Infectious Diseases

To the Editor:

A 50-year old man with Fitzpatrick skin type IV, human immunodeficiency virus (HIV), fatty liver disease, and moderate psoriasis (10% body surface area [BSA] affected) currently treated with clobetasol spray and calcitriol ointment presented with persistent psoriatic lesions on the trunk, arms, legs, and buttocks. His CD4 count was 460 and his HIV RNA count was 48 copies/mL on polymerase chain reaction 2 months prior to the current presentation. He had been undergoing phototherapy 3 times weekly for the last 5 months for treatment of psoriasis.

At the current presentation, he was started on an apremilast starter pack with the dosage titrated from 10 mg to 30 mg over the course of 1 week. He was maintained on a dose of 30 mg twice daily after 1 week and continued clobetasol spray, calcitriol ointment, and phototherapy 3 times weekly with the intent to reduce the frequency after adequate control of psoriasis was achieved. After 3 months of treatment, the affected BSA was 0%. He continued apremilast, and phototherapy was reduced to once weekly. Phototherapy was discontinued after 7 months of concomitant treatment with apremilast after clearance was maintained. It was reinitiated twice weekly after a mild flare (3% BSA affected). After 20 total months of treatment, the patient was no longer able to afford apremilast treatment and presented with a severe psoriasis flare (40% BSA affected). He was switched to acitretin with a plan to apply for apremilast financial assistance programs.

Psoriasis treatment in the HIV population poses a challenge given the immunosuppressed state of these patients, the risk of reactivation of latent infections, and the refractory nature of psoriasis in the setting of HIV. Two of the authors (S.P.R. and J.J.W.) previously reported a case of moderate to severe psoriasis in a patient with HIV and hepatitis C who demonstrated treatment success with apremilast until it was discontinued due to financial implications.¹ Currently, apremilast is not widely used to treat psoriasis in the HIV population. The National Psoriasis Foundation 2010 guidelines recommended UV light therapy for treatment of moderate to severe psoriasis in HIV-positive patients, with oral retinoids as the second-line treatment.² There remains a need for updated guidelines on the use of systemic agents for psoriasis treatment in the HIV population.

Apremilast, a phosphodiesterase 4 inhibitor, is an oral therapy that restores the balance of proinflammatory and anti-inflammatory cytokines by inhibiting inflammatory cytokine (eg, tumor necrosis factor α, IFN-γ, IL-2, IL-12, IL-23) secretion and stimulating anti-inflammatory cytokine (eg, IL-6, IL-10) production. In 2015, the phase 3 ESTEEM 1³ and ESTEEM 2⁴ trials demonstrated the efficacy of apremilast 30 mg twice daily for treatment of psoriasis. In both trials, the psoriasis area and severity index 75 response rate at week 16 was significantly higher with apremilast compared to placebo alone (33.1% and 28.8% vs 5.2% and 5.8%, respectively; P<.001 for both trials). Apremilast also was noted to improve difficult-to-treat nail, scalp, and palmoplantar psoriasis.^3,4

Use of other systemic agents such as tumor necrosis factor α inhibitors and ustekinumab has been reported in HIV-positive patients.^5-7 There is no current data on IL-17 and IL-23 inhibitors. Acitretin generally is recommended as a second-line agent in HIV patients given its lack of immunosuppression²; however, methotrexate and cyclosporine should be avoided given the risk of opportunistic infections.⁸

Apremilast is a promising therapy with a favorable safety profile that should be considered as an adjuvant treatment to first-line agents such as phototherapy in HIV-positive patients. Apremilast has been successfully used in an HIV patient with a concomitant chronic hepatitis C infection.¹ Systemic medications such as apremilast should be managed in coordination with infectious disease specialists with close monitoring of CD4 levels and viral loads as well as prophylactic agents.

To the Editor:

A 50-year old man with Fitzpatrick skin type IV, human immunodeficiency virus (HIV), fatty liver disease, and moderate psoriasis (10% body surface area [BSA] affected) currently treated with clobetasol spray and calcitriol ointment presented with persistent psoriatic lesions on the trunk, arms, legs, and buttocks. His CD4 count was 460 and his HIV RNA count was 48 copies/mL on polymerase chain reaction 2 months prior to the current presentation. He had been undergoing phototherapy 3 times weekly for the last 5 months for treatment of psoriasis.

At the current presentation, he was started on an apremilast starter pack with the dosage titrated from 10 mg to 30 mg over the course of 1 week. He was maintained on a dose of 30 mg twice daily after 1 week and continued clobetasol spray, calcitriol ointment, and phototherapy 3 times weekly with the intent to reduce the frequency after adequate control of psoriasis was achieved. After 3 months of treatment, the affected BSA was 0%. He continued apremilast, and phototherapy was reduced to once weekly. Phototherapy was discontinued after 7 months of concomitant treatment with apremilast after clearance was maintained. It was reinitiated twice weekly after a mild flare (3% BSA affected). After 20 total months of treatment, the patient was no longer able to afford apremilast treatment and presented with a severe psoriasis flare (40% BSA affected). He was switched to acitretin with a plan to apply for apremilast financial assistance programs.

Psoriasis treatment in the HIV population poses a challenge given the immunosuppressed state of these patients, the risk of reactivation of latent infections, and the refractory nature of psoriasis in the setting of HIV. Two of the authors (S.P.R. and J.J.W.) previously reported a case of moderate to severe psoriasis in a patient with HIV and hepatitis C who demonstrated treatment success with apremilast until it was discontinued due to financial implications.¹ Currently, apremilast is not widely used to treat psoriasis in the HIV population. The National Psoriasis Foundation 2010 guidelines recommended UV light therapy for treatment of moderate to severe psoriasis in HIV-positive patients, with oral retinoids as the second-line treatment.² There remains a need for updated guidelines on the use of systemic agents for psoriasis treatment in the HIV population.

Apremilast, a phosphodiesterase 4 inhibitor, is an oral therapy that restores the balance of proinflammatory and anti-inflammatory cytokines by inhibiting inflammatory cytokine (eg, tumor necrosis factor α, IFN-γ, IL-2, IL-12, IL-23) secretion and stimulating anti-inflammatory cytokine (eg, IL-6, IL-10) production. In 2015, the phase 3 ESTEEM 1³ and ESTEEM 2⁴ trials demonstrated the efficacy of apremilast 30 mg twice daily for treatment of psoriasis. In both trials, the psoriasis area and severity index 75 response rate at week 16 was significantly higher with apremilast compared to placebo alone (33.1% and 28.8% vs 5.2% and 5.8%, respectively; P<.001 for both trials). Apremilast also was noted to improve difficult-to-treat nail, scalp, and palmoplantar psoriasis.^3,4

Use of other systemic agents such as tumor necrosis factor α inhibitors and ustekinumab has been reported in HIV-positive patients.^5-7 There is no current data on IL-17 and IL-23 inhibitors. Acitretin generally is recommended as a second-line agent in HIV patients given its lack of immunosuppression²; however, methotrexate and cyclosporine should be avoided given the risk of opportunistic infections.⁸

Apremilast is a promising therapy with a favorable safety profile that should be considered as an adjuvant treatment to first-line agents such as phototherapy in HIV-positive patients. Apremilast has been successfully used in an HIV patient with a concomitant chronic hepatitis C infection.¹ Systemic medications such as apremilast should be managed in coordination with infectious disease specialists with close monitoring of CD4 levels and viral loads as well as prophylactic agents.

To the Editor:

A 50-year old man with Fitzpatrick skin type IV, human immunodeficiency virus (HIV), fatty liver disease, and moderate psoriasis (10% body surface area [BSA] affected) currently treated with clobetasol spray and calcitriol ointment presented with persistent psoriatic lesions on the trunk, arms, legs, and buttocks. His CD4 count was 460 and his HIV RNA count was 48 copies/mL on polymerase chain reaction 2 months prior to the current presentation. He had been undergoing phototherapy 3 times weekly for the last 5 months for treatment of psoriasis.

At the current presentation, he was started on an apremilast starter pack with the dosage titrated from 10 mg to 30 mg over the course of 1 week. He was maintained on a dose of 30 mg twice daily after 1 week and continued clobetasol spray, calcitriol ointment, and phototherapy 3 times weekly with the intent to reduce the frequency after adequate control of psoriasis was achieved. After 3 months of treatment, the affected BSA was 0%. He continued apremilast, and phototherapy was reduced to once weekly. Phototherapy was discontinued after 7 months of concomitant treatment with apremilast after clearance was maintained. It was reinitiated twice weekly after a mild flare (3% BSA affected). After 20 total months of treatment, the patient was no longer able to afford apremilast treatment and presented with a severe psoriasis flare (40% BSA affected). He was switched to acitretin with a plan to apply for apremilast financial assistance programs.

Psoriasis treatment in the HIV population poses a challenge given the immunosuppressed state of these patients, the risk of reactivation of latent infections, and the refractory nature of psoriasis in the setting of HIV. Two of the authors (S.P.R. and J.J.W.) previously reported a case of moderate to severe psoriasis in a patient with HIV and hepatitis C who demonstrated treatment success with apremilast until it was discontinued due to financial implications.¹ Currently, apremilast is not widely used to treat psoriasis in the HIV population. The National Psoriasis Foundation 2010 guidelines recommended UV light therapy for treatment of moderate to severe psoriasis in HIV-positive patients, with oral retinoids as the second-line treatment.² There remains a need for updated guidelines on the use of systemic agents for psoriasis treatment in the HIV population.

Apremilast, a phosphodiesterase 4 inhibitor, is an oral therapy that restores the balance of proinflammatory and anti-inflammatory cytokines by inhibiting inflammatory cytokine (eg, tumor necrosis factor α, IFN-γ, IL-2, IL-12, IL-23) secretion and stimulating anti-inflammatory cytokine (eg, IL-6, IL-10) production. In 2015, the phase 3 ESTEEM 1³ and ESTEEM 2⁴ trials demonstrated the efficacy of apremilast 30 mg twice daily for treatment of psoriasis. In both trials, the psoriasis area and severity index 75 response rate at week 16 was significantly higher with apremilast compared to placebo alone (33.1% and 28.8% vs 5.2% and 5.8%, respectively; P<.001 for both trials). Apremilast also was noted to improve difficult-to-treat nail, scalp, and palmoplantar psoriasis.^3,4

Use of other systemic agents such as tumor necrosis factor α inhibitors and ustekinumab has been reported in HIV-positive patients.^5-7 There is no current data on IL-17 and IL-23 inhibitors. Acitretin generally is recommended as a second-line agent in HIV patients given its lack of immunosuppression²; however, methotrexate and cyclosporine should be avoided given the risk of opportunistic infections.⁸

Apremilast is a promising therapy with a favorable safety profile that should be considered as an adjuvant treatment to first-line agents such as phototherapy in HIV-positive patients. Apremilast has been successfully used in an HIV patient with a concomitant chronic hepatitis C infection.¹ Systemic medications such as apremilast should be managed in coordination with infectious disease specialists with close monitoring of CD4 levels and viral loads as well as prophylactic agents.

