(Reuters) - One of the top U.S. public health officials on Sunday warned that the mosquito-borne Zika virus could extend its reach across the U.S. Gulf Coast after officials last week confirmed it as active in the popular tourist destination of Miami Beach.

The possibility of transmission in Gulf States such as Louisiana and Texas will likely fuel concerns that the virus, which has been shown to cause microcephaly, could spread across the continental United States, even though officials have played down such an outcome.

Concern has mounted since confirmation that Zika has expanded into a second region of the tourist hub of Miami-Dade County in Florida. Miami's Wynwood arts neighborhood last month became the site of the first locally transmitted cases of Zika in the continental United States.

"It would not be surprising we would see additional cases perhaps in other Gulf Coast states," Dr. Anthony Fauci, director of the allergy and infectious diseases unit of the National Institutes of Health (NIH), said in an interview on Sunday morning with ABC News.

Fauci noted that record flooding this month in Louisiana - which has killed at least 13 people and damaged some 60,000 homes damaged - has boosted the likelihood Zika will spread into that state.

"There's going to be a lot of problems getting rid of standing water" that could stymie the mosquito control efforts that are the best way to control Zika's spread, he said.

The connection between Zika and microcephaly first came to light last fall in Brazil, which has now confirmed 1,835 cases of microcephaly that it considers to be related to Zika infections in the mothers.

On Friday, Florida Governor Rick Scott confirmed that state health officials had identified five cases of Zika believed to be contracted in Miami Beach.

The U.S. Centers for Disease Control and Prevention told pregnant women they should avoid the trendy area and suggested those especially worried about exposure might consider avoiding all of Miami-Dade County.

NIH's Fauci on Sunday said the conditions of most of the country make it unlikely there would be a "diffuse, broad outbreak," even though officials need to prepare for that possibility.

He compared it with diseases such as dengue, which is endemic in certain tropical and subtropical regions of the world but rarely occurs in the continental United States. In Miami's Wynwood area, experts have seen "substantial" knockdowns of mosquito populations.

Still, its containment is more complicated because Zika can be sexually transmitted, Fauci said.

"This is something that could hang around for a year or two," he said.

The World Health Organization has said there is strong scientific consensus that Zika can also cause Guillain-Barre syndrome.

(c) Copyright Thomson Reuters 2016.

(Reuters) - One of the top U.S. public health officials on Sunday warned that the mosquito-borne Zika virus could extend its reach across the U.S. Gulf Coast after officials last week confirmed it as active in the popular tourist destination of Miami Beach.

The possibility of transmission in Gulf States such as Louisiana and Texas will likely fuel concerns that the virus, which has been shown to cause microcephaly, could spread across the continental United States, even though officials have played down such an outcome.

Concern has mounted since confirmation that Zika has expanded into a second region of the tourist hub of Miami-Dade County in Florida. Miami's Wynwood arts neighborhood last month became the site of the first locally transmitted cases of Zika in the continental United States.

"It would not be surprising we would see additional cases perhaps in other Gulf Coast states," Dr. Anthony Fauci, director of the allergy and infectious diseases unit of the National Institutes of Health (NIH), said in an interview on Sunday morning with ABC News.

Fauci noted that record flooding this month in Louisiana - which has killed at least 13 people and damaged some 60,000 homes damaged - has boosted the likelihood Zika will spread into that state.

"There's going to be a lot of problems getting rid of standing water" that could stymie the mosquito control efforts that are the best way to control Zika's spread, he said.

The connection between Zika and microcephaly first came to light last fall in Brazil, which has now confirmed 1,835 cases of microcephaly that it considers to be related to Zika infections in the mothers.

On Friday, Florida Governor Rick Scott confirmed that state health officials had identified five cases of Zika believed to be contracted in Miami Beach.

The U.S. Centers for Disease Control and Prevention told pregnant women they should avoid the trendy area and suggested those especially worried about exposure might consider avoiding all of Miami-Dade County.

NIH's Fauci on Sunday said the conditions of most of the country make it unlikely there would be a "diffuse, broad outbreak," even though officials need to prepare for that possibility.

He compared it with diseases such as dengue, which is endemic in certain tropical and subtropical regions of the world but rarely occurs in the continental United States. In Miami's Wynwood area, experts have seen "substantial" knockdowns of mosquito populations.

Still, its containment is more complicated because Zika can be sexually transmitted, Fauci said.

"This is something that could hang around for a year or two," he said.

The World Health Organization has said there is strong scientific consensus that Zika can also cause Guillain-Barre syndrome.

(c) Copyright Thomson Reuters 2016.

(Reuters) - One of the top U.S. public health officials on Sunday warned that the mosquito-borne Zika virus could extend its reach across the U.S. Gulf Coast after officials last week confirmed it as active in the popular tourist destination of Miami Beach.

The possibility of transmission in Gulf States such as Louisiana and Texas will likely fuel concerns that the virus, which has been shown to cause microcephaly, could spread across the continental United States, even though officials have played down such an outcome.

Concern has mounted since confirmation that Zika has expanded into a second region of the tourist hub of Miami-Dade County in Florida. Miami's Wynwood arts neighborhood last month became the site of the first locally transmitted cases of Zika in the continental United States.

"It would not be surprising we would see additional cases perhaps in other Gulf Coast states," Dr. Anthony Fauci, director of the allergy and infectious diseases unit of the National Institutes of Health (NIH), said in an interview on Sunday morning with ABC News.

Fauci noted that record flooding this month in Louisiana - which has killed at least 13 people and damaged some 60,000 homes damaged - has boosted the likelihood Zika will spread into that state.

"There's going to be a lot of problems getting rid of standing water" that could stymie the mosquito control efforts that are the best way to control Zika's spread, he said.

The connection between Zika and microcephaly first came to light last fall in Brazil, which has now confirmed 1,835 cases of microcephaly that it considers to be related to Zika infections in the mothers.

On Friday, Florida Governor Rick Scott confirmed that state health officials had identified five cases of Zika believed to be contracted in Miami Beach.

The U.S. Centers for Disease Control and Prevention told pregnant women they should avoid the trendy area and suggested those especially worried about exposure might consider avoiding all of Miami-Dade County.

NIH's Fauci on Sunday said the conditions of most of the country make it unlikely there would be a "diffuse, broad outbreak," even though officials need to prepare for that possibility.

He compared it with diseases such as dengue, which is endemic in certain tropical and subtropical regions of the world but rarely occurs in the continental United States. In Miami's Wynwood area, experts have seen "substantial" knockdowns of mosquito populations.

Still, its containment is more complicated because Zika can be sexually transmitted, Fauci said.

"This is something that could hang around for a year or two," he said.

The World Health Organization has said there is strong scientific consensus that Zika can also cause Guillain-Barre syndrome.

(c) Copyright Thomson Reuters 2016.

The rates of cataract surgery, the most commonly performed ophthalmic procedure in the U.S., have increased in the past few decades with an estimated rate of 1,100 surgeries per 100,000 people in 2011.^1,2 Several emerging practices have the potential to radically impact the efficacy, safety, and cost of cataract surgery.^3-5 These practices include femtosecond laser-assisted cataract surgery, intracameral antibiotics, and bilateral same-day cataract surgery.

The femtosecond laser is capable of producing precise incisions in the cornea for access by surgical instruments and reduction of astigmatism. Laser pulses also can create a perfectly round incision of the anterior lens capsule, which surrounds and supports the crystalline lens, and make incisions into the cataractous lens to facilitate disassembly for easy removal of fragments.

Placement of antibiotics internally into the anterior chamber, the space between the crystalline lens and the posterior cornea (intracameral space), is a more direct method to prevent bacterial infection within the eye (endophthalmitis), compared with current external methods, including injections under the conjunctiva (subconjunctival) and/or use of antibiotic drops directly onto the eye surface (topical).⁶

Routine cataract surgery is typically staged, with a period of time between sequential surgeries of 1 week or more to allow for observation of infection (delayed sequential surgery). In view of the very low rate of infection and the impact of staged surgery on patients, including additional visits and copays, some surgeons have begun to perform bilateral surgery (immediate sequential bilateral surgery, using separate patient safety checklists, surgical preps, instruments, and medications) on the same day for patients with significant cataracts in both eyes to promote rapid restoration of binocular vision as well reduce the number of patient visits.

