% of the patients were female, and 93% were white; the small percentage of black patients is representative of the county's overall population.

As of January 2008, 19% (202) of registry participants had died—a rate seven times greater than age- and sex-matched people in the general population. Of those 202 participants, 95 were men and 107 were women.

The cumulative survival rates were 98% at 10 years, 93% at 20 years, 81% at 30 years, and 68% at 40 years. “What this tells is that about one-third of people with childhood-onset type 1 diabetes diagnosed in the 1960s will die within 40 years of their diagnosis,” Dr. Orchard said.

Although women within the cohort were not significantly more likely to die than men, “striking differences” emerged when the diabetes group was compared to the background population.

“Compared to the standardized mortality rate of the county, women [in the cohort] were 13 times more likely to die, and men were 5 times more likely to die,” Dr. Orchard said. The relative mortality differences between cohort and community and the sex differences in relative mortality were highly statistically significant, he said.

Race also factored significantly into the survival curve. “We saw a tremendously high mortality in blacks, such that 30-year survival was down to 57%, compared to 83% in whites,” Dr. Orchard said. “However, the standardized mortality ratio for blacks is very much the same [compared with the local county] as it is for whites, illustrating the relatively high mortality rate in the black background community.”

There were 32 deaths among black patients—41% of the black cohort. All of the deaths among blacks were directly related to diabetes.

“We noted that as this increase did include both acute and chronic complications of diabetes, it is most likely related to access to care and/or the ability to follow through with that care,” Dr. Orchard said.

“The finding that there was no significant difference in the mortality rates compared to the background population suggests that there is a general socioeconomic status situation that affects outcomes in all diseases,” he said.

After 30 years, the death rate was 22% in those diagnosed in 1965-1969, and 15% in the 1975-1979 cohort.

Source DR. ORCHARD

Major Finding: Patients with childhood-onset type 1 diabetes are living longer than they did 40 years ago, but still face a sevenfold increase in the risk of death, compared with those without the disease.

Data Source: The Allegheny County Type 1 Diabetes Registry consisting of 1,075 subjects diagnosed from 1965 to 1979. Compared with the standardized background mortality rate, women were 13 times more likely to die, and men were 5 times more likely to die.

Disclosures: The National Institutes of Health sponsored the study. Neither Dr. Orchard nor Mr. Secrest reported any financial conflicts.

ORLANDO — Despite a steadily improving mortality picture, patients with childhood-onset type 1 diabetes still faced significantly increased mortality risks in a 40-year prospective follow-up study.

Women were particularly at risk, with a 13-fold greater risk of death than women in the same Pennsylvania community who were free of the disease, Dr. Trevor J. Orchard said at the meeting.

However, the follow-up study did show improving survival rates. After 30 years, the death rate among those diagnosed in the earliest cohort (1965-1969) was 22%. That dropped to 19% in the 1970-1974 cohort, and to 15% in the 1975-1979 cohort.

“We believe this reflects better care, resulting in fewer deaths early in diagnosis and—more recently—lower rates of diabetes complications,” Dr. Orchard, professor of epidemiology at the University of Pittsburgh, said in an interview.

“A lot of patients and the public feel that individuals with childhood-onset type 1 have lower life expectancy. These data firmly support that this is rapidly changing, and most people with type 1 diabetes can look forward to a normal life span if they keep their blood glucose and other risk factors under control,” he added.

Dr. Orchard presented data collected by his colleague, Aaron Secrest, who is a Ph.D. candidate at the university.

Mr. Secrest used the Allegheny County Type 1 Diabetes Registry as the basis of his analysis. The registry is one of the largest population-based registries of the disease. “It has been used in a number of studies as a representative cohort of the United States,” Dr. Orchard noted.

The analysis included a total of 1,075 residents of Allegheny County, Pa., who were diagnosed with childhood-onset type 1 diabetes in 1965-1979. The population was stratified into three time cohorts: those diagnosed in 1965-1969, in 1970-1974, and in 1975-1979, with about one-third of the cohort included in each time period. In all, 48% of the patients were female, and 93% were white; the small percentage of black patients is representative of the county's overall population.

As of January 2008, 19% (202) of registry participants had died—a rate seven times greater than age- and sex-matched people in the general population. Of those 202 participants, 95 were men and 107 were women.

The cumulative survival rates were 98% at 10 years, 93% at 20 years, 81% at 30 years, and 68% at 40 years. “What this tells is that about one-third of people with childhood-onset type 1 diabetes diagnosed in the 1960s will die within 40 years of their diagnosis,” Dr. Orchard said.

Although women within the cohort were not significantly more likely to die than men, “striking differences” emerged when the diabetes group was compared to the background population.

“Compared to the standardized mortality rate of the county, women [in the cohort] were 13 times more likely to die, and men were 5 times more likely to die,” Dr. Orchard said. The relative mortality differences between cohort and community and the sex differences in relative mortality were highly statistically significant, he said.

Race also factored significantly into the survival curve. “We saw a tremendously high mortality in blacks, such that 30-year survival was down to 57%, compared to 83% in whites,” Dr. Orchard said. “However, the standardized mortality ratio for blacks is very much the same [compared with the local county] as it is for whites, illustrating the relatively high mortality rate in the black background community.”

There were 32 deaths among black patients—41% of the black cohort. All of the deaths among blacks were directly related to diabetes.

“We noted that as this increase did include both acute and chronic complications of diabetes, it is most likely related to access to care and/or the ability to follow through with that care,” Dr. Orchard said.

“The finding that there was no significant difference in the mortality rates compared to the background population suggests that there is a general socioeconomic status situation that affects outcomes in all diseases,” he said.

After 30 years, the death rate was 22% in those diagnosed in 1965-1969, and 15% in the 1975-1979 cohort.

Source DR. ORCHARD

Major Finding: Patients with childhood-onset type 1 diabetes are living longer than they did 40 years ago, but still face a sevenfold increase in the risk of death, compared with those without the disease.

Data Source: The Allegheny County Type 1 Diabetes Registry consisting of 1,075 subjects diagnosed from 1965 to 1979. Compared with the standardized background mortality rate, women were 13 times more likely to die, and men were 5 times more likely to die.

Disclosures: The National Institutes of Health sponsored the study. Neither Dr. Orchard nor Mr. Secrest reported any financial conflicts.

ORLANDO — Despite a steadily improving mortality picture, patients with childhood-onset type 1 diabetes still faced significantly increased mortality risks in a 40-year prospective follow-up study.

Women were particularly at risk, with a 13-fold greater risk of death than women in the same Pennsylvania community who were free of the disease, Dr. Trevor J. Orchard said at the meeting.

However, the follow-up study did show improving survival rates. After 30 years, the death rate among those diagnosed in the earliest cohort (1965-1969) was 22%. That dropped to 19% in the 1970-1974 cohort, and to 15% in the 1975-1979 cohort.

“We believe this reflects better care, resulting in fewer deaths early in diagnosis and—more recently—lower rates of diabetes complications,” Dr. Orchard, professor of epidemiology at the University of Pittsburgh, said in an interview.

