Bianca Nogrady

Androgen-deprivation therapy for prostate cancer may increase the risk of cardiac death among men who have congestive heart failure or who have experienced a previous myocardial infarction, a retrospective cohort study has found.

The study of 5,077 men, whose prostate cancer was treated with brachytherapy with or without neoadjuvant androgen-deprivation therapy (ADT), showed that ADT was associated with a greater-than-threefold increase in the risk of cardiac specific mortality among men with heart failure or myocardial infarction (adjusted hazard ratio, 3.28; 95% confidence interval, 1.01-10.64; P = .048), representing a 5% increase in absolute risk over 5 years.

However, researchers saw no association between ADT and cardiac death among men with no cardiac risk factors, or those with diabetes mellitus, hypertension, or hypercholesterolemia, according to a paper published online Oct. 29 in BJU International (2014 [doi:10.1111/bju.12905]).

“These results add vital detail to past work that showed that the delivery of ADT to men with moderate to severe comorbidity is associated with no survival benefit, and that delivery of ADT to men with [HF] or past MI is associated with increased risk of death from any cause,” wrote Dr. David R. Ziehr from Harvard Medical School, Boston, and his colleagues.

The study was supported by Fitz’s CancerWarriors, David and Cynthia Chapin, the Prostate Cancer Foundation, Hugh Simons in honor of Frank and Anne Simons, and a grant from an anonymous family foundation. Some authors declared consultancies, lectureships, and advisory board positions for pharmaceutical companies.

Androgen-deprivation therapy for prostate cancer may increase the risk of cardiac death among men who have congestive heart failure or who have experienced a previous myocardial infarction, a retrospective cohort study has found.

The study of 5,077 men, whose prostate cancer was treated with brachytherapy with or without neoadjuvant androgen-deprivation therapy (ADT), showed that ADT was associated with a greater-than-threefold increase in the risk of cardiac specific mortality among men with heart failure or myocardial infarction (adjusted hazard ratio, 3.28; 95% confidence interval, 1.01-10.64; P = .048), representing a 5% increase in absolute risk over 5 years.

However, researchers saw no association between ADT and cardiac death among men with no cardiac risk factors, or those with diabetes mellitus, hypertension, or hypercholesterolemia, according to a paper published online Oct. 29 in BJU International (2014 [doi:10.1111/bju.12905]).

“These results add vital detail to past work that showed that the delivery of ADT to men with moderate to severe comorbidity is associated with no survival benefit, and that delivery of ADT to men with [HF] or past MI is associated with increased risk of death from any cause,” wrote Dr. David R. Ziehr from Harvard Medical School, Boston, and his colleagues.

The study was supported by Fitz’s CancerWarriors, David and Cynthia Chapin, the Prostate Cancer Foundation, Hugh Simons in honor of Frank and Anne Simons, and a grant from an anonymous family foundation. Some authors declared consultancies, lectureships, and advisory board positions for pharmaceutical companies.

Androgen-deprivation therapy for prostate cancer may increase the risk of cardiac death among men who have congestive heart failure or who have experienced a previous myocardial infarction, a retrospective cohort study has found.

The study of 5,077 men, whose prostate cancer was treated with brachytherapy with or without neoadjuvant androgen-deprivation therapy (ADT), showed that ADT was associated with a greater-than-threefold increase in the risk of cardiac specific mortality among men with heart failure or myocardial infarction (adjusted hazard ratio, 3.28; 95% confidence interval, 1.01-10.64; P = .048), representing a 5% increase in absolute risk over 5 years.

However, researchers saw no association between ADT and cardiac death among men with no cardiac risk factors, or those with diabetes mellitus, hypertension, or hypercholesterolemia, according to a paper published online Oct. 29 in BJU International (2014 [doi:10.1111/bju.12905]).

“These results add vital detail to past work that showed that the delivery of ADT to men with moderate to severe comorbidity is associated with no survival benefit, and that delivery of ADT to men with [HF] or past MI is associated with increased risk of death from any cause,” wrote Dr. David R. Ziehr from Harvard Medical School, Boston, and his colleagues.

The study was supported by Fitz’s CancerWarriors, David and Cynthia Chapin, the Prostate Cancer Foundation, Hugh Simons in honor of Frank and Anne Simons, and a grant from an anonymous family foundation. Some authors declared consultancies, lectureships, and advisory board positions for pharmaceutical companies.

First-line treatment with metformin for diabetes is associated with significantly less intensification of treatment, and fewer short-term adverse outcomes such as cardiovascular events, emergency department visits, and hypoglycemia, compared with other oral glucose-lowering medications.

A retrospective cohort study of 15,516 patients prescribed an oral glucose-lowering medication found that 25% of patients initially prescribed metformin required a second oral agent, compared with 37% of patients prescribed a sulfonylurea, 40% of those prescribed a thiazolidinedione, and 36% of those prescribed a dipeptidyl peptidase–4 inhibitor, according to a retrospective study published online Oct. 27 (JAMA Intern. Med. 2014 Oct. 27 [doi: 10.1001/jamainternmed.2014.5294]).

©Wavebreakmedia Ltd

While numerous guidelines recommend metformin as the first-line choice of glucose-lowering agents, only 58% of patients started therapy with metformin, with a sulfonylurea the second-most-popular choice, despite its increased risk of adverse cardiovascular events.

“Because underuse of metformin may lead to important harms and costs in the treatment of patients with diabetes, multilevel interventions to increase prescribing quality may be needed,” wrote Dr. Seth A. Berkowitz of Harvard University, Boston, and his colleagues.

The study was supported by an unrestricted grant from CVS Health to Brigham and Women’s Hospital, Boston. One author declared funding from an Institutional National Research Service Award, the Ryoichi Sasakawa Fellowship Fund, and Massachusetts General Hospital. There were no other conflicts of interest declared.

First-line treatment with metformin for diabetes is associated with significantly less intensification of treatment, and fewer short-term adverse outcomes such as cardiovascular events, emergency department visits, and hypoglycemia, compared with other oral glucose-lowering medications.