The extent of adaptation of femtosecond laser surgery, intracameral antibiotics, and immediate sequential bilateral surgery in the U.S. is currently unknown.^7,8 To provide an updated snapshot of these cataract surgery practices, the authors report on the results of a brief survey administered to ophthalmology section chiefs in the VHA, the largest integrated health care system and the largest provider of health care training in the U.S.

Methods

Following institutional review board approval from the Providence VA Medical Center, the office of the National Program Director of VA Ophthalmology provided a list of all VHA ophthalmology section chiefs and their contact information. The study targeted section chiefs because they are responsible for all eye surgery performed at their respective VAMCs. The survey queried the section chiefs on femtosecond laser-assisted cataract surgery, intracameral antibiotics, immediate sequential bilateral cataract surgery, and resident training at their institutions (Table).

The survey was administered using the web-based Research Electronic Data Capture (REDCap) software.⁹ The initial survey was e-mailed in April 2015, followed by 2 reminder e-mails 1 week apart and then 2 phone calls 1 week apart to nonresponders.

The survey responses were stored anonymously in the REDCap database and analyzed using descriptive statistics.

Results

The original list from the office of the National Program Director included 114 ophthalmology section chiefs (excluding one of the authors). After follow-up phone calls, 9 individuals were identified who were not ophthalmologists (eg, optometrists or nonophthalmic surgeons) or who were incorrectly listed as section chiefs, and 9 were duplicates from institutions that were represented twice on the contact list. These 18 individuals, none of whom had responded to the survey, were removed from the eligible sample. Hence, the analysis included 86% (95/111) of the VAMCs where cataract surgery is performed.¹⁰ Sixty-five responses were received for an overall response rate of 68% (65/96), including 1 ophthalmologist who responded to the survey twice.

Most section chiefs (86%, 56/65) trained ophthalmology residents at their respective medical centers (Table). Eleven VAMCs (17%) offered femtosecond laser-assisted cataract surgery; 8 of those 11 (73%) also offered resident training in this surgery. At 12 VAMCs (18%), cataract surgeons used intracameral antibiotics, which included vancomycin (4), cefuroxime (4), moxifloxacin (3), and unspecified (1); at 10 of these VAMCs (83%), surgeons used intracameral and postoperative topical antibiotics concomitantly; 8 VAMCs (67%) compounded the intracameral antibiotics—either in the hospital pharmacy (5) or within the operating room (3). The 2 most common reasons cited for not using intracameral antibiotics were risk of dilution error (28%; 15/53) and a lack of evidence for use (25%; 13/53). Only 2 medical centers (3.1%) offered immediate sequential bilateral cataract surgery.

Discussion

This survey provides updated information on the role of emerging cataract surgery practices in the VHA. These trends may impact future U.S. cataract surgery practice patterns given the large number of ophthalmology residents who receive training in the VHA.

Only 17% of VAMCs offered femtosecond laser-assisted cataract surgery. Reasons for this low rate may include (a) the high cost of the femtosecond laser units (the lowest average cost of a laser is $400,000, while the average costs of services can be $40,000 or more per year); and (b) the lack of evidence that a femtosecond laser improves cataract surgery outcomes relative to standard phacoemulsification.^4,11-15 Another potential barrier to procurement of femtosecond lasers is the emphasis within VHA to increase access to care for the many newly enrolled veterans, which this technology does not address. However, most of the VAMCs with a femtosecond laser unit offered resident training in this technique, confirming early reports on the potential for incorporating femtosecond laser-assisted cataract surgery into ophthalmic graduate medical education.¹⁶

In 2007, the multicenter, prospective, randomized European Society of Cataract and Refractive Surgery Endophthalmitis Study demonstrated that intracameral cefuroxime was associated with a 5-fold decrease in the risk of postoperative endophthalmitis.¹⁷ In 2011, a statement from the American Society of Cataract and Refractive Surgery (ASCRS) Cataract Clinical Committee noted that the method of antibiotic prophylaxis with the strongest evidence base is “a direct intracameral bolus at the conclusion of surgery.”¹⁸ However, surgeons used intracameral antibiotics in only 19% of VAMCs. Although this is a higher rate than those reported in older surveys of VHA ophthalmologists (14%)⁷ and ASCRS members (15%), it is still significantly lower than the 74% reported in a recent survey of the European Society of Cataract and Refractive Surgeons.^3,8

The most common reasons given for not using intracameral antibiotics included risk of a dilution error when preparing the antibiotics and lack of evidence supporting their effectiveness. Less common reasons included risk of contamination, lack of pharmacy approval, and increasing bacterial resistance to commonly used antibiotics. Most of these concerns have been previously cited as barriers to the adoption of intracameral antibiotics.¹⁹ The availability of a prepackaged intracameral antibiotic (eg, cefuroxime in Europe) would help address the risks of compounding dilution errors and contamination in the U.S.⁶ The publication of 3 large observational studies in 2016 has also significantly strengthened the evidence base supporting the use of intracameral antibiotics.^20-22

Only 2 VAMCs (3%) offered immediate sequential bilateral cataract surgery. The advocates of this practice have touted its potential cost savings, patient convenience, and the opportunity for more rapid visual rehabilitation.²³ Recently, several multicenter, randomized clinical trials have reported similar refractive outcomes, complication rates, and patient satisfaction for immediate and delayed bilateral cataract surgery.^24,25 Hence, it is possible that rates of immediate sequential bilateral cataract surgery may increase in the VHA over the next few years.

Strengths/Limitations

A strength of this survey is its high response rate (67.7%), which exceeds the 53% and 33% rates reported in previous surveys of cataract surgery practice patterns among VHA ophthalmologistsand ASCRS members, respectively.^7,8 Another strength is lack of financial incentive for adaptation of any new practices by VHA surgeons, suggesting that these decisions have been made to improve patient safety, quality of care, and/or resident education. A limitation of this study is that its findings may not be generalizable to ophthalmologists practicing in the private sector or in teaching hospitals outside the VHA.

Conclusion

This study suggests that femtosecond laser-assisted cataract surgery, intracameral antibiotics, and immediate sequential bilateral cataract surgery have limited roles in VHA cataract surgery. More research and clinical experience are needed to understand the barriers to more widespread acceptance and to assess the impact of these emerging practices on cataract surgery in the U.S.

The rates of cataract surgery, the most commonly performed ophthalmic procedure in the U.S., have increased in the past few decades with an estimated rate of 1,100 surgeries per 100,000 people in 2011.^1,2 Several emerging practices have the potential to radically impact the efficacy, safety, and cost of cataract surgery.^3-5 These practices include femtosecond laser-assisted cataract surgery, intracameral antibiotics, and bilateral same-day cataract surgery.

The femtosecond laser is capable of producing precise incisions in the cornea for access by surgical instruments and reduction of astigmatism. Laser pulses also can create a perfectly round incision of the anterior lens capsule, which surrounds and supports the crystalline lens, and make incisions into the cataractous lens to facilitate disassembly for easy removal of fragments.

Placement of antibiotics internally into the anterior chamber, the space between the crystalline lens and the posterior cornea (intracameral space), is a more direct method to prevent bacterial infection within the eye (endophthalmitis), compared with current external methods, including injections under the conjunctiva (subconjunctival) and/or use of antibiotic drops directly onto the eye surface (topical).⁶

Routine cataract surgery is typically staged, with a period of time between sequential surgeries of 1 week or more to allow for observation of infection (delayed sequential surgery). In view of the very low rate of infection and the impact of staged surgery on patients, including additional visits and copays, some surgeons have begun to perform bilateral surgery (immediate sequential bilateral surgery, using separate patient safety checklists, surgical preps, instruments, and medications) on the same day for patients with significant cataracts in both eyes to promote rapid restoration of binocular vision as well reduce the number of patient visits.

The extent of adaptation of femtosecond laser surgery, intracameral antibiotics, and immediate sequential bilateral surgery in the U.S. is currently unknown.^7,8 To provide an updated snapshot of these cataract surgery practices, the authors report on the results of a brief survey administered to ophthalmology section chiefs in the VHA, the largest integrated health care system and the largest provider of health care training in the U.S.

Methods

Following institutional review board approval from the Providence VA Medical Center, the office of the National Program Director of VA Ophthalmology provided a list of all VHA ophthalmology section chiefs and their contact information. The study targeted section chiefs because they are responsible for all eye surgery performed at their respective VAMCs. The survey queried the section chiefs on femtosecond laser-assisted cataract surgery, intracameral antibiotics, immediate sequential bilateral cataract surgery, and resident training at their institutions (Table).