“A lot of patients and the public feel that individuals with childhood-onset type 1 have lower life expectancy. These data firmly support that this is rapidly changing, and most people with type 1 diabetes can look forward to a normal life span if they keep their blood glucose and other risk factors under control,” he added.

Dr. Orchard presented data collected by his colleague, Aaron Secrest, who is a Ph.D. candidate at the university.

Mr. Secrest used the Allegheny County Type 1 Diabetes Registry as the basis of his analysis. The registry is one of the largest population-based registries of the disease. “It has been used in a number of studies as a representative cohort of the United States,” Dr. Orchard noted.

The analysis included a total of 1,075 residents of Allegheny County, Pa., who were diagnosed with childhood-onset type 1 diabetes in 1965-1979. The population was stratified into three time cohorts: those diagnosed in 1965-1969, in 1970-1974, and in 1975-1979, with about one-third of the cohort included in each time period. In all, 48% of the patients were female, and 93% were white; the small percentage of black patients is representative of the county's overall population.

As of January 2008, 19% (202) of registry participants had died—a rate seven times greater than age- and sex-matched people in the general population. Of those 202 participants, 95 were men and 107 were women.

The cumulative survival rates were 98% at 10 years, 93% at 20 years, 81% at 30 years, and 68% at 40 years. “What this tells is that about one-third of people with childhood-onset type 1 diabetes diagnosed in the 1960s will die within 40 years of their diagnosis,” Dr. Orchard said.

Although women within the cohort were not significantly more likely to die than men, “striking differences” emerged when the diabetes group was compared to the background population.

“Compared to the standardized mortality rate of the county, women [in the cohort] were 13 times more likely to die, and men were 5 times more likely to die,” Dr. Orchard said. The relative mortality differences between cohort and community and the sex differences in relative mortality were highly statistically significant, he said.

Race also factored significantly into the survival curve. “We saw a tremendously high mortality in blacks, such that 30-year survival was down to 57%, compared to 83% in whites,” Dr. Orchard said. “However, the standardized mortality ratio for blacks is very much the same [compared with the local county] as it is for whites, illustrating the relatively high mortality rate in the black background community.”

There were 32 deaths among black patients—41% of the black cohort. All of the deaths among blacks were directly related to diabetes.

“We noted that as this increase did include both acute and chronic complications of diabetes, it is most likely related to access to care and/or the ability to follow through with that care,” Dr. Orchard said.

“The finding that there was no significant difference in the mortality rates compared to the background population suggests that there is a general socioeconomic status situation that affects outcomes in all diseases,” he said.

After 30 years, the death rate was 22% in those diagnosed in 1965-1969, and 15% in the 1975-1979 cohort.

Source DR. ORCHARD

Major Finding: Patients with type 2 diabetes and cardiovascular risk factors who took metformin had a 24% decrease in the risk of death over a 2-year period.

Data Source: A subanalysis of the international REACH Registry, focusing on 19,699 patients with type 2 diabetes.

Disclosures: The registry is sponsored by Sanofi-Aventis, Bristol-Myers Squibb, and the Waksman Foundation, Tokyo. Dr. Roussel disclosed that he has received research support or consulting fees from Sanofi-Aventis, Servier Laboratories, Roche, Eli Lilly & Co., Novo Nordisk Inc., Medtronic Inc., and LifeScan Inc.

ORLANDO — Metformin use was associated with a significant decrease in the risk of all-cause death among diabetic patients at risk for cardiovascular events.

The subanalysis of the Reduction of Atherothrombosis for Continued Health (REACH) Registry found that subjects with type 2 diabetes who took metformin were 24% less likely to die from all-cause mortality over 2 years than were those who did not take the drug. The association remained significant even after researchers controlled for age and gender, and after factoring in a number of baseline characteristics that varied significantly between the groups.

“Given the diversity of the 44 countries and widely different practice settings involved in the registry, we think these data are highly relevant,” Dr. Ronan Roussel said at the annual meeting of the American Diabetes Association. While perhaps not sufficient to make practice recommendations, he did say the results are strong enough to prompt clinical trials, especially when viewed in the context of the growing body of evidence about metformin's cardioprotective effects.

The REACH Registry was established to track outcomes in patients with atherothrombosis or atherothrombotic risk factors. Almost 70,000 patients were enrolled. They were either symptomatic, with documented cardiovascular, coronary artery or peripheral artery disease; or asymptomatic with at least three risk factors for atherothrombosis. Of this group, 19,699 had type 2 diabetes and 2-year outcomes data. Dr. Roussel of the Groupe Hospitalier Bichat-Claude Bernard, Paris, and his colleagues compared those who were taking metformin at baseline with those who were not. Metformin was taken by 40% of the patients.

There were some significant baseline differences between the groups, Dr. Roussel noted. Patients taking metformin were significantly younger (67 vs. 69 years), had a higher average fasting blood glucose (138 vs. 131 mg/dL), and higher systolic blood pressure (138 vs. 136 mm Hg). Prior arterial disease was present in 80% of those taking metformin and 75% of those not. Metformin users were also taking significantly more cardiovascular drugs, including aspirin (74% vs. 69%), statins (75% vs. 67%), and angiotensin-converting enzyme inhibitors (54% vs. 49%).

Over the 2-year follow-up period, there were 1,270 deaths. After researchers adjusted for gender and age only, metformin was associated with a 33% reduction in the risk of all-cause death. A Kaplan-Meier analysis showed that the mortality trajectories began to separate early, with a significant difference appearing around 6 months.

After adjustment for the other factors, the mortality difference still remained significant in favor of metformin use, with a 24% risk reduction in all-cause death.

In an age analysis, with subjects split into groups 40-65 years, 65-80 years, and older than 80 years, the risk reductions were significant for the youngest group (37%), and the middle group (23%). The oldest subjects did not have a survival advantage with the drug.

Metformin also improved the odds of survival in patients with existing congestive heart failure, conferring a significant 31% reduction in the risk of death.

While renal insufficiency is considered a contraindication to metformin use, Dr. Roussel noted that REACH subjects with moderately impaired renal function appeared to benefit from the drug. Those with a glomerular filtration rate of 30-60 mL/min had a significant 36% reduction in the risk of death; those with a GFR of less than 30 mL/min or greater than 60 mL/min did not gain a significant survival advantage.

Subjects who were taking insulin as well as metformin benefited more than did those who were taking metformin alone (hazard ratio 0.64 vs. 0.80).

Major Finding: Patients with type 2 diabetes and cardiovascular risk factors who took metformin had a 24% decrease in the risk of death over a 2-year period.

Data Source: A subanalysis of the international REACH Registry, focusing on 19,699 patients with type 2 diabetes.

Disclosures: The registry is sponsored by Sanofi-Aventis, Bristol-Myers Squibb, and the Waksman Foundation, Tokyo. Dr. Roussel disclosed that he has received research support or consulting fees from Sanofi-Aventis, Servier Laboratories, Roche, Eli Lilly & Co., Novo Nordisk Inc., Medtronic Inc., and LifeScan Inc.

