From Staff Reports

Reporters and editors from Elsevier's “The Pink Sheet” contributed to this column.

Merck, Galapagos Make Deal

Galapagos, a Belgian firm already partnered with Eli Lilly & Co. on products for osteoporosis, has struck a deal with Merck to seek novel therapies for obesity and diabetes. Merck will pay Galapagos $2.01 million up front along with discovery, development, and regulatory milestones that could pass $228.3 million for multiple products. Under the arrangement, Galapagos will perform preclinical research on targets selected by a joint screening committee. Merck will then have the option to take candidates produced by this process into development, although Galapagos may perform some phase I clinical studies and will retain development and commercialization rights to any compounds Merck does not pick up.

Kaufman Takes Medtronic Post

Dr. Francine Kaufman has been named vice president of global medical affairs for Medtronic's diabetes business. In that role, she will be “a key architect of the company's global diabetes strategy,” Medtronic officials said in a statement. Dr. Kaufman will retain her title as distinguished professor of pediatrics and communications at the University of Southern California, Los Angeles. “After a full and complete career in academic medicine, patient care, and advocacy, taking on an industry role with Medtronic represents an exciting new phase in my career,” said Dr. Kaufman, who also recently began a 3-year term as chair of the federal government's National Diabetes Education Program.

Metabasis Cuts Staff by 43%

Metabasis Therapeutics Inc. announced last month that it was laying off 38 employees, or 43% of its staff. The San Diego-based biotechnology company develops treatments for type 2 diabetes, hyperlipidemia, and liver disease. The company said it will focus on two product candidates, MB07811 for the treatment of hyperlipidemia and MB07803 for the treatment of type 2 diabetes, and also will work on advancing its glucagon antagonist program. “Given the tough market conditions, we have decided to refine our research and development focus,” said Dr. Mark Erion, president and chief executive officer of Metabasis. “We continue to make progress toward recommending a glucagon antagonist for development and as such are optimistic that this program will result in a significant collaboration.” The company also will look for a strategic collaboration for MB07803, its second generation fructose-1,6-bisphosphatase inhibitor for type 2 diabetes, he said. The company will take an estimated $1.4 million charge in connection with one-time employee termination costs.

Akesis Files for Bankruptcy

Also last month, Akesis Pharmaceuticals Inc. announced that it has discontinued its only clinical development program, which is for AKP-020, a phase IIa diabetes drug candidate. “After analyzing the data from our 3-month preclinical safety program, we have decided to discontinue the diabetes program,” said company president Carl LeBel, Ph.D. Because the AKP-020 program is being discontinued, the San Diego-based company is also filing for Chapter 7 liquidation. “We have determined that we can no longer operate as a business enterprise,” Dr. LeBel added.

Device Partnership Extended

Continuous glucose monitor maker DexCom Inc. has amended its joint development agreement with insulin pump maker Animas. The revised agreement gives Animas, a unit of Johnson & Johnson, exclusive rights to DexCom CGM technology for integration into Animas insulin pumps outside the United States. Animas will pay DexCom $5 million for the first regulatory body approval outside the United States for the new system. DexCom anticipates the integrated system will be available to patients in the first half of 2010.

Reporters and editors from Elsevier's “The Pink Sheet” contributed to this column.

Merck, Galapagos Make Deal

Galapagos, a Belgian firm already partnered with Eli Lilly & Co. on products for osteoporosis, has struck a deal with Merck to seek novel therapies for obesity and diabetes. Merck will pay Galapagos $2.01 million up front along with discovery, development, and regulatory milestones that could pass $228.3 million for multiple products. Under the arrangement, Galapagos will perform preclinical research on targets selected by a joint screening committee. Merck will then have the option to take candidates produced by this process into development, although Galapagos may perform some phase I clinical studies and will retain development and commercialization rights to any compounds Merck does not pick up.

Kaufman Takes Medtronic Post

Dr. Francine Kaufman has been named vice president of global medical affairs for Medtronic's diabetes business. In that role, she will be “a key architect of the company's global diabetes strategy,” Medtronic officials said in a statement. Dr. Kaufman will retain her title as distinguished professor of pediatrics and communications at the University of Southern California, Los Angeles. “After a full and complete career in academic medicine, patient care, and advocacy, taking on an industry role with Medtronic represents an exciting new phase in my career,” said Dr. Kaufman, who also recently began a 3-year term as chair of the federal government's National Diabetes Education Program.

Metabasis Cuts Staff by 43%

Metabasis Therapeutics Inc. announced last month that it was laying off 38 employees, or 43% of its staff. The San Diego-based biotechnology company develops treatments for type 2 diabetes, hyperlipidemia, and liver disease. The company said it will focus on two product candidates, MB07811 for the treatment of hyperlipidemia and MB07803 for the treatment of type 2 diabetes, and also will work on advancing its glucagon antagonist program. “Given the tough market conditions, we have decided to refine our research and development focus,” said Dr. Mark Erion, president and chief executive officer of Metabasis. “We continue to make progress toward recommending a glucagon antagonist for development and as such are optimistic that this program will result in a significant collaboration.” The company also will look for a strategic collaboration for MB07803, its second generation fructose-1,6-bisphosphatase inhibitor for type 2 diabetes, he said. The company will take an estimated $1.4 million charge in connection with one-time employee termination costs.

Akesis Files for Bankruptcy

Also last month, Akesis Pharmaceuticals Inc. announced that it has discontinued its only clinical development program, which is for AKP-020, a phase IIa diabetes drug candidate. “After analyzing the data from our 3-month preclinical safety program, we have decided to discontinue the diabetes program,” said company president Carl LeBel, Ph.D. Because the AKP-020 program is being discontinued, the San Diego-based company is also filing for Chapter 7 liquidation. “We have determined that we can no longer operate as a business enterprise,” Dr. LeBel added.

Device Partnership Extended

Continuous glucose monitor maker DexCom Inc. has amended its joint development agreement with insulin pump maker Animas. The revised agreement gives Animas, a unit of Johnson & Johnson, exclusive rights to DexCom CGM technology for integration into Animas insulin pumps outside the United States. Animas will pay DexCom $5 million for the first regulatory body approval outside the United States for the new system. DexCom anticipates the integrated system will be available to patients in the first half of 2010.

Reporters and editors from Elsevier's “The Pink Sheet” contributed to this column.

Merck, Galapagos Make Deal

Galapagos, a Belgian firm already partnered with Eli Lilly & Co. on products for osteoporosis, has struck a deal with Merck to seek novel therapies for obesity and diabetes. Merck will pay Galapagos $2.01 million up front along with discovery, development, and regulatory milestones that could pass $228.3 million for multiple products. Under the arrangement, Galapagos will perform preclinical research on targets selected by a joint screening committee. Merck will then have the option to take candidates produced by this process into development, although Galapagos may perform some phase I clinical studies and will retain development and commercialization rights to any compounds Merck does not pick up.

Kaufman Takes Medtronic Post

Dr. Francine Kaufman has been named vice president of global medical affairs for Medtronic's diabetes business. In that role, she will be “a key architect of the company's global diabetes strategy,” Medtronic officials said in a statement. Dr. Kaufman will retain her title as distinguished professor of pediatrics and communications at the University of Southern California, Los Angeles. “After a full and complete career in academic medicine, patient care, and advocacy, taking on an industry role with Medtronic represents an exciting new phase in my career,” said Dr. Kaufman, who also recently began a 3-year term as chair of the federal government's National Diabetes Education Program.

Metabasis Cuts Staff by 43%

Metabasis Therapeutics Inc. announced last month that it was laying off 38 employees, or 43% of its staff. The San Diego-based biotechnology company develops treatments for type 2 diabetes, hyperlipidemia, and liver disease. The company said it will focus on two product candidates, MB07811 for the treatment of hyperlipidemia and MB07803 for the treatment of type 2 diabetes, and also will work on advancing its glucagon antagonist program. “Given the tough market conditions, we have decided to refine our research and development focus,” said Dr. Mark Erion, president and chief executive officer of Metabasis. “We continue to make progress toward recommending a glucagon antagonist for development and as such are optimistic that this program will result in a significant collaboration.” The company also will look for a strategic collaboration for MB07803, its second generation fructose-1,6-bisphosphatase inhibitor for type 2 diabetes, he said. The company will take an estimated $1.4 million charge in connection with one-time employee termination costs.

Akesis Files for Bankruptcy

Also last month, Akesis Pharmaceuticals Inc. announced that it has discontinued its only clinical development program, which is for AKP-020, a phase IIa diabetes drug candidate. “After analyzing the data from our 3-month preclinical safety program, we have decided to discontinue the diabetes program,” said company president Carl LeBel, Ph.D. Because the AKP-020 program is being discontinued, the San Diego-based company is also filing for Chapter 7 liquidation. “We have determined that we can no longer operate as a business enterprise,” Dr. LeBel added.

Device Partnership Extended

Continuous glucose monitor maker DexCom Inc. has amended its joint development agreement with insulin pump maker Animas. The revised agreement gives Animas, a unit of Johnson & Johnson, exclusive rights to DexCom CGM technology for integration into Animas insulin pumps outside the United States. Animas will pay DexCom $5 million for the first regulatory body approval outside the United States for the new system. DexCom anticipates the integrated system will be available to patients in the first half of 2010.

Reporters and editors from Elsevier's “The Pink Sheet” contributed to this column.

Dutogliptin Deal Announced

Forest Laboratories Inc. and Phenomix Corp. have agreed to collaborate on the development and commercialization of dutogliptin in North America. Dutogliptin, a dipeptidyl-peptidase-4 (DPP-4) inhibitor, is currently undergoing phase III clinical trials for type 2 diabetes. Forest will pay Phenomix $75 million, and the two companies will jointly develop and commercialize the drug in the United States; they will equally share profits and expenses and copromote it once it comes to market. Under their agreement, Forest retains the exclusive right to develop and commercialize dutogliptin in Canada and Mexico, and Phenomix will receive a royalty on Canadian and Mexican sales in exchange for the rights to use data from jointly funded trials in those countries. Phenomix could receive up to $340 million in upfront and milestone payments for the successful development and commercialization of dutogliptin in the United States.

Amylin Cuts Jobs, Expenses

Amylin will lay off 340 employees and reduce 2009 cash expenses by more than $80 million, the company announced last month. The cost-savings program comes as the company seeks to calm investors concerned over slower growth of exenatide (Byetta) and prospects for a long-acting formula. The cuts will not impact sales efforts for Byetta or Amylin's other diabetes drug, pramlintide (Symlin), the company assured investors. The reductions will affect administration, operations, and research and development. Although the company said it will continue to advance its two obesity drug candidates—a pramlintide/metreleptin combination and AC2307—it will attempt to prioritize programs and run research and development more efficiently. “Sales revenues have not met the expectations we had when we scaled up our organization,” Amylin CEO Daniel Bradbury said in a statement. The company reported $179.9 million in net product sales for Byetta in the third quarter, up almost 12% over the year-ago period. However, sales were up only 1% versus the second quarter, suggesting that reports linking Byetta with cases of pancreatitis are having an impact. Prescriptions declined “modestly” in the third quarter compared with the second quarter, Amylin reported.

CLX Buys ThryoTest

CLX Medical Inc. has purchased the ThyroTest hypothyroidism screening test from ThyroTec LLC for $750,000 plus 750,000 shares of preferred stock. The deal completes the purchase agreement entered into by the two companies in September. The $750,000 will be paid in the form of a note issued at 6% interest for a term of 30 months. Until the principal is paid in full, CLX agreed to pay ThyroTec a 10% royalty on net sales of ThyroTest. “We are pleased to enter into this agreement, which allows CLX to close the acquisition of ThyroTest without raising additional capital,” said Vera Leonard, chief executive officer of CLX Medical.

Bayhill to Get Vaccine Funding

Bayhill Therapeutics Inc. will receive up to $3 million from the Juvenile Diabetes Research Foundation to support its ongoing phase I/II clinical trial of BHT-3021, a type 1 diabetes vaccine. BHT-3021 is an antigen-specific immunotherapeutic DNA vaccine designed to reverse the underlying autoimmune disease process in diabetes, and slow down or halt further loss of pancreatic beta cell function. “We are very pleased to have the support of JDRF as we advance the clinical development of BHT-3021,” said Bayhill President and CEO Mark W. Schwartz, Ph.D. “This agreement demonstrates JDRF's commitment to funding ground-breaking clinical research and to the development of novel therapeutics that can potentially have an important impact on the lives of people with diabetes.” Funding will be based on Bayhill's attaining specific clinical milestones expected to be reached by the third quarter of 2009.

Xoma Intensifies Diabetes Focus

With $10.6 million cash on hand at the end of the third quarter, Xoma has shelved some clinical trials to focus resources on developing its anti-inflammatory candidate 052, an antibody interleukin-1b inhibitor, in type 2 diabetes. Citing unprecedented general economic conditions, Xoma executives unveiled restructuring plans on their Nov. 10 earnings call. Although the executives said that Xoma 052 had “blockbuster potential,” they announced that they were suspending studies not directly related to the diabetes indication—such as a phase I trial in gout patients—to reduce research and development expenses. The company has also put on hold the development of its antimicrobial peptide Xoma 629.

Reporters and editors from Elsevier's “The Pink Sheet” contributed to this column.

Dutogliptin Deal Announced

Forest Laboratories Inc. and Phenomix Corp. have agreed to collaborate on the development and commercialization of dutogliptin in North America. Dutogliptin, a dipeptidyl-peptidase-4 (DPP-4) inhibitor, is currently undergoing phase III clinical trials for type 2 diabetes. Forest will pay Phenomix $75 million, and the two companies will jointly develop and commercialize the drug in the United States; they will equally share profits and expenses and copromote it once it comes to market. Under their agreement, Forest retains the exclusive right to develop and commercialize dutogliptin in Canada and Mexico, and Phenomix will receive a royalty on Canadian and Mexican sales in exchange for the rights to use data from jointly funded trials in those countries. Phenomix could receive up to $340 million in upfront and milestone payments for the successful development and commercialization of dutogliptin in the United States.

Amylin Cuts Jobs, Expenses

Amylin will lay off 340 employees and reduce 2009 cash expenses by more than $80 million, the company announced last month. The cost-savings program comes as the company seeks to calm investors concerned over slower growth of exenatide (Byetta) and prospects for a long-acting formula. The cuts will not impact sales efforts for Byetta or Amylin's other diabetes drug, pramlintide (Symlin), the company assured investors. The reductions will affect administration, operations, and research and development. Although the company said it will continue to advance its two obesity drug candidates—a pramlintide/metreleptin combination and AC2307—it will attempt to prioritize programs and run research and development more efficiently. “Sales revenues have not met the expectations we had when we scaled up our organization,” Amylin CEO Daniel Bradbury said in a statement. The company reported $179.9 million in net product sales for Byetta in the third quarter, up almost 12% over the year-ago period. However, sales were up only 1% versus the second quarter, suggesting that reports linking Byetta with cases of pancreatitis are having an impact. Prescriptions declined “modestly” in the third quarter compared with the second quarter, Amylin reported.