The survey was administered using the web-based Research Electronic Data Capture (REDCap) software.⁹ The initial survey was e-mailed in April 2015, followed by 2 reminder e-mails 1 week apart and then 2 phone calls 1 week apart to nonresponders.

The survey responses were stored anonymously in the REDCap database and analyzed using descriptive statistics.

Results

The original list from the office of the National Program Director included 114 ophthalmology section chiefs (excluding one of the authors). After follow-up phone calls, 9 individuals were identified who were not ophthalmologists (eg, optometrists or nonophthalmic surgeons) or who were incorrectly listed as section chiefs, and 9 were duplicates from institutions that were represented twice on the contact list. These 18 individuals, none of whom had responded to the survey, were removed from the eligible sample. Hence, the analysis included 86% (95/111) of the VAMCs where cataract surgery is performed.¹⁰ Sixty-five responses were received for an overall response rate of 68% (65/96), including 1 ophthalmologist who responded to the survey twice.

Most section chiefs (86%, 56/65) trained ophthalmology residents at their respective medical centers (Table). Eleven VAMCs (17%) offered femtosecond laser-assisted cataract surgery; 8 of those 11 (73%) also offered resident training in this surgery. At 12 VAMCs (18%), cataract surgeons used intracameral antibiotics, which included vancomycin (4), cefuroxime (4), moxifloxacin (3), and unspecified (1); at 10 of these VAMCs (83%), surgeons used intracameral and postoperative topical antibiotics concomitantly; 8 VAMCs (67%) compounded the intracameral antibiotics—either in the hospital pharmacy (5) or within the operating room (3). The 2 most common reasons cited for not using intracameral antibiotics were risk of dilution error (28%; 15/53) and a lack of evidence for use (25%; 13/53). Only 2 medical centers (3.1%) offered immediate sequential bilateral cataract surgery.

Discussion

This survey provides updated information on the role of emerging cataract surgery practices in the VHA. These trends may impact future U.S. cataract surgery practice patterns given the large number of ophthalmology residents who receive training in the VHA.

Only 17% of VAMCs offered femtosecond laser-assisted cataract surgery. Reasons for this low rate may include (a) the high cost of the femtosecond laser units (the lowest average cost of a laser is $400,000, while the average costs of services can be $40,000 or more per year); and (b) the lack of evidence that a femtosecond laser improves cataract surgery outcomes relative to standard phacoemulsification.^4,11-15 Another potential barrier to procurement of femtosecond lasers is the emphasis within VHA to increase access to care for the many newly enrolled veterans, which this technology does not address. However, most of the VAMCs with a femtosecond laser unit offered resident training in this technique, confirming early reports on the potential for incorporating femtosecond laser-assisted cataract surgery into ophthalmic graduate medical education.¹⁶

In 2007, the multicenter, prospective, randomized European Society of Cataract and Refractive Surgery Endophthalmitis Study demonstrated that intracameral cefuroxime was associated with a 5-fold decrease in the risk of postoperative endophthalmitis.¹⁷ In 2011, a statement from the American Society of Cataract and Refractive Surgery (ASCRS) Cataract Clinical Committee noted that the method of antibiotic prophylaxis with the strongest evidence base is “a direct intracameral bolus at the conclusion of surgery.”¹⁸ However, surgeons used intracameral antibiotics in only 19% of VAMCs. Although this is a higher rate than those reported in older surveys of VHA ophthalmologists (14%)⁷ and ASCRS members (15%), it is still significantly lower than the 74% reported in a recent survey of the European Society of Cataract and Refractive Surgeons.^3,8

The most common reasons given for not using intracameral antibiotics included risk of a dilution error when preparing the antibiotics and lack of evidence supporting their effectiveness. Less common reasons included risk of contamination, lack of pharmacy approval, and increasing bacterial resistance to commonly used antibiotics. Most of these concerns have been previously cited as barriers to the adoption of intracameral antibiotics.¹⁹ The availability of a prepackaged intracameral antibiotic (eg, cefuroxime in Europe) would help address the risks of compounding dilution errors and contamination in the U.S.⁶ The publication of 3 large observational studies in 2016 has also significantly strengthened the evidence base supporting the use of intracameral antibiotics.^20-22

Only 2 VAMCs (3%) offered immediate sequential bilateral cataract surgery. The advocates of this practice have touted its potential cost savings, patient convenience, and the opportunity for more rapid visual rehabilitation.²³ Recently, several multicenter, randomized clinical trials have reported similar refractive outcomes, complication rates, and patient satisfaction for immediate and delayed bilateral cataract surgery.^24,25 Hence, it is possible that rates of immediate sequential bilateral cataract surgery may increase in the VHA over the next few years.

Strengths/Limitations

A strength of this survey is its high response rate (67.7%), which exceeds the 53% and 33% rates reported in previous surveys of cataract surgery practice patterns among VHA ophthalmologistsand ASCRS members, respectively.^7,8 Another strength is lack of financial incentive for adaptation of any new practices by VHA surgeons, suggesting that these decisions have been made to improve patient safety, quality of care, and/or resident education. A limitation of this study is that its findings may not be generalizable to ophthalmologists practicing in the private sector or in teaching hospitals outside the VHA.

Conclusion

This study suggests that femtosecond laser-assisted cataract surgery, intracameral antibiotics, and immediate sequential bilateral cataract surgery have limited roles in VHA cataract surgery. More research and clinical experience are needed to understand the barriers to more widespread acceptance and to assess the impact of these emerging practices on cataract surgery in the U.S.

The rates of cataract surgery, the most commonly performed ophthalmic procedure in the U.S., have increased in the past few decades with an estimated rate of 1,100 surgeries per 100,000 people in 2011.^1,2 Several emerging practices have the potential to radically impact the efficacy, safety, and cost of cataract surgery.^3-5 These practices include femtosecond laser-assisted cataract surgery, intracameral antibiotics, and bilateral same-day cataract surgery.

The femtosecond laser is capable of producing precise incisions in the cornea for access by surgical instruments and reduction of astigmatism. Laser pulses also can create a perfectly round incision of the anterior lens capsule, which surrounds and supports the crystalline lens, and make incisions into the cataractous lens to facilitate disassembly for easy removal of fragments.

Placement of antibiotics internally into the anterior chamber, the space between the crystalline lens and the posterior cornea (intracameral space), is a more direct method to prevent bacterial infection within the eye (endophthalmitis), compared with current external methods, including injections under the conjunctiva (subconjunctival) and/or use of antibiotic drops directly onto the eye surface (topical).⁶

Routine cataract surgery is typically staged, with a period of time between sequential surgeries of 1 week or more to allow for observation of infection (delayed sequential surgery). In view of the very low rate of infection and the impact of staged surgery on patients, including additional visits and copays, some surgeons have begun to perform bilateral surgery (immediate sequential bilateral surgery, using separate patient safety checklists, surgical preps, instruments, and medications) on the same day for patients with significant cataracts in both eyes to promote rapid restoration of binocular vision as well reduce the number of patient visits.

The extent of adaptation of femtosecond laser surgery, intracameral antibiotics, and immediate sequential bilateral surgery in the U.S. is currently unknown.^7,8 To provide an updated snapshot of these cataract surgery practices, the authors report on the results of a brief survey administered to ophthalmology section chiefs in the VHA, the largest integrated health care system and the largest provider of health care training in the U.S.

Methods

Following institutional review board approval from the Providence VA Medical Center, the office of the National Program Director of VA Ophthalmology provided a list of all VHA ophthalmology section chiefs and their contact information. The study targeted section chiefs because they are responsible for all eye surgery performed at their respective VAMCs. The survey queried the section chiefs on femtosecond laser-assisted cataract surgery, intracameral antibiotics, immediate sequential bilateral cataract surgery, and resident training at their institutions (Table).

The survey was administered using the web-based Research Electronic Data Capture (REDCap) software.⁹ The initial survey was e-mailed in April 2015, followed by 2 reminder e-mails 1 week apart and then 2 phone calls 1 week apart to nonresponders.

The survey responses were stored anonymously in the REDCap database and analyzed using descriptive statistics.