ORLANDO — Metformin use was associated with a significant decrease in the risk of all-cause death among diabetic patients at risk for cardiovascular events.

The subanalysis of the Reduction of Atherothrombosis for Continued Health (REACH) Registry found that subjects with type 2 diabetes who took metformin were 24% less likely to die from all-cause mortality over 2 years than were those who did not take the drug. The association remained significant even after researchers controlled for age and gender, and after factoring in a number of baseline characteristics that varied significantly between the groups.

“Given the diversity of the 44 countries and widely different practice settings involved in the registry, we think these data are highly relevant,” Dr. Ronan Roussel said at the annual meeting of the American Diabetes Association. While perhaps not sufficient to make practice recommendations, he did say the results are strong enough to prompt clinical trials, especially when viewed in the context of the growing body of evidence about metformin's cardioprotective effects.

The REACH Registry was established to track outcomes in patients with atherothrombosis or atherothrombotic risk factors. Almost 70,000 patients were enrolled. They were either symptomatic, with documented cardiovascular, coronary artery or peripheral artery disease; or asymptomatic with at least three risk factors for atherothrombosis. Of this group, 19,699 had type 2 diabetes and 2-year outcomes data. Dr. Roussel of the Groupe Hospitalier Bichat-Claude Bernard, Paris, and his colleagues compared those who were taking metformin at baseline with those who were not. Metformin was taken by 40% of the patients.

There were some significant baseline differences between the groups, Dr. Roussel noted. Patients taking metformin were significantly younger (67 vs. 69 years), had a higher average fasting blood glucose (138 vs. 131 mg/dL), and higher systolic blood pressure (138 vs. 136 mm Hg). Prior arterial disease was present in 80% of those taking metformin and 75% of those not. Metformin users were also taking significantly more cardiovascular drugs, including aspirin (74% vs. 69%), statins (75% vs. 67%), and angiotensin-converting enzyme inhibitors (54% vs. 49%).

Over the 2-year follow-up period, there were 1,270 deaths. After researchers adjusted for gender and age only, metformin was associated with a 33% reduction in the risk of all-cause death. A Kaplan-Meier analysis showed that the mortality trajectories began to separate early, with a significant difference appearing around 6 months.

After adjustment for the other factors, the mortality difference still remained significant in favor of metformin use, with a 24% risk reduction in all-cause death.

In an age analysis, with subjects split into groups 40-65 years, 65-80 years, and older than 80 years, the risk reductions were significant for the youngest group (37%), and the middle group (23%). The oldest subjects did not have a survival advantage with the drug.

Metformin also improved the odds of survival in patients with existing congestive heart failure, conferring a significant 31% reduction in the risk of death.

While renal insufficiency is considered a contraindication to metformin use, Dr. Roussel noted that REACH subjects with moderately impaired renal function appeared to benefit from the drug. Those with a glomerular filtration rate of 30-60 mL/min had a significant 36% reduction in the risk of death; those with a GFR of less than 30 mL/min or greater than 60 mL/min did not gain a significant survival advantage.

Subjects who were taking insulin as well as metformin benefited more than did those who were taking metformin alone (hazard ratio 0.64 vs. 0.80).

Major Finding: Patients with type 2 diabetes and cardiovascular risk factors who took metformin had a 24% decrease in the risk of death over a 2-year period.

Data Source: A subanalysis of the international REACH Registry, focusing on 19,699 patients with type 2 diabetes.

Disclosures: The registry is sponsored by Sanofi-Aventis, Bristol-Myers Squibb, and the Waksman Foundation, Tokyo. Dr. Roussel disclosed that he has received research support or consulting fees from Sanofi-Aventis, Servier Laboratories, Roche, Eli Lilly & Co., Novo Nordisk Inc., Medtronic Inc., and LifeScan Inc.

ORLANDO — Metformin use was associated with a significant decrease in the risk of all-cause death among diabetic patients at risk for cardiovascular events.

The subanalysis of the Reduction of Atherothrombosis for Continued Health (REACH) Registry found that subjects with type 2 diabetes who took metformin were 24% less likely to die from all-cause mortality over 2 years than were those who did not take the drug. The association remained significant even after researchers controlled for age and gender, and after factoring in a number of baseline characteristics that varied significantly between the groups.

“Given the diversity of the 44 countries and widely different practice settings involved in the registry, we think these data are highly relevant,” Dr. Ronan Roussel said at the annual meeting of the American Diabetes Association. While perhaps not sufficient to make practice recommendations, he did say the results are strong enough to prompt clinical trials, especially when viewed in the context of the growing body of evidence about metformin's cardioprotective effects.

The REACH Registry was established to track outcomes in patients with atherothrombosis or atherothrombotic risk factors. Almost 70,000 patients were enrolled. They were either symptomatic, with documented cardiovascular, coronary artery or peripheral artery disease; or asymptomatic with at least three risk factors for atherothrombosis. Of this group, 19,699 had type 2 diabetes and 2-year outcomes data. Dr. Roussel of the Groupe Hospitalier Bichat-Claude Bernard, Paris, and his colleagues compared those who were taking metformin at baseline with those who were not. Metformin was taken by 40% of the patients.

There were some significant baseline differences between the groups, Dr. Roussel noted. Patients taking metformin were significantly younger (67 vs. 69 years), had a higher average fasting blood glucose (138 vs. 131 mg/dL), and higher systolic blood pressure (138 vs. 136 mm Hg). Prior arterial disease was present in 80% of those taking metformin and 75% of those not. Metformin users were also taking significantly more cardiovascular drugs, including aspirin (74% vs. 69%), statins (75% vs. 67%), and angiotensin-converting enzyme inhibitors (54% vs. 49%).

Over the 2-year follow-up period, there were 1,270 deaths. After researchers adjusted for gender and age only, metformin was associated with a 33% reduction in the risk of all-cause death. A Kaplan-Meier analysis showed that the mortality trajectories began to separate early, with a significant difference appearing around 6 months.

After adjustment for the other factors, the mortality difference still remained significant in favor of metformin use, with a 24% risk reduction in all-cause death.

In an age analysis, with subjects split into groups 40-65 years, 65-80 years, and older than 80 years, the risk reductions were significant for the youngest group (37%), and the middle group (23%). The oldest subjects did not have a survival advantage with the drug.

Metformin also improved the odds of survival in patients with existing congestive heart failure, conferring a significant 31% reduction in the risk of death.

While renal insufficiency is considered a contraindication to metformin use, Dr. Roussel noted that REACH subjects with moderately impaired renal function appeared to benefit from the drug. Those with a glomerular filtration rate of 30-60 mL/min had a significant 36% reduction in the risk of death; those with a GFR of less than 30 mL/min or greater than 60 mL/min did not gain a significant survival advantage.

Subjects who were taking insulin as well as metformin benefited more than did those who were taking metformin alone (hazard ratio 0.64 vs. 0.80).