CLX Buys ThryoTest

CLX Medical Inc. has purchased the ThyroTest hypothyroidism screening test from ThyroTec LLC for $750,000 plus 750,000 shares of preferred stock. The deal completes the purchase agreement entered into by the two companies in September. The $750,000 will be paid in the form of a note issued at 6% interest for a term of 30 months. Until the principal is paid in full, CLX agreed to pay ThyroTec a 10% royalty on net sales of ThyroTest. “We are pleased to enter into this agreement, which allows CLX to close the acquisition of ThyroTest without raising additional capital,” said Vera Leonard, chief executive officer of CLX Medical.

Bayhill to Get Vaccine Funding

Bayhill Therapeutics Inc. will receive up to $3 million from the Juvenile Diabetes Research Foundation to support its ongoing phase I/II clinical trial of BHT-3021, a type 1 diabetes vaccine. BHT-3021 is an antigen-specific immunotherapeutic DNA vaccine designed to reverse the underlying autoimmune disease process in diabetes, and slow down or halt further loss of pancreatic beta cell function. “We are very pleased to have the support of JDRF as we advance the clinical development of BHT-3021,” said Bayhill President and CEO Mark W. Schwartz, Ph.D. “This agreement demonstrates JDRF's commitment to funding ground-breaking clinical research and to the development of novel therapeutics that can potentially have an important impact on the lives of people with diabetes.” Funding will be based on Bayhill's attaining specific clinical milestones expected to be reached by the third quarter of 2009.

Xoma Intensifies Diabetes Focus

With $10.6 million cash on hand at the end of the third quarter, Xoma has shelved some clinical trials to focus resources on developing its anti-inflammatory candidate 052, an antibody interleukin-1b inhibitor, in type 2 diabetes. Citing unprecedented general economic conditions, Xoma executives unveiled restructuring plans on their Nov. 10 earnings call. Although the executives said that Xoma 052 had “blockbuster potential,” they announced that they were suspending studies not directly related to the diabetes indication—such as a phase I trial in gout patients—to reduce research and development expenses. The company has also put on hold the development of its antimicrobial peptide Xoma 629.

Reporters and editors from Elsevier's “The Pink Sheet” contributed to this column.

Dutogliptin Deal Announced

Forest Laboratories Inc. and Phenomix Corp. have agreed to collaborate on the development and commercialization of dutogliptin in North America. Dutogliptin, a dipeptidyl-peptidase-4 (DPP-4) inhibitor, is currently undergoing phase III clinical trials for type 2 diabetes. Forest will pay Phenomix $75 million, and the two companies will jointly develop and commercialize the drug in the United States; they will equally share profits and expenses and copromote it once it comes to market. Under their agreement, Forest retains the exclusive right to develop and commercialize dutogliptin in Canada and Mexico, and Phenomix will receive a royalty on Canadian and Mexican sales in exchange for the rights to use data from jointly funded trials in those countries. Phenomix could receive up to $340 million in upfront and milestone payments for the successful development and commercialization of dutogliptin in the United States.

Amylin Cuts Jobs, Expenses

Amylin will lay off 340 employees and reduce 2009 cash expenses by more than $80 million, the company announced last month. The cost-savings program comes as the company seeks to calm investors concerned over slower growth of exenatide (Byetta) and prospects for a long-acting formula. The cuts will not impact sales efforts for Byetta or Amylin's other diabetes drug, pramlintide (Symlin), the company assured investors. The reductions will affect administration, operations, and research and development. Although the company said it will continue to advance its two obesity drug candidates—a pramlintide/metreleptin combination and AC2307—it will attempt to prioritize programs and run research and development more efficiently. “Sales revenues have not met the expectations we had when we scaled up our organization,” Amylin CEO Daniel Bradbury said in a statement. The company reported $179.9 million in net product sales for Byetta in the third quarter, up almost 12% over the year-ago period. However, sales were up only 1% versus the second quarter, suggesting that reports linking Byetta with cases of pancreatitis are having an impact. Prescriptions declined “modestly” in the third quarter compared with the second quarter, Amylin reported.

CLX Buys ThryoTest

CLX Medical Inc. has purchased the ThyroTest hypothyroidism screening test from ThyroTec LLC for $750,000 plus 750,000 shares of preferred stock. The deal completes the purchase agreement entered into by the two companies in September. The $750,000 will be paid in the form of a note issued at 6% interest for a term of 30 months. Until the principal is paid in full, CLX agreed to pay ThyroTec a 10% royalty on net sales of ThyroTest. “We are pleased to enter into this agreement, which allows CLX to close the acquisition of ThyroTest without raising additional capital,” said Vera Leonard, chief executive officer of CLX Medical.

Bayhill to Get Vaccine Funding

Bayhill Therapeutics Inc. will receive up to $3 million from the Juvenile Diabetes Research Foundation to support its ongoing phase I/II clinical trial of BHT-3021, a type 1 diabetes vaccine. BHT-3021 is an antigen-specific immunotherapeutic DNA vaccine designed to reverse the underlying autoimmune disease process in diabetes, and slow down or halt further loss of pancreatic beta cell function. “We are very pleased to have the support of JDRF as we advance the clinical development of BHT-3021,” said Bayhill President and CEO Mark W. Schwartz, Ph.D. “This agreement demonstrates JDRF's commitment to funding ground-breaking clinical research and to the development of novel therapeutics that can potentially have an important impact on the lives of people with diabetes.” Funding will be based on Bayhill's attaining specific clinical milestones expected to be reached by the third quarter of 2009.

Xoma Intensifies Diabetes Focus

With $10.6 million cash on hand at the end of the third quarter, Xoma has shelved some clinical trials to focus resources on developing its anti-inflammatory candidate 052, an antibody interleukin-1b inhibitor, in type 2 diabetes. Citing unprecedented general economic conditions, Xoma executives unveiled restructuring plans on their Nov. 10 earnings call. Although the executives said that Xoma 052 had “blockbuster potential,” they announced that they were suspending studies not directly related to the diabetes indication—such as a phase I trial in gout patients—to reduce research and development expenses. The company has also put on hold the development of its antimicrobial peptide Xoma 629.

AtheroGenics Seeks Chapter 11

AtheroGenics Inc., a pharmaceutical company that had been developing a diabetes drug, said it has consented to the involuntary Chapter 7 petition filed against it on Sept. 15 in federal bankruptcy court, and is seeking to convert the case under Chapter 11 of the U.S. Bankruptcy Code. It said the filing was necessary because of the company's substantial debt, which has created a significant impediment to AtheroGenics' ability to effectively develop its primary drug, AGI-1067, for the treatment of type 2 diabetes. During bankruptcy proceedings, AtheroGenics said it expects to sell the company and/or its key assets. Proceeds will be distributed first to stakeholders, including creditors, so it is not clear whether any of the proceeds will be distributed to shareholders. Dr. Russell M. Medford, the company's president and chief executive, said the company remains “hopeful that AGI-1067 will ultimately continue to be developed.” AtheroGenics had a net loss of $29.2 million, or 74 cents a share, for the 6 months ending June 30.

Lilly to Buy ImClone

Eli Lilly & Co. announced last month that it is acquiring cancer drug manufacturer ImClone for $6.5 billion. The acquisition gives Lilly its first targeted cancer drug, Erbitux, and five additional drugs in clinical development, including a number of biologics. The $6.5 billion purchase price makes ImClone Lilly's largest acquisition to date. In recent weeks, Lilly's stock price has been hit hard by negative news, including increased risk of pancreatitis associated with its diabetes drug Byetta and the delay in U.S. approval of prasugrel. The ImClone purchase seems to be signaling a shift away from riskier primary care blockbuster drugs to the specialty-focused oncology arena, where unmet medical need is greater and the regulatory path to market is more certain. The company's purchase of ImClone comes in the wake of a hostile takeover bid by BristolMyers Squibb, which had a 17% stake in the company. Eli Lilly's offer represents a 51% premium over ImClone's closing stock price on June 30.

GSK Declines to Option Thyroid Drug

GlaxoSmithKline has decided to decline its option to license XL184, Exelixis' late-stage small-molecule oncology drug candidate and four earlier-stage compounds, effectively ending a 6-year research collaboration between the two firms. XL184 is being studied in a phase III trial in patients with medullary thyroid cancer. In an interview, Exelixis president and CEO George Scangos said GSK's decision did not reflect poorly on the company's research and development programs or chances of success with XL184 and the other compounds. “I can speculate that [GSK's decision] on XL184 was largely because of a mechanistic overlap with XL880,” another small-molecule cancer compound from Exilixis that GSK is already developing, he said.

Phenomix, Forest Diabetes Partnership

Phenomix, a privately held biotechnology firm, signed a licensing pact last month with specialty pharmaceutical company Forest Laboratories to develop and commercialize Phenomix's dutogliptin, a dipeptidyl-peptidase-4 inhibitor drug for type 2 diabetes that is now in phase III trials. The deal will provide much-needed financial resources for Phenomix, which recently scrapped a public stock offering, citing market conditions. Forest, meanwhile, is facing impending generic versions of several of its own drugs and badly needs late-stage products. Under terms of the agreement, Forest will pay Phenomix $75 million up front and as much as $265 million in additional milestones. The two companies will develop and commercialize the drug jointly in this country, with both parties equally sharing profits and expenses. Phenomix will promote the product to diabetologists and endocrinologists, while Forest will market it to primary care physicians.

Chattem Launches Updated Dexatrim

Chattem Inc. hopes to increase sales of its Dexatrim weight-loss brand and compete with GlaxoSmithKline's Alli (orlistat) with the recent launch of Dexatrim Max Complex 7, a reformulated version of the over-the-counter dietary supplement. Meanwhile, the European Medicines Agency recently recommended Alli for nonprescription status across the European Union. Complex 7 contains the same ingredients as other Dexatrim products, but also contains “7-Keto,” an ingredient provided by Humanetics, of Eden Prairie, Minn. Humanetics says 7-Keto is a natural metabolite produced from dehydroepiandrosterone (DHEA) in the body.

Reporters and editors from Elsevier's “The Pink Sheet” and “The Tan Sheet” contributed to this column.

AtheroGenics Seeks Chapter 11

AtheroGenics Inc., a pharmaceutical company that had been developing a diabetes drug, said it has consented to the involuntary Chapter 7 petition filed against it on Sept. 15 in federal bankruptcy court, and is seeking to convert the case under Chapter 11 of the U.S. Bankruptcy Code. It said the filing was necessary because of the company's substantial debt, which has created a significant impediment to AtheroGenics' ability to effectively develop its primary drug, AGI-1067, for the treatment of type 2 diabetes. During bankruptcy proceedings, AtheroGenics said it expects to sell the company and/or its key assets. Proceeds will be distributed first to stakeholders, including creditors, so it is not clear whether any of the proceeds will be distributed to shareholders. Dr. Russell M. Medford, the company's president and chief executive, said the company remains “hopeful that AGI-1067 will ultimately continue to be developed.” AtheroGenics had a net loss of $29.2 million, or 74 cents a share, for the 6 months ending June 30.

Lilly to Buy ImClone

Eli Lilly & Co. announced last month that it is acquiring cancer drug manufacturer ImClone for $6.5 billion. The acquisition gives Lilly its first targeted cancer drug, Erbitux, and five additional drugs in clinical development, including a number of biologics. The $6.5 billion purchase price makes ImClone Lilly's largest acquisition to date. In recent weeks, Lilly's stock price has been hit hard by negative news, including increased risk of pancreatitis associated with its diabetes drug Byetta and the delay in U.S. approval of prasugrel. The ImClone purchase seems to be signaling a shift away from riskier primary care blockbuster drugs to the specialty-focused oncology arena, where unmet medical need is greater and the regulatory path to market is more certain. The company's purchase of ImClone comes in the wake of a hostile takeover bid by BristolMyers Squibb, which had a 17% stake in the company. Eli Lilly's offer represents a 51% premium over ImClone's closing stock price on June 30.

GSK Declines to Option Thyroid Drug

GlaxoSmithKline has decided to decline its option to license XL184, Exelixis' late-stage small-molecule oncology drug candidate and four earlier-stage compounds, effectively ending a 6-year research collaboration between the two firms. XL184 is being studied in a phase III trial in patients with medullary thyroid cancer. In an interview, Exelixis president and CEO George Scangos said GSK's decision did not reflect poorly on the company's research and development programs or chances of success with XL184 and the other compounds. “I can speculate that [GSK's decision] on XL184 was largely because of a mechanistic overlap with XL880,” another small-molecule cancer compound from Exilixis that GSK is already developing, he said.

Phenomix, Forest Diabetes Partnership

Phenomix, a privately held biotechnology firm, signed a licensing pact last month with specialty pharmaceutical company Forest Laboratories to develop and commercialize Phenomix's dutogliptin, a dipeptidyl-peptidase-4 inhibitor drug for type 2 diabetes that is now in phase III trials. The deal will provide much-needed financial resources for Phenomix, which recently scrapped a public stock offering, citing market conditions. Forest, meanwhile, is facing impending generic versions of several of its own drugs and badly needs late-stage products. Under terms of the agreement, Forest will pay Phenomix $75 million up front and as much as $265 million in additional milestones. The two companies will develop and commercialize the drug jointly in this country, with both parties equally sharing profits and expenses. Phenomix will promote the product to diabetologists and endocrinologists, while Forest will market it to primary care physicians.

Chattem Launches Updated Dexatrim

Chattem Inc. hopes to increase sales of its Dexatrim weight-loss brand and compete with GlaxoSmithKline's Alli (orlistat) with the recent launch of Dexatrim Max Complex 7, a reformulated version of the over-the-counter dietary supplement. Meanwhile, the European Medicines Agency recently recommended Alli for nonprescription status across the European Union. Complex 7 contains the same ingredients as other Dexatrim products, but also contains “7-Keto,” an ingredient provided by Humanetics, of Eden Prairie, Minn. Humanetics says 7-Keto is a natural metabolite produced from dehydroepiandrosterone (DHEA) in the body.

Reporters and editors from Elsevier's “The Pink Sheet” and “The Tan Sheet” contributed to this column.