A retrospective cohort study of 15,516 patients prescribed an oral glucose-lowering medication found that 25% of patients initially prescribed metformin required a second oral agent, compared with 37% of patients prescribed a sulfonylurea, 40% of those prescribed a thiazolidinedione, and 36% of those prescribed a dipeptidyl peptidase–4 inhibitor, according to a retrospective study published online Oct. 27 (JAMA Intern. Med. 2014 Oct. 27 [doi: 10.1001/jamainternmed.2014.5294]).

©Wavebreakmedia Ltd

While numerous guidelines recommend metformin as the first-line choice of glucose-lowering agents, only 58% of patients started therapy with metformin, with a sulfonylurea the second-most-popular choice, despite its increased risk of adverse cardiovascular events.

“Because underuse of metformin may lead to important harms and costs in the treatment of patients with diabetes, multilevel interventions to increase prescribing quality may be needed,” wrote Dr. Seth A. Berkowitz of Harvard University, Boston, and his colleagues.

The study was supported by an unrestricted grant from CVS Health to Brigham and Women’s Hospital, Boston. One author declared funding from an Institutional National Research Service Award, the Ryoichi Sasakawa Fellowship Fund, and Massachusetts General Hospital. There were no other conflicts of interest declared.

First-line treatment with metformin for diabetes is associated with significantly less intensification of treatment, and fewer short-term adverse outcomes such as cardiovascular events, emergency department visits, and hypoglycemia, compared with other oral glucose-lowering medications.

A retrospective cohort study of 15,516 patients prescribed an oral glucose-lowering medication found that 25% of patients initially prescribed metformin required a second oral agent, compared with 37% of patients prescribed a sulfonylurea, 40% of those prescribed a thiazolidinedione, and 36% of those prescribed a dipeptidyl peptidase–4 inhibitor, according to a retrospective study published online Oct. 27 (JAMA Intern. Med. 2014 Oct. 27 [doi: 10.1001/jamainternmed.2014.5294]).

©Wavebreakmedia Ltd

While numerous guidelines recommend metformin as the first-line choice of glucose-lowering agents, only 58% of patients started therapy with metformin, with a sulfonylurea the second-most-popular choice, despite its increased risk of adverse cardiovascular events.

“Because underuse of metformin may lead to important harms and costs in the treatment of patients with diabetes, multilevel interventions to increase prescribing quality may be needed,” wrote Dr. Seth A. Berkowitz of Harvard University, Boston, and his colleagues.

The study was supported by an unrestricted grant from CVS Health to Brigham and Women’s Hospital, Boston. One author declared funding from an Institutional National Research Service Award, the Ryoichi Sasakawa Fellowship Fund, and Massachusetts General Hospital. There were no other conflicts of interest declared.

The introduction of antibiotic prophylaxis in the Netherlands to prevent invasive neonatal group B streptococcus infection has failed to achieve a decrease in the incidence of infection, prompting calls for guidelines to be reassessed and alternative prevention methods considered.

Analysis of nationwide surveillance data from 1987 to 2011 showed that the incidence of invasive group B streptococcus in infants aged 3 months and under actually increased from 0.20 per 1,000 live births to 0.32 per 1,000 (P < .0001), while the incidence of early-onset disease increased from 0.11 per 1,000 live births to 0.19 per 1,000 (P < .0001).

Courtesy CDC / Melissa Brower

Researchers also noted an increase in cases of disease caused by clonal complex 17 – which has been associated with invasive disease in neonates – and fewer cases caused by clonal complex 19, as well as a nonsignificant increase in the incidence of invasive Escherichia coli infection after the 1999 implementation of intravenous antibiotic prophylaxis during labor.

“Our findings offer no explanation for the increase in incidence over the past 25 years in Netherlands, [however] possible explanations include changes in the host, medical practice, increased submission of isolates to the National Laboratory, or the pathogen itself,” wrote Dr. Vincent Bekker, from the Emma Children’s Hospital, Academic Medical Center, Amsterdam, and colleagues (Lancet Infect. Dis. 2014 Oct. 19).

In an accompanying editorial, Dr. Shannon D. Manning of Michigan State University, East Lansing, pointed out that the results ran counter to those of other studies, such as one from the United States which showed that intrapartum antibiotic prophylaxis was associated with a 65% reduction in early-onset disease.

“The findings of Bekker and colleagues confirm that group B streptococcus disease in babies remains a global public health concern and show the importance of continuous surveillance in different geographic locations,” Dr. Manning noted.

The study was supported by the National Institute of Public Health and the Environment. There were no other conflicts of interest declared.

The introduction of antibiotic prophylaxis in the Netherlands to prevent invasive neonatal group B streptococcus infection has failed to achieve a decrease in the incidence of infection, prompting calls for guidelines to be reassessed and alternative prevention methods considered.

Analysis of nationwide surveillance data from 1987 to 2011 showed that the incidence of invasive group B streptococcus in infants aged 3 months and under actually increased from 0.20 per 1,000 live births to 0.32 per 1,000 (P < .0001), while the incidence of early-onset disease increased from 0.11 per 1,000 live births to 0.19 per 1,000 (P < .0001).

Courtesy CDC / Melissa Brower

Researchers also noted an increase in cases of disease caused by clonal complex 17 – which has been associated with invasive disease in neonates – and fewer cases caused by clonal complex 19, as well as a nonsignificant increase in the incidence of invasive Escherichia coli infection after the 1999 implementation of intravenous antibiotic prophylaxis during labor.

“Our findings offer no explanation for the increase in incidence over the past 25 years in Netherlands, [however] possible explanations include changes in the host, medical practice, increased submission of isolates to the National Laboratory, or the pathogen itself,” wrote Dr. Vincent Bekker, from the Emma Children’s Hospital, Academic Medical Center, Amsterdam, and colleagues (Lancet Infect. Dis. 2014 Oct. 19).

In an accompanying editorial, Dr. Shannon D. Manning of Michigan State University, East Lansing, pointed out that the results ran counter to those of other studies, such as one from the United States which showed that intrapartum antibiotic prophylaxis was associated with a 65% reduction in early-onset disease.

“The findings of Bekker and colleagues confirm that group B streptococcus disease in babies remains a global public health concern and show the importance of continuous surveillance in different geographic locations,” Dr. Manning noted.

The study was supported by the National Institute of Public Health and the Environment. There were no other conflicts of interest declared.

The introduction of antibiotic prophylaxis in the Netherlands to prevent invasive neonatal group B streptococcus infection has failed to achieve a decrease in the incidence of infection, prompting calls for guidelines to be reassessed and alternative prevention methods considered.