Oral rotavirus vaccination had a strong protective effect against laboratory-confirmed rotavirus infection in the first 2 years of the U.K. infant immunization program, investigators are reporting.

CDC/Dr. Erskine Palmer

The estimated effectiveness was 77% for all infants with confirmed infection, and greater than 80% for those under 12 months of age, according to the report. The vaccine did not demonstrate efficacy against all-cause acute gastroenteritis, although this was likely because of high, sustained vaccine coverage coupled with the “substantial impact” of the rotavirus vaccine, wrote investigators led by Sara L. Thomas, MB BS, PhD, of the London School of Hygiene & Tropical Medicine.

Taken together, these findings provide “reassurance” that rotavirus vaccine is effective in a real-world setting and set the stage for future analyses of cost effectiveness, Dr. Thomas and coauthors said in a report on the study appearing in Vaccine: X, the open access mirror journal of Vaccine.

“As data accumulate in the post-vaccination era, more detailed assessment of waning of effectiveness over time can be undertaken, and investigation of rotavirus strain-specific protection,” they wrote.

Oral live-attenuated rotavirus vaccine (Rotarix) was introduced in the U.K. in 2013 as a two-dose schedule at 2 and 3 months of age. Vaccine uptake by the age of 25 weeks was rapid and sustained, exceeding 90%, according to previous reports. Declines in hospital admissions and primary care for all-cause acute gastroenteritis were substantial, associated with an estimated reduction of £12.5 million in health care costs in the first year of the program for children 5 years of age and younger.

To assess rotavirus vaccine effectiveness in the public health setting, Dr. Thomas and colleagues conducted a pair of studies: one designed to evaluate vaccine effectiveness against laboratory-confirmed rotavirus infections using laboratory surveillance data for 1,869 children and 1,032 controls and another to estimate vaccine effectiveness against all-cause acute gastroenteritis using electronic health data on 40,723 children.

In U.K. children with confirmed wild-type rotavirus infection aged 5 years and under, vaccine effectiveness was 69% for one dose and 77% for two doses. Stratified by age, the data showed that vaccine effectiveness was 85% in those younger than 12 months, and 54% for older children.

By contrast, they found no evidence that the rotavirus vaccine protected against all-cause acute gastroenteritis in an analysis that adjusted for age and other factors. Analysis also suggested a lack of effectiveness against hospitalized acute gastroenteritis, according to the study authors.

In prelicensure trials, oral live-attenuated rotavirus vaccine in middle- and high-income settings had efficacy against severe rotavirus-confirmed gastroenteritis of greater than 85% and efficacy against severe all-cause gastroenteritis up to 40%, investigators noted.

The lack of vaccine efficacy on all-cause acute gastroenteritis is likely because of “highly effective implementation” of the vaccine program and rapid attainment of coverage, plus high vaccine effectiveness against rotavirus-specific acute gastroenteritis, the investigators said.

“As a result, almost all AGE in the study population in the post-vaccine era was likely to have been due to nonrotavirus organisms or non-infectious causes,” said Dr. Thomas and coauthors.

This highlights the importance of choosing “specific outcomes” to study when vaccine coverage and effectiveness are both high, they concluded.

Funding for this research came from the National Institute for Health Research Health Protection Research Unit in Immunisation at the London School of Hygiene and Tropical Medicine in partnership with Public Health England. The Immunisation and Countermeasures Division of Public Health England provided vaccine manufacturers with postmarketing surveillance reports, according to the article’s disclosure section.

SOURCE: Walker JL et al. Vaccine: X. 2019 Apr 11. doi: 10.1016/j.jvacx.2019.100005.
 

Oral rotavirus vaccination had a strong protective effect against laboratory-confirmed rotavirus infection in the first 2 years of the U.K. infant immunization program, investigators are reporting.

CDC/Dr. Erskine Palmer

The estimated effectiveness was 77% for all infants with confirmed infection, and greater than 80% for those under 12 months of age, according to the report. The vaccine did not demonstrate efficacy against all-cause acute gastroenteritis, although this was likely because of high, sustained vaccine coverage coupled with the “substantial impact” of the rotavirus vaccine, wrote investigators led by Sara L. Thomas, MB BS, PhD, of the London School of Hygiene & Tropical Medicine.

Taken together, these findings provide “reassurance” that rotavirus vaccine is effective in a real-world setting and set the stage for future analyses of cost effectiveness, Dr. Thomas and coauthors said in a report on the study appearing in Vaccine: X, the open access mirror journal of Vaccine.

“As data accumulate in the post-vaccination era, more detailed assessment of waning of effectiveness over time can be undertaken, and investigation of rotavirus strain-specific protection,” they wrote.

Oral live-attenuated rotavirus vaccine (Rotarix) was introduced in the U.K. in 2013 as a two-dose schedule at 2 and 3 months of age. Vaccine uptake by the age of 25 weeks was rapid and sustained, exceeding 90%, according to previous reports. Declines in hospital admissions and primary care for all-cause acute gastroenteritis were substantial, associated with an estimated reduction of £12.5 million in health care costs in the first year of the program for children 5 years of age and younger.

To assess rotavirus vaccine effectiveness in the public health setting, Dr. Thomas and colleagues conducted a pair of studies: one designed to evaluate vaccine effectiveness against laboratory-confirmed rotavirus infections using laboratory surveillance data for 1,869 children and 1,032 controls and another to estimate vaccine effectiveness against all-cause acute gastroenteritis using electronic health data on 40,723 children.

In U.K. children with confirmed wild-type rotavirus infection aged 5 years and under, vaccine effectiveness was 69% for one dose and 77% for two doses. Stratified by age, the data showed that vaccine effectiveness was 85% in those younger than 12 months, and 54% for older children.

By contrast, they found no evidence that the rotavirus vaccine protected against all-cause acute gastroenteritis in an analysis that adjusted for age and other factors. Analysis also suggested a lack of effectiveness against hospitalized acute gastroenteritis, according to the study authors.

In prelicensure trials, oral live-attenuated rotavirus vaccine in middle- and high-income settings had efficacy against severe rotavirus-confirmed gastroenteritis of greater than 85% and efficacy against severe all-cause gastroenteritis up to 40%, investigators noted.

The lack of vaccine efficacy on all-cause acute gastroenteritis is likely because of “highly effective implementation” of the vaccine program and rapid attainment of coverage, plus high vaccine effectiveness against rotavirus-specific acute gastroenteritis, the investigators said.

“As a result, almost all AGE in the study population in the post-vaccine era was likely to have been due to nonrotavirus organisms or non-infectious causes,” said Dr. Thomas and coauthors.

This highlights the importance of choosing “specific outcomes” to study when vaccine coverage and effectiveness are both high, they concluded.

Funding for this research came from the National Institute for Health Research Health Protection Research Unit in Immunisation at the London School of Hygiene and Tropical Medicine in partnership with Public Health England. The Immunisation and Countermeasures Division of Public Health England provided vaccine manufacturers with postmarketing surveillance reports, according to the article’s disclosure section.

SOURCE: Walker JL et al. Vaccine: X. 2019 Apr 11. doi: 10.1016/j.jvacx.2019.100005.
 

Oral rotavirus vaccination had a strong protective effect against laboratory-confirmed rotavirus infection in the first 2 years of the U.K. infant immunization program, investigators are reporting.

CDC/Dr. Erskine Palmer

The estimated effectiveness was 77% for all infants with confirmed infection, and greater than 80% for those under 12 months of age, according to the report. The vaccine did not demonstrate efficacy against all-cause acute gastroenteritis, although this was likely because of high, sustained vaccine coverage coupled with the “substantial impact” of the rotavirus vaccine, wrote investigators led by Sara L. Thomas, MB BS, PhD, of the London School of Hygiene & Tropical Medicine.

Taken together, these findings provide “reassurance” that rotavirus vaccine is effective in a real-world setting and set the stage for future analyses of cost effectiveness, Dr. Thomas and coauthors said in a report on the study appearing in Vaccine: X, the open access mirror journal of Vaccine.

“As data accumulate in the post-vaccination era, more detailed assessment of waning of effectiveness over time can be undertaken, and investigation of rotavirus strain-specific protection,” they wrote.

Oral live-attenuated rotavirus vaccine (Rotarix) was introduced in the U.K. in 2013 as a two-dose schedule at 2 and 3 months of age. Vaccine uptake by the age of 25 weeks was rapid and sustained, exceeding 90%, according to previous reports. Declines in hospital admissions and primary care for all-cause acute gastroenteritis were substantial, associated with an estimated reduction of £12.5 million in health care costs in the first year of the program for children 5 years of age and younger.

To assess rotavirus vaccine effectiveness in the public health setting, Dr. Thomas and colleagues conducted a pair of studies: one designed to evaluate vaccine effectiveness against laboratory-confirmed rotavirus infections using laboratory surveillance data for 1,869 children and 1,032 controls and another to estimate vaccine effectiveness against all-cause acute gastroenteritis using electronic health data on 40,723 children.

In U.K. children with confirmed wild-type rotavirus infection aged 5 years and under, vaccine effectiveness was 69% for one dose and 77% for two doses. Stratified by age, the data showed that vaccine effectiveness was 85% in those younger than 12 months, and 54% for older children.

By contrast, they found no evidence that the rotavirus vaccine protected against all-cause acute gastroenteritis in an analysis that adjusted for age and other factors. Analysis also suggested a lack of effectiveness against hospitalized acute gastroenteritis, according to the study authors.

In prelicensure trials, oral live-attenuated rotavirus vaccine in middle- and high-income settings had efficacy against severe rotavirus-confirmed gastroenteritis of greater than 85% and efficacy against severe all-cause gastroenteritis up to 40%, investigators noted.

The lack of vaccine efficacy on all-cause acute gastroenteritis is likely because of “highly effective implementation” of the vaccine program and rapid attainment of coverage, plus high vaccine effectiveness against rotavirus-specific acute gastroenteritis, the investigators said.

“As a result, almost all AGE in the study population in the post-vaccine era was likely to have been due to nonrotavirus organisms or non-infectious causes,” said Dr. Thomas and coauthors.

This highlights the importance of choosing “specific outcomes” to study when vaccine coverage and effectiveness are both high, they concluded.

Funding for this research came from the National Institute for Health Research Health Protection Research Unit in Immunisation at the London School of Hygiene and Tropical Medicine in partnership with Public Health England. The Immunisation and Countermeasures Division of Public Health England provided vaccine manufacturers with postmarketing surveillance reports, according to the article’s disclosure section.

SOURCE: Walker JL et al. Vaccine: X. 2019 Apr 11. doi: 10.1016/j.jvacx.2019.100005.
 