Major Finding: Among 875 patients with osteoarthritis, those who took 200 mg of celecoxib every day had significantly fewer flares than those who took the drug only during a flare.

Data Source: A three-phase randomized, placebo-controlled trial.

Disclosures: Pfizer Inc. sponsored the study; the data were reported by Pfizer employee Dr. Sands.

CANCUN, MEXICO — Osteoarthritis flares were reduced by 42% in patients who took 200 mg of celecoxib daily, compared with those who took the medication only when they experienced a disease flare, judging from findings from a randomized, placebo-controlled trial.

Osteoarthritis patients who took the drug daily were no more likely than intermittent users to have either new-onset hypertension or an aggravation of existing hypertension, Dr. George Sands reported.

“Over the 22-week treatment period, continuous daily celecoxib was more effective in terms of fewer osteoarthritis flares, less pain, and less stiffness than intermittent celecoxib, with no difference in overall adverse effects or in hypertension,” said Dr. Sands, senior medical director at Pfizer Inc., which sponsored the study.

The study group comprised 875 patients with hip or knee osteoarthritis. All patients had to be taking a daily NSAID to control their disease. The study had three phases: In phase I, patients stopped their NSAID until they had a flare at their index joint. In phase II, patients with flares received open-label celecoxib until the flare resolved. Phase III consisted of the 22-week randomized, placebo-controlled study. Patients had two study medications, one for daily use and one for use during a flare. Half of the patients (440) received celecoxib every day and a placebo during the flare. The rest of the group (435) received daily placebo and celecoxib during the flare. Treatment continued for 22 weeks.

“Only patients who had resolved flares could be entered into the trial,” Dr. Sands said. “This is different from the usual arthritis studies, where they stop their NSAID, get worse, and are treated. In this study, patients were randomized after a successful treatment of a flare.”

The patients' mean age was 58 years; 30% were 65 or older. Their mean weight was 83 kg. Most (80%) had knee osteoarthritis; the hip was the affected joint in the remaining 20%. The baseline WOMAC (Western Ontario and McMaster Universities) Osteoarthritis Index score was 25 in both groups. Hypertension was present in 45%. Most of the continuous-use patients (80%) and 74% of the intermittent-use patients completed the trial.

The primary end point was the number of flares occurring during the randomized portion of the study. The median time to first flare was significantly longer in the continuous-use group than in the intermittent-use group (16 days vs. 8 days, respectively). “This is not surprising, since in this part of the study, before anyone had a flare, you were testing celecoxib against placebo,” noted Dr. Sands.

By the end of the 22-week treatment period, continuous users had a mean of 0.54 flares per month, significantly fewer than the mean 0.93 flares experienced by the intermittent users. This translates into 42% fewer flares per month, or about two fewer flares per month, Dr. Sands said.

At the end of the treatment period, WOMAC scores were significantly better in the continuous-use group. The change in total WOMAC score was 1.6 in the continuous users vs. 4.99 in the intermittent users.

At the final visit, 23% of the continuous-use group and 11% of the intermittent-use group had been flare free—a significant difference. Adverse events occurred in 57% of the continuous users and 59% of the intermittent users.

The continuous users of celecoxib had a mean of 0.54 flares per month, vs. 0.93 flares for the intermittent users.

Source DR. SANDS

Major Finding: Among 875 patients with osteoarthritis, those who took 200 mg of celecoxib every day had significantly fewer flares than those who took the drug only during a flare.

Data Source: A three-phase randomized, placebo-controlled trial.

Disclosures: Pfizer Inc. sponsored the study; the data were reported by Pfizer employee Dr. Sands.

CANCUN, MEXICO — Osteoarthritis flares were reduced by 42% in patients who took 200 mg of celecoxib daily, compared with those who took the medication only when they experienced a disease flare, judging from findings from a randomized, placebo-controlled trial.

Osteoarthritis patients who took the drug daily were no more likely than intermittent users to have either new-onset hypertension or an aggravation of existing hypertension, Dr. George Sands reported.

“Over the 22-week treatment period, continuous daily celecoxib was more effective in terms of fewer osteoarthritis flares, less pain, and less stiffness than intermittent celecoxib, with no difference in overall adverse effects or in hypertension,” said Dr. Sands, senior medical director at Pfizer Inc., which sponsored the study.

The study group comprised 875 patients with hip or knee osteoarthritis. All patients had to be taking a daily NSAID to control their disease. The study had three phases: In phase I, patients stopped their NSAID until they had a flare at their index joint. In phase II, patients with flares received open-label celecoxib until the flare resolved. Phase III consisted of the 22-week randomized, placebo-controlled study. Patients had two study medications, one for daily use and one for use during a flare. Half of the patients (440) received celecoxib every day and a placebo during the flare. The rest of the group (435) received daily placebo and celecoxib during the flare. Treatment continued for 22 weeks.

“Only patients who had resolved flares could be entered into the trial,” Dr. Sands said. “This is different from the usual arthritis studies, where they stop their NSAID, get worse, and are treated. In this study, patients were randomized after a successful treatment of a flare.”

The patients' mean age was 58 years; 30% were 65 or older. Their mean weight was 83 kg. Most (80%) had knee osteoarthritis; the hip was the affected joint in the remaining 20%. The baseline WOMAC (Western Ontario and McMaster Universities) Osteoarthritis Index score was 25 in both groups. Hypertension was present in 45%. Most of the continuous-use patients (80%) and 74% of the intermittent-use patients completed the trial.

The primary end point was the number of flares occurring during the randomized portion of the study. The median time to first flare was significantly longer in the continuous-use group than in the intermittent-use group (16 days vs. 8 days, respectively). “This is not surprising, since in this part of the study, before anyone had a flare, you were testing celecoxib against placebo,” noted Dr. Sands.

By the end of the 22-week treatment period, continuous users had a mean of 0.54 flares per month, significantly fewer than the mean 0.93 flares experienced by the intermittent users. This translates into 42% fewer flares per month, or about two fewer flares per month, Dr. Sands said.

At the end of the treatment period, WOMAC scores were significantly better in the continuous-use group. The change in total WOMAC score was 1.6 in the continuous users vs. 4.99 in the intermittent users.

At the final visit, 23% of the continuous-use group and 11% of the intermittent-use group had been flare free—a significant difference. Adverse events occurred in 57% of the continuous users and 59% of the intermittent users.

The continuous users of celecoxib had a mean of 0.54 flares per month, vs. 0.93 flares for the intermittent users.

Source DR. SANDS

Major Finding: Among 875 patients with osteoarthritis, those who took 200 mg of celecoxib every day had significantly fewer flares than those who took the drug only during a flare.

Data Source: A three-phase randomized, placebo-controlled trial.

Disclosures: Pfizer Inc. sponsored the study; the data were reported by Pfizer employee Dr. Sands.

CANCUN, MEXICO — Osteoarthritis flares were reduced by 42% in patients who took 200 mg of celecoxib daily, compared with those who took the medication only when they experienced a disease flare, judging from findings from a randomized, placebo-controlled trial.