AtheroGenics Seeks Chapter 11

AtheroGenics Inc., a pharmaceutical company that had been developing a diabetes drug, said it has consented to the involuntary Chapter 7 petition filed against it on Sept. 15 in federal bankruptcy court, and is seeking to convert the case under Chapter 11 of the U.S. Bankruptcy Code. It said the filing was necessary because of the company's substantial debt, which has created a significant impediment to AtheroGenics' ability to effectively develop its primary drug, AGI-1067, for the treatment of type 2 diabetes. During bankruptcy proceedings, AtheroGenics said it expects to sell the company and/or its key assets. Proceeds will be distributed first to stakeholders, including creditors, so it is not clear whether any of the proceeds will be distributed to shareholders. Dr. Russell M. Medford, the company's president and chief executive, said the company remains “hopeful that AGI-1067 will ultimately continue to be developed.” AtheroGenics had a net loss of $29.2 million, or 74 cents a share, for the 6 months ending June 30.

Lilly to Buy ImClone

Eli Lilly & Co. announced last month that it is acquiring cancer drug manufacturer ImClone for $6.5 billion. The acquisition gives Lilly its first targeted cancer drug, Erbitux, and five additional drugs in clinical development, including a number of biologics. The $6.5 billion purchase price makes ImClone Lilly's largest acquisition to date. In recent weeks, Lilly's stock price has been hit hard by negative news, including increased risk of pancreatitis associated with its diabetes drug Byetta and the delay in U.S. approval of prasugrel. The ImClone purchase seems to be signaling a shift away from riskier primary care blockbuster drugs to the specialty-focused oncology arena, where unmet medical need is greater and the regulatory path to market is more certain. The company's purchase of ImClone comes in the wake of a hostile takeover bid by BristolMyers Squibb, which had a 17% stake in the company. Eli Lilly's offer represents a 51% premium over ImClone's closing stock price on June 30.

GSK Declines to Option Thyroid Drug

GlaxoSmithKline has decided to decline its option to license XL184, Exelixis' late-stage small-molecule oncology drug candidate and four earlier-stage compounds, effectively ending a 6-year research collaboration between the two firms. XL184 is being studied in a phase III trial in patients with medullary thyroid cancer. In an interview, Exelixis president and CEO George Scangos said GSK's decision did not reflect poorly on the company's research and development programs or chances of success with XL184 and the other compounds. “I can speculate that [GSK's decision] on XL184 was largely because of a mechanistic overlap with XL880,” another small-molecule cancer compound from Exilixis that GSK is already developing, he said.

Phenomix, Forest Diabetes Partnership

Phenomix, a privately held biotechnology firm, signed a licensing pact last month with specialty pharmaceutical company Forest Laboratories to develop and commercialize Phenomix's dutogliptin, a dipeptidyl-peptidase-4 inhibitor drug for type 2 diabetes that is now in phase III trials. The deal will provide much-needed financial resources for Phenomix, which recently scrapped a public stock offering, citing market conditions. Forest, meanwhile, is facing impending generic versions of several of its own drugs and badly needs late-stage products. Under terms of the agreement, Forest will pay Phenomix $75 million up front and as much as $265 million in additional milestones. The two companies will develop and commercialize the drug jointly in this country, with both parties equally sharing profits and expenses. Phenomix will promote the product to diabetologists and endocrinologists, while Forest will market it to primary care physicians.

Chattem Launches Updated Dexatrim

Chattem Inc. hopes to increase sales of its Dexatrim weight-loss brand and compete with GlaxoSmithKline's Alli (orlistat) with the recent launch of Dexatrim Max Complex 7, a reformulated version of the over-the-counter dietary supplement. Meanwhile, the European Medicines Agency recently recommended Alli for nonprescription status across the European Union. Complex 7 contains the same ingredients as other Dexatrim products, but also contains “7-Keto,” an ingredient provided by Humanetics, of Eden Prairie, Minn. Humanetics says 7-Keto is a natural metabolite produced from dehydroepiandrosterone (DHEA) in the body.

Reporters and editors from Elsevier's “The Pink Sheet” and “The Tan Sheet” contributed to this column.

CLX to Buy ThyroTest

CLX Medical has entered into a letter of intent with ThyroTec, LLC, to acquire ThyroTest, a rapid thyroid-stimulating hormone (TSH) screening device used for the detection of hypothyroidism in adults. The company expects to announce a definitive agreement for the acquisition of ThyroTest very shortly, CLX said in a statement. ThyroTest is FDA-cleared and has also achieved Clinical Laboratory Improvement Amendments (CLIA)-waived status, so it can be administered in the more than 100,000 CLIA-waived doctors' offices in the United States, as well as in any nonwaived laboratory. CLX Medical also holds a 51% equity interest in Zonda Inc., which has developed several rapid point-of-care tests, including one for chlamydia.

Zentiva Agrees to Sanofi Takeover

The board of directors of Czech generic pharmaceutical maker Zentiva has agreed to recommend to shareholders that the company accept a takeover offer from Sanofi-Aventis for about $1.8 billion in cash. The price represents a 26% increase over the value of Zentiva stock on April 30, the last day of trading before the intention to make an offer was announced. Zentiva sells generic drugs in the Czech Republic, Slovakia, Romania, and Turkey, and is growing rapidly in Poland, Russia, Bulgaria, Hungary, the Ukraine, and the Baltic States, according to a statement by Sanofi. “Sanofi-Aventis believes that the operations of Zentiva present a compelling fit with this strategy and provide Sanofi-Aventis with a unique opportunity to accelerate its strategy in the markets that Zentiva serves,” the company said. “It is intended that Zentiva will become a platform for Sanofi-Aventis's further growth in the Central and Eastern European markets, focused upon providing affordable pharmaceuticals to patients in this region.”

NDA for Gencaro

ARCA Biopharma has filed a new drug application for Gencaro (bucindolol), which could be the first cardiovascular drug approved with an accompanying pharmacogenomic test, according to the company. “While currently available ?-blockers are a mainstay in medicine, it is difficult for physicians to predict which patients will respond to which therapy,” Michael Bristow, ARCA chairman, said in a statement. “Bucindolol interacts with certain polymorphism of adrenergic receptors that help regulate cardiac function, allowing us to predict patient clinical response using a simple genetic test.” Last year, ARCA signed a collaboration agreement with Laboratory Corporation of America, which is preparing a premarket approval application for the genomic test to submit to FDA's Center for Devices and Radiological Health.

Tethys Buys Lipomics Technologies

Diagnostics start-up Tethys Bioscience acquired Lipomics Technologies last month for an undisclosed sum. The purchase was thought to be made in order to shore up the technology expertise of the company, which launched its first diabetes risk assessment tool, PreDx, earlier this year. PreDx measures blood-borne biomarkers related to inflammation, lipid and carbohydrate metabolism, and coagulation to calculate a score identifying the patient's risk for developing diabetes. Lipomics specializes in profiling lipids, which can be evaluated in combination with proteins as an effective risk assessment tool for chronic conditions, according to Tethys. Lipomics's current business centers on contracting to perform biomarker research for drug company development projects, partnerships that could be helpful to Tethys's plan to establish drug-diagnostic comarketing agreements.

Shionogi Aims for Sciele Pharma

Japanese drugmaker Shionogi and Co. is planning to buy Atlanta-based Sciele Pharma for $1.42 billion—a transaction approved by both companies' boards, Shionogi announced last month. Sciele specializes in developing and marketing branded drugs that target cardiovascular health/diabetes, women's health, and pediatrics. Their products include novel formulations of off-patent drugs. “The acquisition is part of the medium- and long-term goals [at Shionogi] to establish a sales infrastructure in the U.S.,” a Shionogi spokesman said. The company's U.S. presence so far has been limited to Shionogi USA, a small subsidiary based in New Jersey, which was set up in 2001 to support drug development. The firm's primary revenue in this country has come from royalties on AstraZeneca's sales of Crestor (rosuvastatin), which was developed by Shionogi. Shionogi is offering $31 per share for Sciele, which represents a 60% premium over the company's average share price in recent months. The transaction is expected to close in the fourth quarter of 2008.

Reporters and editors from Elsevier's “The Pink Sheet” and “The Gray Sheet” contributed to this column.

CLX to Buy ThyroTest

CLX Medical has entered into a letter of intent with ThyroTec, LLC, to acquire ThyroTest, a rapid thyroid-stimulating hormone (TSH) screening device used for the detection of hypothyroidism in adults. The company expects to announce a definitive agreement for the acquisition of ThyroTest very shortly, CLX said in a statement. ThyroTest is FDA-cleared and has also achieved Clinical Laboratory Improvement Amendments (CLIA)-waived status, so it can be administered in the more than 100,000 CLIA-waived doctors' offices in the United States, as well as in any nonwaived laboratory. CLX Medical also holds a 51% equity interest in Zonda Inc., which has developed several rapid point-of-care tests, including one for chlamydia.

Zentiva Agrees to Sanofi Takeover

The board of directors of Czech generic pharmaceutical maker Zentiva has agreed to recommend to shareholders that the company accept a takeover offer from Sanofi-Aventis for about $1.8 billion in cash. The price represents a 26% increase over the value of Zentiva stock on April 30, the last day of trading before the intention to make an offer was announced. Zentiva sells generic drugs in the Czech Republic, Slovakia, Romania, and Turkey, and is growing rapidly in Poland, Russia, Bulgaria, Hungary, the Ukraine, and the Baltic States, according to a statement by Sanofi. “Sanofi-Aventis believes that the operations of Zentiva present a compelling fit with this strategy and provide Sanofi-Aventis with a unique opportunity to accelerate its strategy in the markets that Zentiva serves,” the company said. “It is intended that Zentiva will become a platform for Sanofi-Aventis's further growth in the Central and Eastern European markets, focused upon providing affordable pharmaceuticals to patients in this region.”

NDA for Gencaro

ARCA Biopharma has filed a new drug application for Gencaro (bucindolol), which could be the first cardiovascular drug approved with an accompanying pharmacogenomic test, according to the company. “While currently available ?-blockers are a mainstay in medicine, it is difficult for physicians to predict which patients will respond to which therapy,” Michael Bristow, ARCA chairman, said in a statement. “Bucindolol interacts with certain polymorphism of adrenergic receptors that help regulate cardiac function, allowing us to predict patient clinical response using a simple genetic test.” Last year, ARCA signed a collaboration agreement with Laboratory Corporation of America, which is preparing a premarket approval application for the genomic test to submit to FDA's Center for Devices and Radiological Health.

Tethys Buys Lipomics Technologies

Diagnostics start-up Tethys Bioscience acquired Lipomics Technologies last month for an undisclosed sum. The purchase was thought to be made in order to shore up the technology expertise of the company, which launched its first diabetes risk assessment tool, PreDx, earlier this year. PreDx measures blood-borne biomarkers related to inflammation, lipid and carbohydrate metabolism, and coagulation to calculate a score identifying the patient's risk for developing diabetes. Lipomics specializes in profiling lipids, which can be evaluated in combination with proteins as an effective risk assessment tool for chronic conditions, according to Tethys. Lipomics's current business centers on contracting to perform biomarker research for drug company development projects, partnerships that could be helpful to Tethys's plan to establish drug-diagnostic comarketing agreements.

Shionogi Aims for Sciele Pharma

Japanese drugmaker Shionogi and Co. is planning to buy Atlanta-based Sciele Pharma for $1.42 billion—a transaction approved by both companies' boards, Shionogi announced last month. Sciele specializes in developing and marketing branded drugs that target cardiovascular health/diabetes, women's health, and pediatrics. Their products include novel formulations of off-patent drugs. “The acquisition is part of the medium- and long-term goals [at Shionogi] to establish a sales infrastructure in the U.S.,” a Shionogi spokesman said. The company's U.S. presence so far has been limited to Shionogi USA, a small subsidiary based in New Jersey, which was set up in 2001 to support drug development. The firm's primary revenue in this country has come from royalties on AstraZeneca's sales of Crestor (rosuvastatin), which was developed by Shionogi. Shionogi is offering $31 per share for Sciele, which represents a 60% premium over the company's average share price in recent months. The transaction is expected to close in the fourth quarter of 2008.

Reporters and editors from Elsevier's “The Pink Sheet” and “The Gray Sheet” contributed to this column.

CLX to Buy ThyroTest

CLX Medical has entered into a letter of intent with ThyroTec, LLC, to acquire ThyroTest, a rapid thyroid-stimulating hormone (TSH) screening device used for the detection of hypothyroidism in adults. The company expects to announce a definitive agreement for the acquisition of ThyroTest very shortly, CLX said in a statement. ThyroTest is FDA-cleared and has also achieved Clinical Laboratory Improvement Amendments (CLIA)-waived status, so it can be administered in the more than 100,000 CLIA-waived doctors' offices in the United States, as well as in any nonwaived laboratory. CLX Medical also holds a 51% equity interest in Zonda Inc., which has developed several rapid point-of-care tests, including one for chlamydia.

Zentiva Agrees to Sanofi Takeover

The board of directors of Czech generic pharmaceutical maker Zentiva has agreed to recommend to shareholders that the company accept a takeover offer from Sanofi-Aventis for about $1.8 billion in cash. The price represents a 26% increase over the value of Zentiva stock on April 30, the last day of trading before the intention to make an offer was announced. Zentiva sells generic drugs in the Czech Republic, Slovakia, Romania, and Turkey, and is growing rapidly in Poland, Russia, Bulgaria, Hungary, the Ukraine, and the Baltic States, according to a statement by Sanofi. “Sanofi-Aventis believes that the operations of Zentiva present a compelling fit with this strategy and provide Sanofi-Aventis with a unique opportunity to accelerate its strategy in the markets that Zentiva serves,” the company said. “It is intended that Zentiva will become a platform for Sanofi-Aventis's further growth in the Central and Eastern European markets, focused upon providing affordable pharmaceuticals to patients in this region.”

NDA for Gencaro

ARCA Biopharma has filed a new drug application for Gencaro (bucindolol), which could be the first cardiovascular drug approved with an accompanying pharmacogenomic test, according to the company. “While currently available ?-blockers are a mainstay in medicine, it is difficult for physicians to predict which patients will respond to which therapy,” Michael Bristow, ARCA chairman, said in a statement. “Bucindolol interacts with certain polymorphism of adrenergic receptors that help regulate cardiac function, allowing us to predict patient clinical response using a simple genetic test.” Last year, ARCA signed a collaboration agreement with Laboratory Corporation of America, which is preparing a premarket approval application for the genomic test to submit to FDA's Center for Devices and Radiological Health.

Tethys Buys Lipomics Technologies

Diagnostics start-up Tethys Bioscience acquired Lipomics Technologies last month for an undisclosed sum. The purchase was thought to be made in order to shore up the technology expertise of the company, which launched its first diabetes risk assessment tool, PreDx, earlier this year. PreDx measures blood-borne biomarkers related to inflammation, lipid and carbohydrate metabolism, and coagulation to calculate a score identifying the patient's risk for developing diabetes. Lipomics specializes in profiling lipids, which can be evaluated in combination with proteins as an effective risk assessment tool for chronic conditions, according to Tethys. Lipomics's current business centers on contracting to perform biomarker research for drug company development projects, partnerships that could be helpful to Tethys's plan to establish drug-diagnostic comarketing agreements.