Analysis of nationwide surveillance data from 1987 to 2011 showed that the incidence of invasive group B streptococcus in infants aged 3 months and under actually increased from 0.20 per 1,000 live births to 0.32 per 1,000 (P < .0001), while the incidence of early-onset disease increased from 0.11 per 1,000 live births to 0.19 per 1,000 (P < .0001).

Courtesy CDC / Melissa Brower

Researchers also noted an increase in cases of disease caused by clonal complex 17 – which has been associated with invasive disease in neonates – and fewer cases caused by clonal complex 19, as well as a nonsignificant increase in the incidence of invasive Escherichia coli infection after the 1999 implementation of intravenous antibiotic prophylaxis during labor.

“Our findings offer no explanation for the increase in incidence over the past 25 years in Netherlands, [however] possible explanations include changes in the host, medical practice, increased submission of isolates to the National Laboratory, or the pathogen itself,” wrote Dr. Vincent Bekker, from the Emma Children’s Hospital, Academic Medical Center, Amsterdam, and colleagues (Lancet Infect. Dis. 2014 Oct. 19).

In an accompanying editorial, Dr. Shannon D. Manning of Michigan State University, East Lansing, pointed out that the results ran counter to those of other studies, such as one from the United States which showed that intrapartum antibiotic prophylaxis was associated with a 65% reduction in early-onset disease.

“The findings of Bekker and colleagues confirm that group B streptococcus disease in babies remains a global public health concern and show the importance of continuous surveillance in different geographic locations,” Dr. Manning noted.

The study was supported by the National Institute of Public Health and the Environment. There were no other conflicts of interest declared.

In a first for human embryonic stem cell therapy, use of the pluripotent cells to treat macular dystrophy and macular degeneration significantly improved visual acuity without adverse proliferation, rejection, or serious systemic safety issues for a median of nearly 2 years after transplantation.

“The results of this study provide the first evidence of the medium-term to long-term safety, graft survival, and possible biological activity of pluripotent stem cell progeny in individuals with any disease,” wrote Dr. Steven D. Schwartz, from the Jules Stein Eye Institute Retina Division, Los Angeles, and colleagues.

“Our results suggest that hESC-derived cells could provide a potentially safe new source of cells for the treatment of a variety of unmet medical conditions caused by tissue loss or dysfunction,” the authors noted.

In two prospective phase I/II studies using human embryonic stem cell therapy (hESC)-derived retinal pigment epithelium – one involving nine patients with Stargardt’s macular dystrophy, and the second in nine patients with atrophic age-related macular degeneration – 13 (72%) patients showed an increase in subretinal pigmentation after transplantation of the cells into the subretinal space.

Six months after the transplant, patients with age-related macular degeneration showed improvements in visual acuity by at least 15 letters in four eyes (which the authors described as a clinically significant measure of improvement) and 11-14 letters in two eyes. Visual acuity remained stable (equal to or less than 10 letters) in three eyes, according to a paper published online in the Oct. 15 issue of the Lancet.

In the patients with Stargardt’s macular dystrophy, visual acuity data from eight patients at the 6-month follow up showed improvement by at least 15 letters in three eyes, stable in four eyes, and decreased by 11 letters in one eye (Lancet 2014, Oct. 15 [http://dx.doi.org/10.1016/S0140-6736(14)61376-3]).

Four treated eyes developed visually significant progression of cataracts. One patient with Stargardt’s macular dystrophy developed severe vitreous cavity inflammation consistent with acute postoperative endophthalmitis in one eye within 4 days of surgery, while another eye developed vitreous inflammation. All of those adverse events are associated with vitreoretinal surgery and immunosuppression.

“Additionally, there were no occurrences of adverse proliferation, growth of transplanted tissue at the injection site that was suggestive of a teratoma, ectopic tissue (nonretinal pigment epithelium), or other significant ocular adverse safety issues related to the hESC-retinal pigment epithelium cells in any patient during the observation period,” the researchers wrote.

In the eyes with age-related macular degeneration that did not develop cataracts in the first 6 months of follow-up, researchers noted a median improvement in visual acuity of 16 letters at 6 months, and 14 letters at 12 months, compared with no improvements at 6 months or 12 months in the untreated fellow eyes.

The treatment was delivered to sites with native but compromised retinal pigment epithelium and overlying photoreceptors, with the goal of improving the chances of transplant integration and photoreceptor cell rescue.

Patients from each study were divided into three dose cohorts receiving 50,000, 100,000, and 150,000 cells, and all received immunosuppressive therapy with tacrolimus and mycophenolate mofetil, from 1 week before the surgical procedure until 12 weeks after it.

The work is a “major accomplishment” that has already facilitated other trials of human embryonic stem cell therapy, noted Dr. Anthony Atala of the Wake Forest Institute for Regenerative Medicine, Winston-Salem, N.C., in an accompanying editorial (Lancet 2014, Oct. 15 [http://dx.doi.org/10.1016/S0140-6736(14)61820-1]).

“Now, we have follow-up that extends to longer than 3 years in patients treated with hESC-derived stem cells, showing both safety and apparent efficacy,” he wrote.

Advanced Cell Technology funded the study. Dr. Schwartz has received research support and consulting fees from Alcon, Allergan, Avalanche, Bausch and Lomb, Genentech, and Regeneron. Six of the study authors were employees of Advanced Cell Technology. The editorial author declared no conflicts of interest.

In a first for human embryonic stem cell therapy, use of the pluripotent cells to treat macular dystrophy and macular degeneration significantly improved visual acuity without adverse proliferation, rejection, or serious systemic safety issues for a median of nearly 2 years after transplantation.

“The results of this study provide the first evidence of the medium-term to long-term safety, graft survival, and possible biological activity of pluripotent stem cell progeny in individuals with any disease,” wrote Dr. Steven D. Schwartz, from the Jules Stein Eye Institute Retina Division, Los Angeles, and colleagues.

“Our results suggest that hESC-derived cells could provide a potentially safe new source of cells for the treatment of a variety of unmet medical conditions caused by tissue loss or dysfunction,” the authors noted.