Osteoarthritis patients who took the drug daily were no more likely than intermittent users to have either new-onset hypertension or an aggravation of existing hypertension, Dr. George Sands reported.

“Over the 22-week treatment period, continuous daily celecoxib was more effective in terms of fewer osteoarthritis flares, less pain, and less stiffness than intermittent celecoxib, with no difference in overall adverse effects or in hypertension,” said Dr. Sands, senior medical director at Pfizer Inc., which sponsored the study.

The study group comprised 875 patients with hip or knee osteoarthritis. All patients had to be taking a daily NSAID to control their disease. The study had three phases: In phase I, patients stopped their NSAID until they had a flare at their index joint. In phase II, patients with flares received open-label celecoxib until the flare resolved. Phase III consisted of the 22-week randomized, placebo-controlled study. Patients had two study medications, one for daily use and one for use during a flare. Half of the patients (440) received celecoxib every day and a placebo during the flare. The rest of the group (435) received daily placebo and celecoxib during the flare. Treatment continued for 22 weeks.

“Only patients who had resolved flares could be entered into the trial,” Dr. Sands said. “This is different from the usual arthritis studies, where they stop their NSAID, get worse, and are treated. In this study, patients were randomized after a successful treatment of a flare.”

The patients' mean age was 58 years; 30% were 65 or older. Their mean weight was 83 kg. Most (80%) had knee osteoarthritis; the hip was the affected joint in the remaining 20%. The baseline WOMAC (Western Ontario and McMaster Universities) Osteoarthritis Index score was 25 in both groups. Hypertension was present in 45%. Most of the continuous-use patients (80%) and 74% of the intermittent-use patients completed the trial.

The primary end point was the number of flares occurring during the randomized portion of the study. The median time to first flare was significantly longer in the continuous-use group than in the intermittent-use group (16 days vs. 8 days, respectively). “This is not surprising, since in this part of the study, before anyone had a flare, you were testing celecoxib against placebo,” noted Dr. Sands.

By the end of the 22-week treatment period, continuous users had a mean of 0.54 flares per month, significantly fewer than the mean 0.93 flares experienced by the intermittent users. This translates into 42% fewer flares per month, or about two fewer flares per month, Dr. Sands said.

At the end of the treatment period, WOMAC scores were significantly better in the continuous-use group. The change in total WOMAC score was 1.6 in the continuous users vs. 4.99 in the intermittent users.

At the final visit, 23% of the continuous-use group and 11% of the intermittent-use group had been flare free—a significant difference. Adverse events occurred in 57% of the continuous users and 59% of the intermittent users.

The continuous users of celecoxib had a mean of 0.54 flares per month, vs. 0.93 flares for the intermittent users.

Source DR. SANDS

CANCÚN, MEXICO — Female family physicians tend to engage more emotionally with patients than their male colleagues, and they also report more job-related stress, a survey has found.

Such gender differences are particularly relevant now that many more women are entering medical school. “Women are coming to medical school in huge numbers, even overtaking the number of males,” Dr. Brenda Lovell said.

The preponderance of literature shows that patients really benefit from having a trusting relationship with their physicians, she continued. “I think it's especially important for family physicians to build a strong doctor-patient relationship because, unlike specialists who may only see someone once or twice, family doctors see their patients over and over, sometimes for many years.”

This deeper relationship, however, seems to carry a burden of greater stress for women physicians, who reported more headaches, sleep difficulties, gastrointestinal problems, and family stresses than their male colleagues.

Dr. Lovell of the University of Manitoba, Winnipeg, and her colleagues surveyed 110 family physicians in Canada about the way they interact with patients, how they cope with stress and burnout, and how stress affects them physically. Respondents used a one-to-five scale to describe how frequently they experience these issues.

The study cohort consisted of 70 men and 40 women. Men had been in practice significantly longer than women (mean 22 years vs. 15 years). Although men saw almost an equal percentage of male and female patients (55% and 45%, respectively), women saw a preponderance of female patients (67% vs. 33% men). Women also reported spending significantly more time with each patient (17.8 minutes vs. 13.3 minutes).

Women engaged emotionally with their patients significantly more often than men, taking the time to “listen carefully, show respect, provide simple explanations of diagnosis and treatment, and allow time for questions.” Women also were significantly more likely to use relationship-building techniques, including sharing emotions, expressing a wide variety of emotions, and using positive emotions like smiling and reassurance.

Women experienced physical signs of stress significantly more often. They were also more likely than men to rely on social support from friends and family and to seek professional help to deal with these issues. The women more often actively tried relaxing to relieve tension.

A second portion of the survey allowed physicians to freely express thoughts on their daily practice. When discussing practice constraints, women tended to list issues like “the politics of health care” and interpersonal factors, such as unpleasant office interactions and lack of collegial support.

Men focused more on administrative issues, such as staffing difficulties, lack of resources, and business competition.

Women said that they felt pressure to see more patients in less time and complained about administrative decisions from superiors that added to job stress. Men said they felt a loss of control because of numerous protocols that must be followed and expressed frustration at not being adequately recognized for their skills.

Decreased bureaucracy and better working conditions would go a long way toward improving the life of the family physician, “even more than higher pay,” she said.

CANCÚN, MEXICO — Female family physicians tend to engage more emotionally with patients than their male colleagues, and they also report more job-related stress, a survey has found.

Such gender differences are particularly relevant now that many more women are entering medical school. “Women are coming to medical school in huge numbers, even overtaking the number of males,” Dr. Brenda Lovell said.

The preponderance of literature shows that patients really benefit from having a trusting relationship with their physicians, she continued. “I think it's especially important for family physicians to build a strong doctor-patient relationship because, unlike specialists who may only see someone once or twice, family doctors see their patients over and over, sometimes for many years.”

This deeper relationship, however, seems to carry a burden of greater stress for women physicians, who reported more headaches, sleep difficulties, gastrointestinal problems, and family stresses than their male colleagues.

Dr. Lovell of the University of Manitoba, Winnipeg, and her colleagues surveyed 110 family physicians in Canada about the way they interact with patients, how they cope with stress and burnout, and how stress affects them physically. Respondents used a one-to-five scale to describe how frequently they experience these issues.

The study cohort consisted of 70 men and 40 women. Men had been in practice significantly longer than women (mean 22 years vs. 15 years). Although men saw almost an equal percentage of male and female patients (55% and 45%, respectively), women saw a preponderance of female patients (67% vs. 33% men). Women also reported spending significantly more time with each patient (17.8 minutes vs. 13.3 minutes).

Women engaged emotionally with their patients significantly more often than men, taking the time to “listen carefully, show respect, provide simple explanations of diagnosis and treatment, and allow time for questions.” Women also were significantly more likely to use relationship-building techniques, including sharing emotions, expressing a wide variety of emotions, and using positive emotions like smiling and reassurance.

Women experienced physical signs of stress significantly more often. They were also more likely than men to rely on social support from friends and family and to seek professional help to deal with these issues. The women more often actively tried relaxing to relieve tension.