Shionogi Aims for Sciele Pharma

Japanese drugmaker Shionogi and Co. is planning to buy Atlanta-based Sciele Pharma for $1.42 billion—a transaction approved by both companies' boards, Shionogi announced last month. Sciele specializes in developing and marketing branded drugs that target cardiovascular health/diabetes, women's health, and pediatrics. Their products include novel formulations of off-patent drugs. “The acquisition is part of the medium- and long-term goals [at Shionogi] to establish a sales infrastructure in the U.S.,” a Shionogi spokesman said. The company's U.S. presence so far has been limited to Shionogi USA, a small subsidiary based in New Jersey, which was set up in 2001 to support drug development. The firm's primary revenue in this country has come from royalties on AstraZeneca's sales of Crestor (rosuvastatin), which was developed by Shionogi. Shionogi is offering $31 per share for Sciele, which represents a 60% premium over the company's average share price in recent months. The transaction is expected to close in the fourth quarter of 2008.

Reporters and editors from Elsevier's “The Pink Sheet” and “The Gray Sheet” contributed to this column.

Lower Exercise Intensity in Obese Boys

Obese adolescent boys have a limited capacity to metabolize fat by exercising at the recommended moderate intensity level, and might do better with lower-intensity activity, according to Dr. Gautier Zunquin, a sports medicine researcher at the University of the Littoral Opal Coast, Dunkirk, France, and associates.

To date, no studies have compared the rate of fat oxidation during exercise in obese children with rates in lean children using the same protocol. Dr. Zunquin and associates did so because they suspected current exercise guidelines should be altered for obese adolescents (Br. J. Sports Med. 2008 April 1 [doi:10.1136/bjsm.2007.044529]).

They calculated the fat oxidation rate in 13 lean and 17 obese 12-year-old boys, which allowed them “to construct a curve of fat oxidation vs. exercise intensity for each individual.” The maximal fat oxidation rate occurred at a lower level of exercise in the obese boys than in the lean boys. The lean boys metabolized the most fat exercising at 50%–60% of peak oxygen consumption, whereas the obese boys metabolized the most fat exercising at 30%–50% of peak oxygen consumption.

“Muscular modifications induced by obesity and being sedentary may partially explain the differences in fuel oxidation mechanisms,” wrote the authors. Differences between the two groups in hormonal changes during exercise, fatty-acid mobilization, and activation of α₂-adrenergic receptors might also play a role.

“Exercise intensity should be adapted to [children's] metabolic capacities during weight management programs,” they said.

Breast-Feeding and Type 2 Diabetes

Breast-fed babies may be protected against developing type 2 diabetes during childhood regardless of ethnicity, according to results from a study adjunct to the ongoing SEARCH for Diabetes in Youth investigation, by Elizabeth J. Mayer-Davis, Ph.D., of the University of South Carolina, Columbia, and her colleagues.

Their case-control study, conducted at two of the SEARCH study sites, included 80 participants aged 10–21 years with type 2 diabetes and 167 age-matched controls (Diabetes Care 2008;31:470–5).

Overall, the prevalence of breast-feeding for any length of time was significantly lower in youth with type 2 diabetes, compared with controls (31% vs. 64%).

Breast-feeding was also significantly associated with lower body mass index z scores in the controls and with lower (but not significantly lower) BMI z scores in the youth with type 2 diabetes. The average duration of breast-feeding was significantly longer in the controls.

When participants were divided into three ethnic groups, prevalence of breast-feeding was lower in black youth with type 2 diabetes than in controls (20% vs. 27%), but this difference was not statistically significant. The difference remained significant in Hispanics (50% vs. 84%) and in non-Hispanic whites (39% vs. 78%).

The researchers noted previous evidence that a lower prevalence of breast-feeding in blacks, compared with other ethnicities, might be a confounding variable, but they said that the overall presence of a protective effect of breast-feeding against type 2 diabetes suggests that all populations might benefit it.

Vitamin D Cuts Risk of Type 1 Diabetes

Children receiving vitamin D supplementation are significantly less likely to develop type 1 diabetes, according to an analysis of observational studies led by Dr. Christos Zipitis of St. Mary's Hospital for Women and Children, Manchester, England.

In four case-control studies of 6,684 subjects in several European countries, children who received vitamin D supplementation in early childhood had a significantly reduced risk of developing type 1 diabetes in later life, compared with those who received no supplementation (pooled odds ratio 0.71), said the researchers (Arch. Dis. Child. 2008 March 13 [Epub doi: 10.1136/adc.2007.128579]).

A cohort study also found significantly reduced risk for regular supplementation and irregular supplementation, when compared with no supplementation.

The authors found five studies that were relevant and fit their inclusion criteria, none of which was a randomized controlled trial. Because the case-control studies were retrospective and did not attempt to objectively confirm whether either cases or controls took vitamin D, nor how much of the vitamin they took, nor how much exposure to the sun they received, the findings could have been biased, they noted.

Lower Exercise Intensity in Obese Boys

Obese adolescent boys have a limited capacity to metabolize fat by exercising at the recommended moderate intensity level, and might do better with lower-intensity activity, according to Dr. Gautier Zunquin, a sports medicine researcher at the University of the Littoral Opal Coast, Dunkirk, France, and associates.

To date, no studies have compared the rate of fat oxidation during exercise in obese children with rates in lean children using the same protocol. Dr. Zunquin and associates did so because they suspected current exercise guidelines should be altered for obese adolescents (Br. J. Sports Med. 2008 April 1 [doi:10.1136/bjsm.2007.044529]).

They calculated the fat oxidation rate in 13 lean and 17 obese 12-year-old boys, which allowed them “to construct a curve of fat oxidation vs. exercise intensity for each individual.” The maximal fat oxidation rate occurred at a lower level of exercise in the obese boys than in the lean boys. The lean boys metabolized the most fat exercising at 50%–60% of peak oxygen consumption, whereas the obese boys metabolized the most fat exercising at 30%–50% of peak oxygen consumption.

“Muscular modifications induced by obesity and being sedentary may partially explain the differences in fuel oxidation mechanisms,” wrote the authors. Differences between the two groups in hormonal changes during exercise, fatty-acid mobilization, and activation of α₂-adrenergic receptors might also play a role.

“Exercise intensity should be adapted to [children's] metabolic capacities during weight management programs,” they said.

Breast-Feeding and Type 2 Diabetes

Breast-fed babies may be protected against developing type 2 diabetes during childhood regardless of ethnicity, according to results from a study adjunct to the ongoing SEARCH for Diabetes in Youth investigation, by Elizabeth J. Mayer-Davis, Ph.D., of the University of South Carolina, Columbia, and her colleagues.

Their case-control study, conducted at two of the SEARCH study sites, included 80 participants aged 10–21 years with type 2 diabetes and 167 age-matched controls (Diabetes Care 2008;31:470–5).

Overall, the prevalence of breast-feeding for any length of time was significantly lower in youth with type 2 diabetes, compared with controls (31% vs. 64%).

Breast-feeding was also significantly associated with lower body mass index z scores in the controls and with lower (but not significantly lower) BMI z scores in the youth with type 2 diabetes. The average duration of breast-feeding was significantly longer in the controls.

When participants were divided into three ethnic groups, prevalence of breast-feeding was lower in black youth with type 2 diabetes than in controls (20% vs. 27%), but this difference was not statistically significant. The difference remained significant in Hispanics (50% vs. 84%) and in non-Hispanic whites (39% vs. 78%).

The researchers noted previous evidence that a lower prevalence of breast-feeding in blacks, compared with other ethnicities, might be a confounding variable, but they said that the overall presence of a protective effect of breast-feeding against type 2 diabetes suggests that all populations might benefit it.

Vitamin D Cuts Risk of Type 1 Diabetes

Children receiving vitamin D supplementation are significantly less likely to develop type 1 diabetes, according to an analysis of observational studies led by Dr. Christos Zipitis of St. Mary's Hospital for Women and Children, Manchester, England.

In four case-control studies of 6,684 subjects in several European countries, children who received vitamin D supplementation in early childhood had a significantly reduced risk of developing type 1 diabetes in later life, compared with those who received no supplementation (pooled odds ratio 0.71), said the researchers (Arch. Dis. Child. 2008 March 13 [Epub doi: 10.1136/adc.2007.128579]).

A cohort study also found significantly reduced risk for regular supplementation and irregular supplementation, when compared with no supplementation.

The authors found five studies that were relevant and fit their inclusion criteria, none of which was a randomized controlled trial. Because the case-control studies were retrospective and did not attempt to objectively confirm whether either cases or controls took vitamin D, nor how much of the vitamin they took, nor how much exposure to the sun they received, the findings could have been biased, they noted.

Lower Exercise Intensity in Obese Boys

Obese adolescent boys have a limited capacity to metabolize fat by exercising at the recommended moderate intensity level, and might do better with lower-intensity activity, according to Dr. Gautier Zunquin, a sports medicine researcher at the University of the Littoral Opal Coast, Dunkirk, France, and associates.

To date, no studies have compared the rate of fat oxidation during exercise in obese children with rates in lean children using the same protocol. Dr. Zunquin and associates did so because they suspected current exercise guidelines should be altered for obese adolescents (Br. J. Sports Med. 2008 April 1 [doi:10.1136/bjsm.2007.044529]).

They calculated the fat oxidation rate in 13 lean and 17 obese 12-year-old boys, which allowed them “to construct a curve of fat oxidation vs. exercise intensity for each individual.” The maximal fat oxidation rate occurred at a lower level of exercise in the obese boys than in the lean boys. The lean boys metabolized the most fat exercising at 50%–60% of peak oxygen consumption, whereas the obese boys metabolized the most fat exercising at 30%–50% of peak oxygen consumption.

“Muscular modifications induced by obesity and being sedentary may partially explain the differences in fuel oxidation mechanisms,” wrote the authors. Differences between the two groups in hormonal changes during exercise, fatty-acid mobilization, and activation of α₂-adrenergic receptors might also play a role.

“Exercise intensity should be adapted to [children's] metabolic capacities during weight management programs,” they said.

Breast-Feeding and Type 2 Diabetes

Breast-fed babies may be protected against developing type 2 diabetes during childhood regardless of ethnicity, according to results from a study adjunct to the ongoing SEARCH for Diabetes in Youth investigation, by Elizabeth J. Mayer-Davis, Ph.D., of the University of South Carolina, Columbia, and her colleagues.

Their case-control study, conducted at two of the SEARCH study sites, included 80 participants aged 10–21 years with type 2 diabetes and 167 age-matched controls (Diabetes Care 2008;31:470–5).

Overall, the prevalence of breast-feeding for any length of time was significantly lower in youth with type 2 diabetes, compared with controls (31% vs. 64%).

Breast-feeding was also significantly associated with lower body mass index z scores in the controls and with lower (but not significantly lower) BMI z scores in the youth with type 2 diabetes. The average duration of breast-feeding was significantly longer in the controls.

When participants were divided into three ethnic groups, prevalence of breast-feeding was lower in black youth with type 2 diabetes than in controls (20% vs. 27%), but this difference was not statistically significant. The difference remained significant in Hispanics (50% vs. 84%) and in non-Hispanic whites (39% vs. 78%).

The researchers noted previous evidence that a lower prevalence of breast-feeding in blacks, compared with other ethnicities, might be a confounding variable, but they said that the overall presence of a protective effect of breast-feeding against type 2 diabetes suggests that all populations might benefit it.

Vitamin D Cuts Risk of Type 1 Diabetes

Children receiving vitamin D supplementation are significantly less likely to develop type 1 diabetes, according to an analysis of observational studies led by Dr. Christos Zipitis of St. Mary's Hospital for Women and Children, Manchester, England.

In four case-control studies of 6,684 subjects in several European countries, children who received vitamin D supplementation in early childhood had a significantly reduced risk of developing type 1 diabetes in later life, compared with those who received no supplementation (pooled odds ratio 0.71), said the researchers (Arch. Dis. Child. 2008 March 13 [Epub doi: 10.1136/adc.2007.128579]).

A cohort study also found significantly reduced risk for regular supplementation and irregular supplementation, when compared with no supplementation.

The authors found five studies that were relevant and fit their inclusion criteria, none of which was a randomized controlled trial. Because the case-control studies were retrospective and did not attempt to objectively confirm whether either cases or controls took vitamin D, nor how much of the vitamin they took, nor how much exposure to the sun they received, the findings could have been biased, they noted.

Statins, Colorectal Cancer Tie Examined

Long-term statin therapy did not protect against colorectal cancer in a large case-control study in the United Kingdom.

However, neither did statins promote colorectal cancer, as has been reported in the international PROSPER (Pravastatin in Elderly Individuals at Risk of Vascular Disease) trial, wrote Yana Vinogradova, a research statistician at the University of Nottingham (England), and her colleagues in the August 2007 issue of Gastroenterology. The results of trials on the risk of cancer in patients on statins “have been equivocal because of inadequate [statistical] power,” they noted.

The current study was designed to have greater statistical power and analyzed data on over 30,000 patients attending 454 general practices in the United Kingdom between 1995 and 2005. A total of 5,686 patients who developed colorectal cancer during the study period were matched to 24,982 control subjects, and their patterns of medication use were compared.

There was no significant association between statin use in general and risk of colorectal cancer, nor was there any association between the disease and any of five individual statins assessed. When colon and rectal cancers were considered separately, there also was no association between the risk of either type of cancer and statin use.

In contrast, the protective effect of NSAIDs reported in several previous studies was confirmed in this study, with prolonged use of NSAIDs being associated with a 25% or greater reduction in colorectal cancer risk, said the authors.

Exercise Pumps Up HDL Levels

Regular aerobic exercise increases HDL cholesterol levels to a modest but still highly significant degree, reported Dr. Satoru Kodama of Ochanomizu University, Tokyo, and associates.

In their meta-analysis of 35 randomized clinical trials that examined the effect of exercise training on serum levels of HDL cholesterol, every 10-minute increase in the duration of exercise beyond a minimum of 120 minutes per week corresponded to a 1.4-mg/dL rise in HDL cholesterol.

The meta-analysis comprised 35 clinical trials that included 1,404 subjects aged 23–75 years who performed at least 15 minutes a day of exercise such as walking, bicycling, or continuous swimming. They performed a mean of 3.7 exercise sessions each week.

The mean estimated relative intensity of activity was 65% of maximal aerobic capacity. The mean increase in HDL cholesterol levels was “modest although statistically significant” at 2.53 mg/dL, the authors said (Arch. Intern. Med. 2007;167:999–1008).