Results

The original list from the office of the National Program Director included 114 ophthalmology section chiefs (excluding one of the authors). After follow-up phone calls, 9 individuals were identified who were not ophthalmologists (eg, optometrists or nonophthalmic surgeons) or who were incorrectly listed as section chiefs, and 9 were duplicates from institutions that were represented twice on the contact list. These 18 individuals, none of whom had responded to the survey, were removed from the eligible sample. Hence, the analysis included 86% (95/111) of the VAMCs where cataract surgery is performed.¹⁰ Sixty-five responses were received for an overall response rate of 68% (65/96), including 1 ophthalmologist who responded to the survey twice.

Most section chiefs (86%, 56/65) trained ophthalmology residents at their respective medical centers (Table). Eleven VAMCs (17%) offered femtosecond laser-assisted cataract surgery; 8 of those 11 (73%) also offered resident training in this surgery. At 12 VAMCs (18%), cataract surgeons used intracameral antibiotics, which included vancomycin (4), cefuroxime (4), moxifloxacin (3), and unspecified (1); at 10 of these VAMCs (83%), surgeons used intracameral and postoperative topical antibiotics concomitantly; 8 VAMCs (67%) compounded the intracameral antibiotics—either in the hospital pharmacy (5) or within the operating room (3). The 2 most common reasons cited for not using intracameral antibiotics were risk of dilution error (28%; 15/53) and a lack of evidence for use (25%; 13/53). Only 2 medical centers (3.1%) offered immediate sequential bilateral cataract surgery.

Discussion

This survey provides updated information on the role of emerging cataract surgery practices in the VHA. These trends may impact future U.S. cataract surgery practice patterns given the large number of ophthalmology residents who receive training in the VHA.

Only 17% of VAMCs offered femtosecond laser-assisted cataract surgery. Reasons for this low rate may include (a) the high cost of the femtosecond laser units (the lowest average cost of a laser is $400,000, while the average costs of services can be $40,000 or more per year); and (b) the lack of evidence that a femtosecond laser improves cataract surgery outcomes relative to standard phacoemulsification.^4,11-15 Another potential barrier to procurement of femtosecond lasers is the emphasis within VHA to increase access to care for the many newly enrolled veterans, which this technology does not address. However, most of the VAMCs with a femtosecond laser unit offered resident training in this technique, confirming early reports on the potential for incorporating femtosecond laser-assisted cataract surgery into ophthalmic graduate medical education.¹⁶

In 2007, the multicenter, prospective, randomized European Society of Cataract and Refractive Surgery Endophthalmitis Study demonstrated that intracameral cefuroxime was associated with a 5-fold decrease in the risk of postoperative endophthalmitis.¹⁷ In 2011, a statement from the American Society of Cataract and Refractive Surgery (ASCRS) Cataract Clinical Committee noted that the method of antibiotic prophylaxis with the strongest evidence base is “a direct intracameral bolus at the conclusion of surgery.”¹⁸ However, surgeons used intracameral antibiotics in only 19% of VAMCs. Although this is a higher rate than those reported in older surveys of VHA ophthalmologists (14%)⁷ and ASCRS members (15%), it is still significantly lower than the 74% reported in a recent survey of the European Society of Cataract and Refractive Surgeons.^3,8

The most common reasons given for not using intracameral antibiotics included risk of a dilution error when preparing the antibiotics and lack of evidence supporting their effectiveness. Less common reasons included risk of contamination, lack of pharmacy approval, and increasing bacterial resistance to commonly used antibiotics. Most of these concerns have been previously cited as barriers to the adoption of intracameral antibiotics.¹⁹ The availability of a prepackaged intracameral antibiotic (eg, cefuroxime in Europe) would help address the risks of compounding dilution errors and contamination in the U.S.⁶ The publication of 3 large observational studies in 2016 has also significantly strengthened the evidence base supporting the use of intracameral antibiotics.^20-22

Only 2 VAMCs (3%) offered immediate sequential bilateral cataract surgery. The advocates of this practice have touted its potential cost savings, patient convenience, and the opportunity for more rapid visual rehabilitation.²³ Recently, several multicenter, randomized clinical trials have reported similar refractive outcomes, complication rates, and patient satisfaction for immediate and delayed bilateral cataract surgery.^24,25 Hence, it is possible that rates of immediate sequential bilateral cataract surgery may increase in the VHA over the next few years.

Strengths/Limitations

A strength of this survey is its high response rate (67.7%), which exceeds the 53% and 33% rates reported in previous surveys of cataract surgery practice patterns among VHA ophthalmologistsand ASCRS members, respectively.^7,8 Another strength is lack of financial incentive for adaptation of any new practices by VHA surgeons, suggesting that these decisions have been made to improve patient safety, quality of care, and/or resident education. A limitation of this study is that its findings may not be generalizable to ophthalmologists practicing in the private sector or in teaching hospitals outside the VHA.

Conclusion

This study suggests that femtosecond laser-assisted cataract surgery, intracameral antibiotics, and immediate sequential bilateral cataract surgery have limited roles in VHA cataract surgery. More research and clinical experience are needed to understand the barriers to more widespread acceptance and to assess the impact of these emerging practices on cataract surgery in the U.S.

Lab mouse

Preclinical research suggests that combining a BCL2 inhibitor with a BCR-ABL tyrosine kinase inhibitor (TKI) can eradicate leukemia stem cells (LSCs) in chronic myeloid leukemia (CML).

In mouse models of CML, combining the TKI nilotinib with the BCL2 inhibitor venetoclax enhanced antileukemic activity and decreased numbers of long-term LSCs.

The 2-drug combination exhibited similar activity in samples from patients with blast crisis CML.

“Our results demonstrate that . . . employing combined blockade of BCL-2 and BCR-ABL has the potential for curing CML and significantly improving outcomes for patients with blast crisis, and, as such, warrants clinical testing,” said Michael Andreeff, MD, of the University of Texas MD Anderson Cancer Center in Houston.

Dr Andreeff and his colleagues reported these results in Science Translational Medicine. The study was funded by National Institutes of Health, the Paul and Mary Haas Chair in Genetics, and Abbvie Inc., the company developing venetoclax.

The researchers noted that, although BCR-ABL TKIs have proven effective against CML, they rarely eliminate CML stem cells.

“It is believed that TKIs do not eliminate residual stem cells because they are not dependent on BCR-ABL signaling,” said study author Bing Carter, PhD, also of MD Anderson Cancer Center. “Hence, cures of CML with TKIs are rare.”

Dr Carter has worked for several years on eliminating residual CML stem cells, which could mean CML patients would no longer require long-term treatment with TKIs. Based on the current study, she and her colleagues believe that combining a TKI with a BCL-2 inhibitor may be a solution.

The researchers found that targeting both BCL-2 and BCR-ABL with venetoclax and nilotinib, respectively, exerted “potent antileukemic activity” and prolonged survival in BCR-ABL transgenic mice.

After stopping treatment, the median survival was 34.5 days for control mice, 70 days for mice treated with nilotinib alone (P=0.2146), 115 days for mice treated with venetoclax alone (P=0.0079), and 168 days for mice treated with nilotinib and venetoclax in combination (P=0.0002).

Subsequent experiments in mice showed that nilotinib alone did not significantly affect the frequency of long-term LSCs, although venetoclax alone did. Treatment with both drugs reduced the frequency of long-term LSCs even more than venetoclax alone.

Finally, the researchers tested venetoclax, nilotinib, and the combination in cells from 6 patients with blast crisis CML, all of whom had failed treatment with at least 1 TKI.

The team found that venetoclax and nilotinib had a synergistic apoptotic effect on bulk and stem/progenitor CML cells.

The researchers said these results suggest that combined inhibition of BCL-2 and BCR-ABL tyrosine kinase has the potential to significantly improve the depth of response and cure rates of chronic phase and blast crisis CML.

“This combination strategy may also apply to other malignancies that depend on kinase signaling for progression and maintenance,” Dr Andreeff added.

Lab mouse

Preclinical research suggests that combining a BCL2 inhibitor with a BCR-ABL tyrosine kinase inhibitor (TKI) can eradicate leukemia stem cells (LSCs) in chronic myeloid leukemia (CML).

In mouse models of CML, combining the TKI nilotinib with the BCL2 inhibitor venetoclax enhanced antileukemic activity and decreased numbers of long-term LSCs.

The 2-drug combination exhibited similar activity in samples from patients with blast crisis CML.