A second portion of the survey allowed physicians to freely express thoughts on their daily practice. When discussing practice constraints, women tended to list issues like “the politics of health care” and interpersonal factors, such as unpleasant office interactions and lack of collegial support.

Men focused more on administrative issues, such as staffing difficulties, lack of resources, and business competition.

Women said that they felt pressure to see more patients in less time and complained about administrative decisions from superiors that added to job stress. Men said they felt a loss of control because of numerous protocols that must be followed and expressed frustration at not being adequately recognized for their skills.

Decreased bureaucracy and better working conditions would go a long way toward improving the life of the family physician, “even more than higher pay,” she said.

CANCÚN, MEXICO — Female family physicians tend to engage more emotionally with patients than their male colleagues, and they also report more job-related stress, a survey has found.

Such gender differences are particularly relevant now that many more women are entering medical school. “Women are coming to medical school in huge numbers, even overtaking the number of males,” Dr. Brenda Lovell said.

The preponderance of literature shows that patients really benefit from having a trusting relationship with their physicians, she continued. “I think it's especially important for family physicians to build a strong doctor-patient relationship because, unlike specialists who may only see someone once or twice, family doctors see their patients over and over, sometimes for many years.”

This deeper relationship, however, seems to carry a burden of greater stress for women physicians, who reported more headaches, sleep difficulties, gastrointestinal problems, and family stresses than their male colleagues.

Dr. Lovell of the University of Manitoba, Winnipeg, and her colleagues surveyed 110 family physicians in Canada about the way they interact with patients, how they cope with stress and burnout, and how stress affects them physically. Respondents used a one-to-five scale to describe how frequently they experience these issues.

The study cohort consisted of 70 men and 40 women. Men had been in practice significantly longer than women (mean 22 years vs. 15 years). Although men saw almost an equal percentage of male and female patients (55% and 45%, respectively), women saw a preponderance of female patients (67% vs. 33% men). Women also reported spending significantly more time with each patient (17.8 minutes vs. 13.3 minutes).

Women engaged emotionally with their patients significantly more often than men, taking the time to “listen carefully, show respect, provide simple explanations of diagnosis and treatment, and allow time for questions.” Women also were significantly more likely to use relationship-building techniques, including sharing emotions, expressing a wide variety of emotions, and using positive emotions like smiling and reassurance.

Women experienced physical signs of stress significantly more often. They were also more likely than men to rely on social support from friends and family and to seek professional help to deal with these issues. The women more often actively tried relaxing to relieve tension.

A second portion of the survey allowed physicians to freely express thoughts on their daily practice. When discussing practice constraints, women tended to list issues like “the politics of health care” and interpersonal factors, such as unpleasant office interactions and lack of collegial support.

Men focused more on administrative issues, such as staffing difficulties, lack of resources, and business competition.

Women said that they felt pressure to see more patients in less time and complained about administrative decisions from superiors that added to job stress. Men said they felt a loss of control because of numerous protocols that must be followed and expressed frustration at not being adequately recognized for their skills.

Decreased bureaucracy and better working conditions would go a long way toward improving the life of the family physician, “even more than higher pay,” she said.

An interactive telephone- and Web-based service now lets Alzheimer's patients, caregivers, and their physicians connect more easily with ongoing clinical trials.

The service—Alzheimer's Association TrialMatch—has the potential to greatly enrich the research into more effective treatment options and the ultimate goal of an Alzheimer's cure, William Thies, Ph.D., chief medical officer of the Alzheimer's Association, said at a press briefing on July 12.

“Alzheimer's disease is clearly the No. 1 health challenge of the 21st century, and research is the only way to solve this problem,” Dr. Thies said at the meeting in Honolulu. “If patients are not enrolling in trials, there can be no advances in diagnosis, treatment, and prevention, making the lack of study participants a significant health issue. TrialMatch provides a first-of-its-kind service in Alzheimer's by delivering a user-friendly and individualized guide to clinical trials for people with Alzheimer's, their health care professionals, caregivers, and healthy volunteers.”

There are about 150 clinical studies for Alzheimer's and dementia ongoing. Unfortunately, not enough patients volunteer for them—a problem that slows recruiting and drags out the overall length of the trial, Dr. Reisa Sperling said in an interview.

“At the rate we have people signing up now, it takes 12–18 months just to complete enrollment for a study,” said Dr. Sperling, director of clinical research at the Memory Disorders Unit, Brigham and Women's Hospital, Boston. “Since each one of these trials lasts for 18–24 months, that means each one takes 3–4 years to get an answer. This is not doable with the current scale of research.” Currently, there are 10 drugs in large-scale clinical trials and another 20 in preclinical studies.

When patients do volunteer for trials, screening eliminates many possible candidates, she said. “For every patient we enroll, we typically need to screen three or four. TrialMatch will collect detailed information in a confidential way, online, and that will speed up the matching process considerably.”

Interested parties visit the TrialMatch Web site (www.alz.org/TrialMatch

TrialMatch includes large, industry-sponsored drug trials, natural history and imaging studies, federally funded trials, and smaller, investigator-initiated studies. All of them are important, Dr. Sperling noted. “We need to rapidly enroll for all these studies, even the smaller ones, which often form the basis for larger studies.”

She expressed the hope that accelerating recruitment will also speed up answers to the problem of Alzheimer's disease—a condition that threatens to overwhelm the national health care scene in the next 50 years. By the middle of this century, there could be 1 million new cases diagnosed each year in the United States alone.

Entering a clinical trial also is an important way for both physicians and patients to claim some power in a situation that can make them feel quite helpless, she added. “I hope this can change the landscape of thinking about what patients and doctors can do to be proactive about this disease. Instead of hiding from it, let's agree to fight it tooth and nail.”

TrialMatch is funded by the Alzheimer's Association. Dr. Sperling had no relevant disclosures.

An interactive telephone- and Web-based service now lets Alzheimer's patients, caregivers, and their physicians connect more easily with ongoing clinical trials.

The service—Alzheimer's Association TrialMatch—has the potential to greatly enrich the research into more effective treatment options and the ultimate goal of an Alzheimer's cure, William Thies, Ph.D., chief medical officer of the Alzheimer's Association, said at a press briefing on July 12.

“Alzheimer's disease is clearly the No. 1 health challenge of the 21st century, and research is the only way to solve this problem,” Dr. Thies said at the meeting in Honolulu. “If patients are not enrolling in trials, there can be no advances in diagnosis, treatment, and prevention, making the lack of study participants a significant health issue. TrialMatch provides a first-of-its-kind service in Alzheimer's by delivering a user-friendly and individualized guide to clinical trials for people with Alzheimer's, their health care professionals, caregivers, and healthy volunteers.”

There are about 150 clinical studies for Alzheimer's and dementia ongoing. Unfortunately, not enough patients volunteer for them—a problem that slows recruiting and drags out the overall length of the trial, Dr. Reisa Sperling said in an interview.