The findings also showed that there is a minimum amount of exercise—120 minutes a week—below which HDL cholesterol levels will not be affected. To raise HDL cholesterol, an increase in the time of each exercise session would be more effective than an increase in the intensity of the activity, because neither the intensity nor the frequency of exercise was found to correlate with cholesterol levels in this study.

Light Cigarettes Heavy on the Heart

Low-tar, low-nicotine cigarettes impede the coronary flow velocity reserve (CFVR) of smokers as much as do regular cigarettes, according to data from a small study.

The researchers found similar changes in other hemodynamic and coronary flow measurements, all of which contradict the belief that light cigarettes are less dangerous to coronary health.

Forty smokers—half of whom smoked light cigarettes (8 mg tar, 0.6 mg nicotine, and 9 mg CO) and half of whom smoked regular cigarettes (12 mg tar, 0.9 mg nicotine, and 12 mg CO)—had similarly, and significantly, reduced CFVR values, compared with 22 healthy nonsmokers. The mean age was 24–25 years, and smokers had steadily smoked the same kind of cigarette for at least 3 years (Heart 2007 May 15 [Epub doi: 10.1136/hrt.2006.100255]).

Coronary flow velocity reserve at the distal left anterior descending artery was measured using echocardiography, first after a 12-hour fasting and smokeless period and, 2 days later, after the tobacco users smoked two of their usual cigarettes within 15 minutes. Similar decreases in CFVR after smoking were seen in light (2.68 to 2.05) and regular cigarette smokers (2.65 to 2.18). The baseline values in both smoker groups were significantly lower than those of controls.

Similar impairments also were seen between the two smoker groups in mean systolic blood pressure, diastolic blood pressure, and heart rate. The impairment of vascular function was statistically significant, but not clinically disabling.

Statins, Colorectal Cancer Tie Examined

Long-term statin therapy did not protect against colorectal cancer in a large case-control study in the United Kingdom.

However, neither did statins promote colorectal cancer, as has been reported in the international PROSPER (Pravastatin in Elderly Individuals at Risk of Vascular Disease) trial, wrote Yana Vinogradova, a research statistician at the University of Nottingham (England), and her colleagues in the August 2007 issue of Gastroenterology. The results of trials on the risk of cancer in patients on statins “have been equivocal because of inadequate [statistical] power,” they noted.

The current study was designed to have greater statistical power and analyzed data on over 30,000 patients attending 454 general practices in the United Kingdom between 1995 and 2005. A total of 5,686 patients who developed colorectal cancer during the study period were matched to 24,982 control subjects, and their patterns of medication use were compared.

There was no significant association between statin use in general and risk of colorectal cancer, nor was there any association between the disease and any of five individual statins assessed. When colon and rectal cancers were considered separately, there also was no association between the risk of either type of cancer and statin use.

In contrast, the protective effect of NSAIDs reported in several previous studies was confirmed in this study, with prolonged use of NSAIDs being associated with a 25% or greater reduction in colorectal cancer risk, said the authors.

Exercise Pumps Up HDL Levels

Regular aerobic exercise increases HDL cholesterol levels to a modest but still highly significant degree, reported Dr. Satoru Kodama of Ochanomizu University, Tokyo, and associates.

In their meta-analysis of 35 randomized clinical trials that examined the effect of exercise training on serum levels of HDL cholesterol, every 10-minute increase in the duration of exercise beyond a minimum of 120 minutes per week corresponded to a 1.4-mg/dL rise in HDL cholesterol.

The meta-analysis comprised 35 clinical trials that included 1,404 subjects aged 23–75 years who performed at least 15 minutes a day of exercise such as walking, bicycling, or continuous swimming. They performed a mean of 3.7 exercise sessions each week.

The mean estimated relative intensity of activity was 65% of maximal aerobic capacity. The mean increase in HDL cholesterol levels was “modest although statistically significant” at 2.53 mg/dL, the authors said (Arch. Intern. Med. 2007;167:999–1008).

The findings also showed that there is a minimum amount of exercise—120 minutes a week—below which HDL cholesterol levels will not be affected. To raise HDL cholesterol, an increase in the time of each exercise session would be more effective than an increase in the intensity of the activity, because neither the intensity nor the frequency of exercise was found to correlate with cholesterol levels in this study.

Light Cigarettes Heavy on the Heart

Low-tar, low-nicotine cigarettes impede the coronary flow velocity reserve (CFVR) of smokers as much as do regular cigarettes, according to data from a small study.

The researchers found similar changes in other hemodynamic and coronary flow measurements, all of which contradict the belief that light cigarettes are less dangerous to coronary health.

Forty smokers—half of whom smoked light cigarettes (8 mg tar, 0.6 mg nicotine, and 9 mg CO) and half of whom smoked regular cigarettes (12 mg tar, 0.9 mg nicotine, and 12 mg CO)—had similarly, and significantly, reduced CFVR values, compared with 22 healthy nonsmokers. The mean age was 24–25 years, and smokers had steadily smoked the same kind of cigarette for at least 3 years (Heart 2007 May 15 [Epub doi: 10.1136/hrt.2006.100255]).

Coronary flow velocity reserve at the distal left anterior descending artery was measured using echocardiography, first after a 12-hour fasting and smokeless period and, 2 days later, after the tobacco users smoked two of their usual cigarettes within 15 minutes. Similar decreases in CFVR after smoking were seen in light (2.68 to 2.05) and regular cigarette smokers (2.65 to 2.18). The baseline values in both smoker groups were significantly lower than those of controls.

Similar impairments also were seen between the two smoker groups in mean systolic blood pressure, diastolic blood pressure, and heart rate. The impairment of vascular function was statistically significant, but not clinically disabling.

Statins, Colorectal Cancer Tie Examined

Long-term statin therapy did not protect against colorectal cancer in a large case-control study in the United Kingdom.

However, neither did statins promote colorectal cancer, as has been reported in the international PROSPER (Pravastatin in Elderly Individuals at Risk of Vascular Disease) trial, wrote Yana Vinogradova, a research statistician at the University of Nottingham (England), and her colleagues in the August 2007 issue of Gastroenterology. The results of trials on the risk of cancer in patients on statins “have been equivocal because of inadequate [statistical] power,” they noted.

The current study was designed to have greater statistical power and analyzed data on over 30,000 patients attending 454 general practices in the United Kingdom between 1995 and 2005. A total of 5,686 patients who developed colorectal cancer during the study period were matched to 24,982 control subjects, and their patterns of medication use were compared.

There was no significant association between statin use in general and risk of colorectal cancer, nor was there any association between the disease and any of five individual statins assessed. When colon and rectal cancers were considered separately, there also was no association between the risk of either type of cancer and statin use.

In contrast, the protective effect of NSAIDs reported in several previous studies was confirmed in this study, with prolonged use of NSAIDs being associated with a 25% or greater reduction in colorectal cancer risk, said the authors.

Exercise Pumps Up HDL Levels

Regular aerobic exercise increases HDL cholesterol levels to a modest but still highly significant degree, reported Dr. Satoru Kodama of Ochanomizu University, Tokyo, and associates.

In their meta-analysis of 35 randomized clinical trials that examined the effect of exercise training on serum levels of HDL cholesterol, every 10-minute increase in the duration of exercise beyond a minimum of 120 minutes per week corresponded to a 1.4-mg/dL rise in HDL cholesterol.

The meta-analysis comprised 35 clinical trials that included 1,404 subjects aged 23–75 years who performed at least 15 minutes a day of exercise such as walking, bicycling, or continuous swimming. They performed a mean of 3.7 exercise sessions each week.

The mean estimated relative intensity of activity was 65% of maximal aerobic capacity. The mean increase in HDL cholesterol levels was “modest although statistically significant” at 2.53 mg/dL, the authors said (Arch. Intern. Med. 2007;167:999–1008).

The findings also showed that there is a minimum amount of exercise—120 minutes a week—below which HDL cholesterol levels will not be affected. To raise HDL cholesterol, an increase in the time of each exercise session would be more effective than an increase in the intensity of the activity, because neither the intensity nor the frequency of exercise was found to correlate with cholesterol levels in this study.

Light Cigarettes Heavy on the Heart

Low-tar, low-nicotine cigarettes impede the coronary flow velocity reserve (CFVR) of smokers as much as do regular cigarettes, according to data from a small study.

The researchers found similar changes in other hemodynamic and coronary flow measurements, all of which contradict the belief that light cigarettes are less dangerous to coronary health.

Forty smokers—half of whom smoked light cigarettes (8 mg tar, 0.6 mg nicotine, and 9 mg CO) and half of whom smoked regular cigarettes (12 mg tar, 0.9 mg nicotine, and 12 mg CO)—had similarly, and significantly, reduced CFVR values, compared with 22 healthy nonsmokers. The mean age was 24–25 years, and smokers had steadily smoked the same kind of cigarette for at least 3 years (Heart 2007 May 15 [Epub doi: 10.1136/hrt.2006.100255]).

Coronary flow velocity reserve at the distal left anterior descending artery was measured using echocardiography, first after a 12-hour fasting and smokeless period and, 2 days later, after the tobacco users smoked two of their usual cigarettes within 15 minutes. Similar decreases in CFVR after smoking were seen in light (2.68 to 2.05) and regular cigarette smokers (2.65 to 2.18). The baseline values in both smoker groups were significantly lower than those of controls.

Similar impairments also were seen between the two smoker groups in mean systolic blood pressure, diastolic blood pressure, and heart rate. The impairment of vascular function was statistically significant, but not clinically disabling.

Depressive Symptoms Linked to CAD

Depressive symptoms appear to correlate with the development of coronary artery disease, but hostility and anxiety may not, reported Jesse C. Stewart, Ph.D., and his associates.

Several studies have linked various negative emotions with the development of coronary artery disease in initially healthy subjects. But teasing out the relative contributions of depression, anxiety, and hostility has been difficult because they tend to overlap. The researchers, of the University of Pittsburgh, assessed a range of such symptoms in a prospective cohort study of subclinical atherosclerosis in healthy subjects aged 50–70 years.

The 324 subjects underwent ultrasonographic assessment of carotid intima-media thickness (IMT), a noninvasive measure of subclinical atherosclerosis, as well as a battery of tests evaluating emotional factors, including the Beck Depression Inventory, the Beck Anxiety Inventory, the Cooke-Medley Hostility Scale, and the State-Trait Anger Expression Inventory.

During 3-year follow-up, only mild to moderate depressive symptoms correlated with the decreasing carotid IMT that signals progression of subclinical atherosclerosis. Symptoms of anxiety, hostility, the experience of anger, and the expression of anger showed no correlation with carotid IMT change. This suggests depression, but not anxiety or hostility, is involved in the initiation and/or the progression of atherosclerosis. This study is the first ever to report an association between depressive symptoms and carotid IMT change, the investigators said (Arch. Gen. Psychiatry 2007;64:225–33). The exact mechanism underlying this association is unclear, but depression is known to affect physiologic pathways also involved in atherosclerosis, they said.

Grief Begins to Ease at 6 Months

The normal grief response to the natural death of a loved one seems to start declining within 6 months of the loss, said Paul K. Maciejewski, Ph.D., of Yale University, New Haven, Conn., and his associates.

“The notion that a natural psychological response to loss involves an orderly progression through distinct stages of bereavement has been widely accepted,” but no study has tested progression through disbelief, anger, yearning, depression, and acceptance (JAMA 2007;297:716–23).

They assessed data from the Yale Bereavement Study, a longitudinal study of grief in a sample of 317 subjects interviewed between 2000 and 2003 within 1–6 months of the death of a spouse (84%) or adult children, parents, or siblings. The 233 subjects whose loved ones died of natural rather than traumatic causes were included.

Disbelief declined from the first month onward. Yearning rose until 4 months after the loss, then declined. Anger peaked at 5 months, and its decline was accompanied by a rise in depressive mood, which peaked at 6 months and then diminished over the next 18 months. Acceptance was noted immediately after the loss and increased steadily over the next 2 years.

All the grief indicators peaked and began to decline within 6 months, so those experiencing significant levels of these emotions beyond 6 months seem to deviate from the normal response, lending some support for the stage theory of grief.

But “counter to the stage theory, disbelief was not the initial, dominant grief indicator. Acceptance was the most often endorsed item,” the authors wrote. Yearning was the most common negative psychological response reported at all time points during the 2-year follow-up, and was significantly more common than was depressed mood. Since depressed mood is the focus of the bereavement section in the DSM-IV, “these results imply a need for revision.”

Delinquent Teens at Risk for Suicide

Teenage delinquency was significantly associated with an increased risk for suicidal behavior in girls, according to data from a sample of American teens.

Previous studies have shown an association between delinquency and suicide, but none has studied the association in delinquent vs. nondelinquent youth.

Martie P. Thompson, Ph.D., and her colleagues at Clemson (S.C.) University reviewed data on 15,034 teens aged 12–17 years from the National Longitudinal Study of Adolescent Health, a survey of factors that affect teens' health and behavior (J. Adolesc. Health 2007;40:232–7).

They assessed delinquency using a 15-item survey of behaviors in the previous 12 months. After controlling for age, race, gender, and urban dwelling status, delinquent teens were significantly more likely than their nondelinquent peers to report suicidal ideation, suicide attempts, and treatment for suicide attempts at both 1 year and 7 years' follow-up. After controlling for behavioral risk factors such as depression, impulsivity, religiosity, and problem drinking, delinquency remained significantly associated with suicidal ideation 1 year later and with suicide attempts 1 and 7 years later in girls. The association for boys remained, but the differences weren't significant.

Depressive Symptoms Linked to CAD

Depressive symptoms appear to correlate with the development of coronary artery disease, but hostility and anxiety may not, reported Jesse C. Stewart, Ph.D., and his associates.

Several studies have linked various negative emotions with the development of coronary artery disease in initially healthy subjects. But teasing out the relative contributions of depression, anxiety, and hostility has been difficult because they tend to overlap. The researchers, of the University of Pittsburgh, assessed a range of such symptoms in a prospective cohort study of subclinical atherosclerosis in healthy subjects aged 50–70 years.

The 324 subjects underwent ultrasonographic assessment of carotid intima-media thickness (IMT), a noninvasive measure of subclinical atherosclerosis, as well as a battery of tests evaluating emotional factors, including the Beck Depression Inventory, the Beck Anxiety Inventory, the Cooke-Medley Hostility Scale, and the State-Trait Anger Expression Inventory.

During 3-year follow-up, only mild to moderate depressive symptoms correlated with the decreasing carotid IMT that signals progression of subclinical atherosclerosis. Symptoms of anxiety, hostility, the experience of anger, and the expression of anger showed no correlation with carotid IMT change. This suggests depression, but not anxiety or hostility, is involved in the initiation and/or the progression of atherosclerosis. This study is the first ever to report an association between depressive symptoms and carotid IMT change, the investigators said (Arch. Gen. Psychiatry 2007;64:225–33). The exact mechanism underlying this association is unclear, but depression is known to affect physiologic pathways also involved in atherosclerosis, they said.