“Our results demonstrate that . . . employing combined blockade of BCL-2 and BCR-ABL has the potential for curing CML and significantly improving outcomes for patients with blast crisis, and, as such, warrants clinical testing,” said Michael Andreeff, MD, of the University of Texas MD Anderson Cancer Center in Houston.

Dr Andreeff and his colleagues reported these results in Science Translational Medicine. The study was funded by National Institutes of Health, the Paul and Mary Haas Chair in Genetics, and Abbvie Inc., the company developing venetoclax.

The researchers noted that, although BCR-ABL TKIs have proven effective against CML, they rarely eliminate CML stem cells.

“It is believed that TKIs do not eliminate residual stem cells because they are not dependent on BCR-ABL signaling,” said study author Bing Carter, PhD, also of MD Anderson Cancer Center. “Hence, cures of CML with TKIs are rare.”

Dr Carter has worked for several years on eliminating residual CML stem cells, which could mean CML patients would no longer require long-term treatment with TKIs. Based on the current study, she and her colleagues believe that combining a TKI with a BCL-2 inhibitor may be a solution.

The researchers found that targeting both BCL-2 and BCR-ABL with venetoclax and nilotinib, respectively, exerted “potent antileukemic activity” and prolonged survival in BCR-ABL transgenic mice.

After stopping treatment, the median survival was 34.5 days for control mice, 70 days for mice treated with nilotinib alone (P=0.2146), 115 days for mice treated with venetoclax alone (P=0.0079), and 168 days for mice treated with nilotinib and venetoclax in combination (P=0.0002).

Subsequent experiments in mice showed that nilotinib alone did not significantly affect the frequency of long-term LSCs, although venetoclax alone did. Treatment with both drugs reduced the frequency of long-term LSCs even more than venetoclax alone.

Finally, the researchers tested venetoclax, nilotinib, and the combination in cells from 6 patients with blast crisis CML, all of whom had failed treatment with at least 1 TKI.

The team found that venetoclax and nilotinib had a synergistic apoptotic effect on bulk and stem/progenitor CML cells.

The researchers said these results suggest that combined inhibition of BCL-2 and BCR-ABL tyrosine kinase has the potential to significantly improve the depth of response and cure rates of chronic phase and blast crisis CML.

“This combination strategy may also apply to other malignancies that depend on kinase signaling for progression and maintenance,” Dr Andreeff added.

Lab mouse

Preclinical research suggests that combining a BCL2 inhibitor with a BCR-ABL tyrosine kinase inhibitor (TKI) can eradicate leukemia stem cells (LSCs) in chronic myeloid leukemia (CML).

In mouse models of CML, combining the TKI nilotinib with the BCL2 inhibitor venetoclax enhanced antileukemic activity and decreased numbers of long-term LSCs.

The 2-drug combination exhibited similar activity in samples from patients with blast crisis CML.

“Our results demonstrate that . . . employing combined blockade of BCL-2 and BCR-ABL has the potential for curing CML and significantly improving outcomes for patients with blast crisis, and, as such, warrants clinical testing,” said Michael Andreeff, MD, of the University of Texas MD Anderson Cancer Center in Houston.

Dr Andreeff and his colleagues reported these results in Science Translational Medicine. The study was funded by National Institutes of Health, the Paul and Mary Haas Chair in Genetics, and Abbvie Inc., the company developing venetoclax.

The researchers noted that, although BCR-ABL TKIs have proven effective against CML, they rarely eliminate CML stem cells.

“It is believed that TKIs do not eliminate residual stem cells because they are not dependent on BCR-ABL signaling,” said study author Bing Carter, PhD, also of MD Anderson Cancer Center. “Hence, cures of CML with TKIs are rare.”

Dr Carter has worked for several years on eliminating residual CML stem cells, which could mean CML patients would no longer require long-term treatment with TKIs. Based on the current study, she and her colleagues believe that combining a TKI with a BCL-2 inhibitor may be a solution.

The researchers found that targeting both BCL-2 and BCR-ABL with venetoclax and nilotinib, respectively, exerted “potent antileukemic activity” and prolonged survival in BCR-ABL transgenic mice.

After stopping treatment, the median survival was 34.5 days for control mice, 70 days for mice treated with nilotinib alone (P=0.2146), 115 days for mice treated with venetoclax alone (P=0.0079), and 168 days for mice treated with nilotinib and venetoclax in combination (P=0.0002).

Subsequent experiments in mice showed that nilotinib alone did not significantly affect the frequency of long-term LSCs, although venetoclax alone did. Treatment with both drugs reduced the frequency of long-term LSCs even more than venetoclax alone.

Finally, the researchers tested venetoclax, nilotinib, and the combination in cells from 6 patients with blast crisis CML, all of whom had failed treatment with at least 1 TKI.

The team found that venetoclax and nilotinib had a synergistic apoptotic effect on bulk and stem/progenitor CML cells.

The researchers said these results suggest that combined inhibition of BCL-2 and BCR-ABL tyrosine kinase has the potential to significantly improve the depth of response and cure rates of chronic phase and blast crisis CML.

“This combination strategy may also apply to other malignancies that depend on kinase signaling for progression and maintenance,” Dr Andreeff added.

Blood samples

Photo by Graham Colm

Factors related to blood sample collection and storage can have a substantial impact on the biomolecular composition of the sample, according to research published in EBioMedicine.

The study showed that freezer storage time and the month and season during which a blood sample is collected can affect protein concentrations.

In fact, researchers said these factors should be considered covariates of the same importance as the sample provider’s age or gender.

“This discovery will change the way the entire world works with biobank blood,” said study author Stefan Enroth, PhD, of Uppsala University in Sweden.

“All research on, and analysis of, biobank blood going forward should also take into account what we have discovered—namely, the time aspect. It is completely new.”

As part of their research on uterine cancer, Dr Enroth and his colleagues looked at plasma samples collected from 1988 to 2014. There were 380 samples from 106 women between the ages of 29 and 73.

The researchers looked at the duration of sample storage, the women’s chronological age at sample collection, and the season and month of the year the sample was collected, assessing the impact of these factors on the abundance levels of 108 proteins.

When studying the impact of storage time, the researchers used only samples from 50-year-old women in order to isolate the time effect. The team found that storage time affected 18 proteins and explained 4.8% to 34.9% of the variance observed.

The women’s chronological age at the time of sample collection, after the adjustment for storage time, affected 70 proteins and explained 1.1% to 33.5% of the variance.

“We suspected that we’d find an influence from storage time, but we thought it would be much less,” said study author Ulf Gyllensten, PhD, of Uppsala University.

“It has now been demonstrated that storage time can be a factor at least as important as the age of the individual at sampling.”

The other major finding of the study is that protein levels vary depending on the season or month in which the samples were taken.

The researchers said results in the month analysis corresponded with the seasonal analysis, so they hypothesized that sunlight hours at the time of sampling could explain some of the variance they observed in plasma protein abundance levels.

The team found the number of sunlight hours affected 36 proteins and explained up to 4.5% of the variance observed after adjusting for storage time and age.

The researchers said these results suggest that information on the sample handling history should be regarded as “equally prominent covariates” as age or gender. Therefore, the information should be included in epidemiological studies involving protein levels.

Blood samples

Photo by Graham Colm

Factors related to blood sample collection and storage can have a substantial impact on the biomolecular composition of the sample, according to research published in EBioMedicine.

The study showed that freezer storage time and the month and season during which a blood sample is collected can affect protein concentrations.

In fact, researchers said these factors should be considered covariates of the same importance as the sample provider’s age or gender.

“This discovery will change the way the entire world works with biobank blood,” said study author Stefan Enroth, PhD, of Uppsala University in Sweden.

“All research on, and analysis of, biobank blood going forward should also take into account what we have discovered—namely, the time aspect. It is completely new.”

As part of their research on uterine cancer, Dr Enroth and his colleagues looked at plasma samples collected from 1988 to 2014. There were 380 samples from 106 women between the ages of 29 and 73.

The researchers looked at the duration of sample storage, the women’s chronological age at sample collection, and the season and month of the year the sample was collected, assessing the impact of these factors on the abundance levels of 108 proteins.

When studying the impact of storage time, the researchers used only samples from 50-year-old women in order to isolate the time effect. The team found that storage time affected 18 proteins and explained 4.8% to 34.9% of the variance observed.