The risk of HIV transmission between serodiscordant male gay couples is effectively zero if the viral load is completely suppressed with antiretroviral therapy, according to a new paper published in the Lancet.

NIAID

The prospective observational PARTNER2 study (Lancet 2019 May 2. doi: 10.1016/S0140-6736[19]304018-0) followed 782 serodiscordant gay couples from 14 European countries, where the HIV-positive partner had to be virally suppressed to below 200 copies of HIV-1 RNA per milliliter, and the couple was engaging in condomless sex without using pre- or postexposure prophylaxis.

After a median follow-up of 2 years, there was not a single case of HIV transmission between couples, representing a transmission rate of zero. The study did record 15 new HIV infections during follow-up but these were all phylogenetically linked to sources other than the HIV-positive partner.

The HIV-positive partners had been on antiretroviral therapy for a median of 4.3 years – most on regimens of three or more drugs – with high levels of adherence. During the follow-up period, 37 HIV-positive partners (5%) reported missing their antiretroviral therapy for more than 4 consecutive days.

“Our results give equivalence of evidence for gay men as for heterosexual couples and indicate that the risk of HIV transmission when HIV viral load is suppressed is effectively zero for both anal and vaginal sex,” wrote Dr. Alison J. Rodger of the Institute for Global Health at University College London, and coauthors. “These findings emphasize the importance of regular monitoring to ensure HIV viral load remains suppressed and supporting HIV-positive people with long-term adherence.”

Around one-quarter of the HIV-negative men and 27% of the HIV-positive men reported a sexually-transmitted infection during follow-up; the most common infections were syphilis, gonorrhea, and chlamydia.

The study noted six additional cases of seroconversion of HIV-negative partners. However, these occurred outside the eligible couple-years of the follow-up period. They were ineligible due to no questionnaire about sexual behavior having been completed by either partner in the couple, a lack of condomless sex between the couple, use of postexposure prophylaxis, or a lack of viral load measurement for the HIV-positive partner in the past year.

The authors did note that the study population was predominantly white and with a median age of 38 years, while most HIV transmission occurs in young people aged under 25 years.

“The results from the PARTNER studies support wider dissemination of the message of the U=U [Undetectable equals Untransmittable] campaign that risk of transmission of HIV in the context of virally suppressive ART is zero,” they wrote.

The study was supported by the National Institute for Health Research, the British HIV Association, the Danish National Research Foundation, ViiV Healthcare, Gilead Sciences, Augustinus Fonden, and A P Møller Fonden. Fourteen authors declared grants, personal fees and other support from the pharmaceutical sector.

SOURCE: Rodger A et al. Lancet 2019, May 2. doi: 10.1016/S0140-6736[19]304018-0.

The risk of HIV transmission between serodiscordant male gay couples is effectively zero if the viral load is completely suppressed with antiretroviral therapy, according to a new paper published in the Lancet.

NIAID

The prospective observational PARTNER2 study (Lancet 2019 May 2. doi: 10.1016/S0140-6736[19]304018-0) followed 782 serodiscordant gay couples from 14 European countries, where the HIV-positive partner had to be virally suppressed to below 200 copies of HIV-1 RNA per milliliter, and the couple was engaging in condomless sex without using pre- or postexposure prophylaxis.

After a median follow-up of 2 years, there was not a single case of HIV transmission between couples, representing a transmission rate of zero. The study did record 15 new HIV infections during follow-up but these were all phylogenetically linked to sources other than the HIV-positive partner.

The HIV-positive partners had been on antiretroviral therapy for a median of 4.3 years – most on regimens of three or more drugs – with high levels of adherence. During the follow-up period, 37 HIV-positive partners (5%) reported missing their antiretroviral therapy for more than 4 consecutive days.

“Our results give equivalence of evidence for gay men as for heterosexual couples and indicate that the risk of HIV transmission when HIV viral load is suppressed is effectively zero for both anal and vaginal sex,” wrote Dr. Alison J. Rodger of the Institute for Global Health at University College London, and coauthors. “These findings emphasize the importance of regular monitoring to ensure HIV viral load remains suppressed and supporting HIV-positive people with long-term adherence.”

Around one-quarter of the HIV-negative men and 27% of the HIV-positive men reported a sexually-transmitted infection during follow-up; the most common infections were syphilis, gonorrhea, and chlamydia.

The study noted six additional cases of seroconversion of HIV-negative partners. However, these occurred outside the eligible couple-years of the follow-up period. They were ineligible due to no questionnaire about sexual behavior having been completed by either partner in the couple, a lack of condomless sex between the couple, use of postexposure prophylaxis, or a lack of viral load measurement for the HIV-positive partner in the past year.

The authors did note that the study population was predominantly white and with a median age of 38 years, while most HIV transmission occurs in young people aged under 25 years.

“The results from the PARTNER studies support wider dissemination of the message of the U=U [Undetectable equals Untransmittable] campaign that risk of transmission of HIV in the context of virally suppressive ART is zero,” they wrote.

The study was supported by the National Institute for Health Research, the British HIV Association, the Danish National Research Foundation, ViiV Healthcare, Gilead Sciences, Augustinus Fonden, and A P Møller Fonden. Fourteen authors declared grants, personal fees and other support from the pharmaceutical sector.

SOURCE: Rodger A et al. Lancet 2019, May 2. doi: 10.1016/S0140-6736[19]304018-0.

The risk of HIV transmission between serodiscordant male gay couples is effectively zero if the viral load is completely suppressed with antiretroviral therapy, according to a new paper published in the Lancet.

NIAID

The prospective observational PARTNER2 study (Lancet 2019 May 2. doi: 10.1016/S0140-6736[19]304018-0) followed 782 serodiscordant gay couples from 14 European countries, where the HIV-positive partner had to be virally suppressed to below 200 copies of HIV-1 RNA per milliliter, and the couple was engaging in condomless sex without using pre- or postexposure prophylaxis.

After a median follow-up of 2 years, there was not a single case of HIV transmission between couples, representing a transmission rate of zero. The study did record 15 new HIV infections during follow-up but these were all phylogenetically linked to sources other than the HIV-positive partner.

The HIV-positive partners had been on antiretroviral therapy for a median of 4.3 years – most on regimens of three or more drugs – with high levels of adherence. During the follow-up period, 37 HIV-positive partners (5%) reported missing their antiretroviral therapy for more than 4 consecutive days.

“Our results give equivalence of evidence for gay men as for heterosexual couples and indicate that the risk of HIV transmission when HIV viral load is suppressed is effectively zero for both anal and vaginal sex,” wrote Dr. Alison J. Rodger of the Institute for Global Health at University College London, and coauthors. “These findings emphasize the importance of regular monitoring to ensure HIV viral load remains suppressed and supporting HIV-positive people with long-term adherence.”

Around one-quarter of the HIV-negative men and 27% of the HIV-positive men reported a sexually-transmitted infection during follow-up; the most common infections were syphilis, gonorrhea, and chlamydia.

The study noted six additional cases of seroconversion of HIV-negative partners. However, these occurred outside the eligible couple-years of the follow-up period. They were ineligible due to no questionnaire about sexual behavior having been completed by either partner in the couple, a lack of condomless sex between the couple, use of postexposure prophylaxis, or a lack of viral load measurement for the HIV-positive partner in the past year.

The authors did note that the study population was predominantly white and with a median age of 38 years, while most HIV transmission occurs in young people aged under 25 years.

“The results from the PARTNER studies support wider dissemination of the message of the U=U [Undetectable equals Untransmittable] campaign that risk of transmission of HIV in the context of virally suppressive ART is zero,” they wrote.

The study was supported by the National Institute for Health Research, the British HIV Association, the Danish National Research Foundation, ViiV Healthcare, Gilead Sciences, Augustinus Fonden, and A P Møller Fonden. Fourteen authors declared grants, personal fees and other support from the pharmaceutical sector.

SOURCE: Rodger A et al. Lancet 2019, May 2. doi: 10.1016/S0140-6736[19]304018-0.

Dialysis patients are commonly infected with hepatitis C virus (HCV), and such infections are associated with increased morbidity and mortality. A team of international researchers assessed trends in the prevalence, incidence, and risk factors for HCV infection among more than 82,000 dialysis patients as defined by a documented diagnosis or antibody positivity using the Dialysis Outcomes and Practice Patterns Study.

Akiromaru/Getty Images

They found that overall, among prevalent hemodialysis patients, HCV prevalence was nearly 10% during 2012-2015. The prevalence ranged from a low of 4% in Belgium to as high as 20% in the Middle East, with intermediate prevalence in China, Japan, Italy, Spain, and Russia. However, the prevalence of HCV decreased over time in most countries participating in more than one phase of DOPPS, and prevalence was around 5% among patients who had initiated dialysis within less than 4 months.

The incidence of HCV infection decreased from 2.9 to 1.2 per 100 patient-years in countries participating in the initial phase of DOPPS. Although most units reported no seroconversions, 10% of units experienced three or more cases over a median of 1.1 years.

The researchers also found that high HCV prevalence in the hemodialysis unit was a powerful facility-level risk factor for seroconversion, but the use of isolation stations for HCV-positive patients was not associated with significantly lower seroconversion rates.

“Overall, despite a trend toward lower HCV prevalence among hemodialysis patients, the prevalence of HCV infection remains higher than in the general population,” wrote Michel Jadoul, MD, Cliniques universitaires Saint-Luc, Université Catholique de Louvain, Brussels, and colleagues.

Their report, sponsored by Merck, appeared in Kidney International. A number of the authors reported being speakers or consultants for a variety of pharmaceutical companies; two of the authors are employees of Merck. Support for the ongoing DOPPS Program is provided without restriction on publications.

[email protected]

SOURCE: Jadoul M et al. Kidney Int. 2019;95:939-47.

Dialysis patients are commonly infected with hepatitis C virus (HCV), and such infections are associated with increased morbidity and mortality. A team of international researchers assessed trends in the prevalence, incidence, and risk factors for HCV infection among more than 82,000 dialysis patients as defined by a documented diagnosis or antibody positivity using the Dialysis Outcomes and Practice Patterns Study.

Akiromaru/Getty Images

They found that overall, among prevalent hemodialysis patients, HCV prevalence was nearly 10% during 2012-2015. The prevalence ranged from a low of 4% in Belgium to as high as 20% in the Middle East, with intermediate prevalence in China, Japan, Italy, Spain, and Russia. However, the prevalence of HCV decreased over time in most countries participating in more than one phase of DOPPS, and prevalence was around 5% among patients who had initiated dialysis within less than 4 months.

The incidence of HCV infection decreased from 2.9 to 1.2 per 100 patient-years in countries participating in the initial phase of DOPPS. Although most units reported no seroconversions, 10% of units experienced three or more cases over a median of 1.1 years.

The researchers also found that high HCV prevalence in the hemodialysis unit was a powerful facility-level risk factor for seroconversion, but the use of isolation stations for HCV-positive patients was not associated with significantly lower seroconversion rates.