Grief Begins to Ease at 6 Months

The normal grief response to the natural death of a loved one seems to start declining within 6 months of the loss, said Paul K. Maciejewski, Ph.D., of Yale University, New Haven, Conn., and his associates.

“The notion that a natural psychological response to loss involves an orderly progression through distinct stages of bereavement has been widely accepted,” but no study has tested progression through disbelief, anger, yearning, depression, and acceptance (JAMA 2007;297:716–23).

They assessed data from the Yale Bereavement Study, a longitudinal study of grief in a sample of 317 subjects interviewed between 2000 and 2003 within 1–6 months of the death of a spouse (84%) or adult children, parents, or siblings. The 233 subjects whose loved ones died of natural rather than traumatic causes were included.

Disbelief declined from the first month onward. Yearning rose until 4 months after the loss, then declined. Anger peaked at 5 months, and its decline was accompanied by a rise in depressive mood, which peaked at 6 months and then diminished over the next 18 months. Acceptance was noted immediately after the loss and increased steadily over the next 2 years.

All the grief indicators peaked and began to decline within 6 months, so those experiencing significant levels of these emotions beyond 6 months seem to deviate from the normal response, lending some support for the stage theory of grief.

But “counter to the stage theory, disbelief was not the initial, dominant grief indicator. Acceptance was the most often endorsed item,” the authors wrote. Yearning was the most common negative psychological response reported at all time points during the 2-year follow-up, and was significantly more common than was depressed mood. Since depressed mood is the focus of the bereavement section in the DSM-IV, “these results imply a need for revision.”

Delinquent Teens at Risk for Suicide

Teenage delinquency was significantly associated with an increased risk for suicidal behavior in girls, according to data from a sample of American teens.

Previous studies have shown an association between delinquency and suicide, but none has studied the association in delinquent vs. nondelinquent youth.

Martie P. Thompson, Ph.D., and her colleagues at Clemson (S.C.) University reviewed data on 15,034 teens aged 12–17 years from the National Longitudinal Study of Adolescent Health, a survey of factors that affect teens' health and behavior (J. Adolesc. Health 2007;40:232–7).

They assessed delinquency using a 15-item survey of behaviors in the previous 12 months. After controlling for age, race, gender, and urban dwelling status, delinquent teens were significantly more likely than their nondelinquent peers to report suicidal ideation, suicide attempts, and treatment for suicide attempts at both 1 year and 7 years' follow-up. After controlling for behavioral risk factors such as depression, impulsivity, religiosity, and problem drinking, delinquency remained significantly associated with suicidal ideation 1 year later and with suicide attempts 1 and 7 years later in girls. The association for boys remained, but the differences weren't significant.

Depressive Symptoms Linked to CAD

Depressive symptoms appear to correlate with the development of coronary artery disease, but hostility and anxiety may not, reported Jesse C. Stewart, Ph.D., and his associates.

Several studies have linked various negative emotions with the development of coronary artery disease in initially healthy subjects. But teasing out the relative contributions of depression, anxiety, and hostility has been difficult because they tend to overlap. The researchers, of the University of Pittsburgh, assessed a range of such symptoms in a prospective cohort study of subclinical atherosclerosis in healthy subjects aged 50–70 years.

The 324 subjects underwent ultrasonographic assessment of carotid intima-media thickness (IMT), a noninvasive measure of subclinical atherosclerosis, as well as a battery of tests evaluating emotional factors, including the Beck Depression Inventory, the Beck Anxiety Inventory, the Cooke-Medley Hostility Scale, and the State-Trait Anger Expression Inventory.

During 3-year follow-up, only mild to moderate depressive symptoms correlated with the decreasing carotid IMT that signals progression of subclinical atherosclerosis. Symptoms of anxiety, hostility, the experience of anger, and the expression of anger showed no correlation with carotid IMT change. This suggests depression, but not anxiety or hostility, is involved in the initiation and/or the progression of atherosclerosis. This study is the first ever to report an association between depressive symptoms and carotid IMT change, the investigators said (Arch. Gen. Psychiatry 2007;64:225–33). The exact mechanism underlying this association is unclear, but depression is known to affect physiologic pathways also involved in atherosclerosis, they said.

Grief Begins to Ease at 6 Months

The normal grief response to the natural death of a loved one seems to start declining within 6 months of the loss, said Paul K. Maciejewski, Ph.D., of Yale University, New Haven, Conn., and his associates.

“The notion that a natural psychological response to loss involves an orderly progression through distinct stages of bereavement has been widely accepted,” but no study has tested progression through disbelief, anger, yearning, depression, and acceptance (JAMA 2007;297:716–23).

They assessed data from the Yale Bereavement Study, a longitudinal study of grief in a sample of 317 subjects interviewed between 2000 and 2003 within 1–6 months of the death of a spouse (84%) or adult children, parents, or siblings. The 233 subjects whose loved ones died of natural rather than traumatic causes were included.

Disbelief declined from the first month onward. Yearning rose until 4 months after the loss, then declined. Anger peaked at 5 months, and its decline was accompanied by a rise in depressive mood, which peaked at 6 months and then diminished over the next 18 months. Acceptance was noted immediately after the loss and increased steadily over the next 2 years.

All the grief indicators peaked and began to decline within 6 months, so those experiencing significant levels of these emotions beyond 6 months seem to deviate from the normal response, lending some support for the stage theory of grief.

But “counter to the stage theory, disbelief was not the initial, dominant grief indicator. Acceptance was the most often endorsed item,” the authors wrote. Yearning was the most common negative psychological response reported at all time points during the 2-year follow-up, and was significantly more common than was depressed mood. Since depressed mood is the focus of the bereavement section in the DSM-IV, “these results imply a need for revision.”

Delinquent Teens at Risk for Suicide

Teenage delinquency was significantly associated with an increased risk for suicidal behavior in girls, according to data from a sample of American teens.

Previous studies have shown an association between delinquency and suicide, but none has studied the association in delinquent vs. nondelinquent youth.

Martie P. Thompson, Ph.D., and her colleagues at Clemson (S.C.) University reviewed data on 15,034 teens aged 12–17 years from the National Longitudinal Study of Adolescent Health, a survey of factors that affect teens' health and behavior (J. Adolesc. Health 2007;40:232–7).

They assessed delinquency using a 15-item survey of behaviors in the previous 12 months. After controlling for age, race, gender, and urban dwelling status, delinquent teens were significantly more likely than their nondelinquent peers to report suicidal ideation, suicide attempts, and treatment for suicide attempts at both 1 year and 7 years' follow-up. After controlling for behavioral risk factors such as depression, impulsivity, religiosity, and problem drinking, delinquency remained significantly associated with suicidal ideation 1 year later and with suicide attempts 1 and 7 years later in girls. The association for boys remained, but the differences weren't significant.

Predictors of Prolonged Otitis Media

The risks of prolonged acute otitis media in children who are not initially treated with antibiotics are twice as high if the patients are aged younger than 2 years and have acute bilateral infection, compared with older children who have unilateral infection, according to a meta-analysis.

“These features … [can] inform parents about the course of their [children's] AOM [acute otitis media] and explain which features should prompt them to contact their clinician for reexamination,” wrote Maroeska M. Rovers, Ph.D., of Julius Center for Health Sciences and Primary Care, and Wilhelmina Children's Hospital, University Medical Center Utrecht, the Netherlands, and coauthors (Pediatrics 2007;119:579–85).

The meta-analysis included six randomized controlled trials of children aged 6 months to 12 years with AOM who were randomized to antibiotic therapy or observation (placebo or no treatment). The 824 patients in the observation arms were included in the analysis. The primary outcome was a prolonged infection defined as fever and/or pain at 3–7 days. The predictors analyzed included age, gender, season, having been breast-fed or not, presence or absence of recurrent AOM, and numerous baseline symptoms. Of the 824 children, 303 (37%) had fever and/or pain at 3–7 days.

The absolute risks of pain and/or fever at follow-up were highest for children aged under 2 years with bilateral infection (55%) and lowest for those aged 2 years or older with unilateral infection (25%). The independent predictors of pain and/or fever at follow-up were age less than 2 years (odds ratio 2.1) and bilateral AOM (OR 1.7).

Pediatric Obesity, OM Link

Obesity may be linked to the development of otitis media with effusion in children, Dr. Jong Bin Kim and coauthors wrote.

They found significantly higher body mass index (BMI) and cholesterol in children hospitalized for ventilation tube insertion because of otitis media with effusion (OME), compared with children undergoing other surgical procedures (Arch. Otolaryngol. Head Neck Surg. 2007;133:379–82).

Dr. Kim of Kyung Hee University, Seoul, Korea, and associates prospectively examined rates of obesity, total cholesterol, and serum triglycerides in 273 hospitalized children aged 2–7 years: One hundred fifty-five received uni- or bilateral ventilation tube insertion for OME, and 118 had other surgical procedures.

The mean BMI was significantly higher in the OME group (22 kg/m

In the OME group alone, they found that significantly more of the children were obese than were not (58% vs. 42%). However, there were no significant associations with the frequency of ventilation tube insertion and BMI, total cholesterol, or total triglycerides.

OM, PET Insertions Down Since PCV7

After the routine administration of the seven-valent pneumococcal conjugate vaccine began in mid-2000, the frequency of otitis media and pressure-equalizing tube (PET) insertions in children in Tennessee and New York born between 2000 and 2001 decreased significantly, compared with children born between 1998 and 1999, data from a large birth cohort analysis showed.

Dr. Katherine A. Poehling of the department of pediatrics at Wake Forest University, Winston-Salem, N.C., and colleagues reviewed the records of 150,122 children enrolled in Tennessee's managed care program, TennCare, and 26,409 children enrolled in three commercial managed care organizations in the Rochester, N.Y., area since birth. They focused on four birth cohorts: children born between July 1, 1998, and June 30, 1999, 1999–2000, 2000–2001, and 2001–2002. For each cohort, they estimated the cumulative proportion of children who developed frequent OM or had PETs inserted (Pediatrics 2007;119:707–15).

The proportion of children who received at least three doses of the PCV7 vaccine increased from 0% in the 1998–1999 birth cohort to about 75% in the 2000–2001 birth cohort. By age 2 years, 29% of children in Tennessee and New York who were born in 2000–2001 developed frequent otitis media and 6% had pressure-equalizing tubes inserted.

When the 2000–2001 and 1998–1999 cohorts were compared, the frequency of OM in Tennessee and New York dipped by 17% and 28%, respectively, and PET insertions by 16% and 23%. When the 2000–2001 and 2001–2002 cohorts were compared, the cases of frequent OM and the need for PET insertion remained stable in New York but increased in Tennessee. The study was funded by the Centers for Disease Control and Prevention, the American Teachers of Preventive Medicine/CDC, the National Institute of Allergy and Infectious Diseases, and the Robert Wood Johnson Generalist Physician Faculty Scholars Program.

Predictors of Prolonged Otitis Media

The risks of prolonged acute otitis media in children who are not initially treated with antibiotics are twice as high if the patients are aged younger than 2 years and have acute bilateral infection, compared with older children who have unilateral infection, according to a meta-analysis.

“These features … [can] inform parents about the course of their [children's] AOM [acute otitis media] and explain which features should prompt them to contact their clinician for reexamination,” wrote Maroeska M. Rovers, Ph.D., of Julius Center for Health Sciences and Primary Care, and Wilhelmina Children's Hospital, University Medical Center Utrecht, the Netherlands, and coauthors (Pediatrics 2007;119:579–85).

The meta-analysis included six randomized controlled trials of children aged 6 months to 12 years with AOM who were randomized to antibiotic therapy or observation (placebo or no treatment). The 824 patients in the observation arms were included in the analysis. The primary outcome was a prolonged infection defined as fever and/or pain at 3–7 days. The predictors analyzed included age, gender, season, having been breast-fed or not, presence or absence of recurrent AOM, and numerous baseline symptoms. Of the 824 children, 303 (37%) had fever and/or pain at 3–7 days.

The absolute risks of pain and/or fever at follow-up were highest for children aged under 2 years with bilateral infection (55%) and lowest for those aged 2 years or older with unilateral infection (25%). The independent predictors of pain and/or fever at follow-up were age less than 2 years (odds ratio 2.1) and bilateral AOM (OR 1.7).

Pediatric Obesity, OM Link

Obesity may be linked to the development of otitis media with effusion in children, Dr. Jong Bin Kim and coauthors wrote.

They found significantly higher body mass index (BMI) and cholesterol in children hospitalized for ventilation tube insertion because of otitis media with effusion (OME), compared with children undergoing other surgical procedures (Arch. Otolaryngol. Head Neck Surg. 2007;133:379–82).

Dr. Kim of Kyung Hee University, Seoul, Korea, and associates prospectively examined rates of obesity, total cholesterol, and serum triglycerides in 273 hospitalized children aged 2–7 years: One hundred fifty-five received uni- or bilateral ventilation tube insertion for OME, and 118 had other surgical procedures.

The mean BMI was significantly higher in the OME group (22 kg/m

In the OME group alone, they found that significantly more of the children were obese than were not (58% vs. 42%). However, there were no significant associations with the frequency of ventilation tube insertion and BMI, total cholesterol, or total triglycerides.

OM, PET Insertions Down Since PCV7

After the routine administration of the seven-valent pneumococcal conjugate vaccine began in mid-2000, the frequency of otitis media and pressure-equalizing tube (PET) insertions in children in Tennessee and New York born between 2000 and 2001 decreased significantly, compared with children born between 1998 and 1999, data from a large birth cohort analysis showed.

Dr. Katherine A. Poehling of the department of pediatrics at Wake Forest University, Winston-Salem, N.C., and colleagues reviewed the records of 150,122 children enrolled in Tennessee's managed care program, TennCare, and 26,409 children enrolled in three commercial managed care organizations in the Rochester, N.Y., area since birth. They focused on four birth cohorts: children born between July 1, 1998, and June 30, 1999, 1999–2000, 2000–2001, and 2001–2002. For each cohort, they estimated the cumulative proportion of children who developed frequent OM or had PETs inserted (Pediatrics 2007;119:707–15).

The proportion of children who received at least three doses of the PCV7 vaccine increased from 0% in the 1998–1999 birth cohort to about 75% in the 2000–2001 birth cohort. By age 2 years, 29% of children in Tennessee and New York who were born in 2000–2001 developed frequent otitis media and 6% had pressure-equalizing tubes inserted.