The women’s chronological age at the time of sample collection, after the adjustment for storage time, affected 70 proteins and explained 1.1% to 33.5% of the variance.

“We suspected that we’d find an influence from storage time, but we thought it would be much less,” said study author Ulf Gyllensten, PhD, of Uppsala University.

“It has now been demonstrated that storage time can be a factor at least as important as the age of the individual at sampling.”

The other major finding of the study is that protein levels vary depending on the season or month in which the samples were taken.

The researchers said results in the month analysis corresponded with the seasonal analysis, so they hypothesized that sunlight hours at the time of sampling could explain some of the variance they observed in plasma protein abundance levels.

The team found the number of sunlight hours affected 36 proteins and explained up to 4.5% of the variance observed after adjusting for storage time and age.

The researchers said these results suggest that information on the sample handling history should be regarded as “equally prominent covariates” as age or gender. Therefore, the information should be included in epidemiological studies involving protein levels.

Blood samples

Photo by Graham Colm

Factors related to blood sample collection and storage can have a substantial impact on the biomolecular composition of the sample, according to research published in EBioMedicine.

The study showed that freezer storage time and the month and season during which a blood sample is collected can affect protein concentrations.

In fact, researchers said these factors should be considered covariates of the same importance as the sample provider’s age or gender.

“This discovery will change the way the entire world works with biobank blood,” said study author Stefan Enroth, PhD, of Uppsala University in Sweden.

“All research on, and analysis of, biobank blood going forward should also take into account what we have discovered—namely, the time aspect. It is completely new.”

As part of their research on uterine cancer, Dr Enroth and his colleagues looked at plasma samples collected from 1988 to 2014. There were 380 samples from 106 women between the ages of 29 and 73.

The researchers looked at the duration of sample storage, the women’s chronological age at sample collection, and the season and month of the year the sample was collected, assessing the impact of these factors on the abundance levels of 108 proteins.

When studying the impact of storage time, the researchers used only samples from 50-year-old women in order to isolate the time effect. The team found that storage time affected 18 proteins and explained 4.8% to 34.9% of the variance observed.

The women’s chronological age at the time of sample collection, after the adjustment for storage time, affected 70 proteins and explained 1.1% to 33.5% of the variance.

“We suspected that we’d find an influence from storage time, but we thought it would be much less,” said study author Ulf Gyllensten, PhD, of Uppsala University.

“It has now been demonstrated that storage time can be a factor at least as important as the age of the individual at sampling.”

The other major finding of the study is that protein levels vary depending on the season or month in which the samples were taken.

The researchers said results in the month analysis corresponded with the seasonal analysis, so they hypothesized that sunlight hours at the time of sampling could explain some of the variance they observed in plasma protein abundance levels.

The team found the number of sunlight hours affected 36 proteins and explained up to 4.5% of the variance observed after adjusting for storage time and age.

The researchers said these results suggest that information on the sample handling history should be regarded as “equally prominent covariates” as age or gender. Therefore, the information should be included in epidemiological studies involving protein levels.

Child receiving RTS,S/AS01

Photo by Caitlin Kleiboer

Results of a phase 2 trial suggest that changing the dosing schedule can improve the efficacy of the malaria vaccine candidate RTS,S/AS01 (Mosquirix).

Researchers tested RTS,S/AS01 in 46 malaria-naïve US adults, using the controlled human malaria infection model (CHMI).

About 87% of subjects who received the modified dosing regimen were protected from malaria, compared to 63% of subjects who received the standard dosing schedule.

Jason Regules, MD, of the US Army Medical Research Institute of Infectious Diseases in Frederick, Maryland, and his colleagues reported these results in the Journal of Infectious Diseases.

The study was funded by GlaxoSmithKline, the US Military Infectious Disease Research Program, and the PATH Malaria Vaccine Initiative. RTS,S/AS01 is being developed by GlaxoSmithKline and the PATH Malaria Vaccine Initiative.

RTS,S/AS01 has been tested in trials of young children in Africa, and early results seemed promising. But long-term follow-up in a phase 2 study and a phase 3 study suggested the vaccine’s efficacy wanes over time.

Therefore, Dr Regules and his colleagues sought to determine if a novel immunization schedule—specifically, delaying RTS,S/AS01 administration and reducing dosage of the third vaccination, as well as any following booster dose—would significantly increase the vaccine’s ability to protect against infection.

The researchers evaluated RTS,S/AS01 in 46 malaria-naïve adults. First, the team immunized the subjects according to 2 regimens:

• A 0-, 1-, 7-month schedule with a fractional third dose (Fx017M)
• A 0-, 1-, 2-month schedule (012M, the current standard).

Following the third vaccination, subjects were exposed to malaria-causing parasites using CHMI, and the researchers evaluated the extent to which each regimen protected against infection.

During follow-up, the team assessed the efficacy of an additional fractional dose, or booster, in protecting against a second CHMI.

Twenty-six of the 30 subjects—86.7%—who received the Fx017M regimen and 10 of the 16—62.5%—who received the 012M regimen were protected from infection following the first CHMI.

In addition to providing more protection from malaria infection, the Fx017M regimen delayed infection longer than the 012M regimen.

About 90% of the Fx017M group who received a fourth fractional booster dose and underwent the second CHMI were protected from infection.

Four out of 5 subjects from both vaccination groups who were infected during the first CHMI were protected against the second, after receiving the fourth (fractional) dose of RTS,S/AS01.

The subjects did not report any serious health events as a result of receiving the vaccinations, and no safety concerns were associated with reducing dosages.

“With these results in hand, we are planning additional studies in the United States and Africa that will seek to further refine the dosing and schedule for maximum impact and to see whether these early stage results in American adults will translate into similarly high efficacy in sub-Saharan Africa, a region that bears much of the malaria disease burden,” said study author Ashley J. Birkett, PhD, director of PATH’s Malaria Vaccine Initiative.

“The results of these planned studies won’t be available for several years, however. It therefore remains critical that the pilot implementation for the recommended pediatric regimen of RTS,S/AS01, being led by the World Health Organization, moves forward as soon as possible. We need to help protect as many children as we can, as soon as we can, while we continue to pursue eradication—the only truly sustainable solution to malaria.”

Child receiving RTS,S/AS01

Photo by Caitlin Kleiboer

Results of a phase 2 trial suggest that changing the dosing schedule can improve the efficacy of the malaria vaccine candidate RTS,S/AS01 (Mosquirix).

Researchers tested RTS,S/AS01 in 46 malaria-naïve US adults, using the controlled human malaria infection model (CHMI).

About 87% of subjects who received the modified dosing regimen were protected from malaria, compared to 63% of subjects who received the standard dosing schedule.

Jason Regules, MD, of the US Army Medical Research Institute of Infectious Diseases in Frederick, Maryland, and his colleagues reported these results in the Journal of Infectious Diseases.

The study was funded by GlaxoSmithKline, the US Military Infectious Disease Research Program, and the PATH Malaria Vaccine Initiative. RTS,S/AS01 is being developed by GlaxoSmithKline and the PATH Malaria Vaccine Initiative.

RTS,S/AS01 has been tested in trials of young children in Africa, and early results seemed promising. But long-term follow-up in a phase 2 study and a phase 3 study suggested the vaccine’s efficacy wanes over time.

Therefore, Dr Regules and his colleagues sought to determine if a novel immunization schedule—specifically, delaying RTS,S/AS01 administration and reducing dosage of the third vaccination, as well as any following booster dose—would significantly increase the vaccine’s ability to protect against infection.

The researchers evaluated RTS,S/AS01 in 46 malaria-naïve adults. First, the team immunized the subjects according to 2 regimens:

• A 0-, 1-, 7-month schedule with a fractional third dose (Fx017M)
• A 0-, 1-, 2-month schedule (012M, the current standard).

Following the third vaccination, subjects were exposed to malaria-causing parasites using CHMI, and the researchers evaluated the extent to which each regimen protected against infection.

During follow-up, the team assessed the efficacy of an additional fractional dose, or booster, in protecting against a second CHMI.

Twenty-six of the 30 subjects—86.7%—who received the Fx017M regimen and 10 of the 16—62.5%—who received the 012M regimen were protected from infection following the first CHMI.

In addition to providing more protection from malaria infection, the Fx017M regimen delayed infection longer than the 012M regimen.