In two prospective phase I/II studies using human embryonic stem cell therapy (hESC)-derived retinal pigment epithelium – one involving nine patients with Stargardt’s macular dystrophy, and the second in nine patients with atrophic age-related macular degeneration – 13 (72%) patients showed an increase in subretinal pigmentation after transplantation of the cells into the subretinal space.

Six months after the transplant, patients with age-related macular degeneration showed improvements in visual acuity by at least 15 letters in four eyes (which the authors described as a clinically significant measure of improvement) and 11-14 letters in two eyes. Visual acuity remained stable (equal to or less than 10 letters) in three eyes, according to a paper published online in the Oct. 15 issue of the Lancet.

In the patients with Stargardt’s macular dystrophy, visual acuity data from eight patients at the 6-month follow up showed improvement by at least 15 letters in three eyes, stable in four eyes, and decreased by 11 letters in one eye (Lancet 2014, Oct. 15 [http://dx.doi.org/10.1016/S0140-6736(14)61376-3]).

Four treated eyes developed visually significant progression of cataracts. One patient with Stargardt’s macular dystrophy developed severe vitreous cavity inflammation consistent with acute postoperative endophthalmitis in one eye within 4 days of surgery, while another eye developed vitreous inflammation. All of those adverse events are associated with vitreoretinal surgery and immunosuppression.

“Additionally, there were no occurrences of adverse proliferation, growth of transplanted tissue at the injection site that was suggestive of a teratoma, ectopic tissue (nonretinal pigment epithelium), or other significant ocular adverse safety issues related to the hESC-retinal pigment epithelium cells in any patient during the observation period,” the researchers wrote.

In the eyes with age-related macular degeneration that did not develop cataracts in the first 6 months of follow-up, researchers noted a median improvement in visual acuity of 16 letters at 6 months, and 14 letters at 12 months, compared with no improvements at 6 months or 12 months in the untreated fellow eyes.

The treatment was delivered to sites with native but compromised retinal pigment epithelium and overlying photoreceptors, with the goal of improving the chances of transplant integration and photoreceptor cell rescue.

Patients from each study were divided into three dose cohorts receiving 50,000, 100,000, and 150,000 cells, and all received immunosuppressive therapy with tacrolimus and mycophenolate mofetil, from 1 week before the surgical procedure until 12 weeks after it.

The work is a “major accomplishment” that has already facilitated other trials of human embryonic stem cell therapy, noted Dr. Anthony Atala of the Wake Forest Institute for Regenerative Medicine, Winston-Salem, N.C., in an accompanying editorial (Lancet 2014, Oct. 15 [http://dx.doi.org/10.1016/S0140-6736(14)61820-1]).

“Now, we have follow-up that extends to longer than 3 years in patients treated with hESC-derived stem cells, showing both safety and apparent efficacy,” he wrote.

Advanced Cell Technology funded the study. Dr. Schwartz has received research support and consulting fees from Alcon, Allergan, Avalanche, Bausch and Lomb, Genentech, and Regeneron. Six of the study authors were employees of Advanced Cell Technology. The editorial author declared no conflicts of interest.

In a first for human embryonic stem cell therapy, use of the pluripotent cells to treat macular dystrophy and macular degeneration significantly improved visual acuity without adverse proliferation, rejection, or serious systemic safety issues for a median of nearly 2 years after transplantation.

“The results of this study provide the first evidence of the medium-term to long-term safety, graft survival, and possible biological activity of pluripotent stem cell progeny in individuals with any disease,” wrote Dr. Steven D. Schwartz, from the Jules Stein Eye Institute Retina Division, Los Angeles, and colleagues.

“Our results suggest that hESC-derived cells could provide a potentially safe new source of cells for the treatment of a variety of unmet medical conditions caused by tissue loss or dysfunction,” the authors noted.

In two prospective phase I/II studies using human embryonic stem cell therapy (hESC)-derived retinal pigment epithelium – one involving nine patients with Stargardt’s macular dystrophy, and the second in nine patients with atrophic age-related macular degeneration – 13 (72%) patients showed an increase in subretinal pigmentation after transplantation of the cells into the subretinal space.

Six months after the transplant, patients with age-related macular degeneration showed improvements in visual acuity by at least 15 letters in four eyes (which the authors described as a clinically significant measure of improvement) and 11-14 letters in two eyes. Visual acuity remained stable (equal to or less than 10 letters) in three eyes, according to a paper published online in the Oct. 15 issue of the Lancet.

In the patients with Stargardt’s macular dystrophy, visual acuity data from eight patients at the 6-month follow up showed improvement by at least 15 letters in three eyes, stable in four eyes, and decreased by 11 letters in one eye (Lancet 2014, Oct. 15 [http://dx.doi.org/10.1016/S0140-6736(14)61376-3]).

Four treated eyes developed visually significant progression of cataracts. One patient with Stargardt’s macular dystrophy developed severe vitreous cavity inflammation consistent with acute postoperative endophthalmitis in one eye within 4 days of surgery, while another eye developed vitreous inflammation. All of those adverse events are associated with vitreoretinal surgery and immunosuppression.

“Additionally, there were no occurrences of adverse proliferation, growth of transplanted tissue at the injection site that was suggestive of a teratoma, ectopic tissue (nonretinal pigment epithelium), or other significant ocular adverse safety issues related to the hESC-retinal pigment epithelium cells in any patient during the observation period,” the researchers wrote.

In the eyes with age-related macular degeneration that did not develop cataracts in the first 6 months of follow-up, researchers noted a median improvement in visual acuity of 16 letters at 6 months, and 14 letters at 12 months, compared with no improvements at 6 months or 12 months in the untreated fellow eyes.

The treatment was delivered to sites with native but compromised retinal pigment epithelium and overlying photoreceptors, with the goal of improving the chances of transplant integration and photoreceptor cell rescue.

Patients from each study were divided into three dose cohorts receiving 50,000, 100,000, and 150,000 cells, and all received immunosuppressive therapy with tacrolimus and mycophenolate mofetil, from 1 week before the surgical procedure until 12 weeks after it.

The work is a “major accomplishment” that has already facilitated other trials of human embryonic stem cell therapy, noted Dr. Anthony Atala of the Wake Forest Institute for Regenerative Medicine, Winston-Salem, N.C., in an accompanying editorial (Lancet 2014, Oct. 15 [http://dx.doi.org/10.1016/S0140-6736(14)61820-1]).