When the 2000–2001 and 1998–1999 cohorts were compared, the frequency of OM in Tennessee and New York dipped by 17% and 28%, respectively, and PET insertions by 16% and 23%. When the 2000–2001 and 2001–2002 cohorts were compared, the cases of frequent OM and the need for PET insertion remained stable in New York but increased in Tennessee. The study was funded by the Centers for Disease Control and Prevention, the American Teachers of Preventive Medicine/CDC, the National Institute of Allergy and Infectious Diseases, and the Robert Wood Johnson Generalist Physician Faculty Scholars Program.

Predictors of Prolonged Otitis Media

The risks of prolonged acute otitis media in children who are not initially treated with antibiotics are twice as high if the patients are aged younger than 2 years and have acute bilateral infection, compared with older children who have unilateral infection, according to a meta-analysis.

“These features … [can] inform parents about the course of their [children's] AOM [acute otitis media] and explain which features should prompt them to contact their clinician for reexamination,” wrote Maroeska M. Rovers, Ph.D., of Julius Center for Health Sciences and Primary Care, and Wilhelmina Children's Hospital, University Medical Center Utrecht, the Netherlands, and coauthors (Pediatrics 2007;119:579–85).

The meta-analysis included six randomized controlled trials of children aged 6 months to 12 years with AOM who were randomized to antibiotic therapy or observation (placebo or no treatment). The 824 patients in the observation arms were included in the analysis. The primary outcome was a prolonged infection defined as fever and/or pain at 3–7 days. The predictors analyzed included age, gender, season, having been breast-fed or not, presence or absence of recurrent AOM, and numerous baseline symptoms. Of the 824 children, 303 (37%) had fever and/or pain at 3–7 days.

The absolute risks of pain and/or fever at follow-up were highest for children aged under 2 years with bilateral infection (55%) and lowest for those aged 2 years or older with unilateral infection (25%). The independent predictors of pain and/or fever at follow-up were age less than 2 years (odds ratio 2.1) and bilateral AOM (OR 1.7).

Pediatric Obesity, OM Link

Obesity may be linked to the development of otitis media with effusion in children, Dr. Jong Bin Kim and coauthors wrote.

They found significantly higher body mass index (BMI) and cholesterol in children hospitalized for ventilation tube insertion because of otitis media with effusion (OME), compared with children undergoing other surgical procedures (Arch. Otolaryngol. Head Neck Surg. 2007;133:379–82).

Dr. Kim of Kyung Hee University, Seoul, Korea, and associates prospectively examined rates of obesity, total cholesterol, and serum triglycerides in 273 hospitalized children aged 2–7 years: One hundred fifty-five received uni- or bilateral ventilation tube insertion for OME, and 118 had other surgical procedures.

The mean BMI was significantly higher in the OME group (22 kg/m

In the OME group alone, they found that significantly more of the children were obese than were not (58% vs. 42%). However, there were no significant associations with the frequency of ventilation tube insertion and BMI, total cholesterol, or total triglycerides.

OM, PET Insertions Down Since PCV7

After the routine administration of the seven-valent pneumococcal conjugate vaccine began in mid-2000, the frequency of otitis media and pressure-equalizing tube (PET) insertions in children in Tennessee and New York born between 2000 and 2001 decreased significantly, compared with children born between 1998 and 1999, data from a large birth cohort analysis showed.

Dr. Katherine A. Poehling of the department of pediatrics at Wake Forest University, Winston-Salem, N.C., and colleagues reviewed the records of 150,122 children enrolled in Tennessee's managed care program, TennCare, and 26,409 children enrolled in three commercial managed care organizations in the Rochester, N.Y., area since birth. They focused on four birth cohorts: children born between July 1, 1998, and June 30, 1999, 1999–2000, 2000–2001, and 2001–2002. For each cohort, they estimated the cumulative proportion of children who developed frequent OM or had PETs inserted (Pediatrics 2007;119:707–15).

The proportion of children who received at least three doses of the PCV7 vaccine increased from 0% in the 1998–1999 birth cohort to about 75% in the 2000–2001 birth cohort. By age 2 years, 29% of children in Tennessee and New York who were born in 2000–2001 developed frequent otitis media and 6% had pressure-equalizing tubes inserted.

When the 2000–2001 and 1998–1999 cohorts were compared, the frequency of OM in Tennessee and New York dipped by 17% and 28%, respectively, and PET insertions by 16% and 23%. When the 2000–2001 and 2001–2002 cohorts were compared, the cases of frequent OM and the need for PET insertion remained stable in New York but increased in Tennessee. The study was funded by the Centers for Disease Control and Prevention, the American Teachers of Preventive Medicine/CDC, the National Institute of Allergy and Infectious Diseases, and the Robert Wood Johnson Generalist Physician Faculty Scholars Program.

Weekend MI Admissions

The higher mortality among acute myocardial infarction patients admitted to the hospital on weekends, compared with weekdays, can be attributed in part to a reduced rate of invasive cardiac procedures on weekends, reported William J. Kostis, Ph.D., of Robert Wood Johnson Medical School, Piscataway, N.J., and his associates.

Dr. Kostis and his associates used information in the Myocardial Infarction Data Acquisition System (MIDAS) database to determine whether MI-related mortality is higher with weekend presentation. The MIDAS database includes the records of more than 231,000 MI patients treated between 1987 and 2002.

Thirty-day mortality showed a significant increase in patients admitted on a Saturday or Sunday rather than on a weekday, representing 9–10 additional deaths per 1,000 admissions per year. This increased mortality persisted for a full year of follow-up (N. Engl. J. Med. 2007;356:1099–109). Patients admitted on weekends were less likely to undergo cardiac catheterization, percutaneous coronary intervention, or coronary artery bypass graft surgery than those admitted on weekdays. When patients did have them, the procedures were more likely to be delayed by several days, compared with procedures for patients who had weekday admissions.

Chest Compression Trumps CPR

Resuscitation by lay rescuers using chest compression alone is equivalent—and even superior in some subgroups—to conventional CPR for adults with cardiac arrest in terms of neurologic benefit, according to Dr. Ken Nagao of Surugadai Nihon University Hospital, Tokyo, and his colleagues from the SOS-KANTO study group.

Cardiac-only resuscitation (chest compression alone) resulted in more patients with favorable neurologic outcomes at 30 days after cardiac arrest than those in the conventional CPR group (chest compression and ventilating breaths) in subgroups with apnea (odds ratio 2.0), ventricular fibrillation or tachycardia as initial cardiac rhythm (OR 1.9), and resuscitation starting within 4 minutes of collapse (OR 2.1).

But the frequency of favorable neurologic outcomes at 30 days for the whole cohort was not significantly different between the cardiac-only and the CPR groups—6% vs. 4%, respectively (Lancet 2007;369:920–6).

The researchers compared 30-day neurologic outcomes for cardiac-only resuscitation with conventional CPR in a prospective, multicenter, observational study involving 4,241 adults who had cardiac arrest. Of those, 1,324 patients received bystander resuscitation: 38% received cardiac-only resuscitation and 62% conventional CPR. The rest received no resuscitation.

The primary end point was favorable neurologic outcomes 30 days after cardiac arrest; the secondary end point was survival at 30 days after cardiac arrest. Cardiac-only resuscitation may be more efficient than CPR because with an open airway, gasping and passive chest recoil provide some air exchange, or mouth-to-mouth ventilation could take time away from the chest compression needed for supporting cerebral and coronary perfusion, they suggested.

Cost Concerns Badger MI Patients

Financial barriers to obtaining health care are a common risk factor in MI patients, even in those who are insured, reported Dr. Ali R. Rahimi of Yale University, New Haven, Conn., and his associates.

In a study of nearly 2,500 MI patients nationwide, about one in five reported that they avoided getting health care services because of the expense, and about one in eight said they avoided medication for the same reason. Both characteristics were strong predictors of adverse outcomes, even after controlling for traditional risk factors.

The researchers assessed financial barriers to care as part of the PREMIER study, a prospective observational study of MI patients treated at 19 U.S. medical centers in 2003–2004. Upon hospitalization, subjects reported whether they had avoided obtaining health care or prescribed medications during the preceding year. They were followed for 1 year after discharge to assess MI-related outcomes.

Subjects who reported having restricted medical services or medications because of costs had a significantly higher prevalence of angina, and poorer quality of life and overall physical and mental function, both at their MI hospitalization and 1 year later. Those who did not adhere to prescription guidelines because of costs had a 50% higher risk of rehospitalization for any cause and a 70% higher risk for cardiac rehospitalization during the year after an MI than did those with no such financial barriers to medication. Inpatient care was almost identical for the two groups, so the disparities in the outcomes can be attributed to the pre-MI and postdischarge periods, the authors noted. In those who cut back on services or medications because of costs, 69% had health insurance, and about 40% had Medicaid or Medicare coverage, suggesting that underinsurance is the problem, they said.

Weekend MI Admissions

The higher mortality among acute myocardial infarction patients admitted to the hospital on weekends, compared with weekdays, can be attributed in part to a reduced rate of invasive cardiac procedures on weekends, reported William J. Kostis, Ph.D., of Robert Wood Johnson Medical School, Piscataway, N.J., and his associates.

Dr. Kostis and his associates used information in the Myocardial Infarction Data Acquisition System (MIDAS) database to determine whether MI-related mortality is higher with weekend presentation. The MIDAS database includes the records of more than 231,000 MI patients treated between 1987 and 2002.

Thirty-day mortality showed a significant increase in patients admitted on a Saturday or Sunday rather than on a weekday, representing 9–10 additional deaths per 1,000 admissions per year. This increased mortality persisted for a full year of follow-up (N. Engl. J. Med. 2007;356:1099–109). Patients admitted on weekends were less likely to undergo cardiac catheterization, percutaneous coronary intervention, or coronary artery bypass graft surgery than those admitted on weekdays. When patients did have them, the procedures were more likely to be delayed by several days, compared with procedures for patients who had weekday admissions.

Chest Compression Trumps CPR

Resuscitation by lay rescuers using chest compression alone is equivalent—and even superior in some subgroups—to conventional CPR for adults with cardiac arrest in terms of neurologic benefit, according to Dr. Ken Nagao of Surugadai Nihon University Hospital, Tokyo, and his colleagues from the SOS-KANTO study group.

Cardiac-only resuscitation (chest compression alone) resulted in more patients with favorable neurologic outcomes at 30 days after cardiac arrest than those in the conventional CPR group (chest compression and ventilating breaths) in subgroups with apnea (odds ratio 2.0), ventricular fibrillation or tachycardia as initial cardiac rhythm (OR 1.9), and resuscitation starting within 4 minutes of collapse (OR 2.1).

But the frequency of favorable neurologic outcomes at 30 days for the whole cohort was not significantly different between the cardiac-only and the CPR groups—6% vs. 4%, respectively (Lancet 2007;369:920–6).

The researchers compared 30-day neurologic outcomes for cardiac-only resuscitation with conventional CPR in a prospective, multicenter, observational study involving 4,241 adults who had cardiac arrest. Of those, 1,324 patients received bystander resuscitation: 38% received cardiac-only resuscitation and 62% conventional CPR. The rest received no resuscitation.

The primary end point was favorable neurologic outcomes 30 days after cardiac arrest; the secondary end point was survival at 30 days after cardiac arrest. Cardiac-only resuscitation may be more efficient than CPR because with an open airway, gasping and passive chest recoil provide some air exchange, or mouth-to-mouth ventilation could take time away from the chest compression needed for supporting cerebral and coronary perfusion, they suggested.

Cost Concerns Badger MI Patients

Financial barriers to obtaining health care are a common risk factor in MI patients, even in those who are insured, reported Dr. Ali R. Rahimi of Yale University, New Haven, Conn., and his associates.

In a study of nearly 2,500 MI patients nationwide, about one in five reported that they avoided getting health care services because of the expense, and about one in eight said they avoided medication for the same reason. Both characteristics were strong predictors of adverse outcomes, even after controlling for traditional risk factors.

The researchers assessed financial barriers to care as part of the PREMIER study, a prospective observational study of MI patients treated at 19 U.S. medical centers in 2003–2004. Upon hospitalization, subjects reported whether they had avoided obtaining health care or prescribed medications during the preceding year. They were followed for 1 year after discharge to assess MI-related outcomes.

Subjects who reported having restricted medical services or medications because of costs had a significantly higher prevalence of angina, and poorer quality of life and overall physical and mental function, both at their MI hospitalization and 1 year later. Those who did not adhere to prescription guidelines because of costs had a 50% higher risk of rehospitalization for any cause and a 70% higher risk for cardiac rehospitalization during the year after an MI than did those with no such financial barriers to medication. Inpatient care was almost identical for the two groups, so the disparities in the outcomes can be attributed to the pre-MI and postdischarge periods, the authors noted. In those who cut back on services or medications because of costs, 69% had health insurance, and about 40% had Medicaid or Medicare coverage, suggesting that underinsurance is the problem, they said.

Weekend MI Admissions

The higher mortality among acute myocardial infarction patients admitted to the hospital on weekends, compared with weekdays, can be attributed in part to a reduced rate of invasive cardiac procedures on weekends, reported William J. Kostis, Ph.D., of Robert Wood Johnson Medical School, Piscataway, N.J., and his associates.

Dr. Kostis and his associates used information in the Myocardial Infarction Data Acquisition System (MIDAS) database to determine whether MI-related mortality is higher with weekend presentation. The MIDAS database includes the records of more than 231,000 MI patients treated between 1987 and 2002.

Thirty-day mortality showed a significant increase in patients admitted on a Saturday or Sunday rather than on a weekday, representing 9–10 additional deaths per 1,000 admissions per year. This increased mortality persisted for a full year of follow-up (N. Engl. J. Med. 2007;356:1099–109). Patients admitted on weekends were less likely to undergo cardiac catheterization, percutaneous coronary intervention, or coronary artery bypass graft surgery than those admitted on weekdays. When patients did have them, the procedures were more likely to be delayed by several days, compared with procedures for patients who had weekday admissions.

Chest Compression Trumps CPR

Resuscitation by lay rescuers using chest compression alone is equivalent—and even superior in some subgroups—to conventional CPR for adults with cardiac arrest in terms of neurologic benefit, according to Dr. Ken Nagao of Surugadai Nihon University Hospital, Tokyo, and his colleagues from the SOS-KANTO study group.

Cardiac-only resuscitation (chest compression alone) resulted in more patients with favorable neurologic outcomes at 30 days after cardiac arrest than those in the conventional CPR group (chest compression and ventilating breaths) in subgroups with apnea (odds ratio 2.0), ventricular fibrillation or tachycardia as initial cardiac rhythm (OR 1.9), and resuscitation starting within 4 minutes of collapse (OR 2.1).

But the frequency of favorable neurologic outcomes at 30 days for the whole cohort was not significantly different between the cardiac-only and the CPR groups—6% vs. 4%, respectively (Lancet 2007;369:920–6).