About 90% of the Fx017M group who received a fourth fractional booster dose and underwent the second CHMI were protected from infection.

Four out of 5 subjects from both vaccination groups who were infected during the first CHMI were protected against the second, after receiving the fourth (fractional) dose of RTS,S/AS01.

The subjects did not report any serious health events as a result of receiving the vaccinations, and no safety concerns were associated with reducing dosages.

“With these results in hand, we are planning additional studies in the United States and Africa that will seek to further refine the dosing and schedule for maximum impact and to see whether these early stage results in American adults will translate into similarly high efficacy in sub-Saharan Africa, a region that bears much of the malaria disease burden,” said study author Ashley J. Birkett, PhD, director of PATH’s Malaria Vaccine Initiative.

“The results of these planned studies won’t be available for several years, however. It therefore remains critical that the pilot implementation for the recommended pediatric regimen of RTS,S/AS01, being led by the World Health Organization, moves forward as soon as possible. We need to help protect as many children as we can, as soon as we can, while we continue to pursue eradication—the only truly sustainable solution to malaria.”

Child receiving RTS,S/AS01

Photo by Caitlin Kleiboer

Results of a phase 2 trial suggest that changing the dosing schedule can improve the efficacy of the malaria vaccine candidate RTS,S/AS01 (Mosquirix).

Researchers tested RTS,S/AS01 in 46 malaria-naïve US adults, using the controlled human malaria infection model (CHMI).

About 87% of subjects who received the modified dosing regimen were protected from malaria, compared to 63% of subjects who received the standard dosing schedule.

Jason Regules, MD, of the US Army Medical Research Institute of Infectious Diseases in Frederick, Maryland, and his colleagues reported these results in the Journal of Infectious Diseases.

The study was funded by GlaxoSmithKline, the US Military Infectious Disease Research Program, and the PATH Malaria Vaccine Initiative. RTS,S/AS01 is being developed by GlaxoSmithKline and the PATH Malaria Vaccine Initiative.

RTS,S/AS01 has been tested in trials of young children in Africa, and early results seemed promising. But long-term follow-up in a phase 2 study and a phase 3 study suggested the vaccine’s efficacy wanes over time.

Therefore, Dr Regules and his colleagues sought to determine if a novel immunization schedule—specifically, delaying RTS,S/AS01 administration and reducing dosage of the third vaccination, as well as any following booster dose—would significantly increase the vaccine’s ability to protect against infection.

The researchers evaluated RTS,S/AS01 in 46 malaria-naïve adults. First, the team immunized the subjects according to 2 regimens:

• A 0-, 1-, 7-month schedule with a fractional third dose (Fx017M)
• A 0-, 1-, 2-month schedule (012M, the current standard).

Following the third vaccination, subjects were exposed to malaria-causing parasites using CHMI, and the researchers evaluated the extent to which each regimen protected against infection.

During follow-up, the team assessed the efficacy of an additional fractional dose, or booster, in protecting against a second CHMI.

Twenty-six of the 30 subjects—86.7%—who received the Fx017M regimen and 10 of the 16—62.5%—who received the 012M regimen were protected from infection following the first CHMI.

In addition to providing more protection from malaria infection, the Fx017M regimen delayed infection longer than the 012M regimen.

About 90% of the Fx017M group who received a fourth fractional booster dose and underwent the second CHMI were protected from infection.

Four out of 5 subjects from both vaccination groups who were infected during the first CHMI were protected against the second, after receiving the fourth (fractional) dose of RTS,S/AS01.

The subjects did not report any serious health events as a result of receiving the vaccinations, and no safety concerns were associated with reducing dosages.

“With these results in hand, we are planning additional studies in the United States and Africa that will seek to further refine the dosing and schedule for maximum impact and to see whether these early stage results in American adults will translate into similarly high efficacy in sub-Saharan Africa, a region that bears much of the malaria disease burden,” said study author Ashley J. Birkett, PhD, director of PATH’s Malaria Vaccine Initiative.

“The results of these planned studies won’t be available for several years, however. It therefore remains critical that the pilot implementation for the recommended pediatric regimen of RTS,S/AS01, being led by the World Health Organization, moves forward as soon as possible. We need to help protect as many children as we can, as soon as we can, while we continue to pursue eradication—the only truly sustainable solution to malaria.”

AML cells

Exosomes shed by acute myeloid leukemia (AML) cells carry microRNAs that directly impair hematopoiesis, according to preclinical research published in Science Signaling.

Previous research suggested that AML exosomes can suppress residual hematopoietic stem and progenitor cell (HSPC) function indirectly through stromal reprogramming of niche retention factors.

The new study indicates that AML exosomes can block hematopoiesis by delivering microRNAs that directly suppress blood production when taken up by HSPCs.

Noah Hornick, of Oregon Health & Science University in Portland, and his colleagues conducted this study,  isolating exosomes from cultures of human AML cells and from the plasma of mice with AML.

The researchers found these exosomes were enriched in 2 microRNAs—miR-150 and miR-155.

When cultured with HSPCs, the exosomes suppressed the expression of the transcription factor c-MYB, which is involved in HSPC proliferation and differentiation.

Blocking the function of miR-155 prevented AML cells or their exosomes from reducing c-MYB abundance and inhibiting the proliferation of cultured HSPCs.

Using a method called RISC-Trap, the researchers identified other targets of microRNAs in AML exosomes, from which they predicted protein networks that could be disrupted in cells taking up the exosomes.

The team said this study suggests that interfering with exosome-delivered microRNAs in the bone marrow or restoring the abundance of their targets may enhance AML patients’ ability to produce healthy blood cells.

AML cells

Exosomes shed by acute myeloid leukemia (AML) cells carry microRNAs that directly impair hematopoiesis, according to preclinical research published in Science Signaling.

Previous research suggested that AML exosomes can suppress residual hematopoietic stem and progenitor cell (HSPC) function indirectly through stromal reprogramming of niche retention factors.

The new study indicates that AML exosomes can block hematopoiesis by delivering microRNAs that directly suppress blood production when taken up by HSPCs.

Noah Hornick, of Oregon Health & Science University in Portland, and his colleagues conducted this study,  isolating exosomes from cultures of human AML cells and from the plasma of mice with AML.

The researchers found these exosomes were enriched in 2 microRNAs—miR-150 and miR-155.

When cultured with HSPCs, the exosomes suppressed the expression of the transcription factor c-MYB, which is involved in HSPC proliferation and differentiation.

Blocking the function of miR-155 prevented AML cells or their exosomes from reducing c-MYB abundance and inhibiting the proliferation of cultured HSPCs.

Using a method called RISC-Trap, the researchers identified other targets of microRNAs in AML exosomes, from which they predicted protein networks that could be disrupted in cells taking up the exosomes.

The team said this study suggests that interfering with exosome-delivered microRNAs in the bone marrow or restoring the abundance of their targets may enhance AML patients’ ability to produce healthy blood cells.

AML cells

Exosomes shed by acute myeloid leukemia (AML) cells carry microRNAs that directly impair hematopoiesis, according to preclinical research published in Science Signaling.

Previous research suggested that AML exosomes can suppress residual hematopoietic stem and progenitor cell (HSPC) function indirectly through stromal reprogramming of niche retention factors.

The new study indicates that AML exosomes can block hematopoiesis by delivering microRNAs that directly suppress blood production when taken up by HSPCs.

Noah Hornick, of Oregon Health & Science University in Portland, and his colleagues conducted this study,  isolating exosomes from cultures of human AML cells and from the plasma of mice with AML.

The researchers found these exosomes were enriched in 2 microRNAs—miR-150 and miR-155.

When cultured with HSPCs, the exosomes suppressed the expression of the transcription factor c-MYB, which is involved in HSPC proliferation and differentiation.

Blocking the function of miR-155 prevented AML cells or their exosomes from reducing c-MYB abundance and inhibiting the proliferation of cultured HSPCs.

Using a method called RISC-Trap, the researchers identified other targets of microRNAs in AML exosomes, from which they predicted protein networks that could be disrupted in cells taking up the exosomes.

The team said this study suggests that interfering with exosome-delivered microRNAs in the bone marrow or restoring the abundance of their targets may enhance AML patients’ ability to produce healthy blood cells.

The first new case of a live-born infant with Zika virus–related birth defects in almost a month was reported during the week ending Sept. 1, bringing the U.S. total to 18 so far, according to the Centers for Disease Control and Prevention.