“Now, we have follow-up that extends to longer than 3 years in patients treated with hESC-derived stem cells, showing both safety and apparent efficacy,” he wrote.

Advanced Cell Technology funded the study. Dr. Schwartz has received research support and consulting fees from Alcon, Allergan, Avalanche, Bausch and Lomb, Genentech, and Regeneron. Six of the study authors were employees of Advanced Cell Technology. The editorial author declared no conflicts of interest.

In a first for human embryonic stem cell therapy, use of the pluripotent cells to treat macular dystrophy and macular degeneration significantly improved visual acuity without adverse proliferation, rejection, or serious systemic safety issues for a median of nearly 2 years after transplantation.

“The results of this study provide the first evidence of the medium-term to long-term safety, graft survival, and possible biological activity of pluripotent stem cell progeny in individuals with any disease,” wrote Dr. Steven D. Schwartz, from the Jules Stein Eye Institute Retina Division, Los Angeles, and colleagues.

Courtesy Wikimedia Commons/ Nissim Benvenisty/Creative Commons License

“Our results suggest that hESC-derived cells could provide a potentially safe new source of cells for the treatment of a variety of unmet medical conditions caused by tissue loss or dysfunction,” the authors noted.

In two prospective phase I/II studies using human embryonic stem cell therapy (hESC)-derived retinal pigment epithelium – one involving nine patients with Stargardt’s macular dystrophy, and the second in nine patients with atrophic age-related macular degeneration – 13 (72%) patients showed an increase in subretinal pigmentation after transplantation of the cells into the subretinal space.

Six months after the transplant, patients with age-related macular degeneration showed improvements in visual acuity by at least 15 letters in four eyes (which the authors described as a clinically significant measure of improvement) and 11-14 letters in two eyes. Visual acuity remained stable (equal to or less than 10 letters) in three eyes, according to a paper published online in the Oct. 15 issue of the Lancet.

In the patients with Stargardt’s macular dystrophy, visual acuity data from eight patients at the 6-month follow up showed improvement by at least 15 letters in three eyes, stable in four eyes, and decreased by 11 letters in one eye (Lancet 2014, Oct. 15 [http://dx.doi.org/10.1016/S0140-6736(14)61376-3]).

Four treated eyes developed visually significant progression of cataracts. One patient with Stargardt’s macular dystrophy developed severe vitreous cavity inflammation consistent with acute postoperative endophthalmitis in one eye within 4 days of surgery, while another eye developed vitreous inflammation. All of those adverse events are associated with vitreoretinal surgery and immunosuppression.

“Additionally, there were no occurrences of adverse proliferation, growth of transplanted tissue at the injection site that was suggestive of a teratoma, ectopic tissue (nonretinal pigment epithelium), or other significant ocular adverse safety issues related to the hESC-retinal pigment epithelium cells in any patient during the observation period,” the researchers wrote.

In the eyes with age-related macular degeneration that did not develop cataracts in the first 6 months of follow-up, researchers noted a median improvement in visual acuity of 16 letters at 6 months, and 14 letters at 12 months, compared with no improvements at 6 months or 12 months in the untreated fellow eyes.

The treatment was delivered to sites with native but compromised retinal pigment epithelium and overlying photoreceptors, with the goal of improving the chances of transplant integration and photoreceptor cell rescue.

Patients from each study were divided into three dose cohorts receiving 50,000, 100,000, and 150,000 cells, and all received immunosuppressive therapy with tacrolimus and mycophenolate mofetil, from 1 week before the surgical procedure until 12 weeks after it.

The work is a “major accomplishment” that has already facilitated other trials of human embryonic stem cell therapy, noted Dr. Anthony Atala of the Wake Forest Institute for Regenerative Medicine, Winston-Salem, N.C., in an accompanying editorial (Lancet 2014, Oct. 15 [http://dx.doi.org/10.1016/S0140-6736(14)61820-1]).

“Now, we have follow-up that extends to longer than 3 years in patients treated with hESC-derived stem cells, showing both safety and apparent efficacy,” he wrote.

Advanced Cell Technology funded the study. Dr. Schwartz has received research support and consulting fees from Alcon, Allergan, Avalanche, Bausch and Lomb, Genentech, and Regeneron. Six of the study authors were employees of Advanced Cell Technology. The editorial author declared no conflicts of interest.

In a first for human embryonic stem cell therapy, use of the pluripotent cells to treat macular dystrophy and macular degeneration significantly improved visual acuity without adverse proliferation, rejection, or serious systemic safety issues for a median of nearly 2 years after transplantation.

“The results of this study provide the first evidence of the medium-term to long-term safety, graft survival, and possible biological activity of pluripotent stem cell progeny in individuals with any disease,” wrote Dr. Steven D. Schwartz, from the Jules Stein Eye Institute Retina Division, Los Angeles, and colleagues.

Courtesy Wikimedia Commons/ Nissim Benvenisty/Creative Commons License

“Our results suggest that hESC-derived cells could provide a potentially safe new source of cells for the treatment of a variety of unmet medical conditions caused by tissue loss or dysfunction,” the authors noted.

In two prospective phase I/II studies using human embryonic stem cell therapy (hESC)-derived retinal pigment epithelium – one involving nine patients with Stargardt’s macular dystrophy, and the second in nine patients with atrophic age-related macular degeneration – 13 (72%) patients showed an increase in subretinal pigmentation after transplantation of the cells into the subretinal space.

Six months after the transplant, patients with age-related macular degeneration showed improvements in visual acuity by at least 15 letters in four eyes (which the authors described as a clinically significant measure of improvement) and 11-14 letters in two eyes. Visual acuity remained stable (equal to or less than 10 letters) in three eyes, according to a paper published online in the Oct. 15 issue of the Lancet.

In the patients with Stargardt’s macular dystrophy, visual acuity data from eight patients at the 6-month follow up showed improvement by at least 15 letters in three eyes, stable in four eyes, and decreased by 11 letters in one eye (Lancet 2014, Oct. 15 [http://dx.doi.org/10.1016/S0140-6736(14)61376-3]).

Four treated eyes developed visually significant progression of cataracts. One patient with Stargardt’s macular dystrophy developed severe vitreous cavity inflammation consistent with acute postoperative endophthalmitis in one eye within 4 days of surgery, while another eye developed vitreous inflammation. All of those adverse events are associated with vitreoretinal surgery and immunosuppression.