“Overall, despite a trend toward lower HCV prevalence among hemodialysis patients, the prevalence of HCV infection remains higher than in the general population,” wrote Michel Jadoul, MD, Cliniques universitaires Saint-Luc, Université Catholique de Louvain, Brussels, and colleagues.

Their report, sponsored by Merck, appeared in Kidney International. A number of the authors reported being speakers or consultants for a variety of pharmaceutical companies; two of the authors are employees of Merck. Support for the ongoing DOPPS Program is provided without restriction on publications.

[email protected]

SOURCE: Jadoul M et al. Kidney Int. 2019;95:939-47.

Dialysis patients are commonly infected with hepatitis C virus (HCV), and such infections are associated with increased morbidity and mortality. A team of international researchers assessed trends in the prevalence, incidence, and risk factors for HCV infection among more than 82,000 dialysis patients as defined by a documented diagnosis or antibody positivity using the Dialysis Outcomes and Practice Patterns Study.

Akiromaru/Getty Images

They found that overall, among prevalent hemodialysis patients, HCV prevalence was nearly 10% during 2012-2015. The prevalence ranged from a low of 4% in Belgium to as high as 20% in the Middle East, with intermediate prevalence in China, Japan, Italy, Spain, and Russia. However, the prevalence of HCV decreased over time in most countries participating in more than one phase of DOPPS, and prevalence was around 5% among patients who had initiated dialysis within less than 4 months.

The incidence of HCV infection decreased from 2.9 to 1.2 per 100 patient-years in countries participating in the initial phase of DOPPS. Although most units reported no seroconversions, 10% of units experienced three or more cases over a median of 1.1 years.

The researchers also found that high HCV prevalence in the hemodialysis unit was a powerful facility-level risk factor for seroconversion, but the use of isolation stations for HCV-positive patients was not associated with significantly lower seroconversion rates.

“Overall, despite a trend toward lower HCV prevalence among hemodialysis patients, the prevalence of HCV infection remains higher than in the general population,” wrote Michel Jadoul, MD, Cliniques universitaires Saint-Luc, Université Catholique de Louvain, Brussels, and colleagues.

Their report, sponsored by Merck, appeared in Kidney International. A number of the authors reported being speakers or consultants for a variety of pharmaceutical companies; two of the authors are employees of Merck. Support for the ongoing DOPPS Program is provided without restriction on publications.

[email protected]

SOURCE: Jadoul M et al. Kidney Int. 2019;95:939-47.

While reviewing some epidemiology data for a lecture recently, I couldn’t believe my eyes: The numbers indicated an increase in sexually transmitted infections (STIs) among older Americans. Filled with doubt about the accuracy, I decided to research further. My first stop was a PA colleague who works with a mobile urgent care company that specializes in retirement communities—and she confirmed that she has witnessed this “trend”!

The fundamental public health concern for older Americans is, of course, long-term illness, disability, and dependency on others. However, experts on aging agree that since the last century, disability rates among those older than 65 have declined, as have the number of seniors living in nursing homes. Suffice it to say, the good news is that Americans are living longer—the bad news, they are doing so with an increased risk for cardiovascular disease and malignant neoplasms. The other downside is that seniors have increased risk for infectious diseases.¹

Healthy People 2020 continues to recognize HIV and other STIs as problems in the United States and to promote efforts to reduce them. Unfortunately, prevention strategies for older adults in primary care settings are often not aimed at these diseases. More broadly, sexual behaviors tend to be discussed less with this population.²

The disturbing climb in STIs among older Americans is part of a more momentous national trend that the CDC says must be tackled. Overall rates of STIs in 2016 were the highest ever recorded in a single year.³ And although STI rates are highest among people ages 15 to 24, the upsurge among older Americans is larger than it is for the rest of the US population. According to the CDC, in 2016, there were 82,938 cases of gonorrhea, syphilis, and chlamydia reported among Americans ages 45 and older—about a 20% percent increase from 2015 and continuing a trend of annual increases since at least 2012.³ The infographic shows the rates for individual STIs.

The CDC notes that STIs put people “at risk for severe, lifelong health outcomes like chronic pain, severe reproductive health complications, and HIV" particularly if left untreated.⁴ Jonathan Mermin, MD, Director of the CDC National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention has described STIs as “a persistent enemy, growing in number and outpacing our ability to respond.”⁵

Over the next 3 weeks, we will explore this public health issue—starting next week with the big question: Why is this trend occurring? In the meantime, feel free to share your thoughts with me at [email protected]. See you next Thursday!

While reviewing some epidemiology data for a lecture recently, I couldn’t believe my eyes: The numbers indicated an increase in sexually transmitted infections (STIs) among older Americans. Filled with doubt about the accuracy, I decided to research further. My first stop was a PA colleague who works with a mobile urgent care company that specializes in retirement communities—and she confirmed that she has witnessed this “trend”!

The fundamental public health concern for older Americans is, of course, long-term illness, disability, and dependency on others. However, experts on aging agree that since the last century, disability rates among those older than 65 have declined, as have the number of seniors living in nursing homes. Suffice it to say, the good news is that Americans are living longer—the bad news, they are doing so with an increased risk for cardiovascular disease and malignant neoplasms. The other downside is that seniors have increased risk for infectious diseases.¹

Healthy People 2020 continues to recognize HIV and other STIs as problems in the United States and to promote efforts to reduce them. Unfortunately, prevention strategies for older adults in primary care settings are often not aimed at these diseases. More broadly, sexual behaviors tend to be discussed less with this population.²

The disturbing climb in STIs among older Americans is part of a more momentous national trend that the CDC says must be tackled. Overall rates of STIs in 2016 were the highest ever recorded in a single year.³ And although STI rates are highest among people ages 15 to 24, the upsurge among older Americans is larger than it is for the rest of the US population. According to the CDC, in 2016, there were 82,938 cases of gonorrhea, syphilis, and chlamydia reported among Americans ages 45 and older—about a 20% percent increase from 2015 and continuing a trend of annual increases since at least 2012.³ The infographic shows the rates for individual STIs.

The CDC notes that STIs put people “at risk for severe, lifelong health outcomes like chronic pain, severe reproductive health complications, and HIV" particularly if left untreated.⁴ Jonathan Mermin, MD, Director of the CDC National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention has described STIs as “a persistent enemy, growing in number and outpacing our ability to respond.”⁵

Over the next 3 weeks, we will explore this public health issue—starting next week with the big question: Why is this trend occurring? In the meantime, feel free to share your thoughts with me at [email protected]. See you next Thursday!

While reviewing some epidemiology data for a lecture recently, I couldn’t believe my eyes: The numbers indicated an increase in sexually transmitted infections (STIs) among older Americans. Filled with doubt about the accuracy, I decided to research further. My first stop was a PA colleague who works with a mobile urgent care company that specializes in retirement communities—and she confirmed that she has witnessed this “trend”!

The fundamental public health concern for older Americans is, of course, long-term illness, disability, and dependency on others. However, experts on aging agree that since the last century, disability rates among those older than 65 have declined, as have the number of seniors living in nursing homes. Suffice it to say, the good news is that Americans are living longer—the bad news, they are doing so with an increased risk for cardiovascular disease and malignant neoplasms. The other downside is that seniors have increased risk for infectious diseases.¹

Healthy People 2020 continues to recognize HIV and other STIs as problems in the United States and to promote efforts to reduce them. Unfortunately, prevention strategies for older adults in primary care settings are often not aimed at these diseases. More broadly, sexual behaviors tend to be discussed less with this population.²

The disturbing climb in STIs among older Americans is part of a more momentous national trend that the CDC says must be tackled. Overall rates of STIs in 2016 were the highest ever recorded in a single year.³ And although STI rates are highest among people ages 15 to 24, the upsurge among older Americans is larger than it is for the rest of the US population. According to the CDC, in 2016, there were 82,938 cases of gonorrhea, syphilis, and chlamydia reported among Americans ages 45 and older—about a 20% percent increase from 2015 and continuing a trend of annual increases since at least 2012.³ The infographic shows the rates for individual STIs.

The CDC notes that STIs put people “at risk for severe, lifelong health outcomes like chronic pain, severe reproductive health complications, and HIV" particularly if left untreated.⁴ Jonathan Mermin, MD, Director of the CDC National Center for HIV/AIDS, Viral Hepatitis, STD, and TB Prevention has described STIs as “a persistent enemy, growing in number and outpacing our ability to respond.”⁵

Over the next 3 weeks, we will explore this public health issue—starting next week with the big question: Why is this trend occurring? In the meantime, feel free to share your thoughts with me at [email protected]. See you next Thursday!

Since the measles outbreak in the Pacific Northwest (where I did my training and remain in touch with colleagues and patients), parents with infants ages 6 to 11 months are requesting vaccinations before 12 months—the standard age to start immunizations.¹ But physicians decline to provide inoculation, citing institutional policy on the risks of early vaccination. What are these risks, and how should we respond when parents ask about early vaccination?

The safety and efficacy of early vaccination are well documented. Early vaccination is a technique employed to curb outbreaks both in the United States and worldwide. Guidelines from the Centers for Disease Control and Prevention (CDC) recommend vaccinating infants at 6 months of age if they will be traveling,² and the World Health Organization (WHO) recommends vaccinations during a measles outbreak as part of intensified service delivery or in settings, such as daycare facilities, in which there is an increased risk for disease exposure during an outbreak.³ Any dose given before 12 months is considered supplemental, and the child must still complete the regular 2-dose vaccine schedule. Studies on the adverse effect profiles of vaccines show that the younger the infant, the fewer adverse events occur—because adverse events reflect the increasingly robust immune response that comes with age.⁴

Many physicians are concerned about adequate immune response. In vaccine research, this is gauged by the proportion of patients with seroconversion after vaccination. This is also reflected in vaccine efficacy (VE), which gradually increases with age and maturity of the immune system. For example, measles VE is 60% to 70% in 6-to-8-month cohorts⁵ and 70% to 80% in 9-to-11-month cohorts.⁶ VE at 12 months is in the 90% range, and completion of the 2-dose series yields a VE of ≥ 95%.⁷ Thus, while the vaccine is more effective at later ages, it still provides protection to younger cohorts.

Early vaccination has few risks and significant benefit. Therefore, relaxing the lower boundary for the measles vaccine is appropriate.

“Blunting” (ie, a reduced immune response to the second dose of vaccine³) is another concern with early measles vaccination, but a WHO meta-analysis proved this concern to be unfounded.^1,3 Twelve papers examining seropositivity in children who received a second measles vaccine after early primary vaccination found a pooled proportion of seropositivity of 97%.^1,8,9 Furthermore, evidence shows that children have sustained measles-specific T-cell responses after early primary measles immunization.¹⁰

Early vaccination has few risks and significant benefit. Therefore, in light of the recent measles outbreak, relaxing the lower boundary for the measles vaccine is appropriate. In addition to physically protecting the patient and general population, honoring parents’ requests for vaccination respects their autonomy and fosters trust. Synthesis of good science with a trusting doctor–patient relationship is key to ending the measles outbreak.