The infant was born in one of the 50 states or the District of Columbia and is the first case of a Zika-related birth defect reported since the week ending Aug. 4. The CDC is not reporting state- or territorial-level data to protect the privacy of affected women and children. There were no new Zika-related pregnancy losses for the week of Sept. 1, so the total remains at six for the states, D.C., and the territories, the CDC reported Sept. 8.

The number of pregnant women with any laboratory evidence of Zika infection increased by 156 during the week ending Sept. 1: 47 new cases in the states/D.C. and 109 new cases in the territories. The total number of pregnant women with Zika for 2016 is now 1,751, the CDC said.

For 2015-2016, there have been 18,833 cases reported in the entire U.S. population: 2,964 in the states/D.C. (all but 44 were travel associated) and 15,869 in the territories. All but 60 cases in the territories were locally acquired, and 98% have occurred in Puerto Rico, the CDC also reported Sept. 8.

The figures for states, territories, and D.C. reflect reporting to the U.S. Zika Pregnancy Registry; data for Puerto Rico are reported to the U.S. Zika Active Pregnancy Surveillance System.

Zika-related birth defects recorded by the CDC could include microcephaly, calcium deposits in the brain indicating possible brain damage, excess fluid in the brain cavities and surrounding the brain, absent or poorly formed brain structures, abnormal eye development, or other problems resulting from brain damage that affect nerves, muscles, and bones. The pregnancy losses encompass any miscarriage, stillbirth, and termination with evidence of birth defects.

[email protected]

The first new case of a live-born infant with Zika virus–related birth defects in almost a month was reported during the week ending Sept. 1, bringing the U.S. total to 18 so far, according to the Centers for Disease Control and Prevention.

The infant was born in one of the 50 states or the District of Columbia and is the first case of a Zika-related birth defect reported since the week ending Aug. 4. The CDC is not reporting state- or territorial-level data to protect the privacy of affected women and children. There were no new Zika-related pregnancy losses for the week of Sept. 1, so the total remains at six for the states, D.C., and the territories, the CDC reported Sept. 8.

The number of pregnant women with any laboratory evidence of Zika infection increased by 156 during the week ending Sept. 1: 47 new cases in the states/D.C. and 109 new cases in the territories. The total number of pregnant women with Zika for 2016 is now 1,751, the CDC said.

For 2015-2016, there have been 18,833 cases reported in the entire U.S. population: 2,964 in the states/D.C. (all but 44 were travel associated) and 15,869 in the territories. All but 60 cases in the territories were locally acquired, and 98% have occurred in Puerto Rico, the CDC also reported Sept. 8.

The figures for states, territories, and D.C. reflect reporting to the U.S. Zika Pregnancy Registry; data for Puerto Rico are reported to the U.S. Zika Active Pregnancy Surveillance System.

Zika-related birth defects recorded by the CDC could include microcephaly, calcium deposits in the brain indicating possible brain damage, excess fluid in the brain cavities and surrounding the brain, absent or poorly formed brain structures, abnormal eye development, or other problems resulting from brain damage that affect nerves, muscles, and bones. The pregnancy losses encompass any miscarriage, stillbirth, and termination with evidence of birth defects.

[email protected]

The first new case of a live-born infant with Zika virus–related birth defects in almost a month was reported during the week ending Sept. 1, bringing the U.S. total to 18 so far, according to the Centers for Disease Control and Prevention.

The infant was born in one of the 50 states or the District of Columbia and is the first case of a Zika-related birth defect reported since the week ending Aug. 4. The CDC is not reporting state- or territorial-level data to protect the privacy of affected women and children. There were no new Zika-related pregnancy losses for the week of Sept. 1, so the total remains at six for the states, D.C., and the territories, the CDC reported Sept. 8.

The number of pregnant women with any laboratory evidence of Zika infection increased by 156 during the week ending Sept. 1: 47 new cases in the states/D.C. and 109 new cases in the territories. The total number of pregnant women with Zika for 2016 is now 1,751, the CDC said.

For 2015-2016, there have been 18,833 cases reported in the entire U.S. population: 2,964 in the states/D.C. (all but 44 were travel associated) and 15,869 in the territories. All but 60 cases in the territories were locally acquired, and 98% have occurred in Puerto Rico, the CDC also reported Sept. 8.

The figures for states, territories, and D.C. reflect reporting to the U.S. Zika Pregnancy Registry; data for Puerto Rico are reported to the U.S. Zika Active Pregnancy Surveillance System.

Zika-related birth defects recorded by the CDC could include microcephaly, calcium deposits in the brain indicating possible brain damage, excess fluid in the brain cavities and surrounding the brain, absent or poorly formed brain structures, abnormal eye development, or other problems resulting from brain damage that affect nerves, muscles, and bones. The pregnancy losses encompass any miscarriage, stillbirth, and termination with evidence of birth defects.

[email protected]

Physicians will have options for when they can start meeting the requirements for the Merit-based Incentive Payment System (MIPS) track under regulations that implement the Medicare Access and CHIP Reauthorization Act.

The options are designed to allow physicians a variety of ways to get started with the new Quality Payment Program – the term CMS has given the MACRA-legislated reforms – and provide more limited ways to participate in 2017.

Option 1: Test the quality payment program in 2017 by submitting data without facing any negative payment adjustments. This will give physicians the year to make sure their processes are in place and ready for broader participation in 2018 and beyond.

Option 2: Delay the start of the performance period and participate for just part of 2017. Depending on how long a physician delays reporting quality information back to CMS, they could still qualify for a smaller bonus payment.

Option 3: Participate for the entire calendar year as called for by the law and be eligible for the full participation bonuses.

Option 4: For those who qualify, participate in an Advanced Alternative Payment Model (APM) beginning next year.

The final regulations for implementing MACRA will be released on Nov. 1, CMS Acting Administrator Andy Slavitt wrote in a blog post published Sept. 8.

“However you choose to participate in 2017, we will have resources available to assist you and walk you through what needs to be done,” Mr. Slavitt wrote.

[email protected]

Physicians will have options for when they can start meeting the requirements for the Merit-based Incentive Payment System (MIPS) track under regulations that implement the Medicare Access and CHIP Reauthorization Act.

The options are designed to allow physicians a variety of ways to get started with the new Quality Payment Program – the term CMS has given the MACRA-legislated reforms – and provide more limited ways to participate in 2017.

Option 1: Test the quality payment program in 2017 by submitting data without facing any negative payment adjustments. This will give physicians the year to make sure their processes are in place and ready for broader participation in 2018 and beyond.

Option 2: Delay the start of the performance period and participate for just part of 2017. Depending on how long a physician delays reporting quality information back to CMS, they could still qualify for a smaller bonus payment.

Option 3: Participate for the entire calendar year as called for by the law and be eligible for the full participation bonuses.

Option 4: For those who qualify, participate in an Advanced Alternative Payment Model (APM) beginning next year.

The final regulations for implementing MACRA will be released on Nov. 1, CMS Acting Administrator Andy Slavitt wrote in a blog post published Sept. 8.

“However you choose to participate in 2017, we will have resources available to assist you and walk you through what needs to be done,” Mr. Slavitt wrote.

[email protected]

Physicians will have options for when they can start meeting the requirements for the Merit-based Incentive Payment System (MIPS) track under regulations that implement the Medicare Access and CHIP Reauthorization Act.

The options are designed to allow physicians a variety of ways to get started with the new Quality Payment Program – the term CMS has given the MACRA-legislated reforms – and provide more limited ways to participate in 2017.

Option 1: Test the quality payment program in 2017 by submitting data without facing any negative payment adjustments. This will give physicians the year to make sure their processes are in place and ready for broader participation in 2018 and beyond.

Option 2: Delay the start of the performance period and participate for just part of 2017. Depending on how long a physician delays reporting quality information back to CMS, they could still qualify for a smaller bonus payment.

Option 3: Participate for the entire calendar year as called for by the law and be eligible for the full participation bonuses.

Option 4: For those who qualify, participate in an Advanced Alternative Payment Model (APM) beginning next year.

The final regulations for implementing MACRA will be released on Nov. 1, CMS Acting Administrator Andy Slavitt wrote in a blog post published Sept. 8.

“However you choose to participate in 2017, we will have resources available to assist you and walk you through what needs to be done,” Mr. Slavitt wrote.

[email protected]