The researchers compared 30-day neurologic outcomes for cardiac-only resuscitation with conventional CPR in a prospective, multicenter, observational study involving 4,241 adults who had cardiac arrest. Of those, 1,324 patients received bystander resuscitation: 38% received cardiac-only resuscitation and 62% conventional CPR. The rest received no resuscitation.

The primary end point was favorable neurologic outcomes 30 days after cardiac arrest; the secondary end point was survival at 30 days after cardiac arrest. Cardiac-only resuscitation may be more efficient than CPR because with an open airway, gasping and passive chest recoil provide some air exchange, or mouth-to-mouth ventilation could take time away from the chest compression needed for supporting cerebral and coronary perfusion, they suggested.

Cost Concerns Badger MI Patients

Financial barriers to obtaining health care are a common risk factor in MI patients, even in those who are insured, reported Dr. Ali R. Rahimi of Yale University, New Haven, Conn., and his associates.

In a study of nearly 2,500 MI patients nationwide, about one in five reported that they avoided getting health care services because of the expense, and about one in eight said they avoided medication for the same reason. Both characteristics were strong predictors of adverse outcomes, even after controlling for traditional risk factors.

The researchers assessed financial barriers to care as part of the PREMIER study, a prospective observational study of MI patients treated at 19 U.S. medical centers in 2003–2004. Upon hospitalization, subjects reported whether they had avoided obtaining health care or prescribed medications during the preceding year. They were followed for 1 year after discharge to assess MI-related outcomes.

Subjects who reported having restricted medical services or medications because of costs had a significantly higher prevalence of angina, and poorer quality of life and overall physical and mental function, both at their MI hospitalization and 1 year later. Those who did not adhere to prescription guidelines because of costs had a 50% higher risk of rehospitalization for any cause and a 70% higher risk for cardiac rehospitalization during the year after an MI than did those with no such financial barriers to medication. Inpatient care was almost identical for the two groups, so the disparities in the outcomes can be attributed to the pre-MI and postdischarge periods, the authors noted. In those who cut back on services or medications because of costs, 69% had health insurance, and about 40% had Medicaid or Medicare coverage, suggesting that underinsurance is the problem, they said.

Four Genes Linked to Diabetes Onset

Scientists have identified four genetic codes associated with the onset of type 2 diabetes mellitus, according to data from a case-control study.

Researchers from Imperial College London, McGill University in Montreal, and other institutions wrote that the genetic loci they identified, along with another previously discovered locus, help explain about 70% of diabetes cases (Nature 2007 Feb. 11 [Epub doi: 10.1038/nature05616]).

The association between each of the loci and the onset of diabetes was fairly weak, but establishing the loci provides new pathways to study in diabetes development.

The researchers compared the genetic makeup of about 700 nonobese French patients with diabetes who have at least one first-degree relative with diabetes with that of 700 controls. They examined genotypes for 393,000 single-nucleotide polymorphisms, looking for mutations that might be statistically linked to diabetes. They then tested the genetic makeup of a further 2,600 diabetes patients, no longer restricted on obesity or familial diabetes criteria, and 2,900 controls to confirm the initial findings.

One of the loci identified is known as TCF7L2, a genetic factor in insulin secretion previously linked to diabetes onset. One newly discovered mutation was in SLC30A8, a zinc transporter involved in insulin biosynthesis. Overexpression of the gene in insulinoma cells increases glucose-stimulated insulin secretion, the authors wrote. Patients with the mutation on a single allele are at 15%–65% higher risk of diabetes depending on the mutation.

Repeat BMD Tests Don't Aid PredictionRepeat bone mineral density testing 8 years after initial measurement does not improve the ability to predict fractures in healthy elderly women, according to Dr. Teresa A. Hillier and her associates.

The Study of Osteoporotic Fractures included 9,704 white women aged 65 years and older who were living in four regions of the United States. Of the women, 4,124 underwent initial BMD measurement in 1989–1990 and then had a repeat BMD measurement a mean of 8 years later, forming the sample for the current study, said Dr. Hillier of Kaiser Permanente Center for Health Research Northwest, Portland, Ore., and her associates (Arch. Intern. Med. 2007;167:155–60).

They were followed for an additional 5 years to track the incidence of fractures. The BMD measurements were taken at the proximal femur, femoral neck, trochanter, intertrochanter, and Ward's triangle.

Both measurements of BMD were significant predictors of hip fracture and nonspinal fracture risks. However, the repeat BMD did not add to the overall predictive value for any type of fracture risk. These results persisted in subgroup analyses of women who used estrogen or bisphosphonate, compared with those who did not.

The findings do not imply that repeat BMD measurement may not be useful for certain individual patients, “particularly if intervening clinical factors are present that would likely accelerate BMD loss greater than average,” they asserted. They also noted that the results may not be generalizable to men, nonwhite women, or women younger than 65 years.

Glycemic Control in Young Diabetics

Poorer glycemic control was independently associated with higher serum lipid levels in children with both type 1 and type 2 diabetes in a large, cross-sectional study.

Higher hemoglobin A_1c levels (HbA_1c) were associated with significantly higher total cholesterol, LDL cholesterol, and triglycerides in a study of 1,963 children aged 10 years and older. The findings were significant even after adjustment for age, gender, diabetes duration, body mass index, and race/ethnicity. Glycemic control did not correlate with HDL cholesterol levels (Arch. Pediatr. Adolesc. Med. 2007;161:159–65).

The data were extracted from the SEARCH for Diabetes in Youth Study, a comprehensive, ethnically diverse study of children with diabetes managed in a variety of settings (J. Pediatr. 2006;149:314–9).

Mean HbA_1c concentration was 8.6% in the 1,680 children with type 1 diabetes and 8.3% in the 283 with type 2 diabetes. In those with type 1 diabetes and poor glycemic control, 35% had high concentrations of total cholesterol (200 mg/dL or greater), 27% had high LDL cholesterol (130 mg/dL or greater), and 12% had high triglycerides (200 mg/dL or greater). In type 2 diabetes patients with poor glycemic control, 65% had high total cholesterol levels, 43% had high LDL cholesterol, and 40% had high triglycerides.

For each unit increase in HbA_1c, the slope of the increase in total cholesterol was 7.8 mg/dL in the type 1 group and 8.1 mg/dL in the type 2 group.

The authors were not able to establish a cause-and-effect relationship between poor glycemic control and elevated serum lipids because of the cross-sectional design of the study.

Four Genes Linked to Diabetes Onset

Scientists have identified four genetic codes associated with the onset of type 2 diabetes mellitus, according to data from a case-control study.

Researchers from Imperial College London, McGill University in Montreal, and other institutions wrote that the genetic loci they identified, along with another previously discovered locus, help explain about 70% of diabetes cases (Nature 2007 Feb. 11 [Epub doi: 10.1038/nature05616]).

The association between each of the loci and the onset of diabetes was fairly weak, but establishing the loci provides new pathways to study in diabetes development.

The researchers compared the genetic makeup of about 700 nonobese French patients with diabetes who have at least one first-degree relative with diabetes with that of 700 controls. They examined genotypes for 393,000 single-nucleotide polymorphisms, looking for mutations that might be statistically linked to diabetes. They then tested the genetic makeup of a further 2,600 diabetes patients, no longer restricted on obesity or familial diabetes criteria, and 2,900 controls to confirm the initial findings.

One of the loci identified is known as TCF7L2, a genetic factor in insulin secretion previously linked to diabetes onset. One newly discovered mutation was in SLC30A8, a zinc transporter involved in insulin biosynthesis. Overexpression of the gene in insulinoma cells increases glucose-stimulated insulin secretion, the authors wrote. Patients with the mutation on a single allele are at 15%–65% higher risk of diabetes depending on the mutation.

Repeat BMD Tests Don't Aid PredictionRepeat bone mineral density testing 8 years after initial measurement does not improve the ability to predict fractures in healthy elderly women, according to Dr. Teresa A. Hillier and her associates.

The Study of Osteoporotic Fractures included 9,704 white women aged 65 years and older who were living in four regions of the United States. Of the women, 4,124 underwent initial BMD measurement in 1989–1990 and then had a repeat BMD measurement a mean of 8 years later, forming the sample for the current study, said Dr. Hillier of Kaiser Permanente Center for Health Research Northwest, Portland, Ore., and her associates (Arch. Intern. Med. 2007;167:155–60).

They were followed for an additional 5 years to track the incidence of fractures. The BMD measurements were taken at the proximal femur, femoral neck, trochanter, intertrochanter, and Ward's triangle.

Both measurements of BMD were significant predictors of hip fracture and nonspinal fracture risks. However, the repeat BMD did not add to the overall predictive value for any type of fracture risk. These results persisted in subgroup analyses of women who used estrogen or bisphosphonate, compared with those who did not.

The findings do not imply that repeat BMD measurement may not be useful for certain individual patients, “particularly if intervening clinical factors are present that would likely accelerate BMD loss greater than average,” they asserted. They also noted that the results may not be generalizable to men, nonwhite women, or women younger than 65 years.

Glycemic Control in Young Diabetics

Poorer glycemic control was independently associated with higher serum lipid levels in children with both type 1 and type 2 diabetes in a large, cross-sectional study.

Higher hemoglobin A_1c levels (HbA_1c) were associated with significantly higher total cholesterol, LDL cholesterol, and triglycerides in a study of 1,963 children aged 10 years and older. The findings were significant even after adjustment for age, gender, diabetes duration, body mass index, and race/ethnicity. Glycemic control did not correlate with HDL cholesterol levels (Arch. Pediatr. Adolesc. Med. 2007;161:159–65).

The data were extracted from the SEARCH for Diabetes in Youth Study, a comprehensive, ethnically diverse study of children with diabetes managed in a variety of settings (J. Pediatr. 2006;149:314–9).

Mean HbA_1c concentration was 8.6% in the 1,680 children with type 1 diabetes and 8.3% in the 283 with type 2 diabetes. In those with type 1 diabetes and poor glycemic control, 35% had high concentrations of total cholesterol (200 mg/dL or greater), 27% had high LDL cholesterol (130 mg/dL or greater), and 12% had high triglycerides (200 mg/dL or greater). In type 2 diabetes patients with poor glycemic control, 65% had high total cholesterol levels, 43% had high LDL cholesterol, and 40% had high triglycerides.

For each unit increase in HbA_1c, the slope of the increase in total cholesterol was 7.8 mg/dL in the type 1 group and 8.1 mg/dL in the type 2 group.

The authors were not able to establish a cause-and-effect relationship between poor glycemic control and elevated serum lipids because of the cross-sectional design of the study.

Four Genes Linked to Diabetes Onset

Scientists have identified four genetic codes associated with the onset of type 2 diabetes mellitus, according to data from a case-control study.

Researchers from Imperial College London, McGill University in Montreal, and other institutions wrote that the genetic loci they identified, along with another previously discovered locus, help explain about 70% of diabetes cases (Nature 2007 Feb. 11 [Epub doi: 10.1038/nature05616]).

The association between each of the loci and the onset of diabetes was fairly weak, but establishing the loci provides new pathways to study in diabetes development.

The researchers compared the genetic makeup of about 700 nonobese French patients with diabetes who have at least one first-degree relative with diabetes with that of 700 controls. They examined genotypes for 393,000 single-nucleotide polymorphisms, looking for mutations that might be statistically linked to diabetes. They then tested the genetic makeup of a further 2,600 diabetes patients, no longer restricted on obesity or familial diabetes criteria, and 2,900 controls to confirm the initial findings.

One of the loci identified is known as TCF7L2, a genetic factor in insulin secretion previously linked to diabetes onset. One newly discovered mutation was in SLC30A8, a zinc transporter involved in insulin biosynthesis. Overexpression of the gene in insulinoma cells increases glucose-stimulated insulin secretion, the authors wrote. Patients with the mutation on a single allele are at 15%–65% higher risk of diabetes depending on the mutation.

Repeat BMD Tests Don't Aid PredictionRepeat bone mineral density testing 8 years after initial measurement does not improve the ability to predict fractures in healthy elderly women, according to Dr. Teresa A. Hillier and her associates.

The Study of Osteoporotic Fractures included 9,704 white women aged 65 years and older who were living in four regions of the United States. Of the women, 4,124 underwent initial BMD measurement in 1989–1990 and then had a repeat BMD measurement a mean of 8 years later, forming the sample for the current study, said Dr. Hillier of Kaiser Permanente Center for Health Research Northwest, Portland, Ore., and her associates (Arch. Intern. Med. 2007;167:155–60).

They were followed for an additional 5 years to track the incidence of fractures. The BMD measurements were taken at the proximal femur, femoral neck, trochanter, intertrochanter, and Ward's triangle.

Both measurements of BMD were significant predictors of hip fracture and nonspinal fracture risks. However, the repeat BMD did not add to the overall predictive value for any type of fracture risk. These results persisted in subgroup analyses of women who used estrogen or bisphosphonate, compared with those who did not.

The findings do not imply that repeat BMD measurement may not be useful for certain individual patients, “particularly if intervening clinical factors are present that would likely accelerate BMD loss greater than average,” they asserted. They also noted that the results may not be generalizable to men, nonwhite women, or women younger than 65 years.

Glycemic Control in Young Diabetics

Poorer glycemic control was independently associated with higher serum lipid levels in children with both type 1 and type 2 diabetes in a large, cross-sectional study.

Higher hemoglobin A_1c levels (HbA_1c) were associated with significantly higher total cholesterol, LDL cholesterol, and triglycerides in a study of 1,963 children aged 10 years and older. The findings were significant even after adjustment for age, gender, diabetes duration, body mass index, and race/ethnicity. Glycemic control did not correlate with HDL cholesterol levels (Arch. Pediatr. Adolesc. Med. 2007;161:159–65).

The data were extracted from the SEARCH for Diabetes in Youth Study, a comprehensive, ethnically diverse study of children with diabetes managed in a variety of settings (J. Pediatr. 2006;149:314–9).

Mean HbA_1c concentration was 8.6% in the 1,680 children with type 1 diabetes and 8.3% in the 283 with type 2 diabetes. In those with type 1 diabetes and poor glycemic control, 35% had high concentrations of total cholesterol (200 mg/dL or greater), 27% had high LDL cholesterol (130 mg/dL or greater), and 12% had high triglycerides (200 mg/dL or greater). In type 2 diabetes patients with poor glycemic control, 65% had high total cholesterol levels, 43% had high LDL cholesterol, and 40% had high triglycerides.

For each unit increase in HbA_1c, the slope of the increase in total cholesterol was 7.8 mg/dL in the type 1 group and 8.1 mg/dL in the type 2 group.

The authors were not able to establish a cause-and-effect relationship between poor glycemic control and elevated serum lipids because of the cross-sectional design of the study.