Rachel Roth, MD
Tel Aviv, Israel

Since the measles outbreak in the Pacific Northwest (where I did my training and remain in touch with colleagues and patients), parents with infants ages 6 to 11 months are requesting vaccinations before 12 months—the standard age to start immunizations.¹ But physicians decline to provide inoculation, citing institutional policy on the risks of early vaccination. What are these risks, and how should we respond when parents ask about early vaccination?

The safety and efficacy of early vaccination are well documented. Early vaccination is a technique employed to curb outbreaks both in the United States and worldwide. Guidelines from the Centers for Disease Control and Prevention (CDC) recommend vaccinating infants at 6 months of age if they will be traveling,² and the World Health Organization (WHO) recommends vaccinations during a measles outbreak as part of intensified service delivery or in settings, such as daycare facilities, in which there is an increased risk for disease exposure during an outbreak.³ Any dose given before 12 months is considered supplemental, and the child must still complete the regular 2-dose vaccine schedule. Studies on the adverse effect profiles of vaccines show that the younger the infant, the fewer adverse events occur—because adverse events reflect the increasingly robust immune response that comes with age.⁴

Many physicians are concerned about adequate immune response. In vaccine research, this is gauged by the proportion of patients with seroconversion after vaccination. This is also reflected in vaccine efficacy (VE), which gradually increases with age and maturity of the immune system. For example, measles VE is 60% to 70% in 6-to-8-month cohorts⁵ and 70% to 80% in 9-to-11-month cohorts.⁶ VE at 12 months is in the 90% range, and completion of the 2-dose series yields a VE of ≥ 95%.⁷ Thus, while the vaccine is more effective at later ages, it still provides protection to younger cohorts.

Early vaccination has few risks and significant benefit. Therefore, relaxing the lower boundary for the measles vaccine is appropriate.

“Blunting” (ie, a reduced immune response to the second dose of vaccine³) is another concern with early measles vaccination, but a WHO meta-analysis proved this concern to be unfounded.^1,3 Twelve papers examining seropositivity in children who received a second measles vaccine after early primary vaccination found a pooled proportion of seropositivity of 97%.^1,8,9 Furthermore, evidence shows that children have sustained measles-specific T-cell responses after early primary measles immunization.¹⁰

Early vaccination has few risks and significant benefit. Therefore, in light of the recent measles outbreak, relaxing the lower boundary for the measles vaccine is appropriate. In addition to physically protecting the patient and general population, honoring parents’ requests for vaccination respects their autonomy and fosters trust. Synthesis of good science with a trusting doctor–patient relationship is key to ending the measles outbreak.

Rachel Roth, MD
Tel Aviv, Israel

Since the measles outbreak in the Pacific Northwest (where I did my training and remain in touch with colleagues and patients), parents with infants ages 6 to 11 months are requesting vaccinations before 12 months—the standard age to start immunizations.¹ But physicians decline to provide inoculation, citing institutional policy on the risks of early vaccination. What are these risks, and how should we respond when parents ask about early vaccination?

The safety and efficacy of early vaccination are well documented. Early vaccination is a technique employed to curb outbreaks both in the United States and worldwide. Guidelines from the Centers for Disease Control and Prevention (CDC) recommend vaccinating infants at 6 months of age if they will be traveling,² and the World Health Organization (WHO) recommends vaccinations during a measles outbreak as part of intensified service delivery or in settings, such as daycare facilities, in which there is an increased risk for disease exposure during an outbreak.³ Any dose given before 12 months is considered supplemental, and the child must still complete the regular 2-dose vaccine schedule. Studies on the adverse effect profiles of vaccines show that the younger the infant, the fewer adverse events occur—because adverse events reflect the increasingly robust immune response that comes with age.⁴

Many physicians are concerned about adequate immune response. In vaccine research, this is gauged by the proportion of patients with seroconversion after vaccination. This is also reflected in vaccine efficacy (VE), which gradually increases with age and maturity of the immune system. For example, measles VE is 60% to 70% in 6-to-8-month cohorts⁵ and 70% to 80% in 9-to-11-month cohorts.⁶ VE at 12 months is in the 90% range, and completion of the 2-dose series yields a VE of ≥ 95%.⁷ Thus, while the vaccine is more effective at later ages, it still provides protection to younger cohorts.

Early vaccination has few risks and significant benefit. Therefore, relaxing the lower boundary for the measles vaccine is appropriate.

“Blunting” (ie, a reduced immune response to the second dose of vaccine³) is another concern with early measles vaccination, but a WHO meta-analysis proved this concern to be unfounded.^1,3 Twelve papers examining seropositivity in children who received a second measles vaccine after early primary vaccination found a pooled proportion of seropositivity of 97%.^1,8,9 Furthermore, evidence shows that children have sustained measles-specific T-cell responses after early primary measles immunization.¹⁰

Early vaccination has few risks and significant benefit. Therefore, in light of the recent measles outbreak, relaxing the lower boundary for the measles vaccine is appropriate. In addition to physically protecting the patient and general population, honoring parents’ requests for vaccination respects their autonomy and fosters trust. Synthesis of good science with a trusting doctor–patient relationship is key to ending the measles outbreak.

Rachel Roth, MD
Tel Aviv, Israel

ILLUSTRATIVE CASE

Ms. M is a 55-year-old woman who is generally healthy, but who was diagnosed recently with severe vitamin D deficiency (serum 25-hydroxyvitamin D level of 8 ng/mL). She is being seen for her second episode of acute viral bronchitis in the past 6 months. She has no significant smoking or exposure history, no history of asthma, and takes no respiratory medications. Standard treatment for her level of vitamin D deficiency is 50,000 IU/week in bolus dosing, but is that your best option in this case?

Acute respiratory tract infections (ARTIs) include nonspecific upper respiratory illnesses, otitis media, sinusitis (~70% viral), pharyngitis, acute bronchitis (also ~70% viral), influenza, respiratory syncytial virus, and pneumonia.^1,2 In the United States, ARTIs strain the health care system and are the most common cause of ambulatory care visits, accounting for almost 120 million, or about 10% of all visits, per year.³ In addition, ARTIs account for almost 50% of antibiotic prescriptions for adults and almost 75% of antibiotic prescriptions for children—many of which are unnecessary.^2,4

While patient and parent education, antibiotic stewardship programs, and demand management may reduce inappropriate antibiotic use and the overall burden of ARTIs on the health care system, prevention of infections is a powerful tool within the overall approach to managing ARTIs.

STUDY SUMMARY

Vitamin D protects against ARTIs, but only in smaller doses

This 2017 systematic review and meta-analysis of 25 trials (N=10,933) evaluated vitamin D supplementation for the prevention of ARTIs in the primary care setting. Individual participant data were reevaluated to reduce risk of bias. The Cochrane risk of bias tool was used to address threats to validity.

The review and meta-analysis included institutional review board–approved, randomized, double-blind, placebo-controlled trials of vitamin D₃ or vitamin D₂ supplementation of any duration and in any language. The incidence of ARTI was a prespecified efficacy outcome. Duration of the included randomized controlled trials (RCTs) ranged from 7 weeks to 1.5 years.

Outcomes. The primary outcome was an incidence of at least 1 ARTI. Secondary outcomes included incidence of upper and lower ARTIs; incidence of adverse reactions to vitamin D; incidence of emergency department visits or hospital admission or both for ARTI; use of antimicrobials for ARTI; absence from work or school due to ARTI, and mortality (ARTI-related and all-cause).

Findings. Daily or weekly vitamin D supplementation (in doses ranging from < 20 to ≥ 50 µg/d) reduced the risk for ARTI (adjusted odds ratio [AOR] = 0.88; 95% confidence interval [CI], 0.81-0.96; number needed to treat [NNT] = 33). In subgroup analysis, daily or weekly vitamin D was protective (AOR = 0.81; 95% CI, 0.72-0.91), but bolus dosing (≥ 30,000 IU) was not (AOR = 0.97; 95% CI, 0.86-1.10).

Continue to: In 2-step analysis...

This study found that low-dose daily or weekly vitamin D supplementation was protective against acute respiratory tract infections, but bolus dosing was not.

In 2-step analysis, patients benefited who: had baseline circulating 25-hydroxyvitamin D concentrations < 10 ng/mL (AOR = 0.30; 95% CI, 0.17-0.53; NNT = 4); had baseline circulating 25-hydroxyvitamin D levels of 10 to 28 ng/mL (AOR = 0.75; 95% CI, 0.60-0.95; NNT = 15); were ages 1.1 to 15.9 years (AOR = 0.59; 95% CI, 0.45-0.79); were ages 16 to 65 years (AOR = 0.79; 95% CI, 0.63-0.99); or had a body mass index < 25 (AOR = 0.82; 95% CI, 0.71-0.95).

Higher D levels are a different story. Vitamin D supplementation in people with circulating levels of 25-hydroxyvitamin D ≥ 30 ng/mL did not appear to provide benefit (AOR = 0.96; 95% CI, 0.78-1.18). Supplementation in this population did not influence any of the secondary outcomes, including risk for all-cause serious adverse events (AOR = 0.98; 95% CI, 0.80-1.20).

WHAT’S NEW

A more accurate snapshot

Previous studies of vitamin D and respiratory tract infections were mostly observational in nature. Those that were RCTs used variable doses of vitamin D, had variable baseline 25-hydroxyvitamin D levels, and employed various methods to monitor ARTI symptoms/incidence.^5-8 This is the first systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials with supplementation using vitamin D₃ or vitamin D₂ that used individual participant-level data, which gives a more accurate estimate of outcomes when compared with traditional meta-analyses.

CAVEATS

Only the most deficient benefit?

Vitamin D supplementation was safe and protected against ARTIs overall, but the greatest effect of vitamin D supplementation on the prevention of ARTIs was noted in those who were most severely vitamin D deficient (those with circulating 25-hydroxyvitamin levels < 10 ng/mL, NNT = 4; 10-28 ng/mL, NNT = 15). There was no demonstrable effect once circulating 25-hydroxyvitamin D levels reached 30 ng/mL.

CHALLENGES TO IMPLEMENTATION

Breaking tradition

The study found that both daily and weekly doses of vitamin D were effective in reducing the incidence of ARTIs, but the doses used were much lower than the commonly used 10,000 to 50,000 IU bolus doses, which were ineffective in reducing ARTIs in the current meta-analysis. Since bolus dosing is an ingrained practice for many providers, changing this may prove challenging.

Continue to: In addition...