“At the rate we have people signing up now, it takes 12–18 months just to complete enrollment for a study,” said Dr. Sperling, director of clinical research at the Memory Disorders Unit, Brigham and Women's Hospital, Boston. “Since each one of these trials lasts for 18–24 months, that means each one takes 3–4 years to get an answer. This is not doable with the current scale of research.” Currently, there are 10 drugs in large-scale clinical trials and another 20 in preclinical studies.

When patients do volunteer for trials, screening eliminates many possible candidates, she said. “For every patient we enroll, we typically need to screen three or four. TrialMatch will collect detailed information in a confidential way, online, and that will speed up the matching process considerably.”

Interested parties visit the TrialMatch Web site (www.alz.org/TrialMatch

TrialMatch includes large, industry-sponsored drug trials, natural history and imaging studies, federally funded trials, and smaller, investigator-initiated studies. All of them are important, Dr. Sperling noted. “We need to rapidly enroll for all these studies, even the smaller ones, which often form the basis for larger studies.”

She expressed the hope that accelerating recruitment will also speed up answers to the problem of Alzheimer's disease—a condition that threatens to overwhelm the national health care scene in the next 50 years. By the middle of this century, there could be 1 million new cases diagnosed each year in the United States alone.

Entering a clinical trial also is an important way for both physicians and patients to claim some power in a situation that can make them feel quite helpless, she added. “I hope this can change the landscape of thinking about what patients and doctors can do to be proactive about this disease. Instead of hiding from it, let's agree to fight it tooth and nail.”

TrialMatch is funded by the Alzheimer's Association. Dr. Sperling had no relevant disclosures.

An interactive telephone- and Web-based service now lets Alzheimer's patients, caregivers, and their physicians connect more easily with ongoing clinical trials.

The service—Alzheimer's Association TrialMatch—has the potential to greatly enrich the research into more effective treatment options and the ultimate goal of an Alzheimer's cure, William Thies, Ph.D., chief medical officer of the Alzheimer's Association, said at a press briefing on July 12.

“Alzheimer's disease is clearly the No. 1 health challenge of the 21st century, and research is the only way to solve this problem,” Dr. Thies said at the meeting in Honolulu. “If patients are not enrolling in trials, there can be no advances in diagnosis, treatment, and prevention, making the lack of study participants a significant health issue. TrialMatch provides a first-of-its-kind service in Alzheimer's by delivering a user-friendly and individualized guide to clinical trials for people with Alzheimer's, their health care professionals, caregivers, and healthy volunteers.”

There are about 150 clinical studies for Alzheimer's and dementia ongoing. Unfortunately, not enough patients volunteer for them—a problem that slows recruiting and drags out the overall length of the trial, Dr. Reisa Sperling said in an interview.

“At the rate we have people signing up now, it takes 12–18 months just to complete enrollment for a study,” said Dr. Sperling, director of clinical research at the Memory Disorders Unit, Brigham and Women's Hospital, Boston. “Since each one of these trials lasts for 18–24 months, that means each one takes 3–4 years to get an answer. This is not doable with the current scale of research.” Currently, there are 10 drugs in large-scale clinical trials and another 20 in preclinical studies.

When patients do volunteer for trials, screening eliminates many possible candidates, she said. “For every patient we enroll, we typically need to screen three or four. TrialMatch will collect detailed information in a confidential way, online, and that will speed up the matching process considerably.”

Interested parties visit the TrialMatch Web site (www.alz.org/TrialMatch

TrialMatch includes large, industry-sponsored drug trials, natural history and imaging studies, federally funded trials, and smaller, investigator-initiated studies. All of them are important, Dr. Sperling noted. “We need to rapidly enroll for all these studies, even the smaller ones, which often form the basis for larger studies.”

She expressed the hope that accelerating recruitment will also speed up answers to the problem of Alzheimer's disease—a condition that threatens to overwhelm the national health care scene in the next 50 years. By the middle of this century, there could be 1 million new cases diagnosed each year in the United States alone.

Entering a clinical trial also is an important way for both physicians and patients to claim some power in a situation that can make them feel quite helpless, she added. “I hope this can change the landscape of thinking about what patients and doctors can do to be proactive about this disease. Instead of hiding from it, let's agree to fight it tooth and nail.”

TrialMatch is funded by the Alzheimer's Association. Dr. Sperling had no relevant disclosures.

ORLANDO — Despite a steadily improving mortality picture, patients with childhood-onset type 1 diabetes still faced significantly increased mortality risks in a 40-year prospective follow-up study.

Women were particularly at risk, with a 13-fold greater risk of death than women in the same Pennsylvania community who were free of the disease, Dr. Trevor J. Orchard said.

However, the follow-up study did show improving survival rates. After 30 years, the death rate among those diagnosed in the earliest cohort (1965–1969) was 22%. That dropped to 19% in the 1970–1974 cohort, and to 15% in the 1975–1979 cohort.

“We believe this reflects better care, resulting in fewer deaths early in diagnosis and—more recently—lower rates of diabetes complications,” Dr. Orchard, professor of epidemiology at the University of Pittsburgh, said in an interview.

“A lot of patients and the public feel that individuals with childhood-onset type 1 have lower life expectancy. These data firmly support that this is rapidly changing, and most people with type 1 diabetes can look forward to a normal life span if they keep their blood glucose and other risk factors under control,” he added.

Dr. Orchard presented data collected by his colleague, Aaron Secrest, a PhD candidate at the university. Mr. Secrest based his analysis on the Allegheny County Type 1 Diabetes Registry, one of the largest population-based registries of the disease.

The analysis included 1,075 residents of Allegheny County, Pa., who were diagnosed with childhood-onset type 1 diabetes in 1965–1979. The population was stratified into three time cohorts: those diagnosed in 1965–1969, in 1970–1974, and in 1975–1979, with about one-third of the cohort included in each time period. In all, 48% of the patients were female, and 93% were white; the small percentage of black patients is representative of the county's overall population.

As of January 2008, 19% (202) of registry participants had died—a rate seven times greater than age- and sex-matched people in the general population. Of those 202 participants, 95 were men and 107 were women.

The cumulative survival rates were 98% at 10 years, 93% at 20 years, 81% at 30 years, and 68% at 40 years. “This tells us that about one-third of people with childhood-onset type 1 diabetes diagnosed in the 1960s will die within 40 years of their diagnosis,” Dr. Orchard said.

Although women within the cohort were not significantly more likely to die than men, “striking differences” emerged when the diabetes group was compared to the background population. “Compared to the standardized mortality rate of the county, women [in the cohort] were 13 times more likely to die, and men were 5 times more likely to die,” Dr. Orchard said. The relative mortality differences between cohort and community and the sex differences in relative mortality were highly statistically significant, he said.

Race also factored significantly into the survival curve. “We saw a tremendously high mortality in blacks, such that 30-year survival was down to 57% compared to 83% in whites,” Dr. Orchard said. “However, the standardized mortality ratio for blacks is very much the same [compared to the local county] as it is for whites, illustrating the relatively high mortality rate in the black background community.”

There were 32 deaths among black patients—41% of the black cohort. All of the deaths among blacks were directly related to diabetes.