“Additionally, there were no occurrences of adverse proliferation, growth of transplanted tissue at the injection site that was suggestive of a teratoma, ectopic tissue (nonretinal pigment epithelium), or other significant ocular adverse safety issues related to the hESC-retinal pigment epithelium cells in any patient during the observation period,” the researchers wrote.

In the eyes with age-related macular degeneration that did not develop cataracts in the first 6 months of follow-up, researchers noted a median improvement in visual acuity of 16 letters at 6 months, and 14 letters at 12 months, compared with no improvements at 6 months or 12 months in the untreated fellow eyes.

The treatment was delivered to sites with native but compromised retinal pigment epithelium and overlying photoreceptors, with the goal of improving the chances of transplant integration and photoreceptor cell rescue.

Patients from each study were divided into three dose cohorts receiving 50,000, 100,000, and 150,000 cells, and all received immunosuppressive therapy with tacrolimus and mycophenolate mofetil, from 1 week before the surgical procedure until 12 weeks after it.

The work is a “major accomplishment” that has already facilitated other trials of human embryonic stem cell therapy, noted Dr. Anthony Atala of the Wake Forest Institute for Regenerative Medicine, Winston-Salem, N.C., in an accompanying editorial (Lancet 2014, Oct. 15 [http://dx.doi.org/10.1016/S0140-6736(14)61820-1]).

“Now, we have follow-up that extends to longer than 3 years in patients treated with hESC-derived stem cells, showing both safety and apparent efficacy,” he wrote.

Advanced Cell Technology funded the study. Dr. Schwartz has received research support and consulting fees from Alcon, Allergan, Avalanche, Bausch and Lomb, Genentech, and Regeneron. Six of the study authors were employees of Advanced Cell Technology. The editorial author declared no conflicts of interest.

In a first for human embryonic stem cell therapy, use of the pluripotent cells to treat macular dystrophy and macular degeneration significantly improved visual acuity without adverse proliferation, rejection, or serious systemic safety issues for a median of nearly 2 years after transplantation.

“The results of this study provide the first evidence of the medium-term to long-term safety, graft survival, and possible biological activity of pluripotent stem cell progeny in individuals with any disease,” wrote Dr. Steven D. Schwartz, from the Jules Stein Eye Institute Retina Division, Los Angeles, and colleagues.

Courtesy Wikimedia Commons/ Nissim Benvenisty/Creative Commons License

“Our results suggest that hESC-derived cells could provide a potentially safe new source of cells for the treatment of a variety of unmet medical conditions caused by tissue loss or dysfunction,” the authors noted.

In two prospective phase I/II studies using human embryonic stem cell therapy (hESC)-derived retinal pigment epithelium – one involving nine patients with Stargardt’s macular dystrophy, and the second in nine patients with atrophic age-related macular degeneration – 13 (72%) patients showed an increase in subretinal pigmentation after transplantation of the cells into the subretinal space.

Six months after the transplant, patients with age-related macular degeneration showed improvements in visual acuity by at least 15 letters in four eyes (which the authors described as a clinically significant measure of improvement) and 11-14 letters in two eyes. Visual acuity remained stable (equal to or less than 10 letters) in three eyes, according to a paper published online in the Oct. 15 issue of the Lancet.

In the patients with Stargardt’s macular dystrophy, visual acuity data from eight patients at the 6-month follow up showed improvement by at least 15 letters in three eyes, stable in four eyes, and decreased by 11 letters in one eye (Lancet 2014, Oct. 15 [http://dx.doi.org/10.1016/S0140-6736(14)61376-3]).

Four treated eyes developed visually significant progression of cataracts. One patient with Stargardt’s macular dystrophy developed severe vitreous cavity inflammation consistent with acute postoperative endophthalmitis in one eye within 4 days of surgery, while another eye developed vitreous inflammation. All of those adverse events are associated with vitreoretinal surgery and immunosuppression.

“Additionally, there were no occurrences of adverse proliferation, growth of transplanted tissue at the injection site that was suggestive of a teratoma, ectopic tissue (nonretinal pigment epithelium), or other significant ocular adverse safety issues related to the hESC-retinal pigment epithelium cells in any patient during the observation period,” the researchers wrote.

In the eyes with age-related macular degeneration that did not develop cataracts in the first 6 months of follow-up, researchers noted a median improvement in visual acuity of 16 letters at 6 months, and 14 letters at 12 months, compared with no improvements at 6 months or 12 months in the untreated fellow eyes.

The treatment was delivered to sites with native but compromised retinal pigment epithelium and overlying photoreceptors, with the goal of improving the chances of transplant integration and photoreceptor cell rescue.

Patients from each study were divided into three dose cohorts receiving 50,000, 100,000, and 150,000 cells, and all received immunosuppressive therapy with tacrolimus and mycophenolate mofetil, from 1 week before the surgical procedure until 12 weeks after it.

The work is a “major accomplishment” that has already facilitated other trials of human embryonic stem cell therapy, noted Dr. Anthony Atala of the Wake Forest Institute for Regenerative Medicine, Winston-Salem, N.C., in an accompanying editorial (Lancet 2014, Oct. 15 [http://dx.doi.org/10.1016/S0140-6736(14)61820-1]).

“Now, we have follow-up that extends to longer than 3 years in patients treated with hESC-derived stem cells, showing both safety and apparent efficacy,” he wrote.

Advanced Cell Technology funded the study. Dr. Schwartz has received research support and consulting fees from Alcon, Allergan, Avalanche, Bausch and Lomb, Genentech, and Regeneron. Six of the study authors were employees of Advanced Cell Technology. The editorial author declared no conflicts of interest.

Rheumatoid arthritis patients with differing prognoses achieved similar improvements in clinical outcomes and functional improvements with initial combination therapy but fared differently when given initial monotherapy, according to the results of a post-hoc analysis of a randomized controlled trial.

The results challenge a recent push to tailor treatment strategy to risk stratification, argued Dr. Iris Markusse of the department of rheumatology at Leiden (the Netherlands) University Medical Center and her coauthors.