In addition, the authors of the study suggest that one of the ways to provide this level of vitamin D is through food fortification, but food fortification is often complicated by emotional and/or political issues that could thwart implementation.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

Ms. M is a 55-year-old woman who is generally healthy, but who was diagnosed recently with severe vitamin D deficiency (serum 25-hydroxyvitamin D level of 8 ng/mL). She is being seen for her second episode of acute viral bronchitis in the past 6 months. She has no significant smoking or exposure history, no history of asthma, and takes no respiratory medications. Standard treatment for her level of vitamin D deficiency is 50,000 IU/week in bolus dosing, but is that your best option in this case?

Acute respiratory tract infections (ARTIs) include nonspecific upper respiratory illnesses, otitis media, sinusitis (~70% viral), pharyngitis, acute bronchitis (also ~70% viral), influenza, respiratory syncytial virus, and pneumonia.^1,2 In the United States, ARTIs strain the health care system and are the most common cause of ambulatory care visits, accounting for almost 120 million, or about 10% of all visits, per year.³ In addition, ARTIs account for almost 50% of antibiotic prescriptions for adults and almost 75% of antibiotic prescriptions for children—many of which are unnecessary.^2,4

While patient and parent education, antibiotic stewardship programs, and demand management may reduce inappropriate antibiotic use and the overall burden of ARTIs on the health care system, prevention of infections is a powerful tool within the overall approach to managing ARTIs.

STUDY SUMMARY

Vitamin D protects against ARTIs, but only in smaller doses

This 2017 systematic review and meta-analysis of 25 trials (N=10,933) evaluated vitamin D supplementation for the prevention of ARTIs in the primary care setting. Individual participant data were reevaluated to reduce risk of bias. The Cochrane risk of bias tool was used to address threats to validity.

The review and meta-analysis included institutional review board–approved, randomized, double-blind, placebo-controlled trials of vitamin D₃ or vitamin D₂ supplementation of any duration and in any language. The incidence of ARTI was a prespecified efficacy outcome. Duration of the included randomized controlled trials (RCTs) ranged from 7 weeks to 1.5 years.

Outcomes. The primary outcome was an incidence of at least 1 ARTI. Secondary outcomes included incidence of upper and lower ARTIs; incidence of adverse reactions to vitamin D; incidence of emergency department visits or hospital admission or both for ARTI; use of antimicrobials for ARTI; absence from work or school due to ARTI, and mortality (ARTI-related and all-cause).

Findings. Daily or weekly vitamin D supplementation (in doses ranging from < 20 to ≥ 50 µg/d) reduced the risk for ARTI (adjusted odds ratio [AOR] = 0.88; 95% confidence interval [CI], 0.81-0.96; number needed to treat [NNT] = 33). In subgroup analysis, daily or weekly vitamin D was protective (AOR = 0.81; 95% CI, 0.72-0.91), but bolus dosing (≥ 30,000 IU) was not (AOR = 0.97; 95% CI, 0.86-1.10).

Continue to: In 2-step analysis...

This study found that low-dose daily or weekly vitamin D supplementation was protective against acute respiratory tract infections, but bolus dosing was not.

In 2-step analysis, patients benefited who: had baseline circulating 25-hydroxyvitamin D concentrations < 10 ng/mL (AOR = 0.30; 95% CI, 0.17-0.53; NNT = 4); had baseline circulating 25-hydroxyvitamin D levels of 10 to 28 ng/mL (AOR = 0.75; 95% CI, 0.60-0.95; NNT = 15); were ages 1.1 to 15.9 years (AOR = 0.59; 95% CI, 0.45-0.79); were ages 16 to 65 years (AOR = 0.79; 95% CI, 0.63-0.99); or had a body mass index < 25 (AOR = 0.82; 95% CI, 0.71-0.95).

Higher D levels are a different story. Vitamin D supplementation in people with circulating levels of 25-hydroxyvitamin D ≥ 30 ng/mL did not appear to provide benefit (AOR = 0.96; 95% CI, 0.78-1.18). Supplementation in this population did not influence any of the secondary outcomes, including risk for all-cause serious adverse events (AOR = 0.98; 95% CI, 0.80-1.20).

WHAT’S NEW

A more accurate snapshot

Previous studies of vitamin D and respiratory tract infections were mostly observational in nature. Those that were RCTs used variable doses of vitamin D, had variable baseline 25-hydroxyvitamin D levels, and employed various methods to monitor ARTI symptoms/incidence.^5-8 This is the first systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials with supplementation using vitamin D₃ or vitamin D₂ that used individual participant-level data, which gives a more accurate estimate of outcomes when compared with traditional meta-analyses.

CAVEATS

Only the most deficient benefit?

Vitamin D supplementation was safe and protected against ARTIs overall, but the greatest effect of vitamin D supplementation on the prevention of ARTIs was noted in those who were most severely vitamin D deficient (those with circulating 25-hydroxyvitamin levels < 10 ng/mL, NNT = 4; 10-28 ng/mL, NNT = 15). There was no demonstrable effect once circulating 25-hydroxyvitamin D levels reached 30 ng/mL.

CHALLENGES TO IMPLEMENTATION

Breaking tradition

The study found that both daily and weekly doses of vitamin D were effective in reducing the incidence of ARTIs, but the doses used were much lower than the commonly used 10,000 to 50,000 IU bolus doses, which were ineffective in reducing ARTIs in the current meta-analysis. Since bolus dosing is an ingrained practice for many providers, changing this may prove challenging.

Continue to: In addition...

In addition, the authors of the study suggest that one of the ways to provide this level of vitamin D is through food fortification, but food fortification is often complicated by emotional and/or political issues that could thwart implementation.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

ILLUSTRATIVE CASE

Ms. M is a 55-year-old woman who is generally healthy, but who was diagnosed recently with severe vitamin D deficiency (serum 25-hydroxyvitamin D level of 8 ng/mL). She is being seen for her second episode of acute viral bronchitis in the past 6 months. She has no significant smoking or exposure history, no history of asthma, and takes no respiratory medications. Standard treatment for her level of vitamin D deficiency is 50,000 IU/week in bolus dosing, but is that your best option in this case?

Acute respiratory tract infections (ARTIs) include nonspecific upper respiratory illnesses, otitis media, sinusitis (~70% viral), pharyngitis, acute bronchitis (also ~70% viral), influenza, respiratory syncytial virus, and pneumonia.^1,2 In the United States, ARTIs strain the health care system and are the most common cause of ambulatory care visits, accounting for almost 120 million, or about 10% of all visits, per year.³ In addition, ARTIs account for almost 50% of antibiotic prescriptions for adults and almost 75% of antibiotic prescriptions for children—many of which are unnecessary.^2,4

While patient and parent education, antibiotic stewardship programs, and demand management may reduce inappropriate antibiotic use and the overall burden of ARTIs on the health care system, prevention of infections is a powerful tool within the overall approach to managing ARTIs.

STUDY SUMMARY

Vitamin D protects against ARTIs, but only in smaller doses

This 2017 systematic review and meta-analysis of 25 trials (N=10,933) evaluated vitamin D supplementation for the prevention of ARTIs in the primary care setting. Individual participant data were reevaluated to reduce risk of bias. The Cochrane risk of bias tool was used to address threats to validity.

The review and meta-analysis included institutional review board–approved, randomized, double-blind, placebo-controlled trials of vitamin D₃ or vitamin D₂ supplementation of any duration and in any language. The incidence of ARTI was a prespecified efficacy outcome. Duration of the included randomized controlled trials (RCTs) ranged from 7 weeks to 1.5 years.

Outcomes. The primary outcome was an incidence of at least 1 ARTI. Secondary outcomes included incidence of upper and lower ARTIs; incidence of adverse reactions to vitamin D; incidence of emergency department visits or hospital admission or both for ARTI; use of antimicrobials for ARTI; absence from work or school due to ARTI, and mortality (ARTI-related and all-cause).

Findings. Daily or weekly vitamin D supplementation (in doses ranging from < 20 to ≥ 50 µg/d) reduced the risk for ARTI (adjusted odds ratio [AOR] = 0.88; 95% confidence interval [CI], 0.81-0.96; number needed to treat [NNT] = 33). In subgroup analysis, daily or weekly vitamin D was protective (AOR = 0.81; 95% CI, 0.72-0.91), but bolus dosing (≥ 30,000 IU) was not (AOR = 0.97; 95% CI, 0.86-1.10).

Continue to: In 2-step analysis...

This study found that low-dose daily or weekly vitamin D supplementation was protective against acute respiratory tract infections, but bolus dosing was not.

In 2-step analysis, patients benefited who: had baseline circulating 25-hydroxyvitamin D concentrations < 10 ng/mL (AOR = 0.30; 95% CI, 0.17-0.53; NNT = 4); had baseline circulating 25-hydroxyvitamin D levels of 10 to 28 ng/mL (AOR = 0.75; 95% CI, 0.60-0.95; NNT = 15); were ages 1.1 to 15.9 years (AOR = 0.59; 95% CI, 0.45-0.79); were ages 16 to 65 years (AOR = 0.79; 95% CI, 0.63-0.99); or had a body mass index < 25 (AOR = 0.82; 95% CI, 0.71-0.95).

Higher D levels are a different story. Vitamin D supplementation in people with circulating levels of 25-hydroxyvitamin D ≥ 30 ng/mL did not appear to provide benefit (AOR = 0.96; 95% CI, 0.78-1.18). Supplementation in this population did not influence any of the secondary outcomes, including risk for all-cause serious adverse events (AOR = 0.98; 95% CI, 0.80-1.20).

WHAT’S NEW

A more accurate snapshot

Previous studies of vitamin D and respiratory tract infections were mostly observational in nature. Those that were RCTs used variable doses of vitamin D, had variable baseline 25-hydroxyvitamin D levels, and employed various methods to monitor ARTI symptoms/incidence.^5-8 This is the first systematic review and meta-analysis of randomized, double-blind, placebo-controlled trials with supplementation using vitamin D₃ or vitamin D₂ that used individual participant-level data, which gives a more accurate estimate of outcomes when compared with traditional meta-analyses.

CAVEATS

Only the most deficient benefit?

Vitamin D supplementation was safe and protected against ARTIs overall, but the greatest effect of vitamin D supplementation on the prevention of ARTIs was noted in those who were most severely vitamin D deficient (those with circulating 25-hydroxyvitamin levels < 10 ng/mL, NNT = 4; 10-28 ng/mL, NNT = 15). There was no demonstrable effect once circulating 25-hydroxyvitamin D levels reached 30 ng/mL.

CHALLENGES TO IMPLEMENTATION

Breaking tradition

The study found that both daily and weekly doses of vitamin D were effective in reducing the incidence of ARTIs, but the doses used were much lower than the commonly used 10,000 to 50,000 IU bolus doses, which were ineffective in reducing ARTIs in the current meta-analysis. Since bolus dosing is an ingrained practice for many providers, changing this may prove challenging.

Continue to: In addition...

In addition, the authors of the study suggest that one of the ways to provide this level of vitamin D is through food fortification, but food fortification is often complicated by emotional and/or political issues that could thwart implementation.