“As this increase did include both acute and chronic complications of diabetes, it is most likely related to access to care and/or the ability to follow through with that care,” Dr. Orchard said.

Disclosures: The National Institutes of Health funded the study. Neither Dr. Orchard nor Mr. Secrest reported any financial disclosures.

After 30 years, the death rate was 22% in those diagnosed in 1965–1969, and 15% in the 1975–1979 cohort.

Source DR. ORCHARD

ORLANDO — Despite a steadily improving mortality picture, patients with childhood-onset type 1 diabetes still faced significantly increased mortality risks in a 40-year prospective follow-up study.

Women were particularly at risk, with a 13-fold greater risk of death than women in the same Pennsylvania community who were free of the disease, Dr. Trevor J. Orchard said.

However, the follow-up study did show improving survival rates. After 30 years, the death rate among those diagnosed in the earliest cohort (1965–1969) was 22%. That dropped to 19% in the 1970–1974 cohort, and to 15% in the 1975–1979 cohort.

“We believe this reflects better care, resulting in fewer deaths early in diagnosis and—more recently—lower rates of diabetes complications,” Dr. Orchard, professor of epidemiology at the University of Pittsburgh, said in an interview.

“A lot of patients and the public feel that individuals with childhood-onset type 1 have lower life expectancy. These data firmly support that this is rapidly changing, and most people with type 1 diabetes can look forward to a normal life span if they keep their blood glucose and other risk factors under control,” he added.

Dr. Orchard presented data collected by his colleague, Aaron Secrest, a PhD candidate at the university. Mr. Secrest based his analysis on the Allegheny County Type 1 Diabetes Registry, one of the largest population-based registries of the disease.

The analysis included 1,075 residents of Allegheny County, Pa., who were diagnosed with childhood-onset type 1 diabetes in 1965–1979. The population was stratified into three time cohorts: those diagnosed in 1965–1969, in 1970–1974, and in 1975–1979, with about one-third of the cohort included in each time period. In all, 48% of the patients were female, and 93% were white; the small percentage of black patients is representative of the county's overall population.

As of January 2008, 19% (202) of registry participants had died—a rate seven times greater than age- and sex-matched people in the general population. Of those 202 participants, 95 were men and 107 were women.

The cumulative survival rates were 98% at 10 years, 93% at 20 years, 81% at 30 years, and 68% at 40 years. “This tells us that about one-third of people with childhood-onset type 1 diabetes diagnosed in the 1960s will die within 40 years of their diagnosis,” Dr. Orchard said.

Although women within the cohort were not significantly more likely to die than men, “striking differences” emerged when the diabetes group was compared to the background population. “Compared to the standardized mortality rate of the county, women [in the cohort] were 13 times more likely to die, and men were 5 times more likely to die,” Dr. Orchard said. The relative mortality differences between cohort and community and the sex differences in relative mortality were highly statistically significant, he said.

Race also factored significantly into the survival curve. “We saw a tremendously high mortality in blacks, such that 30-year survival was down to 57% compared to 83% in whites,” Dr. Orchard said. “However, the standardized mortality ratio for blacks is very much the same [compared to the local county] as it is for whites, illustrating the relatively high mortality rate in the black background community.”

There were 32 deaths among black patients—41% of the black cohort. All of the deaths among blacks were directly related to diabetes.

“As this increase did include both acute and chronic complications of diabetes, it is most likely related to access to care and/or the ability to follow through with that care,” Dr. Orchard said.

Disclosures: The National Institutes of Health funded the study. Neither Dr. Orchard nor Mr. Secrest reported any financial disclosures.

After 30 years, the death rate was 22% in those diagnosed in 1965–1969, and 15% in the 1975–1979 cohort.

Source DR. ORCHARD

ORLANDO — Despite a steadily improving mortality picture, patients with childhood-onset type 1 diabetes still faced significantly increased mortality risks in a 40-year prospective follow-up study.

Women were particularly at risk, with a 13-fold greater risk of death than women in the same Pennsylvania community who were free of the disease, Dr. Trevor J. Orchard said.

However, the follow-up study did show improving survival rates. After 30 years, the death rate among those diagnosed in the earliest cohort (1965–1969) was 22%. That dropped to 19% in the 1970–1974 cohort, and to 15% in the 1975–1979 cohort.

“We believe this reflects better care, resulting in fewer deaths early in diagnosis and—more recently—lower rates of diabetes complications,” Dr. Orchard, professor of epidemiology at the University of Pittsburgh, said in an interview.

“A lot of patients and the public feel that individuals with childhood-onset type 1 have lower life expectancy. These data firmly support that this is rapidly changing, and most people with type 1 diabetes can look forward to a normal life span if they keep their blood glucose and other risk factors under control,” he added.

Dr. Orchard presented data collected by his colleague, Aaron Secrest, a PhD candidate at the university. Mr. Secrest based his analysis on the Allegheny County Type 1 Diabetes Registry, one of the largest population-based registries of the disease.

The analysis included 1,075 residents of Allegheny County, Pa., who were diagnosed with childhood-onset type 1 diabetes in 1965–1979. The population was stratified into three time cohorts: those diagnosed in 1965–1969, in 1970–1974, and in 1975–1979, with about one-third of the cohort included in each time period. In all, 48% of the patients were female, and 93% were white; the small percentage of black patients is representative of the county's overall population.

As of January 2008, 19% (202) of registry participants had died—a rate seven times greater than age- and sex-matched people in the general population. Of those 202 participants, 95 were men and 107 were women.

The cumulative survival rates were 98% at 10 years, 93% at 20 years, 81% at 30 years, and 68% at 40 years. “This tells us that about one-third of people with childhood-onset type 1 diabetes diagnosed in the 1960s will die within 40 years of their diagnosis,” Dr. Orchard said.

Although women within the cohort were not significantly more likely to die than men, “striking differences” emerged when the diabetes group was compared to the background population. “Compared to the standardized mortality rate of the county, women [in the cohort] were 13 times more likely to die, and men were 5 times more likely to die,” Dr. Orchard said. The relative mortality differences between cohort and community and the sex differences in relative mortality were highly statistically significant, he said.

Race also factored significantly into the survival curve. “We saw a tremendously high mortality in blacks, such that 30-year survival was down to 57% compared to 83% in whites,” Dr. Orchard said. “However, the standardized mortality ratio for blacks is very much the same [compared to the local county] as it is for whites, illustrating the relatively high mortality rate in the black background community.”

There were 32 deaths among black patients—41% of the black cohort. All of the deaths among blacks were directly related to diabetes.

“As this increase did include both acute and chronic complications of diabetes, it is most likely related to access to care and/or the ability to follow through with that care,” Dr. Orchard said.

Disclosures: The National Institutes of Health funded the study. Neither Dr. Orchard nor Mr. Secrest reported any financial disclosures.

After 30 years, the death rate was 22% in those diagnosed in 1965–1969, and 15% in the 1975–1979 cohort.

Source DR. ORCHARD