The researchers examined the treatment outcomes of 508 patients with rheumatoid arthritis in a post-hoc analysis of the BEST study in which patients were randomized to one of four treatment groups: sequential monotherapy starting with methotrexate, step-up combination therapy, initial combination therapy with prednisone, or initial combination with infliximab. For this post-hoc analysis of 1-year results, the investigators combined the first two groups that both started with methotrexate monotherapy because they had very similar disease outcomes during the first year of follow-up. The third and fourth groups that received initial combination therapy were combined as well.

The results were analyzed according to whether the patients were classified by disease characteristics and radiographic progression as having a poor or nonpoor prognosis. The researchers defined poor prognosis – 417 of the 508 patients – by the presence of at least three of four poor prognostic factors: Disease Activity Score of 3.7 or greater, swollen joint count of 10 or higher, four or more erosions, and positive results for both rheumatoid factor and anti-citrullinated peptide autoantibodies.

They found little difference between the two prognostic groups, with both showing significantly higher rates of remission and functional improvements with combination therapy than monotherapy, and the differences were preserved at 1 year. Among poor-prognosis patients, 93% achieved an American College of Rheumatology 20 (ACR 20) response at 1 year, compared with 80% of those on initial monotherapy. In the non–poor prognosis patients, initial combination therapy proved significantly better than initial monotherapy at achieving ACR20 response (85% vs. 72%).

Both poor- and non–poor prognosis groups had similar improvements in Health Assessment Questionnaire scores, and there was no significant differences in the toxicity of the treatment approaches in the different prognosis groups based on the numbers of reported adverse events (Arthritis Res. Ther. 2014 Sept. 25 [doi:10.1186/s13075-014-0430-3]).

“These results suggest that prognostic factors associated with future radiographic damage progression contribute little to predict early clinical response to initial treatment, and therefore in our opinion tailored treatment based on prognosis as suggested by the EULAR [European League Against Rheumatism] guidelines is currently not feasible,” Dr. Markusse and her associates wrote.

The study was supported by grants from the Dutch Insurance Companies, Schering-Plough, and Janssen. The authors declared having no other conflicts of interest.

Rheumatoid arthritis patients with differing prognoses achieved similar improvements in clinical outcomes and functional improvements with initial combination therapy but fared differently when given initial monotherapy, according to the results of a post-hoc analysis of a randomized controlled trial.

The results challenge a recent push to tailor treatment strategy to risk stratification, argued Dr. Iris Markusse of the department of rheumatology at Leiden (the Netherlands) University Medical Center and her coauthors.

The researchers examined the treatment outcomes of 508 patients with rheumatoid arthritis in a post-hoc analysis of the BEST study in which patients were randomized to one of four treatment groups: sequential monotherapy starting with methotrexate, step-up combination therapy, initial combination therapy with prednisone, or initial combination with infliximab. For this post-hoc analysis of 1-year results, the investigators combined the first two groups that both started with methotrexate monotherapy because they had very similar disease outcomes during the first year of follow-up. The third and fourth groups that received initial combination therapy were combined as well.

The results were analyzed according to whether the patients were classified by disease characteristics and radiographic progression as having a poor or nonpoor prognosis. The researchers defined poor prognosis – 417 of the 508 patients – by the presence of at least three of four poor prognostic factors: Disease Activity Score of 3.7 or greater, swollen joint count of 10 or higher, four or more erosions, and positive results for both rheumatoid factor and anti-citrullinated peptide autoantibodies.

They found little difference between the two prognostic groups, with both showing significantly higher rates of remission and functional improvements with combination therapy than monotherapy, and the differences were preserved at 1 year. Among poor-prognosis patients, 93% achieved an American College of Rheumatology 20 (ACR 20) response at 1 year, compared with 80% of those on initial monotherapy. In the non–poor prognosis patients, initial combination therapy proved significantly better than initial monotherapy at achieving ACR20 response (85% vs. 72%).

Both poor- and non–poor prognosis groups had similar improvements in Health Assessment Questionnaire scores, and there was no significant differences in the toxicity of the treatment approaches in the different prognosis groups based on the numbers of reported adverse events (Arthritis Res. Ther. 2014 Sept. 25 [doi:10.1186/s13075-014-0430-3]).

“These results suggest that prognostic factors associated with future radiographic damage progression contribute little to predict early clinical response to initial treatment, and therefore in our opinion tailored treatment based on prognosis as suggested by the EULAR [European League Against Rheumatism] guidelines is currently not feasible,” Dr. Markusse and her associates wrote.

The study was supported by grants from the Dutch Insurance Companies, Schering-Plough, and Janssen. The authors declared having no other conflicts of interest.

Rheumatoid arthritis patients with differing prognoses achieved similar improvements in clinical outcomes and functional improvements with initial combination therapy but fared differently when given initial monotherapy, according to the results of a post-hoc analysis of a randomized controlled trial.

The results challenge a recent push to tailor treatment strategy to risk stratification, argued Dr. Iris Markusse of the department of rheumatology at Leiden (the Netherlands) University Medical Center and her coauthors.

The researchers examined the treatment outcomes of 508 patients with rheumatoid arthritis in a post-hoc analysis of the BEST study in which patients were randomized to one of four treatment groups: sequential monotherapy starting with methotrexate, step-up combination therapy, initial combination therapy with prednisone, or initial combination with infliximab. For this post-hoc analysis of 1-year results, the investigators combined the first two groups that both started with methotrexate monotherapy because they had very similar disease outcomes during the first year of follow-up. The third and fourth groups that received initial combination therapy were combined as well.

The results were analyzed according to whether the patients were classified by disease characteristics and radiographic progression as having a poor or nonpoor prognosis. The researchers defined poor prognosis – 417 of the 508 patients – by the presence of at least three of four poor prognostic factors: Disease Activity Score of 3.7 or greater, swollen joint count of 10 or higher, four or more erosions, and positive results for both rheumatoid factor and anti-citrullinated peptide autoantibodies.

They found little difference between the two prognostic groups, with both showing significantly higher rates of remission and functional improvements with combination therapy than monotherapy, and the differences were preserved at 1 year. Among poor-prognosis patients, 93% achieved an American College of Rheumatology 20 (ACR 20) response at 1 year, compared with 80% of those on initial monotherapy. In the non–poor prognosis patients, initial combination therapy proved significantly better than initial monotherapy at achieving ACR20 response (85% vs. 72%).