ACKNOWLEDGEMENT

The PURLs Surveillance System was supported in part by Grant Number UL1RR024999 from the National Center For Research Resources, a Clinical Translational Science Award to the University of Chicago. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Center For Research Resources or the National Institutes of Health.

The mean number of office visits for otitis media in children younger than 5 years dropped significantly after the introduction of the 13-valent pneumococcal conjugate vaccine, according to findings published in the International Journal of Pediatric Otorhinolaryngology.

KatarzynaBialasiewicz/Thinkstock

Previous studies have shown that more than half of children with otitis media (OM) have serotypes included in the PCV7 vaccine (4, 6B, 9V, 14, 18C, 19F, and 23F), wrote Xiaofeng Zhou, MD, of Pfizer, New York, and colleagues.

To assess the impact of PCV13, with the additional serotypes 1, 3, 5, 6A, 7F, and 19A, the researchers analyzed data from the U.S. National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey for three time periods: pre-PCV7 (1997-1999), after the introduction of PCV7 (2001-2009), and after the introduction of PCV13 (2011-2013).

Between the pre-PCV7 and PCV13 time periods, the researchers found significant reductions in the mean rates of OM visits of 48% and 41% among children younger than 2 years and younger than 5 years, respectively; reductions were 24% and 22%, respectively, when comparing PCV13 and PCV7. Ambulatory care visits for skin rash and trauma were not significantly different among the study periods.

Comparing the PCV7 and PCV13 time periods, the mean number of OM visits per 100 children declined from 84 to 64 per 100 children younger than 2 years, 41 to 34 per 100 children between ages 2 and 5 years, and from 59 to 46 per 100 children younger than 5 years.

The study findings were limited by several factors including the use of an ecologic study design, which was chosen to help reduce selection bias, but that did not show evidence of the field effectiveness of the PCV13 vaccine. Another limitation was the potential misclassification of patients with OM given clinician variability in diagnostic criteria, the researchers noted.

“Our results in this study, while not providing direct evidence of causality, nonetheless suggest a significant and positive impact of the PCV13 vaccination program on otitis media for children less than 5 years of age in the U.S., with further reductions in OM visits observed in PCV13 period following a decade of PCV7 use,” Dr. Zhou and associates said.

The investigators are employed by Pfizer, which funded the study.

SOURCE: Zhou X et al. Int J Pediatr Otorhinolaryngol. 2019 Apr. 119:96-102.

The mean number of office visits for otitis media in children younger than 5 years dropped significantly after the introduction of the 13-valent pneumococcal conjugate vaccine, according to findings published in the International Journal of Pediatric Otorhinolaryngology.

KatarzynaBialasiewicz/Thinkstock

Previous studies have shown that more than half of children with otitis media (OM) have serotypes included in the PCV7 vaccine (4, 6B, 9V, 14, 18C, 19F, and 23F), wrote Xiaofeng Zhou, MD, of Pfizer, New York, and colleagues.

To assess the impact of PCV13, with the additional serotypes 1, 3, 5, 6A, 7F, and 19A, the researchers analyzed data from the U.S. National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey for three time periods: pre-PCV7 (1997-1999), after the introduction of PCV7 (2001-2009), and after the introduction of PCV13 (2011-2013).

Between the pre-PCV7 and PCV13 time periods, the researchers found significant reductions in the mean rates of OM visits of 48% and 41% among children younger than 2 years and younger than 5 years, respectively; reductions were 24% and 22%, respectively, when comparing PCV13 and PCV7. Ambulatory care visits for skin rash and trauma were not significantly different among the study periods.

Comparing the PCV7 and PCV13 time periods, the mean number of OM visits per 100 children declined from 84 to 64 per 100 children younger than 2 years, 41 to 34 per 100 children between ages 2 and 5 years, and from 59 to 46 per 100 children younger than 5 years.

The study findings were limited by several factors including the use of an ecologic study design, which was chosen to help reduce selection bias, but that did not show evidence of the field effectiveness of the PCV13 vaccine. Another limitation was the potential misclassification of patients with OM given clinician variability in diagnostic criteria, the researchers noted.

“Our results in this study, while not providing direct evidence of causality, nonetheless suggest a significant and positive impact of the PCV13 vaccination program on otitis media for children less than 5 years of age in the U.S., with further reductions in OM visits observed in PCV13 period following a decade of PCV7 use,” Dr. Zhou and associates said.

The investigators are employed by Pfizer, which funded the study.

SOURCE: Zhou X et al. Int J Pediatr Otorhinolaryngol. 2019 Apr. 119:96-102.

The mean number of office visits for otitis media in children younger than 5 years dropped significantly after the introduction of the 13-valent pneumococcal conjugate vaccine, according to findings published in the International Journal of Pediatric Otorhinolaryngology.

KatarzynaBialasiewicz/Thinkstock

Previous studies have shown that more than half of children with otitis media (OM) have serotypes included in the PCV7 vaccine (4, 6B, 9V, 14, 18C, 19F, and 23F), wrote Xiaofeng Zhou, MD, of Pfizer, New York, and colleagues.

To assess the impact of PCV13, with the additional serotypes 1, 3, 5, 6A, 7F, and 19A, the researchers analyzed data from the U.S. National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey for three time periods: pre-PCV7 (1997-1999), after the introduction of PCV7 (2001-2009), and after the introduction of PCV13 (2011-2013).

Between the pre-PCV7 and PCV13 time periods, the researchers found significant reductions in the mean rates of OM visits of 48% and 41% among children younger than 2 years and younger than 5 years, respectively; reductions were 24% and 22%, respectively, when comparing PCV13 and PCV7. Ambulatory care visits for skin rash and trauma were not significantly different among the study periods.

Comparing the PCV7 and PCV13 time periods, the mean number of OM visits per 100 children declined from 84 to 64 per 100 children younger than 2 years, 41 to 34 per 100 children between ages 2 and 5 years, and from 59 to 46 per 100 children younger than 5 years.

The study findings were limited by several factors including the use of an ecologic study design, which was chosen to help reduce selection bias, but that did not show evidence of the field effectiveness of the PCV13 vaccine. Another limitation was the potential misclassification of patients with OM given clinician variability in diagnostic criteria, the researchers noted.

“Our results in this study, while not providing direct evidence of causality, nonetheless suggest a significant and positive impact of the PCV13 vaccination program on otitis media for children less than 5 years of age in the U.S., with further reductions in OM visits observed in PCV13 period following a decade of PCV7 use,” Dr. Zhou and associates said.

The investigators are employed by Pfizer, which funded the study.

SOURCE: Zhou X et al. Int J Pediatr Otorhinolaryngol. 2019 Apr. 119:96-102.

The number of reported cases of Fourier gangrene in patients receiving sodium-glucose cotransporter-2 (SGLT2) inhibitors has surged since the US Food and Drug Administration (FDA) issued a 2018 warning about this rare but serious infection, researchers say.

Health care providers prescribing SGLT2 inhibitors to patients with diabetes should have a high index of suspicion for the signs and symptoms of Fournier gangrene, given its substantial morbidity and mortality, according to Susan J. Bersoff-Matcha, MD, and her colleagues at the FDA.

“Although the risk for [Fournier gangrene] is low, serious infection should be considered and weighed against the benefits of SGLT2 inhibitor therapy,” said Dr. Bersoff-Matcha and co-authors in their recent report published in the Annals of Internal Medicine (2019 May 6. doi: 10.7326/M19-0085).

In the previous warning, FDA officials said 12 cases of Fournier gangrene in patients taking an SGLT2 inhibitor had been reported to the agency or in medical literature from March 2013, when the first such inhibitor was approved, and May 2018.

In this latest report, a total of 55 Fournier gangrene cases had been reported in patients receiving SGLT2 inhibitors from March 2, 2013 through January 31, 2019.

The influx of reports may have been prompted by growing awareness of the safety issue, investigators said, but could also reflect the increasing prevalence of diabetes combined with SGLT2 inhibitor use. The researchers also noted that diabetes is a comorbidity in 32% to 66% of cases of Fournier gangrene.

But the likliehood that diabetes mellitus alone causes Fournier gangrene seems unlikley, given that Dr. Bersoff-Matcha and co-authors only found 19 Fournier gangrene cases associated with other classes of antiglycemic agents reported to the FDA or in the literature over a 35-year time frame.

“If Fournier gangrene were associated only with diabetes mellitus and not SGLT2 inhibitors, we would expect far more cases reported with the other antiglycemic agents, considering the 35-year timeframe and the large number of agents,” they said in their report.

Cases were reported for all FDA-approved SGLT2 inhibitors besides ertugliflozin, an agent approved for use in the U.S. in December 2017. The lack of cases reported for this drug could be related to its limited time on the market, the investigators said.

Fournier gangrene, marked by rapidly progressing necrotizing infection of the genitalia, perineum, and perianal region, requires antibiotics and immediate surgery, according to Dr. Bersoff-Matcha and colleagues.

“Serious complications and death are likely if Fournier gangrene is not recognized immediately and surgical intervention is not carried out within the first few hours of diagnosis,” they said in the report.

Of the 55 cases reported in patients receiving SGLT2 inhibitors, 39 were men and 16 were women, with an average of 9 months from the start of treatment to the event, investigators said.

At least 25 patients required multiple surgeries, including one patient who had 17 trips to the operating room, they said. A total of 8 patients had a fecal diversion procedure, and 4 patients had skin grafting.

Six patients had multiple encounters with a provider before being diagnosed, suggesting that the provider may have not recognized the infection due to its nonspecific symptoms, which include fatigue, fever, and malaise.

“Pain that seems out of proportion to findings on physical examination is a strong clinical indicator of necrotizing fasciitis and may be the most important diagnostic clue,” Dr. Bersoff-Matcha and co-authors said in their report.

The incidence of Fournier gangrene in patients taking SGLT2 inhibitors can’t be established by these cases reported to the FDA, which are spontaneously provided by health care providers and patients, investigators said.

“We suspect that our numbers underestimate the true burden,” they said in their report.

Dr. Bersoff-Matcha and co-authors disclosed no conflicts of interest related to their report.

SOURCE: Bersoff-Matcha SJ, et al. Ann Intern Med. 2019 May 6. Doi: doi:10.7326/M19-0085.

This article was updated May 9, 2019.

The number of reported cases of Fourier gangrene in patients receiving sodium-glucose cotransporter-2 (SGLT2) inhibitors has surged since the US Food and Drug Administration (FDA) issued a 2018 warning about this rare but serious infection, researchers say.

Health care providers prescribing SGLT2 inhibitors to patients with diabetes should have a high index of suspicion for the signs and symptoms of Fournier gangrene, given its substantial morbidity and mortality, according to Susan J. Bersoff-Matcha, MD, and her colleagues at the FDA.

“Although the risk for [Fournier gangrene] is low, serious infection should be considered and weighed against the benefits of SGLT2 inhibitor therapy,” said Dr. Bersoff-Matcha and co-authors in their recent report published in the Annals of Internal Medicine (2019 May 6. doi: 10.7326/M19-0085).

In the previous warning, FDA officials said 12 cases of Fournier gangrene in patients taking an SGLT2 inhibitor had been reported to the agency or in medical literature from March 2013, when the first such inhibitor was approved, and May 2018.

In this latest report, a total of 55 Fournier gangrene cases had been reported in patients receiving SGLT2 inhibitors from March 2, 2013 through January 31, 2019.

The influx of reports may have been prompted by growing awareness of the safety issue, investigators said, but could also reflect the increasing prevalence of diabetes combined with SGLT2 inhibitor use. The researchers also noted that diabetes is a comorbidity in 32% to 66% of cases of Fournier gangrene.

But the likliehood that diabetes mellitus alone causes Fournier gangrene seems unlikley, given that Dr. Bersoff-Matcha and co-authors only found 19 Fournier gangrene cases associated with other classes of antiglycemic agents reported to the FDA or in the literature over a 35-year time frame.

“If Fournier gangrene were associated only with diabetes mellitus and not SGLT2 inhibitors, we would expect far more cases reported with the other antiglycemic agents, considering the 35-year timeframe and the large number of agents,” they said in their report.

Cases were reported for all FDA-approved SGLT2 inhibitors besides ertugliflozin, an agent approved for use in the U.S. in December 2017. The lack of cases reported for this drug could be related to its limited time on the market, the investigators said.

Fournier gangrene, marked by rapidly progressing necrotizing infection of the genitalia, perineum, and perianal region, requires antibiotics and immediate surgery, according to Dr. Bersoff-Matcha and colleagues.

“Serious complications and death are likely if Fournier gangrene is not recognized immediately and surgical intervention is not carried out within the first few hours of diagnosis,” they said in the report.

Of the 55 cases reported in patients receiving SGLT2 inhibitors, 39 were men and 16 were women, with an average of 9 months from the start of treatment to the event, investigators said.

At least 25 patients required multiple surgeries, including one patient who had 17 trips to the operating room, they said. A total of 8 patients had a fecal diversion procedure, and 4 patients had skin grafting.

Six patients had multiple encounters with a provider before being diagnosed, suggesting that the provider may have not recognized the infection due to its nonspecific symptoms, which include fatigue, fever, and malaise.

“Pain that seems out of proportion to findings on physical examination is a strong clinical indicator of necrotizing fasciitis and may be the most important diagnostic clue,” Dr. Bersoff-Matcha and co-authors said in their report.

The incidence of Fournier gangrene in patients taking SGLT2 inhibitors can’t be established by these cases reported to the FDA, which are spontaneously provided by health care providers and patients, investigators said.

“We suspect that our numbers underestimate the true burden,” they said in their report.

Dr. Bersoff-Matcha and co-authors disclosed no conflicts of interest related to their report.

SOURCE: Bersoff-Matcha SJ, et al. Ann Intern Med. 2019 May 6. Doi: doi:10.7326/M19-0085.

This article was updated May 9, 2019.

The number of reported cases of Fourier gangrene in patients receiving sodium-glucose cotransporter-2 (SGLT2) inhibitors has surged since the US Food and Drug Administration (FDA) issued a 2018 warning about this rare but serious infection, researchers say.

Health care providers prescribing SGLT2 inhibitors to patients with diabetes should have a high index of suspicion for the signs and symptoms of Fournier gangrene, given its substantial morbidity and mortality, according to Susan J. Bersoff-Matcha, MD, and her colleagues at the FDA.

“Although the risk for [Fournier gangrene] is low, serious infection should be considered and weighed against the benefits of SGLT2 inhibitor therapy,” said Dr. Bersoff-Matcha and co-authors in their recent report published in the Annals of Internal Medicine (2019 May 6. doi: 10.7326/M19-0085).

In the previous warning, FDA officials said 12 cases of Fournier gangrene in patients taking an SGLT2 inhibitor had been reported to the agency or in medical literature from March 2013, when the first such inhibitor was approved, and May 2018.

In this latest report, a total of 55 Fournier gangrene cases had been reported in patients receiving SGLT2 inhibitors from March 2, 2013 through January 31, 2019.

The influx of reports may have been prompted by growing awareness of the safety issue, investigators said, but could also reflect the increasing prevalence of diabetes combined with SGLT2 inhibitor use. The researchers also noted that diabetes is a comorbidity in 32% to 66% of cases of Fournier gangrene.

But the likliehood that diabetes mellitus alone causes Fournier gangrene seems unlikley, given that Dr. Bersoff-Matcha and co-authors only found 19 Fournier gangrene cases associated with other classes of antiglycemic agents reported to the FDA or in the literature over a 35-year time frame.

“If Fournier gangrene were associated only with diabetes mellitus and not SGLT2 inhibitors, we would expect far more cases reported with the other antiglycemic agents, considering the 35-year timeframe and the large number of agents,” they said in their report.

Cases were reported for all FDA-approved SGLT2 inhibitors besides ertugliflozin, an agent approved for use in the U.S. in December 2017. The lack of cases reported for this drug could be related to its limited time on the market, the investigators said.

Fournier gangrene, marked by rapidly progressing necrotizing infection of the genitalia, perineum, and perianal region, requires antibiotics and immediate surgery, according to Dr. Bersoff-Matcha and colleagues.

“Serious complications and death are likely if Fournier gangrene is not recognized immediately and surgical intervention is not carried out within the first few hours of diagnosis,” they said in the report.

Of the 55 cases reported in patients receiving SGLT2 inhibitors, 39 were men and 16 were women, with an average of 9 months from the start of treatment to the event, investigators said.

At least 25 patients required multiple surgeries, including one patient who had 17 trips to the operating room, they said. A total of 8 patients had a fecal diversion procedure, and 4 patients had skin grafting.

Six patients had multiple encounters with a provider before being diagnosed, suggesting that the provider may have not recognized the infection due to its nonspecific symptoms, which include fatigue, fever, and malaise.

“Pain that seems out of proportion to findings on physical examination is a strong clinical indicator of necrotizing fasciitis and may be the most important diagnostic clue,” Dr. Bersoff-Matcha and co-authors said in their report.

The incidence of Fournier gangrene in patients taking SGLT2 inhibitors can’t be established by these cases reported to the FDA, which are spontaneously provided by health care providers and patients, investigators said.

“We suspect that our numbers underestimate the true burden,” they said in their report.

Dr. Bersoff-Matcha and co-authors disclosed no conflicts of interest related to their report.

SOURCE: Bersoff-Matcha SJ, et al. Ann Intern Med. 2019 May 6. Doi: doi:10.7326/M19-0085.

This article was updated May 9, 2019.

The number of U.S. measles cases in 2019 rose by 60 during the week ending May 3, which puts the new postelimination high at 764 cases for the year, according to the Centers for Disease Control and Prevention.

The CDC is currently tracking nine measles outbreaks in six states. The largest outbreak this year has been in New York City, mainly Brooklyn, which has almost half (367) of all cases in the country. An outbreak in New York’s Rockland County has resulted in another 109 cases so far this year. California is experiencing outbreaks in three counties – Butte, Los Angeles, and Sacramento – and the state was up to 40 confirmed cases as of May 1. The other states with outbreaks are Michigan, New Jersey, Georgia, and Maryland.

Twenty-three states now have reported measles cases in 2019, as officials in Pittsburgh reported Pennsylvania’s first case on April 30. Four additional cases in the area were reported on May 2 by the Allegheny County Health Department. A measles outbreak is “defined as three or more cases” by the CDC, but the situation in Pennsylvania is not yet being reported as such.

One Pennsylvania legislator in the state, Rep. Daryl Metcalfe (R) of Butler County, has authored a bill that would “bar health care practitioners and facilities and insurance companies from denying care if parents refuse or delay” recommended vaccinations, PennLive.com reported.

Pennsylvania Governor Tom Wolf (D) said that the “bill would put children, pregnant women, and vulnerable patients at risk of being exposed to horrific diseases – at the doctor’s office.”

[email protected]

The number of U.S. measles cases in 2019 rose by 60 during the week ending May 3, which puts the new postelimination high at 764 cases for the year, according to the Centers for Disease Control and Prevention.

The CDC is currently tracking nine measles outbreaks in six states. The largest outbreak this year has been in New York City, mainly Brooklyn, which has almost half (367) of all cases in the country. An outbreak in New York’s Rockland County has resulted in another 109 cases so far this year. California is experiencing outbreaks in three counties – Butte, Los Angeles, and Sacramento – and the state was up to 40 confirmed cases as of May 1. The other states with outbreaks are Michigan, New Jersey, Georgia, and Maryland.

Twenty-three states now have reported measles cases in 2019, as officials in Pittsburgh reported Pennsylvania’s first case on April 30. Four additional cases in the area were reported on May 2 by the Allegheny County Health Department. A measles outbreak is “defined as three or more cases” by the CDC, but the situation in Pennsylvania is not yet being reported as such.

One Pennsylvania legislator in the state, Rep. Daryl Metcalfe (R) of Butler County, has authored a bill that would “bar health care practitioners and facilities and insurance companies from denying care if parents refuse or delay” recommended vaccinations, PennLive.com reported.

Pennsylvania Governor Tom Wolf (D) said that the “bill would put children, pregnant women, and vulnerable patients at risk of being exposed to horrific diseases – at the doctor’s office.”

[email protected]

The number of U.S. measles cases in 2019 rose by 60 during the week ending May 3, which puts the new postelimination high at 764 cases for the year, according to the Centers for Disease Control and Prevention.

The CDC is currently tracking nine measles outbreaks in six states. The largest outbreak this year has been in New York City, mainly Brooklyn, which has almost half (367) of all cases in the country. An outbreak in New York’s Rockland County has resulted in another 109 cases so far this year. California is experiencing outbreaks in three counties – Butte, Los Angeles, and Sacramento – and the state was up to 40 confirmed cases as of May 1. The other states with outbreaks are Michigan, New Jersey, Georgia, and Maryland.

Twenty-three states now have reported measles cases in 2019, as officials in Pittsburgh reported Pennsylvania’s first case on April 30. Four additional cases in the area were reported on May 2 by the Allegheny County Health Department. A measles outbreak is “defined as three or more cases” by the CDC, but the situation in Pennsylvania is not yet being reported as such.

One Pennsylvania legislator in the state, Rep. Daryl Metcalfe (R) of Butler County, has authored a bill that would “bar health care practitioners and facilities and insurance companies from denying care if parents refuse or delay” recommended vaccinations, PennLive.com reported.

Pennsylvania Governor Tom Wolf (D) said that the “bill would put children, pregnant women, and vulnerable patients at risk of being exposed to horrific diseases – at the doctor’s office.”

[email protected]