Both poor- and non–poor prognosis groups had similar improvements in Health Assessment Questionnaire scores, and there was no significant differences in the toxicity of the treatment approaches in the different prognosis groups based on the numbers of reported adverse events (Arthritis Res. Ther. 2014 Sept. 25 [doi:10.1186/s13075-014-0430-3]).

“These results suggest that prognostic factors associated with future radiographic damage progression contribute little to predict early clinical response to initial treatment, and therefore in our opinion tailored treatment based on prognosis as suggested by the EULAR [European League Against Rheumatism] guidelines is currently not feasible,” Dr. Markusse and her associates wrote.

The study was supported by grants from the Dutch Insurance Companies, Schering-Plough, and Janssen. The authors declared having no other conflicts of interest.

First-episode schizophrenia spectrum disorders are associated with a significantly higher prevalence of metabolic risk factors, such as smoking, dyslipidemia, and elevated body mass, compared with the general population. Those risk factors are tied to illness duration and are exacerbated by antipsychotic therapy, data from a cross-sectional study of patients with the disorders show.

Among the 394 patients with cardiometabolic data, about half smoked cigarettes, 39.9% had prehypertension, 10.0% had hypertension, and 13.2% had metabolic syndrome, and 48.3% were obese or overweight – a figure similar to that found among a similarly aged U.S. population – while 56.5% had dyslipidemia, which reflects the incidence in a general population 15-20 years older.

Duration of psychiatric illness was significantly associated with higher body mass index, fat mass, fat percentage, and waist circumference. Antipsychotic treatment was linked to higher measures of non-HDL-C, triglyceride levels, and triglyceride to HDL-C ratios but lower HDL-C measures and systolic blood pressure, according to a paper published online Oct. 8 in JAMA Psychiatry ([doi:10.1001/jamapsychiatry.2014.1314]).

“In patients with [first-episode schizophrenia], cardiometabolic risk factors and abnormalities are present early in the illness and likely related to the underlying illness, unhealthy lifestyle, and antipsychotic medications, which interact with each other,” wrote Dr. Christoph U. Correll, professor, psychiatry and molecular medicine at the Hofstra University, Hempstead, N.Y., and his colleagues. “Prevention of and early interventions for psychiatric illness with lower-risk agents, routine antipsychotic adverse effect monitoring, and smoking cessation interventions are needed from the earliest illness phases.”

The study was supported by the National Institute of Mental Health, and the American Recovery and Reinvestment Act. Dr. Correll disclosed acting as a consultant and/or adviser to or receiving honoraria from several companies and entities, including numerous makers of antipsychotics.

First-episode schizophrenia spectrum disorders are associated with a significantly higher prevalence of metabolic risk factors, such as smoking, dyslipidemia, and elevated body mass, compared with the general population. Those risk factors are tied to illness duration and are exacerbated by antipsychotic therapy, data from a cross-sectional study of patients with the disorders show.

Among the 394 patients with cardiometabolic data, about half smoked cigarettes, 39.9% had prehypertension, 10.0% had hypertension, and 13.2% had metabolic syndrome, and 48.3% were obese or overweight – a figure similar to that found among a similarly aged U.S. population – while 56.5% had dyslipidemia, which reflects the incidence in a general population 15-20 years older.

Duration of psychiatric illness was significantly associated with higher body mass index, fat mass, fat percentage, and waist circumference. Antipsychotic treatment was linked to higher measures of non-HDL-C, triglyceride levels, and triglyceride to HDL-C ratios but lower HDL-C measures and systolic blood pressure, according to a paper published online Oct. 8 in JAMA Psychiatry ([doi:10.1001/jamapsychiatry.2014.1314]).

“In patients with [first-episode schizophrenia], cardiometabolic risk factors and abnormalities are present early in the illness and likely related to the underlying illness, unhealthy lifestyle, and antipsychotic medications, which interact with each other,” wrote Dr. Christoph U. Correll, professor, psychiatry and molecular medicine at the Hofstra University, Hempstead, N.Y., and his colleagues. “Prevention of and early interventions for psychiatric illness with lower-risk agents, routine antipsychotic adverse effect monitoring, and smoking cessation interventions are needed from the earliest illness phases.”

The study was supported by the National Institute of Mental Health, and the American Recovery and Reinvestment Act. Dr. Correll disclosed acting as a consultant and/or adviser to or receiving honoraria from several companies and entities, including numerous makers of antipsychotics.

First-episode schizophrenia spectrum disorders are associated with a significantly higher prevalence of metabolic risk factors, such as smoking, dyslipidemia, and elevated body mass, compared with the general population. Those risk factors are tied to illness duration and are exacerbated by antipsychotic therapy, data from a cross-sectional study of patients with the disorders show.

Among the 394 patients with cardiometabolic data, about half smoked cigarettes, 39.9% had prehypertension, 10.0% had hypertension, and 13.2% had metabolic syndrome, and 48.3% were obese or overweight – a figure similar to that found among a similarly aged U.S. population – while 56.5% had dyslipidemia, which reflects the incidence in a general population 15-20 years older.

Duration of psychiatric illness was significantly associated with higher body mass index, fat mass, fat percentage, and waist circumference. Antipsychotic treatment was linked to higher measures of non-HDL-C, triglyceride levels, and triglyceride to HDL-C ratios but lower HDL-C measures and systolic blood pressure, according to a paper published online Oct. 8 in JAMA Psychiatry ([doi:10.1001/jamapsychiatry.2014.1314]).

“In patients with [first-episode schizophrenia], cardiometabolic risk factors and abnormalities are present early in the illness and likely related to the underlying illness, unhealthy lifestyle, and antipsychotic medications, which interact with each other,” wrote Dr. Christoph U. Correll, professor, psychiatry and molecular medicine at the Hofstra University, Hempstead, N.Y., and his colleagues. “Prevention of and early interventions for psychiatric illness with lower-risk agents, routine antipsychotic adverse effect monitoring, and smoking cessation interventions are needed from the earliest illness phases.”

The study was supported by the National Institute of Mental Health, and the American Recovery and Reinvestment Act. Dr. Correll disclosed acting as a consultant and/or adviser to or receiving honoraria from several companies and entities, including numerous makers of antipsychotics.